Stroke Of Undetermined Etiology Research Articles

MRI in the Evaluation of Cryptogenic Stroke and Embolic Stroke of Undetermined Source.

Cryptogenic stroke refers to a stroke of undetermined etiology. It accounts for approximately one-fifth of ischemic strokes and has a higher prevalence in younger patients. Embolic stroke of undetermined source (ESUS) refers to a subgroup of patients with nonlacunar cryptogenic strokes in whom embolism is the suspected stroke mechanism. Under the classifications of cryptogenic stroke or ESUS, there is wide heterogeneity in possible stroke mechanisms. In the absence of a confirmed stroke etiology, there is no established treatment for secondary prevention of stroke in patients experiencing cryptogenic stroke or ESUS, despite several clinical trials, leaving physicians with a clinical dilemma. Both conventional and advanced MRI techniques are available in clinical practice to identify differentiating features and stroke patterns and to determine or infer the underlying etiologic cause, such as atherosclerotic plaques and cardiogenic or paradoxical embolism due to occult pelvic venous thrombi. The aim of this review is to highlight the diagnostic utility of various MRI techniques in patients with cryptogenic stroke or ESUS. Future trends in technological advancement for promoting the adoption of MRI in such a special clinical application are also discussed.

Burden of intracranial artery calcification in white patients with ischemic stroke.

The diagnostic workup of stroke doesn't identify an underlying cause in two-fifths of ischemic strokes. Intracranial arteriosclerosis is acknowledged as a cause of stroke in Asian and Black populations, but is underappreciated as such in whites. We explored the burden of Intracranial Artery Calcification (IAC), a marker of intracranial arteriosclerosis, as a potential cause of stroke among white patients with recent ischemic stroke or TIA. Between December 2005 and October 2010, 943 patients (mean age 63.8 (SD ± 14.0) years, 47.9% female) were recruited, of whom 561 had ischemic stroke and 382 a TIA. CT-angiography was conducted according to stroke analysis protocols. The burden of IAC was quantified on these images, whereafter we assessed the presence of IAC per TOAST etiology underlying the stroke and assessed associations between IAC burden, symptom severity, and short-term functional outcome. IAC was present in 62.4% of patients. Furthermore, IAC was seen in 84.8% of atherosclerotic strokes, and also in the majority of strokes with an undetermined etiology (58.5%). Additionally, patients with larger IAC burden presented with heavier symptoms (adjusted OR 1.56 (95% CI [1.06-2.29]), but there was no difference in short-term functional outcome (1.14 [0.80-1.61]). IAC is seen in the majority of white ischemic stroke patients, aligning with findings from patient studies in other ethnicities. Furthermore, over half of patients with a stroke of undetermined etiology presented with IAC. Assessing IAC burden may help identify the cause in ischemic stroke of undetermined etiology, and could offer important prognostic information.

Differential expression of Semaphorin-7A /CD163-positive macrophages in large artery and cardiogenic stroke.

Identification of the causes of stroke of undetermined etiology, specifically cardioembolism (CE) and non-CE causes, can inform treatment planning and prognosis prediction. The objective of this study was to analyze the disparities in thrombus composition, particularly Semaphorin-7A (Sema7A) and CD163, between patients diagnosed with large-artery atherosclerosis (LAA) and those with CE, and to investigate their potential association with prognosis. Thrombi were collected from patients who underwent mechanical thrombectomy at two hospitals. The patients were categorized into two groups: LAA and CE. We compared the levels of Sema7A and CD163 between these groups and analyzed their relationships with stroke severity, hemorrhagic transformation and prognosis. The study involved a total of 67 patients. Sema7A expression was found to be significantly higher in the CE group compared to LAA (p < 0.001). Conversely, no statistically significant differences were observed for CD163 between the groups. The presence of Sema7A/CD163 did not show any associations with stroke severity or hemorrhagic transformation (all p > 0.05). However, both Sema7A (OR, 2.017; 95% CI, 1.301-3.518; p = 0.005) and CD163 (OR, 2.283; 95% CI, 1.252-5.724; p = 0.03) were associated with the poor prognosis for stroke, after adjusting for stroke severity. This study highlights that CE thrombi exhibited higher levels of Sema7A expression compared to LAA thrombi. Moreover, we found a positive correlation between Sema7A/CD163 levels and the poor prognosis of patients with acute ischemic stroke.

