Large-artery Atherosclerosis Group Research Articles

Abstract WMP114: Putrescine And Kynurenine Are Associated With Large Artery Atherosclerosis Stroke: Targeted Metabolomics Study

Background: Ischemic stroke is a diversified disease with various mechanisms. However, the current subtyping process is complicated and time-consuming. Metabolite-based biomarkers have promising potential to improve classification and profound understanding of the disease. We aimed to identify novel targeted metabolomics-based biomarkers that are clinically relevant to the diagnosis of large-artery atherosclerosis (LAA) stroke. Methods and Results: We acquired serum samples and clinical data from a hospital-based acute stroke registry. Patients experiencing ischemic stroke within a week of symptoms onset were recruited. Finally, 238 acute ischemic stroke participants (97 LAA patients and 141 non-LAA patients) were included. A targeted quantitative and quality-controlled liquid chromatography with tandem mass spectrometry metabolomics analysis was performed, several metabolomic signatures which showed statistically significant differences between LAA and non-LAA groups were selected. A multivariate regression model was created to independently predict the LAA stroke. We obtained 55 serum metabolomics signatures, and of these, 2 biogenic amines (putrescine and kynurenine) were selected as independent discriminants for LAA (odds ratio [OR], 0.0004; 95% confidence interval [CI], 4.819x10 -07 -0.3601 for putrescine; OR, 0.4325; 95% CI, 0.2232-0.8381 for kynurenine) after adjustment for patients’ sex, age, body mass index, stroke severity, and comorbidities. Conclusions: Targeted metabolomics approach provided an enhanced understanding of LAA stroke pathogenesis. We have identified putrescine and kynurenine as novel biomarkers for LAA stroke.

Effect of stroke etiology on endovascular thrombectomy with or without intravenous alteplase: a subgroup analysis of DIRECT-MT

BackgroundStroke etiology might influence the clinical outcomes in patients with large vessel occlusion receiving endovascular treatment (EVT) with or without thrombolysis.ObjectiveTo examine whether stroke etiology resulted in different efficacy and...

Subtypes, Risk Factors and Site of Stenosis of Ischaemic Stroke in a University Hospital in Bangladesh

Stoke is the second most common cause of death and the most common cause of adult disability. To plan an efficient evaluation and treatment of an individual patient with ischaemic stroke, the clinician should be familiar with the subtyping of ischaemic stroke patients and the risk factors analysis of different aetiology. Eight hundred seventy-seven (877) patients have been selected for this cross-sectional study conducted in a university hospital of Bangladesh from 2014 to 2018, to whom brain imaging [Computed Tomography (CT)/ Magnetic Resonance Imaging (MRI)], vascular imaging [Magnetic Resonance Angiogram (MRA), Digital Subtraction Angiogram (DSA)], ECG and echocardiography have been done. We did subtyping according to TOAST criteria. The mean age of patients was 60.5 ± 11 years. Most patients (29.33%) belonged to the age group 51 – 60, where 70.47% of subjects were male and 29.53% were female. In this study, 43.87% of patients were in the large artery atherosclerosis group, 23.83.% in the small vessel occlusion group, 8.46% in the cardiac embolism group, 19.30% in the undetermined aetiology group and 4.54% in other determined aetiology. Among risk factors hypertension, diabetes mellitus, dyslipidaemia was present in 58.15%, 38.42%, and 38.88% of patients, respectively. In ischaemic stroke patients, large artery atherosclerosis was the most common subtype and hypertension was significant in this group. Extracranial stenosis was more common in ischaemic stroke.

Atrial cardiopathy in embolic stroke of undetermined source.

