Etiology Of Acute Ischemic Stroke Research Articles

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.

CT Perfusion Metrics as Indicators of Intracranial Atherosclerotic Stenosis in Acute Ischemic Stroke: A Clinical Analysis.

Intracranial Atherosclerotic Stenosis (ICAS) is a prevalent etiology of acute ischemic stroke (AIS), leading to significant morbidity and mortality. The accurate diagnosis and treatment of ICAS-induced AIS are critical to improving outcomes. This study assesses the application of Computed Tomography Perfusion (CTP) in predicting ICAS in AIS patients and its potential impact on patient management. A retrospective analysis was conducted on 224 AIS patients who underwent endovascular therapy (EVT) at one single Chinese Stroke Center between April 2022 and December 2023. Clinical and radiological data were collected, including patients' demographics, CTP parameters, and 90-day modified Rankin Scale (mRS) scores. Logistic regression and receiver operating characteristic (ROC) curves evaluated the predictive power of CTP parameters for ICAS. CTP analysis revealed significant differences in perfusion parameters between ICASinduced AIS and other etiologies. ICAS patients had a smaller ischemic volume on admission and higher mismatch ratios [Time to Maximum, Tmax＞6s: Other Causes: 132.4 [70.5, 183.3] mL, ICAS: 96.3 [79.8, 107.3] mL, P=0.0064; relative cerebral blood flow, rCBF＜30%: Other Causes: 2.4 [0.0, 10.8] mL, ICAS: 0.6 [0.0, 7.0] mL, p =0.0145; mismatch ratio: 7.4 [2.5, 15.0], ICAS: 11.0 [4.6, 17.8], p =0.0285], indicating more salvageable brain tissue. The 90-day mRS showed better functional outcomes in the ICAS group, with a higher likelihood of minimal to no disability [mRS 90 equals 0-1: ICAS: 53.0% vs. Other Causes: 36.3%, p =0.0122]. The predictive model for ICAS, combining clinical manifestations and CTP parameters, yielded an area under the curve (AUC) of 0.7779, demonstrating good diagnostic performance. CTP is a valuable diagnostic tool for ICAS-induced AIS, offering the potential for early identification and informing the decision for endovascular treatment. The positive correlation between CTP findings and patient outcomes supports its utility in clinical practice.

Proteomic Composition of Acute Ischemic Stroke Thrombi Retrieved via Endovascular Thrombectomy Is Associated with Stroke Etiology.

The objective of this study is to investigate the protein components of acute ischemic stroke (AIS) thrombi using four-dimensional independent data acquisition (4D-DIA) proteomics and reveal the correlations between thrombotic protein components and AIS etiology. From April to September 2023, we enrolled a total of 30 patients who underwent endovascular thrombectomy at our institute and were diagnosed in accordance with large artery atherosclerosis (LAA; n = 15) or cardioembolism (CE; n = 15). Thromboembolic material was collected for 4D-DIA proteomic detection. We then analyzed it for differentially expressed proteins (DEPs; fold change [FC] ≥ 1.5 or ≤ 0.67), performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, and mapped protein-protein interactions (PPIs). In the 30 retrieved clots, 5115 proteins were expressed. Of these, we screened 246 DEPs between the LAA and CE groups, such as histone H4, collagen α1, and differentially expressed in neoplastic versus normal cells domain-containing protein 6A. GO analysis revealed that the DEPs' most important biological process was cellular process, the most important Cell Component was cell part, the molecular function was binding, and the most significantly enriched pathway was thiamine metabolism. PPI results revealed complicated interactions among these DEPs, of which superoxide dismutase, catalase, and γ-enolase might play important roles. This study outlines a promising molecular approach to differentiating the etiology of AIS between CE and LAA through the proteomics of retrieved thrombi, which might also inform future research into thrombotic biology.

