Stroke Etiology Research Articles

Abstract TP122: Impact of 2021 Seconary Stroke Prevention Guidelines on Post Stroke Care Plans for Patients Transferred to Long Term Acute Care Facilities

Background: Classification of etiologic ischemic stroke subtype guides post-stroke care and secondary prevention. Etiologic ischemic stroke subtypes are often not clearly documented in post-stroke care plans especially when transferring from one facility to another. In 2021, AHA/ASA published updated secondary stroke prevention guidelines recommending identifying etiologic ischemic stroke subtypes when possible. The impact of this on post-stroke care is unknown. Methods: Charts of all patients ages 18 and up, admitted from 1/1/20 to 5/23/21 and from 1/1/22 to 5/23/23 to 3 long-term acute care (LTAC) facilities, on antiplatelet therapy, and with an ascertainable history of stroke within 90 days of admission, were retrospectively reviewed to assess for documentation of ischemic stroke subtype at discharge/transfer to an LTAC facility and to assess for appropriateness of secondary stroke prevention therapies. Care plans from those two time periods were compared to assess for any impact the 2021 guidelines may have had on discharge practices. Results: Subtypes were not defined for the majority of ischemic strokes. Classification by etiologic subtype was observed in 33% of cases. Classification by territory or location was more common (Fig. 1). One-quarter of patients were on dual antiplatelet therapy (DAPT) and 75% of patients were on single antiplatelet therapy (SAPT) with more patients on DAPT in the latter time period (Fig. 2A). Rationale for DAPT were not provided for the majority of patients and NIHSS and ABCD2 scored were also not commonly provided for patients on DAPT (Fig. 2B). Close to 90% of patients were treated with antihypertensives and statin therapy at discharge to LTAC; 71% of patients were treated with diabetic therapies at discharge; stroke education at discharge to LTAC was documented for 43% of patients; and LDL was documented in 56% of patients (Fig. 3). Conclusions: Etiologic ischemic stroke subtypes were not documented for the majority of patients transferred to LTACs. Despite recent guideline revisions, an increase in documentation of stroke subtype was not observed. Optimal secondary stroke prevention strategies were difficult to assess without this information including appropriate antiplatelet regimens. Our findings highlight the importance of the need to improve post-stroke care plans at discharge and transfer including documentation of etiologic ischemic stroke subtypes to facilitate optimal post-stroke care across all transitions.

Abstract TP311: Immune Checkpoint Inhibitors and Stroke Etiology in a Retrospective Cohort of Patients with Non-Small Cell Lung Cancer

Abstract TP311: Immune Checkpoint Inhibitors and Stroke Etiology in a Retrospective Cohort of Patients with Non-Small Cell Lung Cancer

Abstract TP332: Assessing the Role of Thyroid Function in Ischemic Stroke: A Retrospective Analysis Across TOAST Classification

Introduction: Subclinical hyperthyroidism has been linked to an increased risk of atrial fibrillation, which elevates the likelihood of cardioembolism, cryptogenic stroke (CS), and embolic stroke of undetermined source (ESUS). However, the broader relationship between thyroid function abnormalities and acute ischemic stroke remains uncertain. This study aims to investigate whether patients with acute ischemic stroke due to cardioembolism, CS, or ESUS are more likely to have abnormal thyroid-stimulating hormone (TSH) levels compared to those with ischemic strokes from other etiologies, as classified by the TOAST criteria. Methods: Utilizing data from the Get With The Guidelines Database, we conducted a retrospective chart review of patients admitted to our single comprehensive stroke center, diagnosed with an acute ischemic stroke between August 2022 and January 2023. The Kruskal-Wallis rank sum test was employed to assess differences in TSH, Free T4, and, if available, one year follow-up TSH levels among patients with ischemic stroke etiologies of small vessel disease, large artery atherosclerosis, cardioembolism, CS, and ESUS. Results: A total of 211 patients were included in the analysis, the distribution of stroke etiologies included 33 (16%) with small vessel disease, 51 (24%) with large artery atherosclerosis, 77 (36%) with cardioembolism, 13 (6.2%) with an undetermined/cryptogenic etiology, and 25 (12%) with ESUS. The majority of patients had normal TSH levels, accounting for 82% of the total cohort, the overall mean TSH level was 2.52 (reference range 0.27-4.2uIU/mL). No significant differences were observed in the mean TSH (p = 0.066), Free T4 (p = 0.13), or follow-up TSH (p = 0.79) levels across each stroke subtype. Conclusions: Our findings suggest that thyroid function does not significantly differ across the various etiologies of acute ischemic stroke, as classified by TOAST criteria. While further large-scale studies are warranted, our results indicate that routine evaluation of thyroid function may not be essential in the determination of stroke etiology.