Abstract TP189: Outcome Differences Between Endovascular Thrombectomy and Medical Management Based on Underlying Stroke Etiology: A Secondary Analysis of SELECT2 Trial

Introduction: In patients with large core ischemic stroke, potential heterogeneity in EVT treatment effect based on underlying etiology is an important question. We explored differences in clinical outcomes and successful recanalization rates between EVT and MM. Methods: From SELECT2 randomized clinical trial, patients were categorized based on Stroke etiology: Large-artery atherosclerosis (LAA), Cardioembolism (CE), Stroke of other determined etiology (SOE), and Stroke of undetermined etiology (SUE). Procedure success, clinical outcomes and EVT treatment effect was compared based on stroke etiology. Results: Cardioembolic stroke was most frequently observed etiology across the trial (41%), followed by stroke of undetermined etiology (29%), large artery atherosclerosis (23%) and stroke of other determined etiology (6%). Proportion of patients achieving successful reperfusion (mTICI 2b-3) after EVT differed significantly across the categories (CE: 87%, LAA: 82%, SOE: 73%, SUE: 66%, p=0.040). However, treatment effect estimates favored EVT across categories of stroke etiology without significant heterogeneity - CE (ref): aGenOR: 1.83 (1.30-2.59) vs LAA: aGenOR: 2.04 (1.24-3.37), p-int: 0.87 vs SOE: aGenOR: 2.06 (0.80-5.28), p-int: 0.79 vs SUE: aGenOR: 1.20 (0.77-1.88), p-int: 0.17. Conclusion: In patients with large core ischemic stroke, proportion of patients achieving successful reperfusion differed based on stroke etiology. However, EVT was associated with better outcomes without evidence of significant heterogeneity. Further optimization of procedure techniques may help improve successful reperfusion rates and clinical outcomes in patients with SUE. Clinicaltrials.gov registration: NCT03876457

Abstract TP271: A Retrospective Analysis of Demographic and Clinical Variables Within a Single Center Young Stroke Cohort

Introduction: Despite significant efforts to increase public awareness of cerebrovascular disease, the incidence of stroke and transient ischemic attack (TIA) in young adults has remained elevated, representing a major public health concern. We sought to better characterize our young stroke population in order to gain insight as to where targeted interventions could be beneficial in community outreach and support of affected patients. Methods: We conducted a retrospective study evaluating young adults (under 50 years of age) presenting to a single urban academic medical center with acute ischemic stroke or TIA between 2013 and 2022. Demographic information and clinical variables (including past medical history, Trial of Org 10172 in Acute Stroke Treatment [TOAST] classification of stroke etiology, and discharge disposition) were extracted from the electronic medical record and descriptive statistics were calculated. Results: A total of 408 patients were reviewed. Within this study population, the median age was 43 years (IQR 38-47 years) and 235 (57.6%) were men. The median initial National Institutes of Health Stroke Scale upon presentation was 3 (IQR 1-7). The most common stroke risk factors were tobacco use (44.6%), pre-existing cardiovascular disease (26.2%), and other substance use (23.8%). The most common TOAST classification upon discharge was Stroke of Undetermined Etiology (32.9%). Most patients (244, 59.8%) were discharged directly to home from the hospital, although 140 (34.3%) were transitioned to another facility, including acute rehabilitation facilities (95, 23.3%), skilled nursing facilities (22, 5.4%), and long-term acute care hospitals (11, 2.7%). Conclusion: Our study highlights that the continued high incidence of stroke in the young may be at least partially attributable to a high prevalence of traditional cardiovascular risk factors, thus emphasizing the importance of smoking cessation counseling and early treatment of hypertension in the primary care setting. In addition, while most young patients will present with minor stroke symptoms, a significant portion are unable to return directly to home upon discharge from the hospital.