Predictive etiological classification of acute ischemic stroke through interpretable machine learning algorithms: a multicenter, prospective cohort study

BackgroundThe prognosis, recurrence rates, and secondary prevention strategies varied significantly among different subtypes of acute ischemic stroke (AIS). Machine learning (ML) techniques can uncover intricate, non-linear relationships within medical data, enabling the identification of factors associated with etiological classification. However, there is currently a lack of research utilizing ML algorithms for predicting AIS etiology.ObjectiveWe aimed to use interpretable ML algorithms to develop AIS etiology prediction models, identify critical factors in etiology classification, and enhance existing clinical categorization.MethodsThis study involved patients with the Third China National Stroke Registry (CNSR-III). Nine models, which included Natural Gradient Boosting (NGBoost), Categorical Boosting (CatBoost), Extreme Gradient Boosting (XGBoost), Random Forest (RF), Light Gradient Boosting Machine (LGBM), Gradient Boosting Decision Tree (GBDT), Adaptive Boosting (AdaBoost), Support Vector Machine (SVM), and logistic regression (LR), were employed to predict large artery atherosclerosis (LAA), small vessel occlusion (SVO), and cardioembolism (CE) using an 80:20 randomly split training and test set. We designed an SFS-XGB with 10-fold cross-validation for feature selection. The primary evaluation metrics for the models included the area under the receiver operating characteristic curve (AUC) for discrimination and the Brier score (or calibration plots) for calibration.ResultsA total of 5,213 patients were included, comprising 2,471 (47.4%) with LAA, 2,153 (41.3%) with SVO, and 589 (11.3%) with CE. In both LAA and SVO models, the AUC values of the ML models were significantly higher than that of the LR model (P < 0.001). The optimal model for predicting SVO (AUC [RF model] = 0.932) outperformed the optimal LAA model (AUC [NGB model] = 0.917) and the optimal CE model (AUC [LGBM model] = 0.846). Each model displayed relatively satisfactory calibration. Further analysis showed that the optimal CE model could identify potential CE patients in the undetermined etiology (SUE) group, accounting for 1,900 out of 4,156 (45.7%).ConclusionsThe ML algorithm effectively classified patients with LAA, SVO, and CE, demonstrating superior classification performance compared to the LR model. The optimal ML model can identify potential CE patients among SUE patients. These newly identified predictive factors may complement the existing etiological classification system, enabling clinicians to promptly categorize stroke patients’ etiology and initiate optimal strategies for secondary prevention.

Investigating the Role of Brain Natriuretic Peptide (BNP) and N-Terminal-proBNP in Thrombosis and Acute Ischemic Stroke Etiology.

The need for biomarkers for acute ischemic stroke (AIS) to understand the mechanisms implicated in pathological clot formation is critical. The levels of the brain natriuretic peptides known as brain natriuretic peptide (BNP) and NT-proBNP have been shown to be increased in patients suffering from heart failure and other heart conditions. We measured their expression in AIS clots of cardioembolic (CE) and large artery atherosclerosis (LAA) etiology, evaluating their location inside the clots, aiming to uncover their possible role in thrombosis. We analyzed 80 thrombi from 80 AIS patients in the RESTORE registry of AIS clots, 40 of which were of CE and 40 of LAA etiology. The localization of BNP and NT-BNP, quantified using immunohistochemistry and immunofluorescence, in AIS-associated white blood cell subtypes was also investigated. We found a statistically significant positive correlation between BNP and NT-proBNP expression levels (Spearman's rho = 0.668 p < 0.0001 *). We did not observe any statistically significant difference between LAA and CE clots in BNP expression (0.66 [0.13-3.54]% vs. 0.53 [0.14-3.07]%, p = 0.923) or in NT-proBNP expression (0.29 [0.11-0.58]% vs. 0.18 [0.05-0.51]%, p = 0.119), although there was a trend of higher NT-proBNP expression in the LAA clots. It was noticeable that BNP was distributed throughout the thrombus and especially within platelet-rich regions. However, NT-proBNP colocalized with neutrophils, macrophages, and T-lymphocytes, suggesting its association with the thrombo-inflammatory process.

Unusual Cause of Acute Stroke in a Young Woman with Patent Foramen Ovale - Duplicated Inferior Vena Cava and May-Thurner Syndrome.