Abstract TP334: Racial Disparities in Functional Outcomes and Stroke Recurrence in Young Patients with Ischemic Stroke

Introduction: Studies have reported racial disparities in acute stroke treatment and follow-up care in young patients which lead to less desirable outcomes for minorities. This study aimed to identify potentially modifiable factors for better stroke treatment and prevention in minority populations. Methods: Young patients aged 18-50 years who were admitted with ischemic stroke during 09/2016-12/2022 were retrospectively identified and stratified as non-Hispanic White (WH), non-Hispanic Black (BL), and Hispanic (HS). Racial differences in risk factors, stroke etiology, acute intervention, and follow-ups were examined using Chi-square and Kruskal-Wallis tests as appropriate. Cumulative probabilities of stroke recurrence were estimated using the Kaplan-Meier (KM) method and tested with the Log-rank (Mantel-Cox) test. A logistic regression was used to evaluate the odds ratio of favorable functional outcomes (mRS ≤2) by 90 days. A backward stepwise Cox regression was conducted to identify predictors of stroke recurrence reported as hazard ratio (HR) and a 95% confidence interval (CI). Results: A total of 318 patients were identified with a median age of 43 and 57.5% male, covering 57.2% WH, 22.3% BL, and 20.4% HS. Compared to WH, more BL and HS were comorbid with diabetes, hypertension, and prior stroke (p<0.05). The rates of other risk factors did not vary by race. The distribution of stroke etiologies and rate of acute interventions (IV tPA, thrombectomy) were similar among the three. After discharge, 77.3% of young patients had ≥1 follow-ups at stroke clinic. The total number of stroke clinic follow-ups were similar among racial groups. At 90 days, 89.6% of patients achieved mRS≤2; the odds of having this favorable functional outcome were similar among racial groups ( p =0.207). The KM curve indicates that the first-year risks of stroke recurrence were similar among racial groups and that a trend showed BL had the highest risk of recurrent strokes, followed by HS, and WH had the lowest risk in 1-3 year follow up. Yet, these differences were not statistically significant ( p =0.056. BL was found to have 2.7 times higher risk to have a recurrent stroke than whites (HR: 3.7; 95% CI: 1.4-10.1; p=0.01). Conclusions: Findings highlighted high prevalence of hypertension and diabetes in young BL and HS and a higher risk of recurrent stroke in young BL, suggesting tailored interventions for comorbidities are urged for better stroke prevention in minorities.

Mendelian randomization and mediation examination of the immune cell-mediated link between sphingomyelin and stroke.

The study established a direct link between stroke and sphingomyelin. The precise biology underlying this connection is yet unknown, though. As a result, we decided to investigate the potential causal relationship between Sphingomyelin and genetic vulnerability to stroke, as well as the potential mediating function that immune cells may play in this process, using Mendelian randomization (MR) approaches. A published genome-wide association study (GWAS) dataset of European populations served as the foundation for the MR Study. The inverse variance weighting (IVW) model is the main technique. Four additional statistical techniques (MR Egger, Weighted median, Simple mode, and Weighted mode) were also employed to enhance the verification process. Reverse MR Analysis was utilized to reinforce the findings, and heterogeneity and horizontal pleipotency were assessed. Additionally, this study looked into potential immune cell mediating roles in the causal link between sphingomyelin and stroke using two-step MR techniques. The IVW metod's results indicated that sphingomyelin genetic susceptibility was linked to a high risk of stroke (OR = 1.045 [95%CI, 1.004-1.087; P = 0.031). Additionally, the statistical result of SSC-A on CD8br and stroke was IVW [P = 0.007, OR(95% CI) 1.020 (1.005-1.034)], which was proportionate to the increased risk of stroke. A lower incidence of stroke IVW is linked to CD45 on CD8br [P=0.004, OR(95% CI) 0.993 (0.988-0.998)]. Furthermore, our results imply that SSC-A on CD8br and CD45 on CD8br contribute to the causative relationship between sphingomyelin and stroke. The percentages of conciliation are 5.38%, 22.7%, 33.5%), and 0.000999, 0.0152, 0.0132, respectively. We confirmed the effect of sphingomyelin on stroke and conducted in-depth studies. SSC-A on CD8br and CD45 on CD8br is latent stroke mediators associated with sphingomyelin. Through two-step mediated Mendelian randomization analysis, we provide new insights into the etiology and treatment of stroke.

