Patients with RBM20 cardiomyopathy present with an aggressive phenotype, associated with premature malignant arrhythmias, sudden cardiac death, and progressive heart failure (HF). This study aimed to investigate genotype-phenotype correlations, clinical outcomes, and causes of death in patients with RBM20-associated cardiomyopathy and review the current literature.

The cohort included patients with cardiomyopathy harboring pathogenic (P) or likely pathogenic (LP) RBM20 variants. For survival and regression analysis, a control group matched for sex, age, and presence of left ventricular dysfunction was included. Additionally, a comprehensive literature search was conducted.

Sixty-two patients (45 % male, 42 ± 15 years at presentation) were included. We found 11 truncating variants. Patients with truncating variants diagnosed with HF were older compared to patients with missense variants (mean age 62 ± 9 vs. 45 ± 14; p = 0.01). Over a median follow-up duration of 5.0 [1.0-10.5] years, 21 (34 %) patients reached the composite endpoint, with 19 (31 %) patients experiencing malignant ventricular arrhythmia (VA) (mean age 45 ± 15 years, 63 % males). Males exhibited higher risk for the composite endpoint (log-rank p = 0.02), particularly for VA (log-rank p = 0.007). The literature review analyzed 34 studies comprising 678 patients (53 % male). In these studies, 123 (24 %) patients experienced a VA, 58 (12 %) underwent a heart transplant or were treated with LVAD, and 52 (11 %) died.

This multicenter study highlights the severe phenotype associated with LP/P RBM20 variants, with a high incidence of VA, particularly in males. Additionally, this study presents 11 truncating variants mainly observed in older individuals.

Patent foramen ovale (PFO) and atrial septal defects (ASDs) are two types of interatrial communications with unique clinical presentations and management strategies. The PFO is a normal part of fetal development that typically closes shortly after birth but may persist in as many as 25% to 30% of adults. The communication between atria may result in paradoxic embolism and embolic stroke. On the other hand, ASDs (anatomically defined as secundum, primum, sinus venosus, and coronary sinus in order of prevalence) typically result in right heart volume overload and are often associated with other congenital defects. The diagnostic methods, treatment options including surgical and percutaneous approaches, and potential complications are described. Both conditions underline the significance of precise diagnosis and appropriate management to mitigate risks and ensure optimal patient outcomes.

Early neurological deterioration (END) is a forecast factor in poor outcomes in minor strokes. END's prevalence and forecast factors in minor strokes caused by small artery occlusion (SAO) are still unclear.

We retrospectively analyzed 451 patients with minor stroke (NIHSS ≤ 5) caused by SAO hospitalized within an initial 24 h at BachMai Hospital's stroke center. END was defined as conditions with an elevated two or more NIHSS points within an initial 72 h. The primary outcome included the determination of the END incidence. The secondary outcome identified forecast factors for END through multivariate logistic regression analyses, and therapeutic impacts of antiplatelet and thrombolytic treatments.

END occurred in 9.5 % (43/451) of patients (62.7 % male, mean age 63.8 ± 11.8 years). Independent forecast included admission SBP ≥ 150 mmHg (OR = 1.99; 95 % CI: 1.01 - 3.94; p = 0.048), diabetes history (OR = 0.58; 95 % CI: 1.05 - 4.33; p = 0.036), admission blood glucose ≥ 14mmol/L (OR = 2.99; 95 % CI: 1.05 - 8.54; p = 0.04), and internal capsule infarction (OR = 2.23; 95 % CI: 1.01 - 4.92; p = 0.048). The patients group admitted within 4.5 h, DAPT has significantly lower END risk compared to SAPT (OR = 0.079; 95 % CI: 0.007 - 0.939; p = 0.04) and altepase (OR = 0.013; 95 % CI: 0.01 - 0.12; p < 0.01). END risk was similar between SAPT and altepase (p = 0.074).

END is a 9.5 % incidence in minor acute ischemic stroke due to SAO. Independent forecasts are admission SBP and blood glucose, diabetes history, and internal capsule infarction. The DAPT group has significantly lower END risk than the SAPT and alteplase groups.

Studies suggest that longer duration of cardiac monitoring after embolic stroke of undetermined source (ESUS) yields higher detection rates for atrial fibrillation (AF). A common strategy for cardiac monitoring after ESUS starts with a 14-day surface monitor, which is easier to administer, and lower cost compared to implantable monitoring. We tested whether cardiac markers associated with higher likelihood of AF detection can be used to identify patients with ESUS who are more likely to benefit from initial short-term monitoring.

We adjudicated stroke etiology from patients with acute ischemic stroke discharged from a tertiary care medical center with 14-day surface cardiac monitor (ZioPatch®) between January 2019 and September 2023. The primary outcome was ≥30 seconds of AF on surface monitoring. Predictors included ECG and echocardiographic markers associated with AF in a general population identified during hospitalization. Associations were analyzed using Chi-squared or Fisher's exact tests and age-adjusted logistic regression.

We identified 415 patients with ESUS (mean age 67.2 years, 49.9% female). 4.3% (n=18/415) developed AF after a median of 13.8 days (IQR 13-15.8) of monitoring. 9.6% (n=8/83) of patients with enlarged left atrial dimension >4cm and 8.0% (n=9/113) of patients with mitral valve regurgitation developed AF. Significantly more patients with AF had a combination of enlarged left atrial dimension and/or mitral valve regurgitation (36.8% with AF vs 61.1% without AF, p=0.037). Adjusting for age, enlarged left atrial dimension remained significantly associated with increased odds of detection of AF (OR 3.17, 95% CI 1.20-8.36).

In patients with ESUS, the rate of AF detection using a surface 14-day cardiac monitor was low. However, the likelihood of detecting AF was higher among patients with enlarged left atrial dimension and mitral valve regurgitation, suggesting this group may benefit most from an initial short-term monitoring strategy.

Poor socioeconomic conditions are linked to increased stroke-related mortality and worse clinical outcomes post-stroke. This study examines the association between neighborhood socio-demographic (NSD) profile and adequate transitions of care (ATOC) in acute ischemic stroke patients one month after discharge.

The Transitions of Care Stroke Disparities Study (TCSD-S) is an observational prospective cohort investigating disparities in stroke care transitions. Data from 1132 acute ischemic stroke (AIS) patients was obtained from three sources: 1) publicly available NSD data using participants' ZIP codes, 2) Structured telephone interviews at 30 days post-discharge to ascertain participants' behavior in six categories, and 3) covariates obtained from Get with the Guidelines-Stroke® (GWTG-S). Logistic regression models examined the relationship between NSDs and achieving ATOC, defined as adherence to at least 75 % of the six behavioral modifications for ATOC, adjusting for patient demographics, social determinants of health, and stroke severity.