IntroductionAtrial cardiopathy is one of the most common potential sources of thromboembolism for embolic stroke of undetermined source (ESUS). The study aims to investigate the incidence of atrial cardiopathy (defined by severe left atrial enlargement (sLAE) or elevated serum N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) > 250 pg/ml) in patients with ESUS and compare with other stroke subtypes.MethodsWe retrospectively collected data of 936 consecutive patients with diffusion‐weighted imaging‐confirmed acute ischemic stroke. The incidence of atrial cardiopathy was examined in ESUS, large artery atherosclerosis (LAA), and small vessel disease (SVD) strokes. Clinical characteristics were compared between ESUS patients with atrial cardiopathy (AC‐ESUS) and patients with atrial fibrillation‐induced cardioembolism (AF‐CE) stroke.Results245 patients were diagnosed with ESUS, while others were diagnosed with LAA (n = 312), SVD (n = 258), and AF‐CE (n = 121) strokes. The incidence of sLAE in ESUS patients was higher than in LAA or SVD group (5.3% vs. 1.6% and 1.2%, respectively, p = .005) and higher than in combined LAA/SVD group (5.3% vs. 1.4%, p = .001). The incidence of elevated serum NT‐proBNP in ESUS patients was not statistically different from that in LAA or SVD group. Compared with patients with AF‐CE stroke, AC‐ESUS patients had milder manifestations, had less hemorrhagic transformation, had better short‐term outcome, and had fewer in‐hospital complications.ConclusionsThe incidence of sLAE was higher in ESUS patients than in patients with noncardioembolic strokes. AC‐ESUS was milder when compared to AF‐CE stroke.

Comparisons of Characteristics and Outcomes after Mechanical Thrombectomy for Vertebrobasilar Occlusion with Cardioembolism or Atherosclerotic Brain Infarction: Data from the Tokyo-Tama-Registry of Acute Endovascular Thrombectomy (TREAT)

Some reports suggest the efficacy of mechanical thrombectomy (MT) for acute vertebrobasilar artery (VBA) occlusion. The major causes of VBA occlusion include cardioembolism (CE) and large-artery atherosclerosis (LAA). However, the clinical characteristics of each cause remain unclear, and they might be important for decision making related to the indications and strategy of MT. This study aimed to compare functional outcomes and factors affecting outcomes between patients with CE and LAA with acute VBA occlusion. This was a retrospective and prospective observational study using data from TREAT (Tokyo-Tama-Registry of Acute Endovascular Thrombectomy), a multicenter registry of MT for acute large-vessel occlusion in the Tokyo metropolitan area. Patients with VBA occlusion classified into CE and LAA groups were analyzed. The primary outcome was a modified Rankin Scale score of 0-2 at 90 days. Seventy-nine patients (57 with CE and 22 with LAA) were eligible from January 2015 to March 2020. Despite significantly shorter puncture-to-recanalization and onset-or-last-well-known-to-recanalization times in the CE group, the primary outcome was not significantly different between the 2 groups (CE, 31.6% vs. LAA, 45.5%; P= 0.248). In the subgroup analysis, patients with CE had worse clinical outcomes in the onset-or-last-well-known-to-door time ≥180 minutes, onset-or-last-well-known-to-door time ≥300 minutes, and low posterior circulation Alberta Stroke Program Early CT Score (≤7) subgroups. Functional outcomes of VBA occlusion were not significantly different between CE and LAA. Based on the subgroup analysis, patients with CE might have poorer collateral status than do patients with LAA, and earlier recanalization might therefore be desired.

Changes of Metabolites in Acute Ischemic Stroke and Its Subtypes.

Existing techniques have many limitations in the diagnosis and classification of ischemic stroke (IS). Considering this, we used metabolomics to screen for potential biomarkers of IS and its subtypes and to explore the underlying related pathophysiological mechanisms. Serum samples from 99 patients with acute ischemic stroke (AIS) [the AIS subtypes included 49 patients with large artery atherosclerosis (LAA) and 50 patients with small artery occlusion (SAO)] and 50 matched healthy controls (HCs) were analyzed by non-targeted metabolomics based on liquid chromatography–mass spectrometry. A multivariate statistical analysis was performed to identify potential biomarkers. There were 18 significantly different metabolites, such as oleic acid, linoleic acid, arachidonic acid, L-glutamine, L-arginine, and L-proline, between patients with AIS and HCs. These different metabolites are closely related to many metabolic pathways, such as fatty acid metabolism and amino acid metabolism. There were also differences in metabolic profiling between the LAA and SAO groups. There were eight different metabolites, including L-pipecolic acid, 1-Methylhistidine, PE, LysoPE, and LysoPC, which affected glycerophospholipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, histidine metabolism, and lysine degradation. Our study effectively identified the metabolic profiles of IS and its subtypes. The different metabolites between LAA and SAO may be potential biomarkers in the context of clinical diagnosis. These results highlight the potential of metabolomics to reveal new pathways for IS subtypes and provide a new avenue to explore the pathophysiological mechanisms underlying IS and its subtypes.