The etiology of acute ischemic stroke (AIS) may often remain uncertain despite diligent work-up, especially in young people. Although patent foramen ovale (PFO) is a frequent association during such work-up, the actual source of thromboembolism, like deep vein thrombosis (DVT), may not be found. Such associative pathology makes it challenging to prescribe anticoagulation for secondary stroke prevention. We describe a young woman with a known history of PFO who presented with AIS and underwent endovascular reperfusion therapy. Post-thrombectomy, she developed hypoxic respiratory failure due to pulmonary embolism. Initiation of therapeutic anticoagulation was complicated by a retroperitoneal bleed necessitating imaging studies for etiological work-up. Computed tomographic angiography and venogram showed no active contrast extravasation but demonstrated duplication of the inferior vena cava with DVT in the right iliofemoral vein (RIFV). The proximity of the right common iliac artery compressing RIFV against the pelvic inlet is described as May-Thurner syndrome (MTS). Afterward, the patient was successfully treated with anticoagulation and PFO closure. MTS is a rare and underdiagnosed cause of iliofemoral DVT. In patients with known PFO, MTS is a possible cause that needs consideration. Hence, appropriate diagnostic tests are necessary to initiate appropriate management and to prevent AIS recurrence.

Patchy profile sign in RAPID software: a specific marker for intracranial atherosclerotic stenosis in acute ischemic stroke.

Identifying the etiology of acute ischemic stroke (AIS) before endovascular treatment (EVT) is important but challenging. In CT perfusion imaging processed by perfusion software, we observed a phenomenon called patchy profile sign (PPS), that is, the hypoperfusion morphology in RAPID software is a discontinuous sheet pattern. This phenomenon is predominantly observed in patients diagnosed with intracranial atherosclerotic stenosis (ICAS). The study intends to assess whether the PPS can be used to differentiate ICAS from intracranial embolism. Patients with AIS due to M1 segment occlusion of the MCA who underwent mechanical thrombectomy were retrospectively enrolled. The receiver operating characteristic (ROC) curve analysis was performed to assess the value of PPS in predicting ICAS. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the PPS for prediction of ICAS were calculated. A total of 51 patients were included in the study. The PPS was observed in 10 of 19 (52.6%) patients with ICAS, and in 2 of 32 (6.3%) patients with intracranial embolism (p < 0.001). Interobserver agreement for identifying PPS was excellent (κ = 0.944). The sensitivity, specificity, PPV, NPV, and accuracy of the PPS for predicting ICAS were 52.6, 93.8, 83.3, 76.9, and 78.4%, respectively. The PPS on RAPID software is an imaging marker with high specificity for ICAS. Larger sample sizes are imperative to validate the findings.

Development of Egyptian Practice Guidelines in Management of Stroke in Pediatrics

Background Pediatric stroke, though not common but it is a severe disease with potentially lifelong restrictions, the etiology of acute ischemic stroke (AIS) in childhood is mostly multifactorial. Better understanding and development of practice guidelines improved the diagnosis and outcome of this disease. Aim of the Work This study aimed to develop Egyptian clinical practice pediatric stroke management guidelines that suitable for all resources at different Egyptian hospitals. Subjects and Methods Twenty six of Egyptian experts in the field of neurology in pediatrics were selected and invited to participate in this project. Two rounds Delphi techniques were applied to build up the consensus among the experts on the formulated guidelines, 75% agreement was used as cut-off. Results The experts agreed on the following, 60% agreed that Face, Arms, Speech, Time indications (the FAST tool) is the commonest presenting symptom of stroke in pediatrics. 80% agreed that the most common risk factors were thrombophilia, cardiac diseases followed by sickle cell disease and 100% that MRI is the best neuroimaging to be ordered for a child with suspected stroke. In terms of treatment, the panel had agreement76.9% on supporting safety of anticoagulation use in AIS and 92.3% on safety of aspirin use in prevention of stroke recurrence after exclusion of hemorrhagic stroke. Conclusion The present Delphi consensus process has supplied useful information on stroke diagnosis and management practice in a multicenter group of pediatric neurologists, influencing the development of a proposed local stroke guideline.

