Etiology Of Ischemic Stroke Research Articles

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 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 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 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

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 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.

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.

Magnetic resonance imaging features and stroke etiology of ischemic stroke in essential thrombocythemia

BackgroundVarious essential thrombocythemia (ET)-related stroke mechanisms have been proposed, including microcirculatory disturbance due to coagulopathy, vasculitis, and embolism due to thrombus formation in large vessels. However, the stroke mechanism in ET remains largely unexplored. The purpose of this study was to evaluate magnetic resonance image (MRI) features of ischemic stroke in ET and determine the potential stroke mechanism. MethodsWe retrospectively collected data from 21 acute ischemic stroke patients with ET who were admitted to two stroke centers between 2010 and 2023. ET was diagnosed according to the World Health Organization criteria. We evaluated MRI features including the diffusion-weighted image (DWI) lesion pattern, and the presence of hemorrhagic transformation and intracranial artery steno-occlusive lesion, as well as other etiological workup results. ResultsOf 21 patients, 20 exhibited multiple ischemic lesions on DWI, mainly within a single vascular territory. Cortical infarcts were observed in 19 patients. Hemorrhagic transformation occurred in 15 patients. Additionally, 15 patients had intracranial steno-occlusive arteries, which regressed to normal in 11 patients during follow-up. Out of all patients, only 2 had potential causes of stroke other than ET (1 with atrial fibrillation and 1 with intracranial atherosclerotic stenosis). The remaining 19 patients had ET as the only identified potential cause. ConclusionsMRI features, including DWI lesion pattern in ischemic stroke patients with ET, suggested embolic etiology despite the absence of major embolic sources. Intra-arterial thrombus appears to be part of the stroke mechanism related to ET and may contribute to ischemic stroke in ET.

Contemporary Management and Outcomes of Carotid Artery Dissection

Carotid artery dissection is a significant cause of stroke and the leading etiology of ischemic stroke in young and middle-aged individuals. The management of carotid artery dissection is continually evolving and varies based on the patient's clinical presentation. While carotid dissection is typically managed medically, endovascular intervention may be warranted in certain cases, and open surgical intervention is rarely employed.This qualitative review examines contemporary management strategies for cervical carotid artery dissection, highlighting three illustrative cases where endovascular intervention was utilized. We present one case of traumatic etiology with acute stroke symptoms, another traumatic case with progressing dissection and pseudoaneurysm evident on imaging, and a case of iatrogenic carotid dissection. Through these cases, we aim to elucidate the decision-making process and outcomes associated with endovascular treatment in the context of carotid artery dissection.

Classification of childhood arterial ischemic stroke

The etiology of childhood arterial ischemic stroke is complex, and identifying the underlying cause is crucial for optimizing treatment and preventing recurrence. Currently, the classification methods for childhood arterial ischemic stroke are largely based on data from international studies, but a unified consensus have not yet been reached. This paper reviews the existing classification methods and their subtype definitions, and points out some doubts and ambiguities. On this basisi, combined with the data collected by Beijing Children's Hospital on Chinese children with arterial ischemic stroke, a new classification method (COIST) was proposed according to the etiology and pathogenesis, namely: inflammation (I), abnormal vascular structure (S), thrombophilia (T), heart disease (C), other identifiable causes (O), and uncertain causes; and various subtypes are listed. It is hoped that this new classification method can attract the attention and discussion of domestic colleagues, with the aim of further refinement, in order to help clinicians better understand and quickly identify the etiologies of childhood ischemic stroke.

A case report about anorexia nervosa and ischemic stroke: what can we learn?