The sample included 56 % males, 51.5 % non-Hispanic White, 22.6 % non-Hispanic Black, and 21.8 % Hispanic individuals, with a median age of 64 (IQR = 55-74 years). ATOC was achieved in 994 (88 %) participants. While NSDs did not independently predict the overall ATOC success, we observed a direct association of NSD profile (education level and median income) with patients' adherence to rehabilitation follow-up (p = 0.03), toxic habit cessation (p = 0.04), and medical appointment attendance (p = 0.04), independent of the effects of individual socioeconomic status.

Neighborhood socioeconomic status directly impacts protective behaviors. This finding can inform future community-level interventions aimed at improving patients' adherence to behavioral modifications.

The risk of stroke among patients with cancer is two times that of the general population due to a combination of cancer-, chemotherapy-, radiotherapy-, and surgery-related factors. There is a paucity of data regarding the optimal antithrombotic therapy for secondary stroke prevention in these patients.

Our goal was to review the stroke recurrence in patients treated with different antithrombotic therapies (antiplatelets, warfarin, heparin, and direct oral anticoagulants). Our secondary objective was to review the bleeding risk across different antithrombotic therapies.

A review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles that adequately assessed secondary prevention of stroke in patients with cancer were selected from the PubMed, Embase, and Scopus databases from inception until March 2, 2025. We performed a network meta-analysis for stroke recurrence, major bleeding, and mortality. The treatments were ranked by P-SCORE. Subgroup analyses were conducted based on median D-dimer levels, multiple territories of stroke, and exclusion of studies with high risk of bias.

We included 11 studies (four RCTs, six retrospective studies, and one case series) with a total of 1319 patients. In the primary analysis, antiplatelets were the highest-ranked treatment for reducing stroke recurrence (RR 0.44 [0.20; 0.96]), followed by LMWH (RR 0.50 [0.26; 0.96]), both significantly superior to no treatment. However, LMWH consistently ranked higher than antiplatelets in all subgroup analyses. There was no difference regarding major bleeding or mortality.

Antiplatelets can be considered an option for secondary prevention of stroke in patients with cancer, especially in patients with a higher bleeding risk. Future research with high-quality studies is needed to confirm our preliminary findings and should focus on identifying subgroups of patients with cancer who may benefit most from specific antithrombotic therapies.

Brain lesion segmentation is challenging in medical image analysis, aiming to delineate lesion regions precisely. Deep learning (DL) techniques have recently demonstrated promising results across various computer vision tasks, including semantic segmentation, object detection, and image classification. This paper offers an overview of recent DL algorithms for brain tumor and stroke segmentation, drawing on literature from 2021 to 2024. It highlights the strengths, limitations, current research challenges, and unexplored areas in imaging-based brain lesion classification based on insights from over 250 recent review papers. Techniques addressing difficulties like class imbalance and multi-modalities are presented. Optimization methods for improving performance regarding computational and structural complexity and processing speed are discussed. These include lightweight neural networks, multilayer architectures, and computationally efficient, highly accurate network designs. The paper also reviews generic and latest frameworks of different brain lesion detection techniques and highlights publicly available benchmark datasets and their issues. Furthermore, open research areas, application prospects, and future directions for DL-based brain lesion classification are discussed. Future directions include integrating neural architecture search methods with domain knowledge, predicting patient survival levels, and learning to separate brain lesions using patient statistics. To ensure patient privacy, future research is anticipated to explore privacy-preserving learning frameworks. Overall, the presented suggestions serve as a guideline for researchers and system designers involved in brain lesion detection and stroke segmentation tasks.

The detection of atrial fibrillation (AF) after a cryptogenic stroke (CS) carries important therapeutic implications. In this study, we aimed to accurately assess the incidence of AF among CS subjects by using an insertable cardiac monitor (ICM).

A prospective, single-arm, multicentre registry was conducted to identify AF in 155 CS subjects using the Confirm Rx ICM (Abbott, California, USA) across 20 global sites. Inclusion criteria comprised participants aged 40 years or older who had experienced CS within a 90-day window. At each follow-up visit, expert electrophysiologists reviewed and adjudicated ICM detected AF episodes. The primary endpoint was the cumulative incidence of true device-detected AF (lasting more than 30 s) at 6 months, evaluated with Kaplan-Meier methods.

AF incidence was 21.3% (95% CI 15.3% to 29.1%) at 6 months, increasing to 48.8% (95% CI 34.7% to 64.9%) at 24 months. Subjects with AF detection experienced an average of 50.9 true AF episodes per subject per year. The median time from implantation to AF detection (>30 s) was 72 days (IQR 7-261). Among subjects with 30 s AF detection, anticoagulation therapy was initiated in 65.2% (30/46) of subjects. Oral anticoagulation medication was prescribed in 8.3% (9/109) of subjects without AF. Recurrent ischaemic stroke or transient ischaemic attack occurred in 5 subjects (3.2%, 5/155).

These results show that ICM-driven long-term continuous AF monitoring is associated with high diagnostic yield in CS subjects.

NCT03505801.

Stroke is one of the leading causes of disability and mortality worldwide, with ischemic stroke representing the most prevalent and devastating form. This review offers an in-depth exploration of the critical role of N-Methyl-D-Aspartate Receptor (NMDAR) signaling in mediating the brain's response to ischemic injury. NMDAR activation triggers glutamate excitotoxicity, setting off a cascade of neurotoxic events that lead to mitochondrial dysfunction and the generation of reactive oxygen species (ROS). These damaging processes not only intensify neuronal injury but also activate apoptotic pathways, including p53-mediated and Notch signaling. Furthermore, the review highlights necroptosis as a key cell death mechanism in ischemic injury and examines the subsequent disruption of the blood-brain barrier (BBB), which exacerbates brain damage. In the context of neuroprotective signaling, we explore the distinct roles of synaptic and extrasynaptic NMDAR activation, neurotrophic factor-mediated signaling, and the intricate crosstalk between neurotoxic and neuroprotective pathways. This review also explores novel hypotheses and emerging perspectives in NMDAR-mediated ischemic stroke, highlighting potential mechanisms and therapeutic implications. Additionally, it covers cutting-edge experimental approaches to investigate NMDAR function in stroke and provides critical insights into conflicting findings in NMDAR research, addressing key controversies and their impact on future studies. Therapeutic strategies targeting ischemic stroke are critically examined, with an emphasis on potential interventions that could mitigate the effects of ischemia. The review also highlights ongoing clinical trials investigating novel therapeutic approaches and outlines the future direction of ischemic stroke therapy. This comprehensive review offers a deep understanding of the complex molecular mechanisms involved in ischemic stroke via NMDAR and provides valuable insights into the promising therapeutic avenues that could lead to more effective treatments.

Paradoxical embolism is a potential pathophysiology in patients with acute ischemic stroke or transient ischemic attack (TIA) and patent foramen ovale (PFO) or atrial septal defect (ASD). We sought to determine the frequency of deep vein thrombosis (DVT) detection by standardized lower extremity venous compression ultrasound (LE-CUS) in patients with acute cerebral ischemia and cardiac right-to left shunt due to PFO or ASD on transoesophageal echocardiogram (TEE).