Abstract 29: Non-gated Dual-source Photon-counting CT Angiography Can Detect Cardioembolic Sources Of Acute Ischemic Stroke At The Primary Investigation: A Retrospective Consecutive Cohort Study

Introduction: Early identification of the etiology of ischemic stroke is crucial for secondary prevention. Recent publications on dedicated ECG-gated cardiac CT showcase the potential to detect sources of cardiac embolism. Photon-counting CT (PCCT) uses semiconductors to convert X-ray photons into electrical signals directly. This allows for improved image quality and lower radiation dose compared to conventional CT. Exploiting PCCT technology with a high-pitch dual-source image acquisition may render an exceptionally high temporal resolution. We hypothesized that non-ECG-gated high-pitch dual-source PCCT angiography from the diaphragm to the brain might provide added clinical value in detecting cardiac stroke sources during initial stroke imaging while maintaining optimal brain and neck image quality. Methods: Consecutive patients with a clinical suspicion of acute stroke imaged with a PCCT system between October 4 th , 2023 and April 13 th , 2024 at a Swedish comprehensive stroke center were included. Diaphragm to brain coverage was obtained in an acquisition time of 1.3 seconds; on average, yielding a dose-length product of 360 mGy*cm for the study participants (2.34 mSv). Image quality was graded using a 4-point Likert scale. Images were assessed for cardiac stroke sources. Where available, reference standard echocardiography results were collected. Results: Of 249 consecutive stroke investigations, 193 included cardiothoracic imaging, which constituted the study population. 126 scans (65.3%) were cases with imaging confirmed ischemic stroke. The median age was 74 (IQR, 61-81) years, 99 were male (51.3%). In total, 39.4% underwent follow-up echocardiography. Image quality of the heart was excellent in 19 scans (9.8%) good in 97 (50.3%), moderate in 72 (37.3%), and poor in 5 scans (2.6%). Fourteen (7.3%) certain or probable interatrial septal defects were found in the study population. In the imaging-confirmed ischemic stroke subgroup, six certain or probable cardiac thrombi were found (4.8%). Additionally, a possible cardiac thrombus was found in 31 instances (24.6%). Three aortic valve vegetations were found (2.4%), all confirmed by echocardiography. Conclusions: Non-ECG-gated high-pitch dual-source PCCT angiography typically provides images of high quality, at virtually no time expense while maintaining a reasonably low radiation exposure. Non-gated PCCT angiography is a promising technique to be used as a primary screening method for cardioembolic stroke.

Abstract 14: A distinct clot transcriptomic signature is associated with atrial fibrillation-derived ischemic stroke in the INSIGHT Registry

Funding: The INSIGHT Registry is funded by Penumbra. Introduction: Rapid and precise determination of the etiology of acute ischemic stroke is crucial in long-term management and prevention of recurrence. Identification of etiology-associated molecular biomarkers following thrombectomy may allow for personalized intervention. Here, we examine the transcriptomics of cardioembolic thrombi as a result of atrial fibrillation, identifying a distinct transcriptomic signature relative to other causes of ischemic stroke. Methods: The INSIGHT registry is a prospective, multicenter, multi-omic registry focused on elucidating the molecular underpinnings of stroke from analysis of clot and interarterial blood. RNA sequencing of 10,990 genes from 292 thrombi from patients undergoing thrombectomy was analyzed using edgeR, sva, and limma/voom. 111 patients had a determined etiology of atrial fibrillation. Controls had unknown, atheroembolic, or coagulopathy stroke etiology. Significant association of thrombus gene expression with atrial fibrillation was conducted using the Wilcoxon Rank Sum test using Benjamini-Hochberg multiple testing correction (FDR <5%). Gene set enrichment was performed using FGSEA using Gene Ontology biological processes gene sets. Co-expression modules were detected using WGCNA and analyzed using cytoscape. Results: 33 genes (27 upregulated, 6 downregulated) within thrombi were significantly associated with atrial fibrillation etiology. These included upregulated endothelial cell markers associated with cardiac endothelial cells (e.g. KDR , AMDHD2 , IL18BP ) compared to thrombi of other etiologies. In addition, upregulated genes were associated with oxidative stress (FDR= 8.46x10 -8 ) and metabolism (1.04x10 -6 ), while adaptive T-cell immunity was downregulated (FDR= 7.52x10 -3 ). Co-expressed gene networks upregulated by atrial fibrillation-associated thrombi included a module implicated in innate immune signaling and cytotoxic granule release (p=0.02), which included key hub genes GZMH and TBX21. Conclusion: Cardioembolic thrombi possess a distinct transcriptomic signature consistent with collection and retainment of cardiac endothelial tissue at origin, and display immunomodulatory activity associated with innate vs adaptive immune balance. This signature suggests the active role thrombi likely play in the vascular microenvironment and may ultimately be used to identify atrial fibrillation as an etiology in strokes of unknown origin.