IntroductionAnorexia Nervosa (AN) is a complex psychiatric illness, characterized by a high risk of developing cardiovascular complications. Given the high risk of vascular diseases in patients with AN, we can assume that patients with severe AN have a high risk of developing ischemic stroke. However, to the best of our knowledge, no reports of patients with AN presenting with ischemic stroke have been published, other than a report of the development of IS during refeeding therapy in patients with severe AN.Case presentationThe present case report is aimed at describing the characteristics of an ischemic stroke occurring in a 19-year-old university student who had a 6-month history of AN. She was a non-smoker, had no relevant medical history and no family history of stroke. Upon hospital admission due to symptoms of stroke (aphasia and facial droop), she exhibited severe malnutrition with a BMI of 12.8 kg/m2. Computerized tomography imaging revealed occlusion of the left M2 branch and a congruous extensive area of hypoperfusion. Further investigations ruled out all common causes of stroke: she had no vascular stenosis, no heart diseases or arrhythmias, and no shunts, and gave negative results in autoimmune, toxicological and thrombophilia screenings.ConclusionClinicians should suspect development of severe complications, including ischemic stroke, in patients with severe AN. Further extensive group studies or group-based studies are needed to elucidate the etiology of ischemic stroke in patients with severe AN. This will enable us to develop more precise and effective interventions.Graphical

Small vessel disease burden and prognosis of recent subcortical ischaemic stroke differ by parent artery atherosclerosis.

Parent artery atherosclerosis is an important aetiology of recent subcortical ischaemic stroke (RSIS). However, comparisons of RSIS with different degrees of parent artery atherosclerosis are lacking. Prospectively collected data from our multicentre cohort (all were tertiary centres) of the Stroke Imaging Package Study between 2015 and 2017 were retrospectively reviewed. The patients with RSIS defined as a single clinically relevant diffusion-weighted imaging positive lesion in the territory of lenticulostriate arteries were categorized into three subgroups: (1) normal middle cerebral artery (MCA) on magnetic resonance angiography and high-resolution magnetic resonance imaging (HR-MRI); (2) low-grade MCA atherosclerosis (normal or <50% stenosis on magnetic resonance angiography and with MCA plaques on HR-MRI); (3) steno-occlusive MCA atherosclerosis (stenosis ≥50% or occlusion). The primary outcome was 90-day functional dependence (modified Rankin Scale score >2). The clinical and imaging findings were compared between subgroups. A total of 239 patients (median age 60.0 [52.0-67.0] years, 72% male) were enrolled, including 140 with normal MCA, 64 with low-grade MCA atherosclerosis and 35 with steno-occlusive MCA atherosclerosis. Patients with steno-occlusive MCA atherosclerosis had the largest infarct volume. Low-grade MCA atherosclerosis was independently associated with cerebral microbleeding, more severe perivascular spaces in basal ganglia and higher total cerebral small vessel disease burden. Low-grade MCA atherosclerosis was an independent determinant of 90-day functional dependence (odds ratio 3.897; 95% confidence interval 1.309-11.604). Our study suggested RSIS with varying severity of parent artery atherosclerosis exhibits distinctive clinical and neuroimaging characteristics, with low-grade MCA atherosclerosis associating with higher cerebral small vessel disease burden and worse prognosis.

Relationship between carotid web morphology on CT angiography and stroke: A pooled multicenter analysis.

The Carotid web (CaW) is a cause of stroke, particularly in younger individuals. However, the frequency and the radiological features of the web's morphology associated with stroke risk are uncertain. We determined the CaW radiological features on computed tomography (CT) angiography associated with ipsilateral stroke. Data from six studies of patients with acute ischemic stroke were pooled. Identification and measurement of CaWs were performed by experienced readers using baseline neck CT angiography. We assessed six 2D CaW radiological features on sagittal oblique images, namely, main axis length, thickness, height, base width, distance to wall, and angle between the web main axis and carotid wall, and CaW volume on 3D images. CaWs were divided into symptomatic if acute ischemic stroke was in the ipsilateral internal carotid artery territory and its etiology was undetermined and asymptomatic if one condition was unmet. Univariable and multivariable analyses were conducted to assess the association between each radiological CaW feature and symptomatic CaW. Of the 3442 patients in the pooled data with assessable CTAs, 60 (1.7%) had CaW. In patients with CaW, median age was 59 (interquartile range [IQR]: 50-68) years, 60% were women, and 3 patients had bilateral CaWs. There were 39 (62%) symptomatic and 24 (38%) asymptomatic CaWs. Patients with symptomatic CaW were younger (55 (IQR: 49-61) years versus 69 (IQR: 52-75) years), had lower rates of hypertension (9 (25.0%) versus 12 (57.1%)) and more intracranial large vessel occlusions compared to patients with asymptomatic CaWs. After adjusting for age, hypertension, and occlusion location, CaW length (adjusted odds ratio (aOR) 1.84 (95% confidence interval [CI]: 1.03-3.28)), thickness (aOR: 2.31 (95% CI 1.08-4.97)), volume (aOR: 1.07 per 1 mm3 increment (95% CI: 1.01-1.12)), and angle relative to the carotid wall (aOR: 0.95 (95% CI: 0.91-0.99)) were associated with symptomatic CaW. Radiological assessment of CaW morphology may determine its potential causal role in ischemic stroke etiology. Symptomatic CaWs tend to be longer, larger, and oriented at more acute angles relative to the carotid wall as compared to asymptomatic CaWs.

