Trial Of Org 10172 In Acute Stroke Treatment Subtype Research Articles

Arterial transit artifact as a short-term prognostic indicator in acute ischemic stroke

BackgroundArterial transit artifact (ATA) observed on arterial spin labeling (ASL) was recently suggested to be associated with improved functional outcomes following acute ischemic stroke (AIS). AIS is a heterogeneous disease with diverse pathogenic mechanisms depending on the stroke subtype. This study aimed to investigate the association between ATA and 3-month functional outcomes in AIS patients according to etiology subtypes.MethodsConsecutive patients with AIS were included. All patients underwent ASL MRI with postlabeling delay (PLD) of 1.5 and 2.5 s. ATA was assessed from the ASL images of both PLDs. Stroke etiologic subtypes were determined according to the modified TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. Short-term functional outcomes were evaluated using the 3-month modified Rankin scale (mRS). Log-binomial regression was applied to analyze the association between ATA and functional outcomes at 3 months after stroke.ResultsNinety-eight AIS patients (62.73 ± 13.05 years; 68 men) were finally included. ATA was detected in forty-six patients and most frequently seen in the large-artery atherosclerosis (LAA) subtype (35/46). The ATA group exhibited a lower percentage of patients with mRS > 2 compared to the group without ATA (36.5% vs. 19.6%; P < 0.001). ATA was independently associated with better 3-month clinical outcomes (adjusted risk ratio, 0.35[95% CI, 0.16—0.74]) in the multivariate log-binomial regression model. After stratification by TOAST subtypes, a significant association was found between ATA and better outcomes in the LAA subtype (adjusted risk ratio, 0.20[ 95% CI, 0.05—0.72]) but not in cardioembolism and small artery occlusion (SVO) subtype.ConclusionATA is associated with better outcomes at 3 months in patients with AIS, especially in the LAA subtype, but this association attenuated in the cardioembolism and SVO subtypes.

Association of HbA1c with functional outcome by ischemic stroke subtypes and age.

To determine whether high HbA1c levels are related to short-and long-term functional outcomes in patients with ischemic stroke (IS) and whether this association differs according to the IS subtype and the patient's age. The data of 7,380 IS patients admitted to 16 hospitals or regional stroke centers in South-Korea, between May 2017 and December 2019, were obtained from the Clinical Research Collaboration for Stroke-Korea-National Institute of Health database and retrospectively analyzed. Among these patients, 4,598 were followed-up for one-year. The HbA1c levels were classified into three groups (<5.7, 5.7 to <6.5%, ≥6.5%). Short-and long-term poor functional outcomes were defined using the modified Rankin Scale score of 2 to 6 at three-months and one-year, respectively. IS subtypes were categorized according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. There was an association between higher HbA1c (≥6.5%) and poor functional outcomes at three-months in all patients (three-months; OR, 1.299, 95% CI 1.098, 1.535, one-year; OR, 1.181, 95% CI 0.952, 1.465). When grouped by age, the associations after both 3 months and 1 year observed in younger adult group (<65 years), but not in group aged 65 years and older (three-months; <65 years OR, 1.467, 95% CI 1.112, 1.936, ≥65 years OR, 1.220, 95% CI 0.987, 1.507, p for interaction = 0.038, one-year; <65 years OR, 1.622, 95% CI 1.101, 2.388, ≥65 years OR, 1.010, 95% CI 0.778, 1.312, p for interaction = 0.018). Among younger adult group, the higher HbA1c level was related to short-and long-term functional loss in patients with the small vessel occlusion subtype (three-months; OR, 2.337, 95%CI 1.334, 4.095, one-year; OR, 3.004, 95% CI 1.301, 6.938). However, in patients with other TOAST subtypes, a high HbA1c level did not increase the risk of poor outcomes, regardless of the age of onset. High HbA1c levels increase the risk of short-and long-term poor functional outcomes after IS onset. However, this association differs according to stroke subtype and age. Thus, pre-stroke hyperglycemia, reflected by HbA1c, may be a significant predictor for a poor prognosis after ischemic stroke, particular in young- and middle-aged adults.