We analysed consecutive patients (01/2015-12/2020) with acute cerebral ischemia and PFO or ASD on TEE, who received DVT screening by LE-CUS per institutional standard. We determined clinical baseline variables including shunt-size categorized as small, medium or large, and analysed the frequency of DVT. We performed multivariable analysis to identify predictors for presence of DVT on LE-CUS.

Among 1564 patients with acute ischemic stroke (n = 1326) or TIA (n = 238) who received TEE, 390 patients had PFO and 10 patients ASD, of whom 274 were screened for DVT by LE-CUS (153 [55.8%] female, age 64 years [51-76], NIHSS score 4 [1-9.5]). Of these, 55 patients (20.1%) had DVT on LE-CUS. Among patients with DVT, 23 of 76 patients (30.3%) who received LE-CUS within 72 h from admission compared to 32 of 198 patients (16.2%) who received LE-CUS at later time points had presence of DVT (p = 0.012). The percentage of patients with DVT tended to be higher among patients with cryptogenic ischemic stroke compared to patients with other stroke etiologies (21.8% [49 of 225] vs. 12.2% [6 of 49]; p = 0.168). Presence of DVT was associated with female sex (OR 2.24, 95%CI 1.09-4.62), NIHSS score (OR 1.06, 95%CI 1.03-1.10), Wells score (OR 1.54, 95%CI 1.11-2.13) and shunt size (OR 3.32, 95%CI 1.86-5.91).

Our data suggest a high diagnostic yield (> 20%) of standardized screening for DVT with LE-CUS in patients with acute cerebral ischemia and PFO or ASD. This particularly applies to females, patients with more severe baseline deficits and large right-to-left shunt. These findings may not be generalizable to all patients with PFO or ASD and need prospective validation.

Early initiation of direct oral anticoagulants (DOACs) after acute ischemic stroke (AIS) in patients with nonvalvular atrial fibrillation (NVAF) can prevent early recurrent AIS but may increase the risk of intracerebral hemorrhage (ICH). The appropriate DOAC initiation time remains uncertain. This systematic review and meta-analysis aimed to determine the optimal timing for DOAC initiation following NVAF-associated AIS.

We systematically searched PubMed, Embase, Scopus, and the Cochrane Library from inception to March 2025. Eligible studies were randomized controlled trials and prospective cohort studies examining the effects of DOAC initiation timing in patients with NVAF-associated AIS. The primary outcome was the pooled risk ratio for a composite measure of ischemic and hemorrhagic events. Secondary outcomes were the pooled risk ratios for symptomatic ICH, recurrent AIS, major extracranial bleeding, and mortality. Subgroup analyses examined patients initiating DOACs within 3 days of stroke onset and compared outcomes based on baseline stroke severity (NIHSS < 5 vs ≥ 5).

Eleven studies from ten cohorts (12,388 participants) met the inclusion criteria. No significant differences were found between early and delayed DOAC initiation for the composite outcomes or for any secondary endpoint. Subgroup analyses revealed a nonsignificant increase in ICH risk among patients with early treatment and higher stroke severity (NIHSS ≥ 5). No significant differences in early ischemic stroke rate were observed in both subgroups.

Early DOAC initiation appears to be safe following NVAF-associated AIS, including in patients with moderate stroke severity. However, the rate of early recurrent ischemic stroke remains comparable between early and delayed initiation groups.

The usual antithrombotic treatment for symptomatic intracranial atherosclerotic stenosis (ICAS) consists of dual treatment with clopidogrel and aspirin for 90 days followed by aspirin alone but the risk of recurrent stroke remains high up to 12 months. The Comparison of Anticoagulation and anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA) trial was designed to determine whether other combinations of dual antithrombotic therapy are superior to clopidogrel and aspirin.

CAPTIVA is an ongoing, prospective, double-blinded, three-arm clinical trial at over 100 sites in the United States and Canada that will randomize 1683 high-risk subjects with a symptomatic infarct attributed to 70-99% stenosis of a major intracranial artery to 12 months of treatment with (1) ticagrelor (180 mg loading dose, then 90 mg twice daily), (2) low-dose rivaroxaban (2.5 mg twice daily), or (3) clopidogrel (600 mg loading dose, then 75 mg daily). All subjects receive aspirin (81 mg daily), intensive risk factor management, and will undergo blinded CYP2C19 genotype analysis. The primary goal of the trial is to determine whether rivaroxaban or ticagrelor or both are superior to clopidogrel for lowering the primary endpoint (ischemic stroke, intracerebral hemorrhage (ICH), or vascular death) within 12 months. A prespecified interim safety analysis will be conducted when the first 450 randomized subjects have been followed for 12 months to evaluate the risk of major hemorrhage in the rivaroxaban and ticagrelor arms.

Enrollment began in August 2022 and, as of 26 June 2024, the 450th subject was randomized into the study.

CAPTIVA is evaluating two alternative dual antithrombotic therapies to clopidogrel and aspirin to maximize the chance of establishing more effective antithrombotic therapy for symptomatic ICAS, one of the most common and high-risk cerebrovascular diseases worldwide.

The diagnostic workup for patients with cryptogenic stroke includes investigating for occult cancer, which is known to increase the risk of stroke. Current guidelines do not provide specific recommendations regarding the optimal approach for occult cancer screening after cryptogenic stroke. We surveyed Canadian stroke and thrombosis physicians to determine current workup preferences for detecting occult cancer after cryptogenic stroke.

We designed and distributed an anonymous online survey targeting physicians who manage patients with cryptogenic stroke through professional memberships of the Canadian Stroke Consortium and Thrombosis Canada. Using 4 clinical scenarios representative of patients with cryptogenic stroke with different ages (younger or older than 50 years) and from both sexes, we asked respondents which tests they routinely recommend when investigating for occult cancer among a list of laboratory investigations, imaging, and procedures. Results were analyzed using descriptive statistics.

We received 138 responses to 5 survey questions. The most commonly recommended investigations were complete blood count (79%), creatinine (63%), and coagulation tests (56%), and the most frequently recommended imaging test was CT of the abdomen and pelvis (39%). A minority of respondents indicated they would order guideline-directed age-appropriate cancer screening. Approximately half of surveyed specialists deferred the workup of cancer to a primary care physician, and 12% did not suggest any cancer workup at all.

This survey of stroke and thrombosis experts found heterogeneity in testing for cancer screening in patients with cryptogenic stroke, with the majority either not screening at all or deferring tests to primary care providers. Our survey highlights the need for better evidence and evidence-based recommendations to guide the approach to cancer screening in this population.