Characteristics of acute ischemic stroke in patients with Nephrotic syndrome

The incidence of ischemic stroke (IS) is higher in nephrotic syndrome (NS) patients compared to general population. However, there is limited information on the specific characteristics to stroke patients with NS. In this study, we aimed to examine the clinical manifestations of acute IS in a large group of NS patients, comparing to those without NS. We conducted a retrospective cohort study to compare the clinical presentations of acute IS in patients with and without NS. This study was a multi-institutional study and used data from Chang Gung Research Database of Taiwan from 1 January 2001, to 31 December 2017. A total of 233 IS patients with NS and 1358 IS patients without NS were enrolled. The median age of participants was 68 (range: 59–79) years. The risk of dependent functional status (modified Rankin Scale score≧3) after IS was higher in NS patients compared to those without NS (Odd ratio (OR) 4.02, 95% confidence interval (CI) 2.39 to 6.76, p < 0.001), particularly in stroke subtypes as small-artery occlusion (OR 8.02, 95% CI 3.94 to 16.32, p < 0.001), and stroke of undetermined etiology (OR 2.47, CI 1.06 to 5.76, p = 037). The risks of mortality or stroke recurrence within 30 days were similar between the two groups for all stroke subtypes. In conclusion, NS was associated with a higher risk of functional dependence following IS. Intensive treatment and rehabilitation should be considered for IS patients with NS.

In young patients with stroke of undetermined etiology, large vessel occlusions are less frequent in the group with high-risk patent foramen ovale

IntroductionPatent foramen ovale (PFO) is present in a significant proportion of young patients with stroke of undetermined etiology, but is not always causal. Therefore, classifications (RoPE, PASCAL) have been developed to determine the probability that PFO is the stroke cause. However, the presence of an initial arterial occlusion as a prediction factor was not studied when these classifications were built. Our aim was to evaluate the presence of arterial occlusion in young patients with stroke of undetermined etiology with/without high-risk PFO. MethodsFrom a prospectively-built monocentric database, we identified patients aged≥18 to<60-years with strokes of undetermined etiology and complete etiological work-up, including transesophageal echocardiography. We divided patients in two groups: (i) with high-risk PFO [i.e. PFO with large interatrial shunt (>30 microbubbles) or associated with atrial septal aneurysm] and (ii) with low-risk/without PFO. We recorded the presence of arterial occlusion and large vessel occlusion (LVO) in the acute phase. ResultsWe included 96 patients; 55 (57%) had high-risk PFO. Their median age was 48 (40–52) years, and 28 (29%) were women. The percentages of patients with arterial occlusion and with LVO were lower in the high-risk PFO group than in the low-risk/without PFO group: 11 (20%) versus 19 (46%) (P=0.008), and 5 (9%) versus 15 (37%) (P=0.002), respectively. There was no difference in the median RoPE score between groups (P=0.30). ConclusionThe presence of LVO could represent a “red flag” of PFO causality in stroke of undetermined etiology, and could be implemented in future PFO-related stroke classifications.

Sex differences in ischemic stroke during COVID-19 first outbreak in northern Italy

IntroductionCOVID-19 pandemic had a great impact on outcome in SARS-CoV-2 positive patients with ischemic stroke during the first wave in Italy. Few data are available on outcome stratified by sex. MethodsThe Italian Society of Hospital Neuroscience conducted a multi-center, retrospective, observational study on neurological complications in COVID-19 patients with ischemic stroke. All the patients admitted from March 1st to April 30th, 2020 in 20 Neurology Units in Northern Italy were recruited. Demographical and clinical features, treatment and outcome data were compared focusing on sex differences. Results812 patients with ischemic stroke were enrolled, of whom 129 with COVID-19; males were 53.8%. In-hospital mortality in COVID-19 patients was 35.3% in males and 27.9% in females while 8.5% in male and 5.8% in female patients without COVID-19. SARS-CoV-2 positive patients had a higher frequency of stroke of undetermined etiology, than negative ones (32.8% vs 22.5%; p = 0.02), especially in females compared to males (36.1% vs 27.9%), albeit without statistical significance. Male patients with SARS-CoV-2 were more likely to require cPAP (30.9% vs 14.8%; p = 0.03), endotracheal tube (14.9% vs 3.3%; p = 0.02) and reperfusion strategies (29.4% vs 11.5%; p = 0.01) than females, as well as to have a higher CRP and D-dimer. These elements together with older age, a total anterior circulation stroke and lymphopenia were predictors of a worse outcome. DiscussionOur study detected some differences due to sex in ischemic stroke with and without COVID-19, supporting the possibility to perform sex analyses for SARS-CoV-2 positive patients for a better clinical management.