Etiologies, mechanisms, and risk factors of ischemic stroke in a young Asian adult cohort

ObjectivesRisk factors and causes of acute ischemic stroke (AIS) are more diverse in young adults, and traditional stroke classifications may be inadequate. Precise characterisation of AIS is important for guiding management and prognostication. We describe stroke subtypes, risk factors and etiologies for AIS in a young Asian adult population. Materials and methodsYoung AIS patients aged 18-50 years admitted to two comprehensive stroke centres from 2020-2022 were included. Stroke etiologies and risk factors were adjudicated using Trial of Org 10172 in Acute Stroke Treatment (TOAST) and International Pediatric Stroke Study (IPSS) risk factors. Potential embolic sources (PES) were identified in a subgroup with embolic stroke of undetermined source (ESUS). These were compared across sex, ethnicities and age groups (18-39 years versus 40-50 years). ResultsA total of 276 AIS patients were included, with mean age 43±5.7 years and 70.3% male. Median duration of follow-up was 5 months (IQR: 3-10). The most common TOAST subtypes were small-vessel disease (32.6%) and undetermined etiology (24.6%). IPSS risk factors were identified in 95% of all patients and 90% with undetermined etiology. IPSS risk factors included atherosclerosis (59.5%), cardiac disorders (18.7%), prothrombotic states (12.4%) and arteriopathy (7.7%). In this cohort, 20.3% had ESUS, of which 73.2% had at least one PES, which increased to 84.2% in those <40 years old. ConclusionsYoung adults have diverse risk factors and causes of AIS. IPSS risk factors and ESUS-PES construct are comprehensive classification systems that may better reflect heterogeneous risk factors and etiologies in young stroke patients.

Trimethylamine N-Oxide and Stroke Recurrence Depends on Ischemic Stroke Subtypes.

Trimethylamine N-oxide (TMAO) has been recognized as a risk factor for cardiovascular disease. However, the role of TMAO in ischemic stroke remains unclear. As we know, ischemic stroke is a heterogeneous disease with variable pathogenesis. Hence, we aimed to investigate the association between TMAO and stroke recurrence according to etiology subtypes. A total of 10 756 ischemic stroke/transient ischemic attack patients from the Third China National Stroke Registry were enrolled, and 1-year follow-up data for stroke recurrence were analyzed. TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria was used to classify the etiology subtypes. Plasma TMAO levels were quantified by liquid chromatography-mass spectrometry. The association between TMAO and stroke outcomes was analyzed using Cox regression models. We also conducted a meta-analysis on the association of TMAO levels and stroke risk. Elevated TMAO level was independently associated with the risk of stroke recurrence (Q4 versus Q1: adjusted hazard ratio, 1.37 [95% CI, 1.15-1.64]) in multivariate Cox regression model. After stratification by TOAST subtypes, there was a significant association between TMAO and stroke recurrence in small artery occlusion subtype (adjusted hazard ratio, 1.43 [95% CI, 1.03-2.00]) but not in the others subtype (large-artery atherosclerosis, 1.19 [0.95-1.48]; cardioembolism, 1.54 [0.95-2.48]; others, 1.19 [0.98-1.44]). The meta-analysis reported on stroke recurrence for the highest versus lowest TMAO levels with a pooled hazard ratio of 1.66 (95% CI, 0.91-3.01) and similarly found an increased risk of stroke recurrence. Elevated TMAO level is associated with increased risk of stroke recurrence in patients with small artery occlusion subtype, but this association seems to be attenuated in large-artery atherosclerosis, cardioembolism, and others subtypes.

Platelet Endothelial Aggregation Receptor 1 Polymorphism Is Associated With Functional Outcome in Small-Artery Occlusion Stroke Patients Treated With Aspirin.