Intracranial atherosclerotic disease (ICAD) is one of the leading causes of ischemic stroke worldwide. Despite advances in its diagnosis and management, there is no clear consensus on best practices to manage ICAD. This report summarizes the ARISE II (Roundtable Discussion With Industry and Stroke Experts) consensus in treating ICAD. The consensus underscored the importance of lifestyle modification and medical management in patients with ICAD. Patients who fail medical management are candidates for endovascular treatment. Open surgery is not recommended in patients who lack demonstrated hemodynamic insufficiency. The consensus also identified gaps in knowledge about the optimal duration of antithrombotics, the effect of the CYP2C19 genotype on medical management, the need for newer devices, and the standardization of antithrombotic protocols before stenting in an acute setting. Optical coherence tomography requires additional clinical data before defining its role in the diagnosis of ICAD.

Stroke is the second leading cause of death worldwide and the third leading cause of death and disability combined. Among ischemic strokes, 25 % to 40 % are classified as cryptogenic, with patent foramen ovale (PFO) identified as a potential underlying cause. PFO is found in 25 % of the general population. Despite the significant occurrence of PFO-associated strokes, the associated costs remain largely unexplored.

This study aimed to evaluate the annual economic burden of PFO-associated stroke in the US.

A cost-of-illness study was performed, encompassing the direct and indirect costs of PFO-associated stroke on both society and the healthcare system. The model adopted a top-down approach and a one-year, US societal perspective. A payer perspective and bottom-up costing approach were included as scenario analyses. Data was obtained by a targeted literature review.

The societal model, assuming 32.5 % cryptogenic strokes, incurs an annual cost of over $1.3 billion in the US, with over $1.0 billion coming from new strokes and over $300 million from recurrent strokes. The majority of the costs are indirect-50 % from productivity losses due to premature death and 27 % from other productivity losses. Direct costs constitute 23 % of the total. From the payer perspective, the annual costs for PFO-associated strokes in the US were estimated at $302 million, with hospitalization costs comprising 44 %, followed by prescriptions and outpatient care at 19 % and 16 %, respectively.

The economic burden of PFO-associated strokes in the US is substantial, exceeding $1.3 billion per year. Different types of medical management or surgical treatments for PFO-associated stroke could lead to gains in both costs and health outcomes.

BACKGROUND: The purpose of this study is to examine factors affecting functional improvement among survivors of stroke during the initial months of stroke recovery. METHODS: A 1-group repeated measures sequential mixed methods design was used. Quantitative longitudinal data were collected on admission, discharge, and postdischarge from the inpatient rehabilitation unit to evaluate the change in patient engagement and the relationship between environmental, personal, and behavioral factors, and functional independence. Semistructured interviews were conducted up to 6 months postdischarge. RESULTS: The sample included 27 participants with a mean age of 64.67 (SD = 13.56). There was a significant increase in patient engagement from admission to discharge ( P < .0001), followed by a nonsignificant decrease from discharge to follow-up ( P = .36). The change in functional improvement from admission to discharge was significant ( P < .0001). Stroke severity was the only significant predictor of functional improvement ( P = .008). There was a significant but weak negative correlation between Patient Health Engagement scale (PHE-s®) total score and sleep disturbance ( r = -0.344, P = .008) and sleep disturbance and self-efficacy ( r = -0.362, P = .005). There was a moderate positive correlation between PHE-s total score and self-efficacy ( r = 0.662, P < .001). Five participants participated in follow-up interviews. The 5 main themes that emerged from interview data were (1) feeling happy to be home, (2) wishing recovery was quicker, (3) living with disability, (4) overcoming obstacles, and (5) social support. CONCLUSION: This pilot study provides insight into the experiences of survivors of stroke during rehabilitation and recovery. The results of this study indicate a need for additional support (eg, transportation, social/emotional) for survivors of stroke after discharge from the rehabilitation unit. Further research to investigate the barriers and facilitators of recovery for survivors of stroke after discharge and the development of interventions aimed at improving sustainable recovery outcomes is needed.

Detection of undiagnosed atrial fibrillation (AF) after ischemic stroke through extended cardiac monitoring is important for preventing recurrent stroke. We evaluated whether a tool that displays clinically predicted AF risk to clinicians caring for stroke patients was associated with the use of extended cardiac monitoring.

We prospectively included hospitalized ischemic stroke patients without known AF in a preintervention (October 2018 - June 2019) and intervention period (March 11, 2021 - March 10, 2022). The intervention consisted of an electronic health record (EHR)-based best-practice advisory (BPA) alert which calculated and displayed 5-year risk of AF. We used a multivariable Fine and Gray model to test for an interaction between predicted AF risk and period (preintervention vs intervention) with regards to incidence of extended cardiac monitoring. We compared the incidence of extended cardiac monitoring within 6-months of discharge between periods, stratified by BPA completion.

We included 805 patients: 493 in the preintervention cohort and 312 in the intervention cohort. In the intervention cohort, the BPA was completed for 180 (58%) patients. The association between predicted clinical risk of AF and incidence of 6-month extended cardiac monitoring was not different by time period (interaction HR = 1.00 [95% Confidence Interval (CI) 0.98; 1.02]). The intervention period was associated with an increased cumulative incidence of cardiac monitoring (adjusted HR = 1.32 [95% CI 1.03-1.69]).

An embedded EHR tool displaying predicted AF risk in a poststroke setting had limited clinician engagement and predicted risk was not associated with the use of extended cardiac monitoring.

NCT04637087.

A growing number of opportunities for paying customers to travel to space are becoming available. Preflight medical screening of these potential private astronauts will likely be performed by local physicians, with referral to specialists in aerospace medicine as required for more in-depth evaluation before flight qualification. Neurologic concerns contribute a portion of the potential medical risks for these private astronauts, especially with the participation of more diversified crews than traditional governmental astronauts. The objective of this article was to review the current knowledge base concerning cerebrovascular adaptation to spaceflight to inform risk factor assessment for flight-associated cerebrovascular emergencies by the neurologic community when performing initial medical screening of potential private astronauts.

A review of published human spaceflight studies and medical guidelines regarding cerebrovascular risks for spaceflight was conducted. Most of the available literature describes cohorts of a small number of astronauts undergoing spaceflight missions of various flight profiles. While there are gaps in the literature, cerebrovascular adaptation to spaceflight occurs, which may alter the medical risk profile in susceptible individuals. The occurrence of an inflight cerebrovascular emergency could have devastating consequences; therefore, additional screening tests may be required, based on risk level and mission profile, in assessing the more diverse commercial spaceflight population expected over the next decade.

With increasing interest in commercial space tourism among diverse participant populations, the stroke risk in microgravity/reduced gravity environments is unknown. Furthermore, stresses of rocket ascent/descent, abnormal fluid dynamics in microgravity, altered atmospheric conditions, and other unknown occupational hazards add additional complexity. Because inflight emergency management protocols have yet to be developed, the most effective tool to ensure spaceflight participant safety is comprehensive preflight preventative screenings. Determining neurologic risk factors is critical for developing evidence-based guidelines for preventative measures and treatment protocols in the future.