Nomogram to Predict Poor Outcome after Mechanical Thrombectomy at Older Age and Histological Analysis of Thrombus Composition.

An easy scoring system to predict the risk of poor outcome after mechanical thrombectomy among the elderly is currently not available. Therefore, we aimed to develop a nomogram for predicting the probability of negative prognosis in aged patients with acute ischemic stroke undergoing thrombectomy. In addition, we sought to investigate the association between histological thrombus composition and stroke characteristics. To this end, we prospectively studied a developed cohort using data collected from a stroke center from November 2015 to December 2019. The main outcome was functional independence, defined as a modified Rankin Scale score ≤ 2 at 90 days following a mechanical thrombectomy. A nomogram model based on multivariate logistic models was generated. The retrieved thrombi were stained with hematoxylin and eosin and assessed according to histological composition. Our results demonstrated that age ≥ 72 years was independently associated with poor outcome. A total of 304 participants completed the follow-up data to generate the nomogram model. After multivariate logistic regression, five variables remained independent predictors of outcome, including older age, hemorrhagic transformation, thrombolysis in cerebral infarction score, National Institute of Health Stroke score, and neutrophil-to-lymphocyte ratio, and were used to generate the nomogram. The area under the receiver-operating characteristic curve of the model was 0.803. The clots from elderly subjects with large-artery atherosclerosis, anterior circulation, and successful recanalization groups had a higher percentage of fibrin compared to those of younger patients. This is the first nomogram to be developed and validated in a stroke center cohort for individualized prediction of poor outcome in elderly patients after mechanical thrombectomy. Clot composition provides valuable information on the underlying pathogenesis of oxidation in older patients.

Retinal Structural and Microvascular Alterations in Different Acute Ischemic Stroke Subtypes.

Introduction Retinal structural and microvascular damages reflect damage to cerebral microvasculature and neurons. We aimed to investigate neovascular unit abnormalities among patients with large-artery atherosclerosis (LAA) or small-vessel occlusion (SAA) and control subjects. Methods Twenty-eight LAA patients, forty-one SAA patients, and sixty-five age- and gender-matched controls were recruited. Based on optical coherence tomography angiography (OCTA), retinal capillary vessel density was assessed in the general and local sectors, and the thickness of individual retinal layer was extracted from retinal structural images. The differences between structural and microvascular were analyzed. Results The superior peripapillary retinal nerve fiber layer (pRNFL) thickness was significantly different among the three groups, and the LAA group had the thinnest thickness. Compared to the control group, the deep retinal capillary vessel density in other two stroke subgroups were significantly reduced in all regions except in the inferior region (P < 0.05), and the fractal dimension in C2 and C4 regions of deep retina was significantly lower in the LAA group (P < 0.05). Discussion. Compared with superficial microvascular network, deep microvascular network is more sensitive to ischemic stroke. In addition, we have demonstrated quadrant-specific pRNFL abnormalities in LAA and SAA patients. Superior quadrant pRNFL thickness differences between stroke subgroups may suggest that changes in retinal nerve fiber layer are more sensitive to subtype identification than changes in retinal microvascular structure. All in all, the alteration in retinal structural and microvascular may further elucidate the role of the neovascular unit in ischemic stroke, suggesting that the combination of these two indicators could be used for subtype identification to guide prognosis and establish a risk prediction model.

Cilostazol Addition to Aspirin could not Reduce the Neurological Deterioration in TOAST Subtypes: ADS Post-Hoc Analysis