Background: The role of genetic polymorphisms is important in defining the patient's prognosis and outcomes in coronary artery disease. The present study aimed to explore the association between platelet endothelial aggregation receptor 1 (PEAR1) rs12041331 polymorphism and the outcomes in patients with acute ischemic stroke treated with aspirin or dual antiplatelet therapy (DAPT) with clopidogrel.Methods: A total of 868 ischemic stroke patients admitted to our hospital from January 1, 2016 to December 30, 2018 were retrospectively studied. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification defined stroke subtypes. These patients were treated with aspirin alone or DAPT. The genotype distribution of PEAR1 rs12041331 single-nucleotide polymorphism (AA, AC, and CC) between different TOAST subtypes and treatment groups was assessed, and the clinical impact of genetic variants on functional outcomes defined by the National Institutes of Health Stroke Scale, modified Rankin Scale, and Barthel Index was analyzed using univariate and multivariate logistic regression models.Results: Among the 868 stroke patients, the PEAR1 AA genotype was 16%, GA was 47%, and GG was 36%. Forty-four percent had aspirin alone, and 56% had DAPT. Overall, the distribution of PEAR single-nucleotide polymorphism was not significant among the two treatment groups or subtypes of TOAST. In contrast, in patients treated with aspirin alone, PEAR1 AA tended to be higher in the small-artery occlusion (SAO) subtype when compared with the no-lacunar subtype, including cardioembolism and large-artery atherosclerosis. PEAR1 AA genotype was significantly associated with favorable functional outcomes at day 7 and discharge only in SAO patients treated with aspirin alone compared with the GG genotype. Multivariate regression models further suggested that AA genotype was independently associated with favorable outcomes in this group after being adjusted for three common stroke risk factors such as age, hypertension history, and C-reactive protein level [odds ratio (OR) 0.23, 95% confidence interval (CI), 0.07–0.64, P = 0.02 for 7-day National Institutes of Health Stroke Scale; OR 0.2, 95% CI, 0.06–0.66, P = 0.03 for 7-day modified Rankin Scale, and OR 0.25, 95% CI, 0.08–0.72, P = 0.03 for 7-day Barthel Index, respectively].Conclusion: The impact of PEAR1 rs12041331 polymorphism on aspirin depends on the TOAST subtype. PEAR1 AA carrier with SAO stroke is most sensitive to aspirin therapy. PEAR1 AA is an independent factor for the short-term functional outcomes in SAO patients treated with aspirin alone.Clinical Registration Number: 1800019911.

Inflammatory markers as independent predictors for stroke outcomes.

BackgroundInflammation plays an important role in the pathophysiology of stroke. The aim of the present study was to investigate the association between various inflammatory risk markers and ischemic stroke outcome and subtype.MethodsA total of 3,013 ischemic stroke patients who were admitted to our hospital from 01/01/2016 to 12/30/2018 were retrospectively studied. Stroke subtypes were defined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Levels of five common inflammatory markers including white blood cell (WBC) count, neutrophil, lymphocyte, serum C‐reactive protein (CRP), and interleukin‐6 (IL‐6) were measured, and eleven conventional risk factors were further evaluated in the prediction of overall mortality as well as three functional outcomes defined by the National Institute of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel Index (BI). Independent predictors of outcome were identified by multivariate logistic regression, and an importance score measured by the area under the receiver operating characteristics curve for each predictor using a Naive Bayes model was reported.ResultsNeutrophil and WBC were significantly higher in large‐artery atherosclerosis (LAA) and cardioembolism (CE) subtype. In contrast, lymphocyte was significantly higher in small‐artery occlusion (SAO). Neutrophil–lymphocyte ratio and CRP level were the best independent predictors, after adjustment for traditional risk factors and TOAST subtype for all four types of outcomes.ConclusionInflammatory risk markers including neutrophil, lymphocyte, and CRP may have strong independent prediction values for stroke outcome.

Risk Factors and Subtyping of Ischemic Stroke in Young Adults in the Indian Population.

Objective: To evaluate the risk factors and etiological subtyping of ischemic stroke in young adults in the Indian population.Methods: This is a retrospective study of 160 patients, in the age group of 18 to 45 years with ischemic stroke, registered at a tertiary care hospital in Delhi, India between March 2014 and January 2018. Hypertension, diabetes mellitus, dyslipidemia, smoking, alcohol consumption, previous history of stroke, valvular heart disease, coronary artery disease (CAD), atrial fibrillation, family history, and migraine were considered as the identifiable risk factors. Stroke subtyping was done according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria.Results: The mean age of the patients was 36.2 years with 74% being males. Headache, vomiting, difficulty in speech, and hemiparesis were the common complaints at presentation. Common risk factors identified were hypertension (50%), prior stroke or transient ischemic attack (TIA; 32%), dyslipidemia (25%), family history of stroke (18%), and smoking (15%). The most common TOAST subtype was undetermined (64%), followed by other determined cause (ODC; 20%), and cardioembolism (15%).Conclusion: There is a certain dissimilarity in the risk factors for ischemic stroke in young adults living in developing countries compared to those belonging to developed nations. Primary and secondary prevention targeted at the modifiable risk factors of ischemic stroke is necessary. Cerebral artery dissection, being a prevalent cause of ischemic stroke in young adults, should be carefully evaluated. A more appropriate stroke classification system specifically tailored for younger patients is needed.