While interindividual variations in concentration and function of coagulation cascade proteins are established risk factors for venous thromboembolism (VTE), their associations with arterial ischemic stroke are less well defined.

We identified and validated genetic proxies for lifelong, randomized perturbations of coagulation cascade proteins in genome-wide association studies of circulating protein levels (deCODE, n=35 559; UK Biobank, n=46 218) and of VTE risk (81 190 cases and 1 419 671 controls). Study participants were all of European ancestry. We performed 2-sample Mendelian randomization and colocalization analyses to test associations of these genetic proxies with risk of ischemic stroke (62 100 cases and 1 234 808 controls from the GIGASTROKE consortium) and ischemic stroke subtypes, and further contextualized associations with VTE and secondary efficacy and safety outcomes.

We identified genetic proxies for 30 coagulation factors, with cross-trait associations recapitulating canonical coagulation biology. Mendelian randomization and colocalization analyses supported causal associations of genetically proxied levels of 5 proteins with risk of ischemic stroke, with all proteins associating with the cardioembolic stroke subtype: factor XI (odds ratio [OR] of cardioembolic stroke per 1-SD increase, 1.31 [95% CI, 1.19-1.44]; P=3.30×10-8), high-molecular-weight kininogen (OR, 1.19 [95% CI, 1.09-1.30]; P=7.79×10-5), prothrombin (OR, 1.83 [95% CI, 1.31-2.57]; P=4.20×10-4), soluble PROCR (protein C receptor; OR, 0.88 [95% CI, 0.82-0.95]; P=6.19×10-4), and γ' fibrinogen (OR per doubling in VTE risk due to lower γ' fibrinogen levels, 1.44 [95% CI, 1.25-1.66]; P=3.96×10-7). γ' Fibrinogen and prothrombin also associated with large artery atherosclerotic stroke, and no proteins were associated with small vessel stroke risk. By contrast, genetic proxies for several coagulation factors (including proteins C and S and factors V and VII) showed selective associations with VTE.

These data highlight specific coagulation cascade components implicated in ischemic stroke pathogenesis, while identifying proteins with distinct roles in VTE. These findings may inform development of novel anticoagulants and optimize their use in targeted populations with stroke.

Advances in genomic technologies have significantly enhanced our understanding of both monogenic and polygenic etiologies of cardiovascular disease. In this review, we explore how the utilization of genomic information is bringing personalized medicine approaches to the forefront of cardiovascular disease management. We describe how genomic data can resolve diagnostic uncertainty, support cascade screening, and inform treatment strategies. We discuss how genome-wide association studies have identified thousands of genetic variants associated with polygenic cardiovascular diseases, and how integrating these insights into polygenic risk scores can enhance personalized risk prediction beyond traditional clinical algorithms. We detail how pharmacogenomics approaches leverage genotype information to guide drug selection and mitigate adverse events. Finally, we present the paradigm-shifting approach of gene therapy, which holds the promise of being a curative intervention for cardiovascular conditions.

Activated platelets modulate immune responses. Platelet activation coincides with poststroke immunosuppression, so we hypothesized that platelet inhibition would mitigate immunosuppression and decrease the risk of infectious complications after stroke. In this study, we aimed to evaluate the contribution of platelet inhibition by antiplatelet agents to poststroke infection.

We performed a prospective cohort study of 975 patients with acute ischemic stroke to compare the differences in the risk of infection within 7 days after admission between aspirin alone, clopidogrel alone and aspirin plus clopidogrel. Multivariable Cox proportional hazards regression model was used to assess the association between antiplatelet therapy and poststroke infection.

Among 975 included patients, 578 received aspirin, 98 received clopidogrel, and 299 received both. A total of 113 patients experienced poststroke infection within 7 days after admission. The combination of aspirin and clopidogrel decreased the risk of poststroke infection compared with aspirin alone (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.22-0.77; P = 0.006), as compared with clopidogrel alone (HR, 0.46; 95% CI, 0.22-1.00; P = 0.050). We found no difference in infection risk between clopidogrel and aspirin. When assessing site-specific infections, a significant difference was observed only in the risk of pneumonia between dual antiplatelet therapy and aspirin alone.

Dual antiplatelet therapy with aspirin and clopidogrel is associated with decreased infection after stroke compared with aspirin or clopidogrel monotherapy. The findings support the net protective effect of aspirin and clopidogrel against poststroke infection.

The prevalence of cerebral small vessel disease (CSVD) imaging markers is high, yet their influence on stroke prognosis remains unclear. This study aimed to estimate the effects of CSVD on the efficacy and safety of clopidogrel+aspirin versus aspirin among patients with minor stroke or high-risk transient ischemic attack.

This was a post hoc subgroup analysis of the INSPIRES trial (Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis), which was a double-blind, placebo-controlled, 2×2 factorial, and randomized clinical trial conducted at 222 centers in China from September 2018 to October 2022. Patients were classified into CSVD score 0 to 2 and CSVD score ≥3 groups based on a modified CSVD burden score without microbleeds. The primary efficacy and safety outcomes were stroke recurrence and moderate-to-severe bleeding risk within 90-day follow-up. We used Cox proportional hazards models to test the treatment-by-CSVD group interaction for stroke and bleeding risk.

A total of 5126 patients (median age, 65 [57-71] years; 3915 [64.2%] males) were enrolled and 2131 (41.57%) had a modified CSVD score ≥3. Patients with CSVD score ≥3 had numerically higher stroke recurrence rate (9.10% versus 8.05%) and lower risk of moderate-to-severe bleeding (0.56% versus 0.80%) than those with CSVD score 0 to 2 within 90 days. Clopidogrel+aspirin versus aspirin reduced stroke recurrence to a similar relative degree in both CSVD score 0 to 2 (adjusted hazard ratio, 0.78 [95% CI, 0.61-1.01]; P=0.06) and CSVD score ≥3 groups (adjusted hazard ratio, 0.82 [95% CI, 0.62-1.09]; P=0.12) with no evidence of statistical interaction (P=0.84). Clopidogrel+aspirin versus aspirin increased bleeding risk to a similar relative degree in both CSVD score 0 to 2 (adjusted hazard ratio, 2.83 [95% CI, 1.52-5.27]; P=0.03) and CSVD score ≥3 groups (adjusted hazard ratio, 2.13 [95% CI, 1.08-4.19]; P=0.22) with no statistical interaction (P=0.68).

In this post hoc subgroup analysis, no significant interaction effect was observed between the antiplatelet treatment and the modified CSVD score, suggesting that clopidogrel+aspirin may not provide a significantly different benefit-risk profile across patients with CSVD score 0 to 2 versus CSVD score ≥3.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03635749.