Abstract TMP53: Vessel Wall MRI: Adding value in the diagnostic evaluation of Cervical Artery Dissection

Introduction: Cervical artery dissections (CAD) are a leading cause of stroke, particularly among younger individuals. Timely and accurate diagnosis is crucial for appropriate treatment and preventing further complications. This study compares a commonly used imaging modality for evaluating CAD; computed tomography angiography (CTA) with a novel imaging modality; Vessel Wall MR Imaging (VW-MRI). The aim is to highlight distinguishing features of CAD on VW-MRI, demonstrating its ability to offer better visualization of vessel wall abnormalities in select cases compared to conventional CTA. Methodology: Patients were selected from the University of Washington (UW) hospital system between 2022 and 2024. The screened patients included those either admitted directly from the Emergency Department due to new onset of neurological symptoms or transferred from Telehealth and affiliated hospitals after extensive disease was detected on CTA head and neck scans as part of stroke protocols. In accordance with our institutional stroke protocol all patients had initial vessel imaging with CTA followed by a VW-MRI which was obtained using a 3.0 Tesla scanner. Results: A total of 47 patients were identified with intracranial abnormalities initially picked on CTA. Of the total cases, 20 were initially suspected of CAD based on CTA, but only 13 were confirmed with dissections on VW-MRI. Amongst the seven cases which did not have a CAD on VW-MRI - two of them turned out to be artifactual, one of them was Fibromuscular Dysplasia (FMD), three showed atherosclerotic plaque and one was suggestive of a vasculitic process. In two cases, intracranial dissections were easily picked on VW-MRI, and in one case mural hematoma and in other two cases intraluminal thrombus were seen easily on VW-MRI, which were primarily missed on CTA. Conclusion: Upon reviewing the patients during this period, it is evident that VW-MRI not only aids in localizing acute ischemic strokes but also plays a critical role in identifying CAD. Additionally, intracranial artery dissections, intramural hematomas, intraluminal thromboses and pseudoaneurysms had a better visualization on VW-MRI than on conventional CTA. VW-MRI adds value to the diagnosis of CAD, which can be beneficial in determining etiology of acute ischemic strokes for cases which have some degree of uncertainty and eventually may prove to be helpful in their long-term management.

Abstract TP144: Telemedicine Appointments early after Acute Ischemic Stroke may Reduce 30-day Emergency Department Visits

Introduction: Limiting the rate of unplanned emergency department (ED) revisits for patients with acute ischemic stroke is an important aspect of secondary stroke prevention. This is influenced by patients’ demographics, comorbidities, stroke severity, disposition destination, and may be impacted by early outpatient follow-up where stroke risk factors and etiology continue to be evaluated. Methods: We retrospectively identified all acute ischemic stroke patients discharged from an 11-hospital network, the largest healthcare system in the state of Georgia, from October 1, 2022 to March 31, 2024; we excluded patients who were discharged to a long-term acute care or hospice facility. Baseline characteristics, inpatient metrics and post-discharge outpatient follow-up were assessed to identify factors associated with ED visits within 30- and 90-days after discharge. Results: Of 2,191 patients, 143 (6.5%) had ED visits within 30 days and 296 (13.5%) within 90 days. The median age was 68 [IQR 57, 77]. History of heart failure (HF), atrial fibrillation (AF), chronic kidney disease and end stage renal disease each increased the likelihood of an ED re-visit within 30 and 90 days whereas diabetes mellitus increased the likelihood of an ED re-visit at 90 days only. In multiple logistic regression analyses, factors independently associated with 30-day ED visit was a history of HF (OR 1.57, 95% CI 1.07-2.28; p=0.02) and AF (OR 1.49, 95% CI 1.00-2.19; p=0.04); at 90 days, only an increased Charlson Comorbidity Index score was associated with ED visit (OR 1.09, 95% CI 1.02-1.16; p=0.01). There were 501 (23%) patients who completed an outpatient neurology clinic follow-up within 30 days of discharge, including 81 patients (4%) who completed a telemedicine outpatient visit; patients completing a telemedicine visit were less likely to have a 30-day ED visit than those who had an in-person visit (OR= 0.13, 95% CI 0.01-0.62; p=0.05). Conclusion: ED revisits after hospitalization for acute ischemic stroke are relatively common and associated with patients who have comorbid conditions including HF and AF. Our study suggests that telemedicine-based follow-ups were associated with lower rates of unplanned ED revisits within 30 days. Efforts to increase outpatient neurology clinic access through telemedicine may reduce ED visits after discharge for acute ischemic stroke patients.