Exome Array Analysis of Early-Onset Ischemic Stroke.

The genetic contribution to ischemic stroke may include rare- or low-frequency variants of high-penetrance and large-effect sizes. Analyses focusing on early-onset disease, an extreme-phenotype, and on the exome, the protein-coding portion of genes, may increase the likelihood of identifying such rare functional variants. To evaluate this hypothesis, we implemented a 2-stage discovery and replication design, and then addressed whether the identified variants also associated with older-onset disease. Discovery was performed in UMD-GEOS Study (University of Maryland-Genetics of Early-Onset Stroke), a biracial population-based study of first-ever ischemic stroke cases 15 to 49 years of age (n=723) and nonstroke controls (n=726). All participants had prior GWAS (Genome Wide Association Study) and underwent Illumina exome-chip genotyping. Logistic-regression was performed to test single-variant associations with all-ischemic stroke and TOAST (Trial of ORG 10172 in Acute Stroke Treatment) subtypes in Whites and Blacks. Population level results were combined using meta-analysis. Gene-based aggregation testing and meta-analysis were performed using seqMeta. Covariates included age and gender, and principal-components for population structure. Pathway analyses were performed across all nominally associated genes for each stroke outcome. Replication was attempted through lookups in a previously reported meta-analysis of early-onset stroke and a large-scale stroke genetics study consisting of primarily older-onset cases. Gene burden tests identified a significant association with NAT10 in small-vessel stroke (P=3.79×10-6). Pathway analysis of the top 517 genes (P<0.05) from the gene-based analysis of small-vessel stroke identified several signaling and metabolism-related pathways related to neurotransmitter, neurodevelopmental notch-signaling, and lipid/glucose metabolism. While no individual SNPs reached chip-wide significance (P<2.05×10-7), several were near, including an intronic variant in LEXM (rs7549251; P=4.08×10-7) and an exonic variant in TRAPPC11 (rs67383011; P=5.19×10-6). Exome-based analysis in the setting of early-onset stroke is a promising strategy for identifying novel genetic risk variants, loci, and pathways.

Etiological Subtypes of Transient Ischemic Attack and Ischemic Stroke in Chronic Kidney Disease: Population-Based Study.

Chronic kidney disease (CKD) is strongly associated with stroke risk, but the mechanisms underlying this association are unclear and might be informed by subtype-specific analyses. However, few studies have reported stroke subtypes in CKD according to established classification systems, such as the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria. We, therefore, aimed to determine which transient ischemic attack and ischemic stroke subtypes using the TOAST classification occur most frequently in patients with CKD. In a population-based study of all transient ischemic attack and stroke (OXVASC [Oxford Vascular Study]; 2002-2017), all ischemic events were classified by TOAST subtypes (cardioembolism, large artery disease, small vessel disease, undetermined, multiple, other etiology, or incompletely investigated). Logistic regression was used to determine the relationship between CKD (defined as an estimated glomerular filtration rate <60 mL/min per 1.73 m2) and transient ischemic attack/stroke subtypes adjusted for age, sex, and hypertension and then stratified by age and estimated glomerular filtration rate category. Among 3178 patients with transient ischemic attack (n=1167), ischemic stroke (n=1802), and intracerebral hemorrhage (n=209), 1267 (40%) had CKD. Although there was a greater prevalence of cardioembolic events (31.8% versus 21.2%; P<0.001) in patients with CKD, this association was lost after adjustment for age, sex, and hypertension (adjusted odds ratio=1.20 [95% CI, 0.99-1.45]; P=0.07). Similarly, although patients with CKD had a lower prevalence of small vessel disease (8.8% versus 13.6%; P<0.001), undetermined (26.1% versus 39.4%; P<0.001), and other etiology (1.0% versus 3.6%; P<0.001) subtypes, these associations were also lost after adjustment (adjusted odds ratio=0.86 [0.65-1.13]; P=0.27 and 0.73 [0.36-1.43]; P=0.37 for small vessel disease and other defined etiology, respectively) for all but undetermined (adjusted odds ratio=0.81 [0.67-0.98]; P=0.03). There were no independent positive associations between CKD and specific TOAST subtypes, which suggest that renal-specific risk factors are unlikely to play an important role in the etiology of particular subtypes. Future studies of stroke and CKD should report subtype-specific analyses to gain further insights into potential mechanisms.