BackgroundOur previous trial acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of short-term neurological worsening in non-cardioembolic stroke patients. Present post-hoc analysis investigated whether the impact of combined cilostazol and aspirin differed among stroke subtypes and factors associated with neurological deterioration and/or stroke recurrence. MethodsUsing the ADS registry, the rate of neurological deterioration, defined as clinical worsening and/or recurrent stroke, including transient ischemic attack was calculated. Stroke subtypes included large-artery atherosclerosis (LAA), small vessel occlusion (SVO), other determined etiology (Others), and undetermined etiology of stroke (Undetermined). ResultsData of 1022 patients were analyzed. Deterioration was seen in 104 (10%) patients, and the rates were not markedly different between patients treated with DAPT vs. aspirin in any stroke subtypes: LAA, 19% vs. 11%, (p=0.192); SVO, 10% vs. 10% (p=1.000); Others, 6% vs. 6% (p=1.000); Undetermined, 11% vs. 8% (p=0.590). Diabetes mellitus was the independent factor associated with deterioration (odds ratio 4.360, 95% confidence interval 1.139–16.691, p=0.032) in the LAA group. Age (1.030 [1.004–1.057], p=0.026), systolic blood pressure (1.012 [1.003–1.022], p=0.010), and infarct size (2.550 [1.488–4.371], p=0.001) were associated with deterioration in SVO group, and intracranial stenosis/occlusion was associated with it in the Undetermined group (3.744 [1.138–12.318], p=0.030). ConclusionsCombined cilostazol and aspirin did not reduce the rate of short-term neurological deterioration in any clinical stroke subtype. The characteristics of patients whose condition deteriorates in the acute period may differ based on the stroke subtypes.

Clinical Features, Risk Factors, and Early Prognosis for Wallerian Degeneration in the Descending Pyramidal Tract after Acute Cerebral Infarction

BackgroundWallerian degeneration(WD) occurs in the descending pyramidal tract(DPT) after cerebral infarction commonly, but studies of its degree evaluation, influencing factors and effects on nervous function are still limited. ObjectivesThe purpose of this study was to describe these findings and estimate their clinical significance. MethodsIn total, 133 patients confirmed acute cerebral infarction and restricted diffusion in the DPT of the cerebral peduncle by MRI scans. These cases were retrospectively reviewed. We describe their clinical characteristics and analyze influence factors of WD, including the timespan from symptom onset to MRI and TOAST classification. Their NIHSS scores at admission and first 7 days NIHSS improvement rate after admission were also analyzed. ResultsThese patients were divided into three groups by timespan ≤7 days(n = 45),7–14 days(n = 70) and >14 days(n = 18). The mean WD degree (%)of these three groups was 44.41 ± 22.51,52.35 ± 22.61and 44.31 ± 19.35,respectively(p = 0.122).According to the TOAST classification, the mean WD degree(%) of the cardioembolism group(n = 28, 62.80 ± 25.12) was significantly different from both the large-artery atherosclerosis group(n = 73,45.08 ± 20.03,p = 0.000) and the small-vessel occlusion group(n = 23,39.68 ± 16.95,p = 0.000). The mean NIHSS score upon admission of the WD degree≤50% group(n = 82,8.17 ± 5.87) was different from that of the >50% group(n = 51,11.31 ± 7.00)(p = 0.006). However, the mean 7 days NIHSS improvement rate(%) of the WD degree≤50% group(n = 79,11.83 ± 23.76)and >50% group(n = 50,13.40 ± 27.88) was not significantly different(p = 0.733). ConclusionsEarly WD in ischemic stroke patients has a correlation with serious baseline functional defects. Therefore, we should give close attention to imaging change, especially in those with cardioembolism .

Large Artery Atherosclerotic Clots are Larger than Clots of other Stroke Etiologies and have Poorer Recanalization rates

ObjectivesThere is a paucity of knowledge in the literature relating to the extent of clot burden and stroke etiology. In this study, we measured the Extracted Clot Area (ECA) retrieved during endovascular treatment (EVT) and investigated relationships with suspected etiology, administration of intravenous thrombolysis and recanalization. Materials and MethodsAs part of the multi-institutional RESTORE registry, the ECA retrieved during mechanical thrombectomy was quantified using ImageJ. The effect of stroke etiology (Large-artery atherosclerosis (LAA), Cardioembolism, Cryptogenic and other) and recombinant tissue plasminogen activator (rtPA) on ECA and recanalization outcome (mTICI) was assessed. Successful recanalization was described as mTICI 2c-3. ResultsA total of 550 patients who underwent EVT with any clot retrieved were included in the study. The ECA was significantly larger in the LAA group compared to all other etiologies. The average ECA size of each etiology was; LAA=109 mm2, Cardioembolic=52 mm2, Cryptogenic=47 mm2 and Other=52 mm2 (p=0.014*). LAA patients also had a significantly poorer rate of successful recanalization (mTICI 2c-3) compared to all other etiologies (p=0.003*). The administration of tPA was associated with a smaller ECA in both LAA (p=0.007*) and cardioembolic (p=0.035*) groups. ConclusionThe ECA of LAA clots was double the size of all other etiologies and this is associated with a lower rate of successful recanalization in LAA stroke subtype. rtPA administration prior to thrombectomy was associated with reduced ECA in LAA and CE clots.