Blunt Traumatic Cerebrovascular Injury and Stroke: The Need for a High Index of Suspicion when Initial Vascular Imaging is Negative - A Single Center Case Series. (P14-5.019)

<h3>Objective:</h3> NA <h3>Background:</h3> Acute ischemic stroke (AIS) from traumatic cerebrovascular injury (TCVI) leads to approximately 4800 US strokes annually; often as sequelae of cervical arterial dissection. CT angiography (CTA) is typically used for screening, but this modality has limitations of low sensitivity, particularly for low-grade dissections. Our case series illustrates the importance of high index of suspicion in trauma patients to pursue further vessel imaging when there is unexplained AIS. <h3>Design/Methods:</h3> Case series. <h3>Results:</h3> Our series consists of 2 patients admitted to Trauma ICU following motor vehicle collisions. The 1st patient was a 22-year-old woman with left precentral gyrus infarction on diffusion-weighted MRI. Initial CTA showed dissection of cervical right internal carotid artery (ICA) which did not explain her infarction. Echocardiogram was also unrevealing so digital subtraction angiography was pursued, which revealed dissection of the left supraclinoid ICA not seen on CTA. The 2nd patient was a 15-year-old man with bilateral frontal infarctions on diffusion-weighted MRI. His initial CTA showed dissection of cervical left ICA. There was no explanation for his right frontal infarction on further workup so CTA was repeated after 4 days, which showed additional dissection involving the right cervical ICA not seen initially. Etiology of AIS in both cases was unexplained initially but repeat or alternate imaging helped unveil previously undetected ipsilateral dissections. <h3>Conclusions:</h3> Undetected traumatic dissection can result in devastating neurologic sequelae including further strokes and worsening dissection. It can also lead to unnecessary workup such as thrombophilia testing in younger patients. These patients are often hidden from the view of neurologists as they are typically managed by trauma surgeons and literature regarding TCVI is predominantly in surgical journals. We hope to increase awareness and emphasize the importance of a high index of suspicion to pursue further vessel imaging in unexplained stroke so that appropriate treatment can be initiated rapidly. <b>Disclosure:</b> Dr. Asif has nothing to disclose. Dr. Habib has nothing to disclose. Dr. Samkutty has nothing to disclose.

Abstract Number ‐ 232: Carotid Webs as an Under‐Reported Etiology of Acute Ischemic Stroke – Current Diagnostic Challenges

Introduction Carotid webs are anatomical variants in the internal carotid artery vasculature that predispose patients to stroke. As of now, optimal treatment has yet to be established given the lack of large, randomized trials. Part of this stems from the fact that carotid webs remain under‐recognized sources of ischemic stroke despite a high rate of reoccurrence. Herein, we aim to shed light on the diagnosis with our respective center’s experience as well as discuss diagnostic challenges associated with carotid webs. Methods We present a case of a 40‐year‐old male with no past medical history who presented to our center after having developed sudden onset left sided weakness and sensory loss, a left homonymous hemianopia, and dysarthria. Vessel imaging confirmed a right middle cerebral artery occlusion, specifically in the M2 segment, in the setting of a right carotid web. Results Once intracerebral hemorrhage was ruled out, tissue plasminogen activator was administered, with improvement in neurologic exam. Mechanical thrombectomy was thus deferred. Review of the MRI brain showed that in addition to an infarct in the right subinsular white matter region, there were scattered multifocal right hemispheric acute to early subacute infarcts raising concern for an underlying embolic etiology. While the right M2 occlusion looked like it had mainly resolved, a new focal non‐occlusive intraluminal thrombus was found in the right carotid bulb on CTA, MRA, and carotid ultrasound, just distal to a small transverse extraluminal carotid web (Figure 1). The decision was made to take the patient for right carotid stenting given that the carotid web served as a high‐risk lesion. A stent was placed in the right carotid artery with no complications, and the patient was continued on dual antiplatelet therapy. Upon being seen in outpatient clinic after discharge, patient had NIHSS score of 0, with no residual deficits, and was continued on DAPT and a statin for secondary stroke prevention. Conclusions Knowing that patients with carotid webs are at increased risk for stroke, recognition and accurate diagnosis of webs is crucial for appropriate treatment. Diagnostic challenges of carotid webs should be highlighted to prevent misdiagnosis. These include heightened awareness of the patient population that is most at risk, radiographic mimics, location of the lesion as a confounder, and rule out of other stroke etiologies. Prompt recognition of this high‐risk vascular lesion using multiple imaging modalities at different time points during the patient’s admission allowed for treatment of the underlying etiology of his stroke. By increasing awareness on the appropriate diagnostic approach for carotid webs, more information can be garnered to elucidate optimal treatment strategies.

Correlation of von Willebrand factor and platelets with acute ischemic stroke etiology and revascularization outcome: an immunohistochemical study

BackgroundPlatelets and von Willebrand factor (vWF) are key components of acute ischemic stroke (AIS) emboli. We aimed to investigate the CD42b (platelets)/vWF expression, its association with stroke etiology and the...