Risk and Secondary Prevention of Stroke Recurrence: A Population-Base Cohort Study.

With recent advances in secondary prevention management, stroke recurrence rates may have changed substantially. We aim to estimate risks and trends of stroke recurrence over the past 2 decades in a population-based cohort of patients with stroke. Patients with a first-ever stroke between 1995 and 2018 in South London, United Kingdom (n=6052) were collected and analyzed. Rates of recurrent stroke with 95% CIs were stratified by 5-year period of index stroke and etiologic TOAST (Trial of ORG 10172 in Acute Stroke Treatment) subtype. Cumulative incidences were estimated and multivariate Cox models applied to examine associations of recurrence and recurrence-free survival. The rate of stroke recurrence at 5 years reduced from 18% (95% CI, 15%-21%) in those who had their stroke in 1995 to 1999 to 12% (10%-15%) in 2000 to 2005, and no improvement since. Recurrence-free survival has improved (35%, 1995-1999; 67%, 2010-2015). Risk of recurrence or death is lowest for small-vessel occlusion strokes and other ischemic causes (36% and 27% at 5 years, respectively). For cardioembolic and hemorrhagic index strokes around half of first recurrences are of the same type (54% and 51%, respectively). Over the whole study period a 54% increased risk of recurrence was observed among those who had atrial fibrillation before the index stroke (hazard ratio, 1.54 [1.09-2.17]). The rate of recurrence reduced until mid-2000s but has not changed over the last decade. The majority of cardioembolic or hemorrhagic strokes that have a recurrence are stroke of the same type indicating that the implementation of effective preventive strategies is still suboptimal in these stroke subtypes.

Alternate approach to stroke phenotyping identifies a genetic risk locus for small vessel stroke

Ischemic stroke (IS), caused by obstruction of cerebral blood flow, is one of the leading causes of death. While neurologists agree on delineation of IS into three subtypes (cardioembolic stroke (CES), large artery stroke (LAS), and small vessel stroke (SVS)), several subtyping systems exist. The most commonly used systems are TOAST (Trial of Org 10172 in Acute Stroke Treatment) and CCS (Causative Classification System for Stroke), but agreement is only moderate. We have compared two approaches to combining the existing subtyping systems for a phenotype suited for a genome-wide association study (GWAS). We used the NINDS Stroke Genetics Network dataset (SiGN, 11,477 cases with CCS and TOAST subtypes and 28,026 controls). We defined two new phenotypes: the intersect, for which an individual must be assigned the same subtype by CCS and TOAST; and the union, for which an individual must be assigned a subtype by either CCS or TOAST. The union yields the largest sample size while the intersect yields a phenotype with less potential misclassification. We performed GWAS for all subtypes, using the original subtyping systems, the intersect, and the union as phenotypes. In each subtype, heritability was higher for the intersect compared with the other phenotypes. We observed stronger effects at known IS variants with the intersect compared with the other phenotypes. With the intersect, we identify rs10029218:G>A as an associated variant with SVS. We conclude that this approach increases the likelihood to detect genetic associations in ischemic stroke.