Fibrin and Platelet-Rich Composition in Retrieved Thrombi Hallmarks Stroke With Active Cancer.

We aim to investigate whether histopathologic examination of thrombi retrieved from acute ischemic stroke patients undergoing endovascular treatment could distinguish cancer-related stroke from other etiologies. Thrombi from patients undergoing endovascular treatment were analyzed. The etiology of stroke was divided into cardioembolism, large artery atherosclerosis, and active cancer groups. All selected thrombi were subjected to hematoxylin and eosin staining. The percentages of fibrin/platelets, red blood cells, and white blood cells within a thrombus were quantified. One-hundred fifty-two patients (active cancer, 19; cardioembolism, 107; large artery atherosclerosis, 26) were included. Thrombi from the active cancer group exhibited a higher fibrin/platelet composition than did those from the cardioembolism and large artery atherosclerosis groups (median, 85.7% versus 43.9% and 42.5%; P<0.001). Fibrin/platelet composition was the only independent factor (odds ratio, 1.05 [95% CI, 1.02-1.08]) in differentiating cancer-related stroke from stroke caused by cardioembolism and large artery atherosclerosis. A fibrin/platelet proportion of ≥65% accurately predicted cancer-related stroke (area under the curve, 0.84; P<0.001). In thrombi retrieved from patients undergoing endovascular treatment, a high fibrin/platelet composition was a probable indicator of cancer-related stroke.

Mean platelet volume and mean platelet volume/platelet count ratio in nonvalvular atrial fibrillation stroke and large artery atherosclerosis stroke.

Ischemic stroke subtypes such as patients with large artery atherosclerosis, cardioembolism, and embolic stroke of undetermined source were investigated. This study was performed aimed to determine mean platelet volume (MPV) and mean platelet volume/platelet count (MPV/Plt) ratio in nonvalvular atrial fibrillation (AF) stroke and large artery atherosclerosis (LAA) stroke.We conducted a retrospective study of consecutive patients for treatment of acute ischemic stroke at Ruian People's Hospital from March 2017 to October 2018. The patients with ischemic stroke caused by AF and LAA were recruited to this study. Ischemic stroke was confirmed by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), ischemic lesions on diffusion-weighted imaging were measured in terms of size, composition, and pattern. MPV and platelet count were examined and (MPV/Plt) ratio was calculated.Three hundred seventy one patients were enrolled composing of 177 (47.7%) nonvalvular AF and 194 (52.2%) with LAA. The MPV (11.3 ± 1.3 vs 10.8 ± 1.0, P < .001) and MPV/Plt ratio (0.066 ± 0.025 vs 0.055 ± 0.20, P < .001) were much higher in AF group than LAA group. Receiver-operating characteristic (ROC) analysis showed MPV (AUC: 0.624, confidence interval: 0.567–0.68, P < .001) and MPV/Plt (AUC: 0.657, confidence interval: 0.601–0.713, P < .001) predicted AF between the 2 groups. MPV/Plt ratio was negatively associated with lesion volume (r = –0.161, P = .033) in AF. The analyses of subtypes of composition of infarcts and infarct pattern showed that MPV/Plt ratio was almost higher in AF than LAA except for subcortical-only pattern. Multivariable regression analyses demonstrated National Institutes of Health Stroke Scale (NIHSS) score (r = 2.74; P < .001), LAD (r = –1.15; P = .025) and MPV/Plt ratio (r = –180.64; P = .021) were correlated with lesion volume.Our results indicated elevated MPV and MPV/Plt ratio for the identification of difference between AF and LAA in patients with ischemic stroke.