Variation in blood viscosity based on the potential cause of stroke of undetermined etiology

Background: This study investigated potential differences in blood viscosity (BV) among patients with stroke of undetermined etiology, negative evaluation (SUDn), specifically those with potential atherothrombosis (SUDn-AT) and those with possible embolism (SUDn-E).Methods: This single-center study employed a retrospective observational design. The participants were patients over 20 years old with the SUDn stroke subtype who were admitted within 5 days of symptom onset. These patients were categorized as SUDn-AT or SUDn-E. Patients in the SUDn-AT group had nonsignificant stenosis (&lt;50%) of a major brain artery relevant to their symptoms and exhibited one or more signs of systemic atherosclerosis, including atherosclerosis of at least one major brain artery other than those clinically relevant, coronary artery disease, and/or peripheral artery disease. For the SUDn-E group, the SUDn criteria from the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification system were strictly applied.Results: The final analysis included 153 patients, with 104 (68%) classified as SUDn-E and the remaining 32% as SUDn-AT. Patients in the SUDn-AT group had a higher systolic BV (P=0.012) and diastolic BV (P=0.020) than those in the SUDn-E group. Multivariable logistic regression analysis revealed that age (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.03–1.13; P=0.003), systolic BV (OR, 3.11; 95% CI, 1.41–6.85; P=0.005), and diastolic BV (OR, 1.08; 95% CI, 1.02–1.14; P=0.009) were associated with SUDn-AT.Conclusions: Within the TOAST system, two SUDn entities may be distinguishable, with potentially different underlying etiologies: atherothrombosis and embolic stroke of undetermined source.

Do stroke services still show sex differences? A multicenter study

BackgroundThe issue of sex differences in stroke has gained concern in the past few years. However, multicenter studies are still required in this field. This study explores sex variation in a large number of patients and compares stroke characteristics among women in different age groups and across different countries.MethodsThis multicenter retrospective cross-sectional study aimed to compare sexes regarding risk factors, stroke severity, quality of services, and stroke outcome. Moreover, conventional risk factors in women according to age groups and among different countries were studied.ResultsEighteen thousand six hundred fifty-nine patients from 9 countries spanning 4 continents were studied. The number of women was significantly lower than men, with older age, more prevalence of AF, hypertension, and dyslipidemia. Ischemic stroke was more severe in women, with worse outcomes among women (p: < 0.0001), although the time to treatment was shorter. Bridging that was more frequent in women (p:0.002). Analyzing only women: ischemic stroke was more frequent among the older, while hemorrhage and TIA prevailed in the younger and stroke of undetermined etiology. Comparison between countries showed differences in age, risk factors, type of stroke, and management.ConclusionWe observed sex differences in risk factors, stroke severity, and outcome in our population. However, access to revascularization was in favor of women.