Lp-PLA2 as a risk factor of early neurological deterioration in acute ischemic stroke with TOAST type of large arterial atherosclerosis

ABSTRACTIntroduction: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a well-known risk factor of atherosclerotic vascular diseases. Nevertheless, its role in the acute phase of ischemic stroke is still unclear. The aim of this study is to identify the relationship between Lp-PLA2 levels and early neurological deterioration (END) in acute ischemic stroke patients with Trial of Org 10 172 in Acute Stroke Treatment (TOAST) subtype of large arterial atherosclerosis (LAA).Methods: We enrolled Chinese patients with first ever acute ischemic stroke admitted to Neurology Department of Shenzhen Second People’s Hospital within 48 h from onset of symptoms during January – November 2015. Demographic and laboratory information were collected while END was defined as an increase in the National Institute of Health Stroke Scale score by ≥ 1 point in motor power, or ≥ 2 points in the total score within 10 days after admission.Results: Overall 181 patients were involved; END was diagnosed in 30 patients within 10 days after admission. The odds ratio for END increased with increasing levels of Lp-PLA2 (intermediate level, OR = 1.96, 95%CI 1.02–4.27, p = 0.041; high level, OR = 2.99, 95%CI 1.26–5.73, p = 0.023).Conclution: Intermediate and high level of Lp-PLA2 was identified as independent predictor of END in multivariate analysis. Lp-PLA2 could be valued as a risk factor of END in patients with acute ischemic stroke with TOAST subtype of LAA.

Development and Reliability of a User-Friendly Multicenter Phenotyping Application for Hemorrhagic and Ischemic Stroke

Annotation and Image Markup on ClearCanvas Enriched Stroke-phenotyping Software (ACCESS) is a novel stand-alone computer software application that allows the creation of simple standardized annotations for reporting brain images of all stroke types. We developed the ACCESS application and determined its inter-rater and intra-rater reliability in the Stroke Investigative Research and Educational Network (SIREN) study to assess its suitability for multicenter studies. One hundred randomly selected stroke imaging reports from 5 SIREN sites were re-evaluated by 4 trained independent raters to determine the inter-rater reliability of the ACCESS (version 12.0) software for stroke phenotyping. To determine intra-rater reliability, 6 raters reviewed the same cases previously reported by them after a month of interval. Ischemic stroke was classified using the Oxfordshire Community Stroke Project (OCSP), Trial of Org 10172 in Acute Stroke Treatment (TOAST), and Atherosclerosis, Small-vessel disease, Cardiac source, Other cause (ASCO) protocols, while hemorrhagic stroke was classified using the Structural lesion, Medication, Amyloid angiopathy, Systemic disease, Hypertensive angiopathy and Undetermined (SMASH-U) protocol in ACCESS. Agreement among raters was measured with Cohen's kappa statistics. For primary stroke type, inter-rater agreement was .98 (95% confidence interval [CI], .94-1.00), while intra-rater agreement was 1.00 (95% CI, 1.00). For OCSP subtypes, inter-rater agreement was .97 (95% CI, .92-1.00) for the partial anterior circulation infarcts, .92 (95% CI, .76-1.00) for the total anterior circulation infarcts, and excellent for both lacunar infarcts and posterior circulation infarcts. Intra-rater agreement was .97 (.90-1.00), while inter-rater agreement was .93 (95% CI, .84-1.00) for TOAST subtypes. Inter-rater agreement ranged between .78 (cardioembolic) and .91 (large artery atherosclerotic) for ASCO subtypes and was .80 (95% CI, .56-1.00) for SMASH-U subtypes. The ACCESS application facilitates a concordant and reproducible classification of stroke subtypes by multiple investigators, making it suitable for clinical use and multicenter research.

Abstract 4: A Functional Variant in the 3’-utr of Vegf Might Affect Stroke Functional Recovery by Interfering With the Binding Efficiency of Microrna