Over the past two decades, there has been a continuous improvement in outcome for patients with indolent lymphoma (iNHL) resulting in a gradual accumulation of survivors. While life expectancy in the current era approaches that of the lymphoma-free population, patients continue to experience lifelong complications of the disease and its treatment affecting general health, emotional, psychological and social wellbeing, relationships, employment, finances, and fitness. Contemporary care models while suited to the management of lymphoma are often lacking when it comes to identification and management of these additional needs. Given improvements in physical survival achieved over the past decades, it is timely for us to focus on other issues affecting patient wellbeing including immunodeficiency and infection, second cancers, cardiovascular disease, bone health, psychological wellbeing, and sexual health. Many of these aspects are in the domain of the primary care physician; however, there is limited guidance on how these issues should be addressed. It is now time for us to engage our patients, their caregivers, and other healthcare providers in care aspects beyond the lymphoma diagnosis, so they can anticipate a rich and full life, free from both direct and indirect consequences of the lymphoma diagnosis.

This study was aimed to investigate the relationship between neuron-specific enolase (NSE) and swallowing dysfunction in patients with acute ischemic stroke (AIS) and evaluate the impact of early enteral nutrition intervention on NSE levels.

A retrospective study was conducted involving 445 AIS patients admitted to the neurology department of the Affiliated Hospital of Jiaxing University between September 2015 and August 2022. Data collected included gender, age, water-swallowing test (WST) score upon admission, and NSE examination results on admission, the 5th day, and the 10th day.

Among 445 enrolled AIS patients, 42.0% (187/445) exhibited swallowing dysfunction. Key findings revealed: (1) Positive correlation between WST severity and serum NSE levels across all timepoints (P < 0.05). (2) Dysphagia patients demonstrated elevated NSE levels versus controls (P < 0.05). (3) Early enteral nutrition intervention (n = 98) significantly reduced NSE levels by day 10 compared to non-intervention group (P < 0.05), though no intergroup differences were observed at admission or day 5 (P > 0.05).

NSE measurement is a simple supplement to the WST. There existed a significant correlation between NSE and swallowing dysfunction, making NSE a potential preliminary screening indicator for evaluating in ischemic stroke patients. And early implementation of enteral nutrition intervention could effectively reduce NSE levels in patients with ischemic stroke.

To prevent stroke recurrence in stroke survivors, effective management of vascular risk factors (VRFs), including hypertension, diabetes, hyperlipidemia, and smoking, is essential. This study aimed to assess the VRF control status and trends among stroke survivors in Korea.

This cross-sectional study analyzed data from 1,261 stroke survivors aged ≥ 19 years (mean age: 65.2 years; 43.1% female) who were part of the Korea National Health and Nutrition Examination Survey from 2010 to 2021. The control status of VRFs was evaluated using standardized criteria: hypertension (blood pressure < 140/90 mmHg), diabetes (hemoglobin A1c < 7%), hyperlipidemia (low-density lipoprotein cholesterol [LDL-C] < 70 mg/dL), and smoking status. Multivariate logistic regression analysis was conducted to identify factors associated with uncontrolled VRFs.

The rates of age-adjusted hypertension, diabetes, and smoking control remained consistent throughout the observation period. However, overall LDL-C control improved from 30.1% in 2010-2012 to 40.4% in 2019-2021 (P = 0.015), particularly in those aged ≥ 65 years. However, in the 19-49 age group, the control rate decreased from 47.0% to 15.8% (P = 0.048). Smoking rates showed no significant improvement (70.2% in 2019-2021 compared to 69.6% in 2010-2012), particularly among men. Living alone (adjusted odds ratio [aOR], 1.85; 95% confidence interval [CI], 1.03-3.32) was significantly associated with uncontrolled hypertension, whereas living in urban areas was linked to uncontrolled diabetes (aOR, 2.75; 95% CI, 1.06-7.17). Non-health screening was significantly associated with uncontrolled hyperlipidemia (aOR, 2.28; 95% CI, 1.25-4.14), and men were more likely to continue smoking (aOR, 4.47; 95% CI, 3.12-6.72).

These findings highlight the need for targeted health strategies to enhance risk-factor management and reduce stroke recurrence.

Atrial fibrillation (AF) is a common comorbidity in patients with extracranial neurovascular disease. When these patients require interventional procedures, the optimal perioperative anticoagulation regimen remains unclear. This study evaluates the safety and efficacy of a perioperative antithrombotic strategy for non-valvular atrial fibrillation (NVAF) patients undergoing carotid artery stenting (CAS) or vertebral artery stenting (VAS).

We retrospectively analyzed clinical data from NVAF patients treated with CAS/VAS between January 2018 and June 2023. The pre-procedural regimen included aspirin (100 mg/day), clopidogrel (75 mg/day), and prophylactic low molecular weight heparin (LMWH). Post-procedural therapy combined a novel oral anticoagulant (NOAC) with a P2Y12 inhibitor.

Thirty patients (71.3 ± 6.9 years; 93.3% male) achieved technical success. Complications included one hemorrhage and one unexplained cerebral embolism. No acute/subacute stent thrombosis or restenosis occurred within 3 months.

Dual antithrombotic therapy (NOAC + P2Y12 inhibitor) post-procedure may balance efficacy and safety in NVAF patients undergoing CAS/VAS. Larger studies are needed for validation.

Background: The prevalence of stroke is projected to rise over the next 30 years, particularly among younger adults (≤65 years of age). Stroke is associated with modifiable risk factors, highlighting the importance of risk factor modification. However, to modify risk factors, it is important to understand younger adult stroke and high-risk patients' lifestyle-related knowledge, behaviors and associated facilitators and barriers, which this study aimed to address with attention to sex, age, and stroke status-related differences. Methods: A cross-sectional study was conducted. Data were collected through an online self-reported survey. Descriptive and inferential statistics were conducted with attention to sex, age, and stroke status differences. Results: A total of 104 participants comprised the sample. Variability in lifestyle-knowledge was found. Most participants ate processed food, moderately exercised, slept <7 hours per night, had a sense of social connectedness, and moderate-to-manageable stress. Emotions, social and family responsibilities influenced diet and exercise. Sex, age, and stroke status differences were observed. Conclusions: Findings have implications on the development of lifestyle medicine prescriptions and interventions as standard of care to support brain health and reduce the risk of stroke and/or its reoccurrence.

Despite many publications about cavernous malformations (CMs), controversy remains regarding diagnostic and management strategies. To update evidence-based guidelines for the clinical management of brain and spinal cord CMs.

The Alliance to Cure CMs, the patient support group in the United States advocating on behalf of patients and research in CM, convened a multidisciplinary writing group comprising expert CM clinicians to help summarize the existing literature related to the clinical care of CM, focusing on 5 topics: (1) epidemiology and natural history, (2) genetic testing and counseling, (3) diagnostic criteria and imaging standards, (4) neurosurgical considerations, and (5) neurological considerations. Building on prior evidence-based recommendations reflecting literature review through October 2014, the group conducted a systematic review of the more recent literature, identified references for mandatory citation, rated evidence, developed recommendations, and established consensus according to a prespecified protocol. Finally, the writing group outlined remaining knowledge gaps and controversies to guide future research.