Differences in Cardiac Etiologies for Ischemic Stroke in Young and Middle-Aged Patients: A Single-Center Experience in Taiwan.

Background: The cardiac etiology of acute ischemic stroke (AIS) plays an important role in young adults; therefore, complete cardiac workups and subsequent prevention methods are important for treating young AIS patients. However, the definition of a young age for AIS patients could be below 45 years old, while in some previous studies, it has been below 55 years old. It remains unclear whether cardiac workups are equally important for AIS patients in the young (the age of 20–45 years old) and middle-aged (46–55 years old) categories. Materials and methods: This prospective study included 103 patients admitted due to a first AIS attack younger than 55 years old during the period from 1 October 2018 to 31 December 2020. All the patients received cardiologist consultations and cardiac workups accordingly. The characteristics of patients, cardiac workups, clinical findings, and management were analyzed. Results: AIS patients in the 46–55-year-old group had a higher prevalence of hypertension (61.4% vs. 39.0%), diabetes mellitus (27.3% vs. 15.3%), a previous history of coronary artery disease (9.1% vs. 1.7%), and atrial fibrillation (9.1% vs. 1.7%) compared to the 20–45-year-old group. After cardiologist consultations, a higher prevalence of newly diagnosed coronary artery disease (6.8% vs. 1.7%) and congestive heart failure (11.4% vs. 1.7%) was noted. Both groups disclosed similar percentages of patent foramen ovale (PFO) (27.3% vs. 22.0%) and valvular disease. These results led to subsequent changes in treatment in both groups. The 20–45-year-old group had higher percentages of receiving PFO occluders (11.9%) compared to the 46–55-year-old group (6.8%). Conclusion: Cardiologist consultations with thorough cardiac workups for AIS patients can reveal many cardiac findings in both young and middle-aged patients. This leads to a subsequent change in treatment, including medical and surgical aspects, which are important as secondary prevention for AIS.

Measurement of Midregional Pro-Atrial Natriuretic Peptide to Discover Atrial Fibrillation in Patients With Ischemic Stroke

BackgroundMidregional pro-atrial natriuretic peptide (MR-proANP) is a promising biomarker to differentiate the underlying etiology of acute ischemic stroke (AIS). ObjectivesThis study aimed to determine the role of MR-proANP for classification as cardioembolic (CE) stroke, identification of newly diagnosed atrial fibrillation (NDAF), and risk assessment for major adverse cardiovascular events (MACE). MethodsThis study measured MR-proANP prospectively collected within 24 hours after symptom-onset in patients with AIS from the multicenter BIOSIGNAL (Biomarker Signature of Stroke Aetiology) cohort study. Primary outcomes were CE stroke etiology and NDAF after prolonged cardiac monitoring, as well as a composite outcome of MACE (recurrent cerebrovascular events, myocardial infarction, or cardiovascular death) within 1 year. Logistic/Poisson and subproportional hazard regression were applied to evaluate the association between MR-proANP levels and outcomes. Additionally, a model for prediction of NDAF was derived and validated as a decision tool for immediate clinical application. ResultsBetween October 1, 2014, and October 31, 2017, this study recruited 1,759 patients. Log10MR-proANP levels were associated with CE stroke (OR: 7.96; 95% CI: 4.82-13.14; risk ratio: 3.12; 95% CI: 2.23-4.37), as well as NDAF (OR: 35.3; 95% CI: 17.58-71.03; risk ratio: 11.47; 95% CI: 6.74-19.53), and MACE (subdistributional HR: 2.02; 95% CI: 1.32-3.08) during follow-up. The model to predict NDAF including only age and MR-proANP levels had a good discriminatory capacity with an area under the curve of 0.81 (95% CI: 0.76-0.86), was well calibrated (calibration in the large: −0.086; calibration slope 1.053), and yielded higher net-benefit compared with validated scores to predict NDAF (AS5F score, CHA2DS2-VASc [Congestive Heart Failure, Hypertension, Age ≥65 or ≥75, Diabetes, Prior Cardioembolic Event, (female) Sex, or Vascular Disease] score). ConclusionsMR-proANP is a valid biomarker to determine risk of NDAF and MACE in patients with AIS and can be used as a decision tool to identify patients for prolonged cardiac monitoring. (Biomarker Signature of Stroke Aetiology Study: The BIOSIGNAL study [BIOSIGNAL]; NCT02274727)

Hyperacute Incidental Late Myocardial Enhancement in Ischemic Stroke Using Chest Spectral CT: Relationship with Etiology.