A novel etiological classification in patients with intracranial large vessel occlusion and endovascular treatment: discordance with the classic and SSS TOAST systems: A retrospective cohort study

Purpose: Among patients with acute ischemic stroke (AIS), those with intracranial large vessel occlusion (LVO) should undertake endovascular treatment (EVT) based on mechanical thrombectomy. Although the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system has been used in overall population of patients with AIS, especially for secondary prevention. In the current study, a new classification system for the LVO population is proposed.Methods: The classic TOAST and Stop Stroke Study TOAST (SSS TOAST) were applied to the LVO population. Based on discordance with those systems, a new LVO classification system was developed and applied to the LVO population. The new system comprised extracranial atherosclerosis (ECAS), intracranial atherosclerosis (ICAS), cardioembolism (CE), cryptogenic embolism, stroke of undetermined etiology (SUE; two or more etiologies), and stroke of other determined etiology (SOE) where small artery occlusion was removed.Results: The LVO classification system comprised 43 ECAS (6.52%), 141 ICAS (21.36%), 303 CE (45.91%), 75 cryptogenic embolism (11.36%), 75 SUE (11.36%; cardioembolic source in 98.67%), and 23 SOE (3.48%) patients. The ICAS group had a significantly longer median onset-to-puncture time than the other groups. In the ICAS group, 102 of 141 (72.34%) remained partial recanalization after EVT.Conclusion: The LVO classification system differentiating ECAS and ICAS in patients with large artery atherosclerosis and classifying cryptogenic embolism is more suitable for patients with EVT for intracranial LVO. Further studies for predicting underlying ICAS and planning treatment strategy should be performed.

Exploration of the etiology of single small subcortical infarctions using high-resolution vessel wall MRI.

We aimed to explore imaging indicators for diagnosing the etiology of single small subcortical infarctions (SSI) using high-resolution vessel wall imaging (HR-VWI). Patients with acute isolated subcortical cerebral infarction were prospectively enrolled and classified as having large artery atherosclerosis (LAA), stroke of undetermined etiology (SUD), or small artery disease (SAD). The infarct information, the cerebral small vessel disease (CSVD) score, morphological characteristics of the lenticulostriate arteries (LSAs), and plaque characteristics were compared between the three groups. Seventy seven patients were enrolled (30 LAA, 28 SUD, and 19 SAD). The total CSVD score of the LAA (P = 0.001) and SUD groups (P = 0.017) was significantly lower than that of the SAD group. The number and total length of LSA branches in the LAA and SUD groups were shorter than in the SAD group. Moreover, the total length laterality index (LI) of the LSAs in the LAA and SUD groups was greater than in the SAD group. The total CSVD score and LI of total length were independent predictors for the SUD and LAA groups. The remodeling index of the SUD group was significantly higher than that of the LAA group (P = 0.002); positive remodeling was dominant in the SUD group (60.7%), whereas remodeling in the LAA group was primarily non-positive (83.3%). SSI with and without plaques on the carrier artery may have different modes of pathogenesis. Patients with plaques may also have a coexisting mechanism of atherosclerosis.

Artificial Intelligence in Acute Ischemic Stroke Subtypes According to Toast Classification: A Comprehensive Narrative Review

The correct recognition of the etiology of ischemic stroke (IS) allows tempestive interventions in therapy with the aim of treating the cause and preventing a new cerebral ischemic event. Nevertheless, the identification of the cause is often challenging and is based on clinical features and data obtained by imaging techniques and other diagnostic exams. TOAST classification system describes the different etiologies of ischemic stroke and includes five subtypes: LAAS (large-artery atherosclerosis), CEI (cardio embolism), SVD (small vessel disease), ODE (stroke of other determined etiology), and UDE (stroke of undetermined etiology). AI models, providing computational methodologies for quantitative and objective evaluations, seem to increase the sensitivity of main IS causes, such as tomographic diagnosis of carotid stenosis, electrocardiographic recognition of atrial fibrillation, and identification of small vessel disease in magnetic resonance images. The aim of this review is to provide overall knowledge about the most effective AI models used in the differential diagnosis of ischemic stroke etiology according to the TOAST classification. According to our results, AI has proven to be a useful tool for identifying predictive factors capable of subtyping acute stroke patients in large heterogeneous populations and, in particular, clarifying the etiology of UDE IS especially detecting cardioembolic sources.

Rare association of a patient with multiple ischemic strokes with thrombotic thrombocytopenic purpura and systemic lupus erythematosus: A case report

The Trial of ORG 10172 in Acute Stroke Treatment categorizes stroke etiology into large artery atherosclerosis, small vessel occlusion, cardio embolism, stroke of undetermined etiology, and stroke of other determined etiology with patients with hematological, and hypercoagulable states falling under the last category.