Abstract WMP49: A machine learning approach to classifying ischemic stroke etiology using variables available in the Get-with-the-Guidelines Stroke Registry

Abstract WMP49: A machine learning approach to classifying ischemic stroke etiology using variables available in the Get-with-the-Guidelines Stroke Registry

Abstract TMP96: The Use of Direct Oral Anticoagulants in Pediatric Arterial Ischemic Stroke

Introduction: Pediatric arterial ischemic stroke (AIS) affects 1-2 per 100,000 children. Although rare, mortality and morbidity is significant with approximately 10% recurrence rate within the first year. Despite this, evidence-based treatment and prevention guidelines of pediatric AIS remain insufficient. Direct oral anticoagulants (DOACs) are approved in many countries for the treatment and prevention of pediatric venous thrombosis but its use in pediatric arterial thrombosis is less established. This study is the first to evaluate the off-label use of rivaroxaban in pediatric AIS. Methods: A retrospective chart review was approved by Cook Children’s Medical Center (CCMC) institutional review board. Patients (0 to <18 years) treated at CCMC for acute AIS that received rivaroxaban between June 21, 2021-April 1, 2024 were reviewed. Patients treated for concomitant venous thrombosis and/or without follow up imaging were excluded. Data was de-identified and SAS 8.3 was used for analysis. Given small sample, data were summarized using descriptive statistics. Results: Thirty-two patients were reviewed and 14 met eligibility criteria. Patient demographics and medical history are summarized in Table 1. All had acute AIS confirmed via brain magnetic resonance imaging (MRI), with most strokes affecting the anterior circulation (8, 57.1%) and with arteriopathy as the most common stroke etiology (10, 71.4%) (Table 2). Thirteen (92.9%) received antithrombotic therapy (heparin, enoxaparin, acetylsalicylic acid) prior to DOAC initiation and all 14 were given rivaroxaban afterwards. At the time of data analysis, patients had a median of 4 months of DOAC therapy (interquartile range: 3-7). Four patients remain on treatment (28.6%), 7 completed treatment (50.0%), 1 stopped due to the rivaroxaban shortage (7.1%), 1 discontinued due to bleeding complications (concomitant antiplatelet therapy) (7.1%), and 1 discontinued due to treatment failure (7.1%). All other adverse events were minor not requiring treatment discontinuation (Table 3). Conclusion: In this study, 14 pediatric AIS patients were treated with rivaroxaban. Only one had it discontinued for patient safety but concomitant therapy with acetylsalicylic acid, made rivaroxaban causality inconclusive. The only treatment failure in our series was a patient with bow hunter syndrome. Even though this study suggests rivaroxaban might be a safe and effective therapeutic option in pediatric AIS, additional research is needed.

Abstract TMP95: Risk Factors, Stroke Characteristics and Outcomes in Children with Inpatient Versus Outpatient Strokes

Children who suffer arterial ischemic stroke (AIS) while hospitalized are often critically ill and may have distinct acute and chronic risk factors, stroke characteristics and outcomes compared to those with outpatient strokes. We sought to evaluate demographic, clinical and imaging profiles of children with inpatient versus outpatient strokes, and compare mortality between the two groups. Methods: The Stanford Pediatric Stroke Registry retrospectively and prospectively enrolled children with acute AIS who were admitted to our tertiary care pediatric hospital between 2007-2024. For this analysis we included patients who met the following criteria: 1) age 30 days-18 years old; 2) new diagnosis of AIS; 3) acute neuroimaging available for direct review. Inpatient strokes were defined as strokes that occurred while the child was hospitalized, either at our center or at an outside facility prior to transfer. Demographic, clinical and radiographic data were compared using chi-squared or Fishers Exact test for categorical variables and Mann-Whitney U test or t-test for continuous variables. Outcomes were reported using descriptive statistics due to the hypothesis-generating nature of the report. Results: A total of 208 children with acute AIS met inclusion criteria; 99 (47.6%) experienced a stroke while hospitalized. Inpatient stroke patients were overall younger and had higher rates of congenital heart diease and cancer than children with outpatient strokes, while trauma was more common in outpatient strokes (Table 1). There were no significant differences in imaging characteristics between groups. Cardioembolism and periprocedural strokes were more prevalent in inpatient strokes, whereas arteriopathy and cryptogenic stroke were the most common stroke etiologies in outpatients (Table 2). A significantly higher proportion of inpatient stroke patients died compared to outpatient strokes (27.3% vs 3.7%, p<0.0001); most patients died prior to discharge (Table 3). Conclusions: In our pediatric AIS cohort, nearly half had a stroke while hospitalized. Our study suggests that stroke and risk factor profiles differ between inpatient and outpatient strokes in multiple domains, and that children with inpatient strokes have higher rates of death. Further prospective studies are needed to determine factors contributing to higher mortality in order to tailor appropriate prevention strategies.