Trousseau Syndrome Related Cerebral Infarction: Clinical Manifestations, Laboratory Findings and Radiological Features

We summarized the clinical manifestations, laboratory data, and brain MRI of patients with Trousseau syndrome related cerebral infarction and compared them to patients with other types of cerebral infarction. Through our present research, we hope to aid the neurologists in recognizing and diagnosing this syndrome. A total of 31 patients at our institution were identified with cerebral infarction resulting from Trousseau syndrome. We have also selected the 180 patients who have suffered from cerebral infarction as control groups and these patients were distributed to large-artery atherosclerosis group; cardio-embolism group; small-artery occlusion group, according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. The clinical data and neuroimage of these patients were collected. All our 31 cancer patients were confirmed by pathological biopsy to be adenocarcinomas and the most common cancers are gastric and lung cancers. Patients with Trousseau syndrome exhibited high serum carbohydrate antigen CEA, CA 125 and CA 199 levels. Compared to patients with other types of cerebral infarction, patients with Trousseau syndrome had an increased severity and worse prognosis. Besides, patients had the highest mean level of plasma D-dimer. We also found multiple lesions in multiple vascular territories was the most frequent type of DWI patterns in patients of Trousseau syndrome. Trousseau syndrome can progress rapidly and become life-threatening. For patients who developed unexplained cerebral infarction involving multiple arterial territories, with elevated plasma D-dimer and cancer antigens, Trousseau syndrome should always be considered.

Biomarkers Associated with Atrial Fibrillation in Patients with Ischemic Stroke: A Pilot Study from the NOR-FIB Study

Background and Purpose: Cardioembolic stroke due to paroxysmal atrial fibrillation (AF) may account for 1 out of 4 cryptogenic strokes (CS) and transient ischemic attacks (TIAs). The purpose of this pilot study was to search for biomarkers potentially predicting incident AF in patients with ischemic stroke or TIA. Methods: Plasma samples were collected from patients aged 18 years and older with ischemic stroke or TIA due to AF (n = 9) and large artery atherosclerosis (LAA) with ipsilateral carotid stenosis (n = 8) and age- and sex-matched controls (n = 10). Analyses were performed with the Olink technology simultaneously measuring 184 biomarkers of cardiovascular disease. For bioinformatics, acquired data were analyzed using gene set enrichment analysis (GSEA). Selected proteins were validated using ELISA. Individual receiver operating characteristic (ROC) curves and odds ratios from logistic regression were calculated. A randomForest (RF) model with out-of-bag estimate was applied for predictive modeling. Results: GSEA indicated enrichment of proteins related to inflammatory response in the AF group. Interleukin (IL)-6, growth differentiation factor (GDF)-15, and pentraxin-related protein PTX3 were the top biomarkers on the ranked list for the AF group compared to the LAA group and the control group. ELISA validated increased expression of all tested proteins (GDF-15, PTX3, and urokinase plasminogen activator surface receptor [U-PAR]), except for IL-6. 19 proteins had the area under the ROC curve (AUC) over 0.85 including all of the proteins with significant evolution in the logistic regression. AUCs were very discriminant in distinguishing patients with and without AF (LAA and control group together). GDF-15 alone reached AUC of 0.95. Based on RF model, all selected participants in the tested group were classified correctly, and the most important protein in the model was GDF-15. Conclusions: Our results demonstrate an association between inflammation and AF and that multiple proteins alone and in combination may potentially be used as indicators of AF in CS and TIA patients. However, further studies including larger samples sizes are needed to support these findings. In the ongoing NOR-FIB study, we plan further biomarker assessments in patients with CS and TIA undergoing long-term cardiac rhythm monitoring with insertable cardiac monitors.

Clinical Features of Embolic Stroke of Undetermined Source.