Abstract Number ‐ 194: Predisposition to Atrial Fibrillation in AIS of Undetermined Source in the Setting of LVO

Introduction It is estimated that 7.6 million Americans report having had a stroke. Every year, approximately 795,000 people develop a stroke, of which 610,000 are for the first time. Although stroke incidence rates in adults ≥ 65 years of age decreased by 32% per decade from 1987 to 2017, it remains both the fifth leading cause of death and the leading cause of disability in the United States1. Ischemic strokes make up 87% of all strokes and can be categorized by the TOAST classification scheme. Etiologies include large‐vessel atherosclerosis, small vessel disease, cardioembolism, stroke of other determined etiology, and stroke of undetermined etiology2. Cardioembolic strokes, accounting for up to 25% of ischemic strokes typically involve a cardiac insult resulting from either atrial disease, valvular heart disease, structural and functional ventricular diseases, or myocardial infarction. The most common etiology of cardioembolic stroke and focus of this study is atrial fibrillation3. Stroke of undetermined etiology, also called cryptogenic stroke accounts for nearly 30% of ischemic strokes and has been recently coined in the literature as embolic stroke of undetermined source (ESUS) due to the presence of embolic features in the majority of these cases. Atrial cardiomyopathy has been identified as a contributing cause to ESUS with the detection of atrial fibrillation sometimes after original classification4. Though a significant portion of ESUS patients are found to have atrial fibrillation, it is not often detected on presentation. Additionally, ESUS patients can present with a large‐vessel occlusion (LVO), often with a high initial NIHSS. It may be of benefit to compare ESUS patients with and without LVO on the basis of detection of atrial fibrillation. Methods This study is a retrospective cohort study of patients discharged from the Neurology general practice unit, Stroke step‐down unit, or Neurosurgical ICU from January 2014 to June 2022.Subject charts will be reviewed for the following variables: 1)Demographics: Age, race, sex, 2)Use of antithrombotics, 3)Specific antithrombotics prescribed, 4)Stroke etiology, 5)Initial NIHSS, 6)Presence of large vessel occlusion (LVO), 7)Received tPA, 8)Received MER, 9)Detection of atrial fibrillation, 10)Detection of arrhythmia, 11)Presence of reduced ejection fraction, 12)Received Holter monitor, 13)Underwent internal loop recorder placement, 14)Recurrence of stroke or TIA. Results ESUS patients often present with atrial fibrillation. ESUS patients can present with a large‐vessel occlusion (LVO). There was a higher rate of detection of atrial fibrillation in patients with ESUS who present with LVO in comparison to patients with ESUS who do not present with LVO. Conclusions This study demonstrated that there may be an increased likelihood of atrial fibrillation in patients with ESUS who present with LVO versus those who do not present with LVO. Areas of further development include prevention of LVO‐related ischemic stroke in patients with atrial fibrillation, targeted LVO education for patients with atrial fibrillation, earlier initiation of anticoagulant stroke preventive medication for high‐risk LVO patients. The study may also help elucidate whether extended cardiac monitoring would be beneficial for patients who present with an LVO.

Impact on etiology diagnosis by high-resolution vessel wall imaging in young adults with ischemic stroke or transient ischemic attack.