Hyperacute cardiac imaging of patients with acute ischemic stroke (AIS), though desirable, is impractical. Using delayed-enhancement, low-dose, non-gated, chest spectral computed tomography scans (DESCT), we explored the prevalence and patterns of incidental myocardial late iodine enhancement (LIE) and embolic sources, and their relationship with stroke etiology. Since July 2020, DESCT was performed after cerebrovascular CT angiography (CTA) among patients with suspected AIS undergoing CT using a dual-layer spectral scanner, without additional contrast administration. Images were analyzed using monoenergetic reconstructions and iodine density maps, and the myocardial extracellular volume fraction (ECV, %) was calculated. Eighty patients with AIS were included. DESCT identified a cardiac thrombi in 6 patients (7.5%), and a complex aortic plaque in 4 (5%) cases; reclassifying 5 embolic strokes of uncertain source (28% of ESUS) to cardioembolic (CE, n = 3) and non-CE (n = 2) etiologies. LIE was identified in 38 (48%) patients, most commonly (82%) of ischemic pattern. We did not identify significant relationships between AIS etiology and the presence, pattern, and extent of LIE (p > 0.05); ECV (p = 0.56), severe aortic (p = 0.25) or valvular (p = 0.26) disease, or the extent of coronary calcification (p = 0.39). Patients with evidence of major cardiovascular DESCT findings had higher rates of all-cause death at 90 days (42% vs. 19%, p = 0.037). In this study, hyperacute cardiac imaging of AIS with DESCT identified a high prevalence of incidental cardiac disease predominantly involving LIE of ischemic etiology and mostly not related to the stroke etiology.

Associations between cerebral magnetic resonance imaging infarct volume and acute ischemic stroke etiology.

BackgroundIdentifying ischemic stroke etiology is necessary for proper treatment and secondary prevention. We sought to define associations between infarct volume and stroke subtypes.Materials and methodsInclusion criteria necessitated a Johns Hopkins Hospital inpatient admission (2017–2019) for ischemic stroke with confirmatory brain magnetic resonance imaging. Infarct volume was calculated using MRIcron© by a masked reviewer. Ischemic strokes were adjudicated using TOAST classification. Multivariable/multinomial logistic regression determined associations between infarct volume and stroke subtypes with interaction terms for infarct number and location. Stepwise adjustment accounted for potential confounders.ResultsPatients (N = 150) were on average 61 years old, male (58%), and black (57%). Each 5mL increase in infarct volume was associated with cardioembolic (OR 1.07, 95%CI 1.01–1.14) and large-artery occlusions (OR 1.10, 95%CI 1.02–1.18), but lower odds of lacunar stroke (OR 0.18, 95%CI 0.06–0.55). There was no difference in risk of cardioembolic (base) and large-artery atherosclerotic strokes with increasing infarct volume (RRR 1.01, 95%CI 0.94–1.09), but risk of lacunar stroke was decreased (RRR 0.17, 95%CI 0.06–0.53). Infarct number (single vs multiple) modified the association between volume and subtype for large-artery occlusions (p-interaction 0.09).ConclusionsIn this study, larger volume infarcts were significantly associated with both cardioembolic and large-artery atherosclerotic strokes (no difference in the degree of association) and decreased odds of lacunar stroke. A single, large-volume stroke was associated with large-artery atherosclerosis, while multiple infarcts were associated with cardioembolism. Given the differential associations between volume, number of lesions, and stroke etiology, defining stroke subtypes in light of infarct volume might aid in clinical practice.