Background and Objective: One-third of ischemic strokes have no identifiable cause following standard evaluation. In 2014, researchers have proposed the concept of Embolic Stroke of Undetermined Source (ESUS). The purpose of this study was to report the clinical characteristics of ESUS and its difference from cardiogenic embolism (CE), large-artery atherosclerosis (LA), and small-artery occlusion lacunar (SA).Methods: Acute ischemic stroke (AIS) patients admitted to the department of Beijing Haidian Hospital from January 2017 to December 2017 were prospectively and consecutively enrolled. Base-line characteristics were collected. Stroke etiologies were presented and compared. We compared the clinical features and infarct sites of patients with acute cerebral infarction of different etiologies.Results: A total of 119 AIS patients were analyzed in the study. There were 33 (27.73%) cases in ESUS group, 11 (9.24%) cases in CE group, 45 (37.82%) cases in LAA group and 30 (25.21%) cases in SA group. There were significant differences between the ESUS group and the CE group in the NIHSS score [3 (1.5–5) vs. 6 (2–20), p = 0.007], Modified Rankin Score [19, (57.58) vs. 9, (81.82), p = 0.008], hemorrhagic transformation [0, (0) vs. 5, (45.45), p < 0.001], and left atrial diameter [37.09 ± 3.16 vs. 41.73 ± 5.00, p = 0.001]. ESUS group and LA group have different mRS scores [19, (57.58) vs. 42, (93.33), p < 0.001]. ESUS group and SA group have different mRS scores [19, (57.58) vs. 28, (93.33), p = 0.001]. During 1 year follow-up, there were 5 cases (15.15%) in ESUS group, 3 cases (27.27%) in CE group, 3 cases (6.67%) in LA group, and 1 case (3.33%) in SA group with ischemic stroke (cerebral infarction or transient ischemic attack).Conclusion: ESUS is more similar to atherosclerotic cerebral infarction in clinical features, but the distribution of lesions is more similar to cardiogenic embolism, suggesting that the pathogenesis of ESUS needs to be further explored.

Abstract TP206: Effects of Smoking Status on the Onset Age of the First-Ever Stroke: Data From Korean Stroke Registry

Background: There is evidence that smoking increases stroke risk. However, the impact of smoking status on age at onset of ischemic stroke has not been studied. The aim of this study is to explore the effect of smoking status on the age at onset of first-ever ischemic stroke using the Korean Stroke Registry(KSR), the nation-wide, multicenter, hospital-based stroke registry in Republic of Korea. Methods: This study used individual data of first-ever ischemic stroke patients from the KSR, between 2014 and 2018. We divided the patients into four groups according to their smoking status; current smokers, past-smokers - quit in recent 5 years, past smokers - quit over than 5 years, and never-smokers. Results: A total of 27,942 patients were included in the analysis. The mean age at onset of the first-ever stroke were 60.0±11.9 in current smokers, 65.9±11.9 past-smokers - quit in recent 5 years, 70.1±10.8 in past smoker - quit over than 5 years, and 70.5±12.8 in never-smokers (p&lt;0.001). In the stroke subtypes analysis, the mean age at onset of the first-ever stroke were 60.9±12.5, 66.7±11.2, 70.7±10.8, and 71.1±11.9 in large artery atherosclerosis group, 58.8±10.8, 63.8±11.1, 68.2±10.4, and 68.6±12.0 in small vessel occlusion group, and 64.1±11.9, 67.7±11.6, 71.8±10.3, and 73.8±11.4 in cardioembolism group, respectively (all p&lt;0.001). Conclusions: The smoking status of patients was associated with an earlier onset age of the first-ever stroke. The onset age tends to be delayed with the longer duration of cessation period.

Cheyne-Stokes Respiration and the Outcome of Acute Ischemic Stroke

Objectives Cheyne-Stokes respiration (CSR) is frequently observed in acute stroke patients. In case of heart failure, CSR has been reported to be a poor prognostic factor. However, whether CSR has negative predictive value in stroke is not established yet. We aimed to investigate the relation between the presence of CSR and the outcome of acute stroke. Methods We investigated the patients who were admitted with acute ischemic stroke and received sleep apnea test. We collected data on demographics, risk factors, etiologic subtypes and the parameters associated with respiratory events in sleep apnea test. Primary outcome was the occurrence of early neurologic deterioration (END) within 3 weeks. Secondary outcome included the modified Rankin Scale (mRS) score at 3 months after stroke. We assessed the risk of poor outcome associated with CSR using multivariate logistic regression. Results Among 182 patients, 35 (19.2%) showed CSR in sleep apnea test. The presence of CSR in acute stroke was not associated with END, but associated with increased risk of 3 or higher mRS score at 3 months (odds ratio, 3.02; 95% confidence interval, 1.39 to 6.55) in univariate analysis. The association was still significant in large artery atherosclerosis group in stratified analysis. However, this association was insignificant in multivariate analysis which revealed that poor outcome at 3 months was associated with obstructive sleep apnea, as well as territory of internal carotid artery or basilar artery, initial National Institutes of Health Stroke Scale, and history of previous stroke. Conclusions The presence of CSR was associated with poor functional outcome after acute stroke. However, large scaled study is needed to confirm the role of CSR as an independent prognostic factor of stroke. Keywords: Cheyne-Stokes respiration, Stroke, Prognosis

Diagnostic Significance of Plasma Levels of Novel Adipokines in Patients With Symptomatic Intra- and Extracranial Atherosclerotic Stenosis.