The etiological features of stroke in young adults are different from those in older adults. We aimed to investigate the impact of high-resolution vessel wall imaging (HRVWI) on etiologic diagnosis in young adults with ischemic stroke or transient ischemic attack (TIA). A total of 253 young adults (aged 18-45years) who consecutively underwent HRVWI for clarifying stroke etiology were retrospectively recruited. Two experienced neurologists classified stroke etiology for each patient using Trial of Org 10,172 in Acute Stroke Treatment categories with and without the inclusion of HRVWI diagnosis. Multivariate logistic regression was performed to determine which etiologic category would be significantly impacted after including HRVWI. The etiologic classification was altered in 39.1% (99/253) of patients after including HRVWI in the conventional investigations. The proportion of patients classified as having stroke of undetermined etiology (SUE) and the proportion of patients classified as having small-artery occlusion (SAO) both significantly decreased (36.4 to 13.8% and 9.1 to 2.0%), whereas the proportion of patients classified as having large artery atherosclerosis (LAA) significantly increased (28.5 to 58.1%) (all P < 0.001). The inclusion of HRVWI had a significant diagnostic impact on young adults who were primarily classified as SAO (odds ratio [OR] 14.4, 95% confidence interval [CI] [2.9, 71.8], P < 0.001) or SUE (OR 8.3, 95% CI [2.2, 31.5], P < 0.01). HRVWI had a substantial impact on etiologic classification in young adults with ischemic stroke or TIA, particularly for those primarily classified as having SAO or SUE. This impact of HRVWI will be beneficial for therapeutic decision-making.

Characteristic of Acute Ischemic Stroke Patients Based on TOAST Classification During COVID-19 Pandemic Era: A Single Centre Study.

The categorization system used in the Trial Org 10172 classification in Acute Stroke Treatment (TOAST) provided more insight into the causal process. The aims of this study were to characterize individuals with acute ischemic stroke using the TOAST criteria and to determine risk variables for patients with acute ischemic stroke during the COVID-19 pandemic. A cross-sectional study was done on the medical records of acute ischemic stroke patients at Hasan Sadikin Hospital (RSHS) Bandung, Indonesia, who were hospitalized in the Neurology Department of Hasan Sadikin Hospital from January to December 2021. Eligible patients were divided into 2 groups, with and without COVID-19 infection. There were 136 participants with acute ischemic stroke. Thirty-one percent of strokes were caused by atherosclerosis in the large arteries (LAA), followed by small-vessel occlusion (SVO) (25%), cardioembolism (CE) (22.1%), an undetermined cause (21.3%), and an other etiology (1.5%). CE risk factor was atrial fibrillation (p < 0.001), while hypertension, diabetes, and smoking were significant for LAA (p < 0.05). However, in patients with COVID-19 who had an acute ischemic stroke, most of the subtypes were stroke of undetermined etiology (76%), and hypercoagulation was the main risk factor (p < 0.001). Patients with and without COVID-19 show varied distributions of stroke subtypes according to the TOAST categorization. Hypercoagulation is a major risk factor for stroke of undetermined etiology in individuals with COVID-19 who suffer from acute ischemic stroke. Increased viral-mediated endothelial inflammation leading to aberrant coagulopathy may explain the correlation between COVID-19 and acute ischemic stroke.

Abstract WP215: Increase In CD11b Positive Inflammatory Cells In Cardioembolic And Cryptogenic Strokes: A Study Of Thrombi From Stroke Patients

Introduction: Around 25-40% of ischemic strokes are cryptogenic or strokes of undetermined etiology. Determination of stroke etiology can be challenging, requiring extensive diagnostic testing including long term monitoring for occult atrial fibrillation. Recent studies suggest that inflammation (monocytes/ macrophages driven) and fibrosis in the atrial substrate leads to atrial fibrillation/ cardioembolic strokes. Therefore, we hypothesized that clots collected from patients with cardioembolic stroke during thrombectomy will have increased myeloid derived inflammatory cells as compared to other stroke etiologies. Methods: 54 thrombi were obtained during mechanical thrombectomy in patients with ischemic strokes after consent. They were formalin fixed, embedded, sliced and stained with CD11b, a marker for myeloid derived cells and some lymphoid cells. Mean of five 20x images from two slices per patient was quantified by image J and used for analysis. The relationship between stroke etiology (TOAST) and number of CD11b positive cells was assessed using Mann-Whitney U test and multilinear regression models. Results: Mean patient age was 64.2±12.5 years, 33.3% were women, 81.5% had hypertension, 22.2% had diabetes mellitus, and 37% had hyperlipidemia. Thrombi with cardioembolic etiology had significantly higher number of CD11b positive cells (248.2±137.4, n=27) as compared to strokes from large artery atherosclerosis (133.3±95.7, n=11), p=0.02. Cryptogenic strokes also had significantly higher number of CD11b positive cells, (212.1± 104.8, n=13) when compared to strokes from large artery atherosclerosis, p=0.04, n=11, even after controlling for hypertension, hyperlipidemia, heart disease, diabetes mellitus and age. No difference was seen in CD11b positive cell numbers between cardioembolic and cryptogenic strokes, p=0.4. Conclusion: Cardioembolic and cryptogenic stroke thrombi have increased CD11b positive cells as compared to strokes from large artery atherosclerosis. The shared histology of cardioembolic and cryptogenic strokes suggests that many of the cryptogenic strokes may be due to undiagnosed cardioembolism. Future studies using flow cytometry on thrombi can be a novel area of research for stroke etiology.