Association between ischaemic stroke aetiology and leptomeningeal collateral status: a retrospective cohort study.

There is limited understanding of the pathomechanistic relationship between leptomeningeal collateral formation and ischaemic stroke aetiology. We aimed to assess the association of leptomeningeal collateral status and ischaemic stroke aetiology, using the widely recognised "Trial of Org 10172 in Acute Stroke Treatment" (TOAST) classification categorising strokes into five distinct aetiologies. Retrospective study of consecutively admitted adult ischaemic stroke patients at a Swiss stroke centre. Leptomeningeal collateral status was assessed on admission with single-phase CT-angiographies using a validated 4-point score. Patients were categorised into large-artery atherosclerosis (LAA), cardioembolic (CE), small-vessel disease (SVD) and cryptogenic (CG) according to the TOAST classification. We performed ordinal and binary (poor [collaterals filling ≤50% of the occluded territory] vs good [collaterals filling >50% of the occluded territory] collateralisation) logistic regression to evaluate the impact of TOAST aetiology on collateral status. Among 191 patients, LAA patients had better collateral status compared to non-LAA aetiology (LAA: 2 vs CE: 2 vs SVD: 3 vs CG: 2, pLAAvsnon-LAA= 0.04). In weighted multivariate logistic regression, LAA and SVD independently predicted better collateral status (binary models [adjusted odds ratio; aOR]: LAA: 3.72 [1.21-11.44] and SVD: 4.19 [1.21-14.52]; ordinal models [adjusted common odds ratio; acOR]: LAA: 2.26 [95% CI: 1.23-4.15] and SVD: 1.94 [1.03-3.66]), while CE predicted worse collateral status (binary models [aOR]: CE: 0.17 [0.07-0.41]; ordinal models [acOR]: CE: 0.24 [0.11-0.51]). The aetiology of ischaemic stroke is associated with leptomeningeal collateral status on single-phase CT-angiography, with LAA and SVD predicting better and CE predicting worse collateral status.

Risk Factors and Etiological Classification of Ischemic Stroke Subtypes in Southwest Iran

Precise categorization of the causes of ischemic stroke (IS) is crucial for optimizing stroke treatment and assessing the prognosis of patients. This cross-sectional study aimed to determine the risk factors and various subcategories of IS in Iranian patients. The study included all patients with IS referred to Golestan Hospital (Ahvaz, Iran) for one year. Their demographics and clinical data were collected. The etiology of IS was classified based on the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria. A total of 1100 patients with IS were evaluated, 658 were male and 442 were female. They had an average age of 66 years (ranging between 20 and 99 years). The majority of them were in the 61-80 age group. The prevalence of risk factors for IS included hypertension (HTN) (71.4%), diabetes (50.4%), smoking (42.4%), history of previous stroke (28%), dyslipidemia (15.4%), and cardiovascular disease (22.5%). Three months after admission, the mortality rate was 10.7% and the majority of patients exhibited a lower level of disability based on the modified Rankin Score (mRS) compared to the time of admission. The frequency of all risk factors, except for HTN, differed significantly between genders (P&lt;0.05). Furthermore, the prevalence of risk factors varied significantly among different stroke etiologic subgroups (P&lt;0.05). The most common etiological factors identified by TOAST classification were associated with large artery atherosclerosis (LAA) and small artery occlusion (SAO). Significant variations were observed in the prevalence of different etiologic subtypes of stroke among genders and across different age groups.