From 2672 publications published between October 1, 2014, and March 15, 2023, and meeting key word criteria, 234 were selected based on prearticulated criteria for mandatory consideration in evidence-based recommendations. Topic authors used these and other supporting references to summarize current knowledge and arrive at 53 management recommendations, with unanimous consensus based on a Delphi process. These were rated by class (strength of recommendation) and level (quality of evidence) per the American Heart Association/American Stroke Association criteria. Eighteen recommendations were class 1 (34%), class 2 in 31 (58%), and class 3 in 4 (8%). Three were level A (6%), 19 (36%) were level B, and 31 (58%) were level C.

Current evidence supports prior and new recommendations for the management of CMs, but many reflect moderate classes and low levels, mandating further research to better inform clinical practice.

A minor ischemic stroke is associated with a higher likelihood of poor clinical outcomes at 90 days when there is early neurological deterioration (END). The objective of this case-control study conducted in a comprehensive stroke facility in Vietnam is to examine the frequency, forecast, and outcomes of patients with END in minor strokes. The study employs a descriptive observational design, longitudinally tracking patients with minor strokes admitted to Bach Mai Hospital's Stroke Center between December 1, 2023, and August 31, 2024. Hospitalized within 24 hours of symptom onset, minor stroke patients with National Institutes of Health Stroke Scale (NIHSS) scores ≤ 5 and items 1a, 1b, and 1c on the NIHSS scale, each equal to 0, were included in the study. The primary measure of interest is the END rate, defined as a rise of 2 or more points in the NIHSS score during the first 72 hours after admission. We conduct a logistic regression analysis to identify forecasting factors for END. Out of 839 patients, 88 (10.5%) had END. In the END group, we found that most patients had complications within the first 24 hours of stroke, accounting for 43.2%; the 24 - 48-hour window accounted for 35.2%, and the 48 - 72-hour window accounted for 21.6%. END was associated with a higher likelihood of poor outcomes (mRS 2 - 6) at discharge (OR = 22.76; 95% CI 11.22 - 46.20; p < 0.01), 30 days post-stroke(OR = 24.38; 95% CI 14.40 - 41.29; p < 0.01), and 90 days post-stroke (OR = 21.74; 95% CI 12.63 - 37.43; p < 0.01). Some of the prognostic factors for END were admission NIHSS score (OR = 1.24; 95% CI 1.03 - 1.49; p = 0.02), admission systolic blood pressure greater than 150mmHg (OR = 1.70; 95% CI 1.03 - 2.81; p = 0.04), admission blood glucose (OR = 1.07; 95% CI 1.01 - 1.14; p = 0.02), reperfusion therapy (OR = 3.35; 95% CI 1.50 - 7.49; p < 0.01), use of antiplatelet monotherapy (OR = 3.69; 95% CI 2.24 - 6.08; p < 0.01), internal capsule infarction (OR = 2.54; 95% CI 1.37 - 4.71; p < 0.01), hemorrhagic transformation (OR = 5.72; 95% CI 1.07 - 30.45; p = 0.04), corresponding extracranial carotid artery occlusion (OR = 4.84; 95% CI 1.26 - 18.65; p = 0.02), and middle cerebral artery occlusion OR = 3.06; 95% CI 1.29 - 7.30; p = 0.01). END in minor stroke patients accounts for 10.5% and is a risk factor for poor neurological outcomes. Admission NIHSS score, higher systolic blood pressure, admission blood glucose, reperfusion therapy, use of antiplatelet monotherapy, internal capsule infarction, hemorrhagic transformation, corresponding extracranial carotid artery occlusion, and middle cerebral artery occlusion were some of the prognostic factors for END in our observational study.

Stroke is the second highest cause of death and leading cause of disability with high economic burden worldwide. The incidence of stroke is increasing faster and more prevalent for the global population over age 65. Ischemic stroke (IS) has a higher incidence than hemorrhagic stroke, accounting over 80 % of the total incidence of stroke. The rate of ischemic stroke is increasing in all age groups and both sexes. In present era, hypertension, high blood pressure and modern lifestyle are considered as the causes of the disease. The treatment options for stroke is still limited, mainly thrombolytic and thrombectomy therapy are available options. In the past decade, a number of therapeutic agents have been studied for the acute ischemic stroke to protect the brain from ischemic injury. Several study methods focus to improve neurons functions around the ischemic core and protect from the shock. Many signalling pathways including NF-kB, NrF, Nrf2-Keap1, PI3K/AKT, JAK/STAT signalling pathways are strongly associated for the indication. Controlling the signalling pathways by small molecules potentially improve the neuronal functions. In this article, we review the recent advancement of the drug discovery, controlling the signalling pathways by small molecules, and kinase inhibitors in ischemic stroke.

Background and Clinical Significance: Carotid stump syndrome (CSS) is a rare and unexpected cause of recurrent ischemic ipsilateral events in the carotid vascular territory despite the demonstrated occlusion of the internal carotid artery (ICA). It is believed to be caused by microemboli due to turbulent blood flow in the patent stump of the occluded ICA that passes through anastomotic channels and retrograde flow into the middle cerebral artery circulation. Case Presentation: We describe the case of a 65-year-old male patient who suffered multiple concurrent transient ischemic attacks (TIAs) with a totally occluded ipsilateral ICA revealed by computed tomography angiography (CTA). He was diagnosed with CSS, which required the safest therapeutic approach. A further investigation with digital subtraction angiography (DSA) was performed, and a trickle of blood flow was observed in the reportedly occluded ICA. The diagnosis of a true ICA occlusion was withdrawn, and a diagnosis of pseudo-occlusion was established, affecting the final treatment strategy. Therefore, the patient underwent an ipsilateral carotid endarterectomy (CEA), and he has remained asymptomatic since then. Conclusions: The differentiation between a pseudo-occlusion and a true ICA occlusion is essential in promptly managing acute recurrent ipsilateral ischemic strokes in the carotid vascular territory. A further investigation with DSA in cases with a totally occluded ICA using CTA is essential for excluding pseudo-occlusions in ipsilaterally symptomatic patients.