Net benefit of diagnostic tests for multistate diseases: an indicator variables approach

ABSTRACT A limitation of the common measures of diagnostic test performance, such as sensitivity and specificity, is that they do not consider the relative importance of false negative and false positive test results, which are likely to have different clinical consequences. Therefore, the use of classification or prediction measures alone to compare diagnostic tests or biomarkers can be inconclusive for clinicians. Comparing tests on net benefit can be more conclusive because clinical consequences of misdiagnoses are considered. The literature suggested evaluating the binary diagnostic tests based on net benefit, but did not consider diagnostic tests that classify more than two disease states, e.g., stroke subtype (large-artery atherosclerosis, cardioembolism, small-vessel occlusion, stroke of other determined etiology, stroke of undetermined etiology), skin lesion subtype, breast cancer subtypes (benign, mass, calcification, architectural distortion, etc.), METAVIR liver fibrosis state (F0- F4), histopathological classification of cervical intraepithelial neoplasia (CIN), prostate Gleason grade, brain injury (intracranial hemorrhage, mass effect, midline shift, cranial fracture) . Other diseases have more than two stages, such as Alzheimer's disease (dementia due to Alzheimer's disease, mild cognitive disability (MCI) due to Alzheimer's disease, and preclinical presymptomatics due to Alzheimer's disease). In diseases with more than two states, the benefits and risks may vary between states. This paper extends the net-benefit approach of evaluating binary diagnostic tests to multi-state clinical conditions to rule-in or rule-out a clinical condition based on adverse consequences of work-up delay (due to false negative test result) and unnecessary workup (due to false positive test result). We demonstrate our approach with numerical examples and real data.

Left atrial late gadolinium enhancement in patients with ischaemic stroke.

To evaluate the extent of left atrial (LA) fibrosis in patients with a recent stroke without atrial fibrillation and controls without established cardiovascular disease. This prospectively designed study used cardiac magnetic resonance to detect LA late gadolinium enhancement as a proxy for LA fibrosis. Between 2019 and 2021, we consecutively included 100 patients free of atrial fibrillation with recent ischaemic stroke (<30 days) and 50 age- and sex-matched controls. LA fibrosis assessment was achieved in 78 patients and 45 controls. Blinded to the cardiac magnetic resonance results, strokes were adjudicated according to modified Trial of Org 10172 in Acute Stroke Treatment classification as undetermined aetiology (n = 42) or as attributable to large- or small-vessel disease (n = 36). Patients with stroke had a larger extent of LA fibrosis [6.9%, interquartile range (IQR) 3.6-15.4%] than matched controls (4.2%, IQR 2.3-7.5%; P = 0.007). No differences in LA fibrosis were observed between patients with stroke of undetermined aetiology and those with large- or small-vessel disease (6.6%, IQR 3.8-16.0% vs. 6.9%, IQR 3.4-14.6%; P = 0.73). LA fibrosis was more extensive in patients with stroke than in age- and sex-matched controls. A similar extent of LA fibrosis was observed in patients with stroke of undetermined aetiology and stroke classified as attributable to large- or small-vessel disease. Our findings suggest that LA structural abnormality is more frequent in patients with stroke than in controls independent of aetiological classification.