Individual participant data analysis comparing acute stroke patients with anterior versus posterior circulation dissections

BackgroundCervical artery dissection (CAD) is a relevant etiology of transient ischemic attacks and strokes. Several trials explored the significance of specific antithrombotic treatments, i.e. oral anticoagulation (OAC) versus antiplatelet treatment (APT), on recurrent ischemic complications and clinical outcomes. As overall incidence rates of complications were low there is still controversy which antithrombotic treatment should be used. However, up to now there has been no systematic investigation among CAD-patients with ischemic stroke specifically comparing clinical course and outcome of patients with anterior versus posterior CAD. MethodsWe performed an individual participant data analysis of patients with CAD and ischemic stroke. Over a five-year period we pooled data from three sites (i.e. West China Hospital, Chengdu, China as well as Erlangen and Giessen University Hospitals, Germany) and enrolled patients with CAD-associated ischemic stroke. Patient demographics, clinical and in-hospital measures as well as radiological data were retrieved from institutional databases. Clinical follow-up was over 6 months and included data on recurrent ischemic strokes and hemorrhages as well as clinical functional outcome assessed by the modified Rankin Scale dichotomized into favourable (mRS=0–2) and unfavourable. ResultsA total of 203 patients with CAD were included of which n=112 had anterior and n=91 had posterior CAD. Patients with posterior CAD were younger (46.0 vs. 41.0 y; p<0.001) than patients with anterior CAD and showed less often arterial hypertension. (42.0 % vs. 28.6 %; p<0.048). Antithrombotic treatment with APT and OAC was similarily distributed among patients with anterior and posterior CAD and not significantly differently related to ischemic or hemorrhagic complications during follow-up (all p=n.s.). Main difference between Chinese and German patients were mode of antithrombotic treatment consisting predominantly of APT in China compared to OAC in Germany. Functional outcome overall was good, yet worse in patients with anterior CAD compared to posterior CAD (80.2 % favorable in anterior CAD vs. 92.2 % in posterior CAD (p=0.014). ConclusionThis study provides evidence that anterior and posterior CAD show baseline imbalances regarding age and comorbidity which may affect clinical outcome. There are no signals of superiority or harm of any specific mode of antithrombotic treatment nor relevant discrepancies in clinical outcome among Chinese and German CAD-associated stroke patients.

StrokeClassifier: ischemic stroke etiology classification by ensemble consensus modeling using electronic health records

Determining acute ischemic stroke (AIS) etiology is fundamental to secondary stroke prevention efforts but can be diagnostically challenging. We trained and validated an automated classification tool, StrokeClassifier, using electronic health record (EHR) text from 2039 non-cryptogenic AIS patients at 2 academic hospitals to predict the 4-level outcome of stroke etiology adjudicated by agreement of at least 2 board-certified vascular neurologists’ review of the EHR. StrokeClassifier is an ensemble consensus meta-model of 9 machine learning classifiers applied to features extracted from discharge summary texts by natural language processing. StrokeClassifier was externally validated in 406 discharge summaries from the MIMIC-III dataset reviewed by a vascular neurologist to ascertain stroke etiology. Compared with vascular neurologists’ diagnoses, StrokeClassifier achieved the mean cross-validated accuracy of 0.74 and weighted F1 of 0.74 for multi-class classification. In MIMIC-III, its accuracy and weighted F1 were 0.70 and 0.71, respectively. In binary classification, the two metrics ranged from 0.77 to 0.96. The top 5 features contributing to stroke etiology prediction were atrial fibrillation, age, middle cerebral artery occlusion, internal carotid artery occlusion, and frontal stroke location. We designed a certainty heuristic to grade the confidence of StrokeClassifier’s diagnosis as non-cryptogenic by the degree of consensus among the 9 classifiers and applied it to 788 cryptogenic patients, reducing cryptogenic diagnoses from 25.2% to 7.2%. StrokeClassifier is a validated artificial intelligence tool that rivals the performance of vascular neurologists in classifying ischemic stroke etiology. With further training, StrokeClassifier may have downstream applications including its use as a clinical decision support system.