Seasonal Variation in Presentation and Time to Revascularization Therapy for Acute Ischemic Stroke

<strong>Objective:</strong> Assess for seasonal variation in patient presentation and time to initiation of revascularization therapy for acute ischemic stroke (AIS). <strong>Background:</strong> Rapid revascularization results in improved outcomes, including early neurological improvement as well as functional outcomes at 90 days, for AIS patients. However, restrictive time windows for alteplase (tPA) and endovascular thrombectomy (ET) limit treatment in the majority of AIS patients. Seasonal variation in AIS etiology, severity, patient eligibility for revascularization therapy, and functional outcomes following treatment have been reported in several large cohort studies abroad. However, seasonal variation in stroke presentation and outcomes in an urban northeastern US population is not well known. Moreover, in patients eligible for treatment, it is unclear whether there are seasonal variations in time to treatment, which may impact functional outcomes. <strong>Methods:</strong> We retrospectively analyzed AIS patients presenting to the Mount Sinai Hospital (MSH) ED from 2016 to 2018 contained in the American Heart Association’s Get With The Guidelines Database. Patients were classified by season of presentation and revascularization modality and primary outcome was door-to-treatment time. Descriptive statistics were used to examine patient characteristics. Non-parametric comparative statistics using Kruskal-Wallis H tests were run between groups to compare door-to-treatment initiation times by season and type of revascularization therapy. <strong>Results: </strong>808 patients presented to the ED for AIS. 28.1% presented during spring (n = 227), 25.7% summer (n = 208), 24.1% winter (n = 195), and 22.0% (n = 178) fall. 14.7% (n = 119) were treated with revascularization therapy, including 57.1% (n = 68) tPA, 26.9% (n = 32) ET, and 16% (n = 19) tPA+ET. Median door-to-treatment time was 60 minutes for tPA, 102.5 minutes ET, and in patients treated with tPA+ET, 55 and 160 minutes for tPA and ET, respectively. Among patients treated with ET, time-to-treatment differed by season with a mean rank time score in minutes of 9.07 for winter, 13.70 spring, 22.38 summer, and 21.00 fall (χ2(3) = 10.2117, p = 0.0169). No significant differences in time-to-treatment were observed by season for patients treated with tPA with or without ET (<em><strong>Table 1</strong></em>). <strong>Conclusions:</strong> Over the two-year period of study, ET time-to-treatment was fastest during spring and winter seasons but there was no difference in time-to-treatment with tPA with or without thrombectomy. This may reflect additional experience with stroke systems of care and improved procedural skill over the course of the academic year, but further study is needed.

Abstract P94: Stroke Etiologies in Patients With Covid-19: The Svin Covid-19 Multinational Registry

Background and purpose: Coronavirus disease 2019 (COVID-19) is associated with a small but clinically significant risk of stroke, the cause of which is frequently cryptogenic. In a large multinational cohort of consecutive COVID-19 patients with stroke, we evaluated clinical predictors of cryptogenic stroke, short-term functional outcomes and in-hospital mortality among patients according to stroke etiology. Methods: We explored clinical characteristics and short-term outcomes of consecutively evaluated patients 18 years of age or older with acute ischemic stroke (AIS) and laboratory-confirmed COVID-19 from 31 hospitals in 4 countries (3/1/20-6/16/20). Results: Of the 14.483 laboratory-confirmed patients with COVID-19, 156 (1.1%) were diagnosed with AIS. Sixty-one (39.4%) were female, 84 (67.2%) white, and 88 (61.5%) were between 60-79 years of age. The most frequently reported etiology of AIS was cryptogenic (55/129, 42.6%), which was associated with significantly higher white blood cell count, c-reactive protein, and D-dimer levels than non-cryptogenic AIS patients (p&lt;/=0.05 for all comparisons). In a multivariable backward stepwise regression model estimating the odds of in-hospital mortality, cryptogenic stroke mechanism was associated with a fivefold greater odds in-hospital mortality than strokes due to any other mechanism (adjusted OR 5.16, 95%CI 1.41-18.87, p=0.01). In that model, older age (aOR 2.05 per decade, 95%CI 1.35-3.11, p&lt;0.01) and higher baseline NIHSS (aOR 1.12, 95%CI 1.02-1.21, p=0.01) were also independently predictive of mortality. Conclusions: Our findings suggest that cryptogenic stroke among COVID-19 patients may be related to more severe disease and carries a significant risk of early mortality.