Internal carotid dissection after the motorcycle accidents

Dear Editor, Extracranial carotid artery dissection (CAD) is one of the major consequences of blunt head and neck trauma, and a main etiology of ischemic stroke in young adults; the carotid lesions are described in accidents of motorcycle drivers with or without the helmet [1-5]. Blunt cervical vascular injury is a nonpenetrating trauma to the carotid or vertebral arteries caused either by direct neck injury or by the shearing of these cervical vessels; the estimated incidence of vascular lesions is low, only near 1% of the blunt trauma.

Analysis of Non-Cardiogenic Young Minor Ischemic Stroke Patients' Risk Factors in Chinese Han Population.

BACKGROUND Young adults with minor ischemic stroke (MIS) often experience early onset and mild symptoms but face a high recurrence rate. Research into risk factors and etiology of young adult MIS in developing countries is limited. We investigated these aspects in young non-cardiogenic MIS patients from the Chinese Han population and identified risk factors for initial stroke and long-term poor prognosis. MATERIAL AND METHODS Data from MIS patients aged 18 to 50 years and a healthy control group at The First Affiliated Hospital of Anhui Medical University and The Third People's Hospital of Hefei City from January 2019 to July 2023 were analyzed. Risk factors and stroke etiology were compared. ROC curves assessed the predictive ability of original and modified Essen Stroke Risk Scores (ESRS). RESULTS Among 155 patients, 25 (16.1%) experienced recurrence within a year. Patients with MIS differed significantly from the control group in sex, hypertension history, diabetes, dyslipidemia, smoking, higher biomarkers (SBP, TG, VLDL-C, hs-CRP, WBC, RBC, NEUT, HB), and lower HDL-C. Univariate analysis found dyslipidemia, moderate to severe vascular stenosis, resting heart rate, and modified ESRS scores linked to recurrence. Multivariate analysis identified dyslipidemia, vascular stenosis, and resting heart rate as key risk factors. Large artery atherosclerosis was the most common stroke etiology (59.2%). ROC curves revealed areas under the curve for ESRS, modified ESRS-1, and modified ESRS-2 as 0.550, 0.660, and 0.937, respectively. CONCLUSIONS MIS was associated with a high recurrence rate and specific risk factors. Improved ESRS effectively predicted stroke recurrence within 1 year, with large artery atherosclerosis being the predominant etiology.

Analysis of etiology and short-term prognosis of childhood arterial ischemic stroke based on the COIST classification

Objective: This study aims to analyze the etiology and short-term prognosis of childhood arterial ischemic stroke (AIS) in Chinese children, based on the COIST classification system. Methods: A total of 380 pediatric patients with a first-ever diagnosis of AIS treated at Beijing Children's Hospital between September 2015 and April 2024 were retrospectively included. Etiology was analyzed according to COIST classification. The patients were categorized into infant and toddler group with 117 cases (>28 days to≤3 years), preschool group with 90 cases (>3 years to≤7 years), school-age group with 90 cases (>7 years to≤11 years), and adolescent group with 83 cases (>11 years to≤18 years). The etiological distribution across age groups and the short-term prognosis of patients with different etiologies were further analyzed. Results: Among the 380 patients, 235 were male (61.8%) and 145 were female (38.2%), with a mean age at presentation of(6.6±4.6)years. Approximately 2/3 of the patients were admitted in the Department of Neurology, with a mean hospital stay of (13.2±6.7)days. (1) Etiological analysis: "Vascular structural abnormalities" were the most common cause, accounting for 38.2% (145/380), followed by "Inflammatory" causes at 31.1% (118/380), "Undetermined" at 11.1% (42/380), "Other identifiable causes" at 9.2% (35/380), "Cardiac diseases" at 6.3% (24/380), and "thrombophilia" at 4.2% (16/380). (2) Etiological distribution by age group: in the infant and toddler group, "vascular structural abnormalities" were 47.9% (56/117), with basal ganglia infarction following minor trauma(combined with basal ganglia calcification) being the most common (40/117). In the preschool group, there were 34 cases (34/90) of "inflammatory" and 33 cases (33/90) of "vascular structural abnormalities", with Moyamoya disease being the most frequent cause (15/90). In the school-age group, there were 37(37/90) cases of "vascular structural abnormalities", with arterial dissection (12/90)being the most common, followed by FCA-i (11/90), and Moyamoya disease (11/90). In the adolescent group, there were 34 cases of "inflammatory"(34/83), with the highest proportion of FCA-i (13/83) in the subgroup, followed by thrombophilia (9/83) and systemic lupus erythematosus (8/83). (3) Short-term prognosis: based on the PSOM scale, 188 cases had good prognosis, accounting for 49.5% (188/380), while 192 cases had poor prognosis, accounting for 50.5% (192/380). According to the mRS score, 207 cases had good prognosis (54.5%) and 173 cases had poor prognosis (45.5%). Subtypes such as "Inflammatory-noninfectious, " FCA-i, Moyamoya disease, and arterial dissection were associated with relatively better outcomes. Less than 1/3 of patients in the "other identifiable causes" group had favorable prognosis. The in-hospital mortality rate was 3.7% (14/380). Conclusions: Vascular structural abnormalities and inflammatory (including infectious and non-infectious) factors are the predominant causes of pediatric AIS; Approximately half of children with AIS had a favorable short-term outcome.