The Roles of NOTCH3 p.R544C and Thrombophilia Genes in Vietnamese Patients With Ischemic Stroke: Study Involving a Hierarchical Cluster Analysis

Background The etiology of ischemic stroke is multifactorial. Several gene mutations have been identified as leading causes of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary disease that causes stroke and other neurological symptoms. Objective We aimed to identify the variants of NOTCH3 and thrombophilia genes, and their complex interactions with other factors. Methods We conducted a hierarchical cluster analysis (HCA) on the data of 100 patients diagnosed with ischemic stroke. The variants of NOTCH3 and thrombophilia genes were identified by polymerase chain reaction with confronting 2-pair primers and real-time polymerase chain reaction. The overall preclinical characteristics, cumulative cutpoint values, and factors associated with these somatic mutations were analyzed in unidimensional and multidimensional scaling models. Results We identified the following optimal cutpoints: creatinine, 83.67 (SD 9.19) µmol/L; age, 54 (SD 5) years; prothrombin (PT) time, 13.25 (SD 0.17) seconds; and international normalized ratio (INR), 1.02 (SD 0.03). Using the Nagelkerke method, cutpoint 50% values of the Glasgow Coma Scale score; modified Rankin scale score; and National Institutes of Health Stroke Scale scores at admission, after 24 hours, and at discharge were 12.77, 2.86 (SD 1.21), 9.83 (SD 2.85), 7.29 (SD 2.04), and 6.85 (SD 2.90), respectively. Conclusions The variants of MTHFR (C677T and A1298C) and NOTCH3 p.R544C may influence the stroke severity under specific conditions of PT, creatinine, INR, and BMI, with risk ratios of 4.8 (95% CI 1.53-15.04) and 3.13 (95% CI 1.60-6.11), respectively (Pfisher&lt;.05). It is interesting that although there are many genes linked to increased atrial fibrillation risk, not all of them are associated with ischemic stroke risk. With the detection of stroke risk loci, more information can be gained on their impacts and interconnections, especially in young patients.

Transcriptomic Analysis of Extracellular Vesicles in the Search for Novel Plasma and Thrombus Biomarkers of Ischemic Stroke Etiologies.

Accurate etiologic diagnosis provides an appropriate secondary prevention and better prognosis in ischemic stroke (IS) patients; still, 45% of IS are cryptogenic, urging us to enhance diagnostic precision. We have studied the transcriptomic content of plasma extracellular vesicles (EVs) (n = 21) to identify potential biomarkers of IS etiologies. The proteins encoded by the selected genes were measured in the sera of IS patients (n = 114) and in hypertensive patients with (n = 78) and without atrial fibrillation (AF) (n = 20). IGFBP-2, the most promising candidate, was studied using immunohistochemistry in the IS thrombi (n = 23) and atrium of AF patients (n = 13). In vitro, the IGFBP-2 blockade was analyzed using thromboelastometry and endothelial cell cultures. We identified 745 differentially expressed genes among EVs of cardioembolic, atherothrombotic, and ESUS groups. From these, IGFBP-2 (cutoff > 247.6 ng/mL) emerged as a potential circulating biomarker of embolic IS [OR = 8.70 (1.84-41.13) p = 0.003], which was increased in patients with AF vs. controls (p < 0.001) and was augmented in cardioembolic vs. atherothrombotic thrombi (p < 0.01). Ex vivo, the blockage of IGFBP-2 reduced clot firmness (p < 0.01) and lysis time (p < 0.001) and in vitro, diminished endothelial permeability (p < 0.05) and transmigration (p = 0.06). IGFBP-2 could be a biomarker of embolic IS and a new therapeutic target involved in clot formation and endothelial dysfunction.