After extensive debate, the percutaneous closure of patent foramen ovale (PFO) has been established as a first-line treatment for the secondary prevention of PFO-related stroke in patients between 18 and 60 years old, whereas the role of PFO closure for primary prevention remains controversial. Additionally, in selected cases, PFO closure may be considered beyond these age limits and for other indications such as the treatment of systemic deoxygenation syndromes and the secondary prevention of systemic embolism or decompression sickness, when the PFO has been determined to be causative in the condition. In all cases, an in-depth diagnostic work-up, requiring collaboration among different specialists, is necessary to estimate the likelihood of PFO being related to the clinical condition. Since the first percutaneous closure of an atrial septal defect in 1976, the technique has been adapted and simplified for PFO. It is now well standardised with double-disc occluders, which are widely adopted because of their ease of use and evidence-based efficacy and safety. The procedure is generally straightforward, but some anatomical characteristics may be challenging. The choice of device and drug therapy after the procedure is currently empirical and guided by patient characteristics. Early and late complications of the procedure are infrequent but require early diagnosis. Further evidence is eagerly awaited to improve diagnosis, define other indications, make better procedural choices, and prescribe the most effective drug therapy after closure.

Ischemic stroke (IS) is emerging as an increasingly serious social issue with elusive etiology, few diagnostic markers, and limited treatment methods. Another concern in contemporary society is the prevalence of obesity, which is indicative of suboptimal well-being. Despite its association with established risk factors for stroke (such as hypertension and diabetes), several studies have reported a controversial phenomenon known as the "obesity paradox," whereby certain obese patients with stroke exhibited unexpectedly positive outcomes. In this study, a total of 68 plasma samples were collected including 36 controls and 32 IS patients, with further differentiation between obese and non-obese individuals in each group. A quantitative metabonomic approach based on 1H nuclear magnetic resonance (1H NMR) was employed to identify differential metabolic markers of IS, and elucidate the impact of obesity on IS. The final results demonstrated that obesity did not have a significant impact on metabolites. It is important to note, however, that reliance on BMI as the sole indicator of obesity may be insufficient. Additional parameters, such as waist-to-hip ratio and waist circumference, should be considered. Furthermore, the impact of obesity on stroke is probably mediated through metabolic health, making it an intermediate factor rather than a direct cause. Additionally, the study identified approximately 30 metabolites exhibiting significant alterations in IS patients, with the primary metabolic pathways being energy metabolism, amino acid metabolism, lipid metabolism, and folic acid deficiency. These findings are significant for comprehending the potential mechanisms of IS and facilitating its rapid and early diagnosis for effective treatment.

The Global Burden of Disease Study 2021 reports that stroke remains a leading cause of death, with ischemic stroke (IS) presenting significant challenges in screening, prevention, and treatment. We explored the causal effects of 1,400 plasma metabolites on IS outcomes using a two-sample Mendelian randomization (MR) framework. We assessed causal relationships between IS and 11 common clinical risk factors and further examined these relationships for metabolites. Mediation analysis identified mechanisms for metabolites affecting both IS and its risk factors. Finally, a phenome-wide association study (PheWAS) MR analysis evaluated the side effects and additional indications of IS-associated metabolites across 3,948 phenotypes from the UKBB GWAS. Nineteen metabolites showed a causal relationship with IS. MR analysis confirmed body mass index (BMI), high-density lipoprotein (HDL), systolic blood pressure (SBP), diastolic blood pressure (DBP), and type 2 diabetes (T2D) as risk factors for IS. Among 136 metabolites associated with at least one IS risk factor, 132 were linked to risk factors but not directly to IS. BMI, DBP, and coffee intake mediated the causal relationship between IS and the levels of 1-stearoyl-GPG (18:0), 1-oleoyl-2-linoleoyl-GPE (18:1/18:2), Octadecadienedioate (C18:2-DC), and X-24,951. Phe-MR analysis indicated that these metabolites were protective and affected other indications similarly to IS. Our findings reveal causal pathways and identify four potential biomarkers for IS, providing new insights for its screening, prevention, and treatment.

Although primarily supplied by the vertebrobasilar system, the hippocampus is partially supplied by ipsilateral carotid artery branches through the anterior choroidal artery or a prominent posterior communicating artery. We report a patient with acute hippocampus infarction likely due to symptomatic ipsilateral tandem carotid stenosis and discuss acute vascular-mediated hippocampal injury.

An 80-year-old female with obesity, dyslipidemia, hypertension, alcohol use disorder, history of breast cancer on letrozole, and traumatic brain injury was brought into our emergency department for 24 hours of confusion. On examination, she exhibited limited registration, recall, and executive dysfunction with otherwise normal language, visuo-spatial orientation, and praxis. Brain MRI showed a small area of diffusion restriction in the anterior right hippocampus with matched FLAIR hyperintensity, consistent with acute infarction. Computed tomography angiogram head and neck showed 90% stenosis of the proximal right internal carotid artery (ICA), <50% narrowing of the proximal left ICA, and moderate bilateral narrowing of the paraclinoid ICAs, all due to calcific atheromatous plaques. The etiology of the hippocampal infarction was suspected embolism from the ipsilateral severe carotid stenosis. Planning for right cervical carotid revascularization ensued.

This case highlights the dual hippocampal vascular supply and that hippocampal embolic infarcts could be a sign of a symptomatic severe carotid artery stenosis that may require urgent revascularization for stroke secondary prevention.

This study employed Transcranial Magnetic Stimulation combined with Electroencephalography (TMS-EEG) to examine the impacts of high-frequency repetitive transcranial magnetic stimulation (rTMS) on brain activity and cognitive function in patients with post-stroke cognitive impairment (PSCI), focusing on changes in connectivity of the left dorsolateral prefrontal cortex (DLPFC) across different frequency bands.

Twenty subacute PSCI patients were recruited for a 20-day rTMS treatment, consisting of 10 days of sham stimulation followed by 10 days of actual stimulation. Clinical function scale data and TMS-EEG data were collected before treatment (Pre), after sham stimulation (Sham), and after rTMS treatment (TMS) to analyze transcranial magnetic stimulation evoked potentials (TEP), time-frequency, and functional connectivity. Additionally, a post hoc subgroup analysis was conducted to assess the impact of education level, time since onset, and lesion size on cognitive score improvement.

Compared to the Pre and Sham conditions, cognitive function and daily living ability scores significantly improved post-rTMS. Although the TEP patterns in the Pre and Sham conditions were similar, rTMS enhanced the early TEP amplitude in the left DLPFC, slowed gamma oscillations, increased connectivity in the theta and alpha bands in the bilateral DLPFC, and altered the connectivity patterns between the left DLPFC and other brain regions. Changes in theta-band wPLI were significantly positively correlated with improvements in MMSE scores (r = 0.465, p = 0.039) and MoCA scores (r = 0.493, p = 0.027). Patients with higher education levels exhibited significant cognitive improvement (p = 0.039), while patients with a time since onset of 60-180 days showed a significant decline in cognitive improvement (p = 0.024).

High-frequency rTMS effectively modulated connectivity patterns between the left DLPFC and other brain regions in PSCI patients, enhancing cognitive functions. Changes in wPLI within the theta frequency band may serve as a potential biomarker for cognitive function improvement in PSCI patients. Education level and time since onset may have a certain impact on cognitive improvement in PSCI patients.