Prevalence of Carotid Plaques with High-risk Features in Embolic Stroke of Undetermined Source: Systematic Review and Meta-Analysis.

Recent evidence suggests a possible role of non-stenotic carotid atherosclerotic plaques in the aetiology of embolic stroke of undetermined source (ESUS). We conducted a systematic review and meta-analysis of prevalence and characteristics of non-stenotic carotid plaques (NSP) with high-risk features (complicated NSP) in internal carotid artery in unilateral ESUS in the anterior circulation. We searched Medline and Ovid-Embase databases. High-risk features were intra-plaque haemorrhage, thickness ≥ 3 mm, ulceration and hypodensity. We assessed the risk-of-bias (RoB), extracted the data, calculated the pooled-prevalence and 95% confidence intervals using Inverse Variance Weighting method and Random Effect models. We included 16 studies and 1406 patients with different imaging for NSP assessment (1 Ultrasound, 11 CT-angiography, 4 MR-angiography). The RoB was moderate to low in most studies. Definition of complicated NSP differed across studies. The combined prevalence of any complicated NSP was 31% (95% CI=27-36%) ipsilateral and 14% (95%CI=9-19%) contralateral to the index stroke, the finding of any high-risk NSP was four-fold higher ipsilateral to the index stroke (OR=3.63; 95%CI=2.09-6.33). Prevalence of single high-risk features ipsilateral to ESUS was as follows: 35% (95%CI= 30-41%) for thickness ≥ 3 mm; 24% (95%CI= 8-39%) for ulceration; 45% (95%CI= -2; 93%) for hypodensity, 16% (95%CI=5-26%) for intraplaque haemorrhage. Complicated NSP are present in around a third of all ESUS, and are four times more frequent ipsilaterally to the index stroke. Our results confirm the possible causal role in ESUS and highlight the need for greater diagnostic uniformity of plaque at risk.

LncRNA, miRNA, and mRNA of plasma and tumor-derived exosomes of cardiac myxoma-related ischaemic stroke

Cardiac myxoma (CM) is an important aetiology of stroke in young adults, and its diagnosis is difficult in patients having stroke because of the lack of diagnostic biomarkers. Tumour-derived exosomes play a crucial role in tumour growth, metastasis, immune regulation, and monitor disease development. Hence,we established an RNA-sequencing dataset for long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) in the plasma and tumour-derived exosomes from four patients with cardiac myxoma-related ischaemic stroke (CM-IS) and six patients with cardiac myxoma without ischaemic stroke (non-IS CM). Moreover, 5,533 lncRNAs, 1,331 known miRNAs, and 412 new miRNAs were identified. Finally, gene expression profiles and differentially expressed genes were analysed in 20 samples. In the plasma samples, 74 miRNAs, 12 lncRNAs, and 693 mRNAs were identified, while tumour-derived tissue samples contained 61 miRNAs, 67 lncRNAs, and 433 mRNAs. This dataset provides a significant resource for relevant researchers to explore the potential dysregulated lncRNAs, miRNAs, and mRNAs of plasma and tumour-derived exosomes in CM-IS.

Clinical and radiological characteristics of calcified cerebral embolism: a large case series including 242 calcified cerebral embolism.

Radiological calcified cerebral embolism (CCE) characteristics have been reported in small case series. Our aim was to describe clinical and radiological CCE characteristics in a large number of CCE and to compare characteristics between different patient groups. Characteristics of 79 stroke patients with CCE were analyzed retrospectively. Clinical characteristics included demographics, cardiovascular risk factors, stroke history, history of surgical/endovascular cardiovascular intervention, NIHSS on admission, stroke etiology, and presumed CCE source. Radiological characteristics included CCE diameter, density, number, involved cerebral artery and segment, and CCE distribution. A total of 242 CCE were analyzed in 79 patients (median age 79, 56% men). Presumed CCE source was vascular in 54%, mixed vascular/cardiac in 32%, and undetermined in 14%. Median CCE diameter was 1.55mm and median density 146HU. Multiple CCE were observed in 34% of patients. The middle cerebral artery was the most frequently (84%) involved artery. CCE predominantly involved distal segments. Single uniterritorial, multiple uniterritorial, and multiterritorial CCE were observed in 63%, 22%, and 15% of patients respectively. Patients with combined vascular/cardiac CCE source were older compared with patients with vascular CCE source (p = 0.0135). Correlation coefficient between CCE diameter and density was 0.69. Clinical characteristics were similar between the groups with single uniterritorial, multiple uniterritorial, and multiterritorial CCE, apart from diabetes (p = 0.0076). Concerning radiological characteristics, median diameter and density differed between these three groups (p = 0.0029 and p = 0.0035, respectively). CCE diameter was larger (p < 0.0001) and density higher (p < 0.0001) when CCE involved proximal arterial segments. Clinical and radiological characteristics of CCE patients and CCE are variable. CCE diameter and density and presence of diabetes history differed between CCE patients with single uniterritorial, multiple uniterritorial, and multiterritorial CCE.