Background: Adipokines have been proven to be associated with atherosclerotic diseases such as ischemic stroke and coronary heart disease. The role of novel adipokines in the development of symptomatic intracranial atherosclerotic stenosis (sICAS) and extracranial atherosclerotic stenosis (sECAS) has not yet been investigated. This study aimed to evaluate the plasma levels of novel adipokines in patients with sICAS and sECAS and their associations with the prognosis of sICAS groups.Methods: A total of 134 patients with acute ischemic stroke attribute to large-artery atherosclerosis (LAA) and 66 age- and sex-matched controls without atherosclerotic stenosis (NCAS) were included in this study. The LAA group was further sub-classified as sICAS (n = 102) and sECAS (n = 32) according to the location of atherosclerosis. Demographics, clinical parameters, angiographical features and plasma levels of novel adipokines (apelin, visfatin, omentin, RBP-4) were assayed and compared among groups.Results: LAA patients had significantly lower levels of omentin [39.92 (30.74–52.61) ng/ml vs. 54.42 (34.73–79.91) ng/ml, P < 0.001] and visfatin [11.32 (7.62–16.44) ng/ml vs. 13.01 (9.46–27.54) ng/ml, P < 0.001] than those in the NCAS group. Multiple logistic regression analysis identified that the lowest tertile of omentin was independently associated with LAA (OR, 3.423; 95% CI, 1.267–9.244, when referenced to the third tertile). Levels of omentin, visfatin and RBP-4 showed no significant difference between sICAS and sECAS groups. However, median concentrations of apelin were lower in sECAS [84.94 (46.88–130.41) ng/mL) than in sICAS [118.64 (93.22–145.08) ng/mL, P = 0.002] and NCAS [114.38 (80.56–162.93) ng/mL, P = 0.004]. Logistic regression analysis showed that the lowermost tertile of apelin was independently associated with sECAS (OR, 5.121; 95% CI, 1.597–16.426) when adjusted for risk factors. As for sICAS patients, spearman coefficient analysis showed no significant correlation between these four adipokines and the severity of sICAS or the number of vessels with intracranial stenoses. Patients with severe stroke had lower levels of apelin (P = 0.005), while the other three adipokines showed no such difference. During follow up, no difference was found between these four novel adipokines and short- and long-term outcome of sICAS.Conclusions: Lower levels of omentin are independent biomarkers of LAA while low apelin plasma levels seem to be risk factors of sECAS.

Impaired Endothelial Function in Embolic Stroke of Undetermined Source

BackgroundImpairment of endothelial function is associated with atherosclerosis and atrial fibrillation, and could underlie several types of ischemic stroke. Embolic stroke of undetermined source (ESUS) recently attracted much attention as the major cause of cryptogenic stroke. This study aimed to clarify the endothelial function of patients with ESUS. Methods and ResultsBetween 2015 September and July 2017 July, we used flow-mediated vasodilation (FMD) test to evaluate vascular endothelial function in 182 patients with any vascular risk factors or a history of cerebrovascular events. The subject group was classified into the No Stroke group and 5 stroke subtype groups, large artery atherosclerosis (LAA), cardiogenic embolism (CE), small vessel disease (SVD), ESUS, and others (Other). Endothelial function was expressed as percentage increase in brachial vessel diameter (%FMD) after the interruption of blood flow with mechanical compression for 5 minutes. Mean FMD in the No stroke, LAA, CE, SVD, ESUS and Other groups were 7.03 ± 2.14%, 5.02 ± 2.75%, 4.97 ± 1.62%, 5.19 ± 2.67%, 3.55 ± 1.42%, and 6.55 ± 3.50%, respectively. After the adjustment for confounding factors, FMD was significantly lower in the ESUS group than in the No stroke, SVD, and Other groups. FMD tended to be lower in the ESUS group than in the LAA and CE groups, but the difference was not significant. ConclusionsEndothelial function was impaired in patients with ESUS and may underlie its pathophysiology.