Stroke etiologies in patients with COVID-19: the SVIN COVID-19 multinational registry

Background and purposeCoronavirus disease 2019 (COVID-19) is associated with a small but clinically significant risk of stroke, the cause of which is frequently cryptogenic. In a large multinational cohort of consecutive COVID-19 patients with stroke, we evaluated clinical predictors of cryptogenic stroke, short-term functional outcomes and in-hospital mortality among patients according to stroke etiology.MethodsWe explored clinical characteristics and short-term outcomes of consecutively evaluated patients 18 years of age or older with acute ischemic stroke (AIS) and laboratory-confirmed COVID-19 from 31 hospitals in 4 countries (3/1/20–6/16/20).ResultsOf the 14.483 laboratory-confirmed patients with COVID-19, 156 (1.1%) were diagnosed with AIS. Sixty-one (39.4%) were female, 84 (67.2%) white, and 88 (61.5%) were between 60 and 79 years of age. The most frequently reported etiology of AIS was cryptogenic (55/129, 42.6%), which was associated with significantly higher white blood cell count, c-reactive protein, and D-dimer levels than non-cryptogenic AIS patients (p</=0.05 for all comparisons). In a multivariable backward stepwise regression model estimating the odds of in-hospital mortality, cryptogenic stroke mechanism was associated with a fivefold greater odds in-hospital mortality than strokes due to any other mechanism (adjusted OR 5.16, 95%CI 1.41–18.87, p = 0.01). In that model, older age (aOR 2.05 per decade, 95%CI 1.35–3.11, p < 0.01) and higher baseline NIHSS (aOR 1.12, 95%CI 1.02–1.21, p = 0.01) were also independently predictive of mortality.ConclusionsOur findings suggest that cryptogenic stroke among COVID-19 patients carries a significant risk of early mortality.

Sudden Onset Hemiplegia and Neglect: A Case Report of Type A Aortic Dissection Presenting as a Code Stroke

Stanford type A acute aortic dissection with ischemic stroke is a rare yet highly morbid presentation of sudden onset neurological symptoms. We present a case of a 57-year-old African American male brought to the emergency department with a witnessed syncopal episode, abdominal pain, right sided gaze preference, and left side weakness. Upon initiation of the hospital’s “Code Stroke” response protocol, a computed tomography angiogram of the neck incidentally identified Stanford type A aortic dissection with extension into and occlusion of the brachiocephalic artery, occlusion of the right common carotid artery and right internal carotid artery, and dissection flap propagation into the origin of the left common carotid artery. Postoperative magnetic resonance imaging of the brain and the entire spine demonstrated multifocal cerebral infarcts, as well as T10 - L1 spinal infarct. Despite provision of multidisciplinary intensive care unit level of care, the patient failed to demonstrate clinically significant neurological recovery and was transitioned to comfort care after 3 weeks of hospitalization. This case highlights the importance of considering acute aortic dissection as a potential etiology of acute ischemic stroke through the use of computed tomography angiography, as this diagnosis carries profoundly different implications for the consideration of thrombolytic agents and other emergent treatment modalities. J Neurol Res. 2020;10(6):248-252 doi: https://doi.org/10.14740/jnr638

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This study was the first study of independent predictors of acute ischemic stroke (AIS) in the oldest-old (>75years) and in the elderly (from 60-75years) patients in Vietnam. The study information was on 308 consecutive AIS patients aged ≥60years (138 aged >75years) admitted to Phutho general hospital from 2014 to 2017. The factors used in this study were including: demographics (age and sex), pre-stroke disability (modified Rankin Scale ≥3) and comorbidities, AIS etiology and subtype, NIH Stroke Scale (NIHSS) score, clinical and laboratory admission parameters and medical complications. The statistical analysis of multiple logistic regressions focused on independent predictors of in-hospital death, incident disability, length of stay, discharge without rehabilitation and no direct discharge home. The poor clinical outcomes of the oldest-old (>75years) and the younger patients (≤75years) were compared, including: NIHSS score, clinical parameters of AIS severity(need for oxygen, indwelling catheter, or nasogastric tube), incidents disability, and medical complications. The result showed a number of factors exacerbated and contributed to poor outcomes in patients over 75years of age with acute ischemic stroke, including medical history, related factors in the first three days of hospitalization, NIHSS score, Glasgow score, paralysis level, mechanical ventilation, gastric catheterization, fever and leukemia increase, complications of pneumonia, urinary inflammation, heart failure, acute renal failure. Therefore, this study showed a relation between independent predictors with ischemic stroke in the elderly patients in Vietnam.