Patterns and predictors of statin therapy after ischemic stroke and TIA: insights from the LIPYDS multicenter study.

Patients with ischemic stroke (IS) or TIA face an elevated cardiovascular risk, warranting intensive lipid-lowering therapy. Despite recommendations, adherence to guidelines is suboptimal, leading to frequent undertreatment. This study aims to evaluate the statin use after IS and TIA. LIPYDS is a multicenter, observational, retrospective study including ≥ 18-year-old patients discharged after IS/TIA from 19 Italian centers in 2021. Multivariable logistic regression analysis was used to determine (1) the association between statin prescription (Any-statin versus No-statin), type (High-Intensity-statin versus Other-statin [Moderate/Low-Intensity]) with stroke etiology (TOAST), (2) clinical variables independently associated with statin prescription in the entire cohort and within TOAST categories. We included 3,740 patients (median age 75 [IQR 64-82]; median LDL-C 104 [IQR 79-131]). At discharge, 1,971 (52.7%) received a High-intensity-statin, 800 (21.4%) Other-statin, 969 (25.9%) No-statin therapy. Among patients not on statin therapy before the event (N = 2686 [71.8%]), 50.1% initiated High-intensity-statin (78.2% of those with Large-Artery-Atherosclerosis, 60.8% Small-Vessel-Disease, 34.7% Cardioembolic, 47.4% Undetermined etiology); in 33% the decision to abstain from initiating statin therapy persisted. Large-Artery-Atherosclerosis showed the strongest association with Any-statin (aOR 3.07 [95%CI 2.39-3.95], p < 0.001) and High-intensity-statin (aOR 4.51 [95%CI 3.39-6.00], p < 0.001), while Cardioembolic stroke showed an inverse association (respectively, aOR 0.36 [95%CI 0.31-0.43], p < 0.001 and aOR 0.52 [95%CI 0.44-0.62], p < 0.001). Stepwise regression highlighted LDL-C and previous statin therapy as consistent predictors of statin at discharge. Older patients and women were less likely to be on a high-intensity formulation. Statins, especially at high-intensity, are under-prescribed after IS and TIA, with older patients, women and those with non-atherosclerotic strokes being the most affected.

Hypercoagulable states in young adults with ischemic stroke in a Stroke Belt state: a retrospective study.

We theorize that the southeastern United States has a higher stroke mortality rate and higher recurrent ischemic stroke rate than the rest of the United States due to (1) an increased prevalence of hypercoagulable states among young adults in the region, (2) failure to diagnose hypercoagulable states as the cause of ischemic stroke in young adults, and (3) underutilization of anticoagulation for ischemic stroke secondary prevention in young adults with hypercoagulable states. In an attempt to investigate this hypothesis, we conducted a retrospective chart review of 311 inpatients with first-ever ischemic stroke from age 18 to 55 years at an Oklahoma academic medical center from 1 July 2011 to 30 April 2017. Using Chi-squared test, we compared the stroke etiologic diagnosis of the attending neurologist at discharge-when hypercoagulable profile results were rarely available-to the diagnosis of a vascular neurologist postdischarge who had access to all available etiologic test results. The inpatient neurologists identified the stroke etiology as hypercoagulable state in 79 patients (25.57%) and undetermined etiology in 105 (33.98%). With the benefit of final hypercoagulable profile results, the postdischarge vascular neurologist identified the stroke etiology as hypercoagulable state in 167 (54.22%, 95% CI 48.64-59.70%, p-value <2.2e-16) and undetermined etiology in 28 (9.09%, 95% CI 6.36-12.83%, p-value 1.03e-14). There was no significant change in the proportion of ischemic strokes classified under all other stroke etiologies. We conclude that hypercoagulable states are a common and underrecognized cause of ischemic stroke in young adults in the U.S. Stroke Belt.