Background and purpose: While remaining the second most common cause of death worldwide, stroke is also a leading cause of significant disability. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis and neurovascular during stroke functional recovery . Therefore, we hypothesized that variants of the microRNA-binding site in VEGF would affect its expression and functional outcome of stroke. However, the effect of VEGF gene 3'UTR polymorphisms on the prognosis in patients with acute ischemic stroke(IS) in Chinese has not been reported. Methods: The association of VEGF gene 3'UTR variant with IS was investigated in 494 patients and 330 controls. IS was classified into subtypes using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) at the time of admission. Patients were assessed 90 days post-stroke using the Modified Rankin Scale (MRS) to determine stroke outcome. The bioinformatics analysis suggested that the 3′-UTR of VEGF may increase miR regulation of VEGF gene expression, Then we construct luciferase reporter gene vectors containing VEGF gene 3'UTR site and detect microRNA binding stability. Results: The TT genotype resulted in a significant increase in ischemic stroke [OR, 1.679 (95% CI, 1.101-2.554), P 0.015]. But no association between genotypes and TOAST subtypes was shown. The novel finding was that the TT genotype of the VEGF was associated with poor outcome of recovery 3 months after stroke onset [OR, 2.143 (95% CI, 1.108-4.145), P 0.022]. MiR-199a could inhibit the expression of VEGF by directly binding to 3’UTR and C→T may influence the stability of this binding. Conclusions: IS patients with the TT genotype in the 3′-UTR of VEGF might affect stroke functional recovery by interfering with the binding efficiency of microRNA

Revised iScore to Predict Outcomes after Acute Ischemic Stroke

The iScore is a validated tool to predict mortality and functional outcome after acute ischemic stroke. It incorporates stroke subtype according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification as one of its factors. However, the TOAST stroke subtype may not be easily determined without extensive investigations. We aimed to test if the stroke subtype can be substituted by the Oxfordshire Community Stroke Project (OCSP) classification. We applied the iScore and the revised iScore, in which the TOAST subtype was replaced by the OCSP classification, to patients admitted to a single hospital for acute ischemic stroke. Outcome measures included poor functional status (modified Rankin scale score, 3-6) at discharge and 3 months. The performance between the iScore and the revised iScore was assessed by determining the discrimination and calibration of the scores. We studied 3196 patients at the acute stage, and among them 2349 patients were available for the 3-month assessment. The discrimination of the revised iScore was comparable with the iScore for poor outcome at discharge (area under the receiver operating characteristic curve, .767 versus .775; P=.06) and at 3-month (.801 versus .810; P=.06). The correlation between the observed and the expected outcomes was high for both the iScore (Pearson correlation coefficient, .993 at discharge and .995 at 3 months; both P<.0001) and the revised iScore (.985 and .993, respectively; both P<.0001). The revised iScore reliably predicts clinical outcomes at discharge and 3 months for patients with acute ischemic stroke.

Multiplicity of Risk Factors in Ischemic Stroke Patients: Relations to Age, Sex, and Subtype - A Study of 2,505 Patients from the Lund Stroke Register

Background: The prevalence of risk factors for ischemic stroke may vary between different groups of stroke patients. We examined the distribution of individual well-established risk factors as well as the multiplicity of risk factors in different age groups and among subtypes. Methods: In the Lund Stroke Register, we consecutively enrolled 2,505 patients with first-ever ischemic stroke from 2001 to 2009 and registered hypertension, diabetes mellitus, heart disease, current smoking, hypercholesterolemia as well as stroke subtype. Results: Among young patients (<55 years), at least 50% had ≥2 risk factors and 20-25% had ≥3 risk factors. In patients aged 55 years or older, the proportion with ≥2 risk factors was 70-80% and with ≥3 risk factors 35-45%. Men and women had a similar burden of risk factors. Approximately 50% of the cases classified as cardioembolism (CE) and large artery atherosclerosis (LAA) had ≥3 risk factors, which was significantly more than the other TOAST (Trial of Org 10172 in Acute Stroke Treatment) subtypes (CE p < 0.001, LAA p = 0.001). Conclusions: The prevalence of well-established risk factors is similar among young and old stroke patients with large proportions (50-80%) having ≥2 risk factors. Even though the prevalence of well-established risk factors differs between pathogenetic subtypes, these risk factors as well as the multiplicity of risk factors seem to be of clinical importance in all major subtypes of ischemic stroke.

Cost-effectiveness analysis of clinical pathway for different TOAST subtypes of patients with acute cerebral infarction

Objective To evaluate the cost-effectiveness of clinical pathway for different Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtypes of patients with acute cerebral infarction (ACI). Methods ACI clinical pathway was developed according to the characteristics of our hospital. A total of 1036 ACI patients were recruited. They were divided into control (n=472) and pathway (n=564) groups. The hospitalization time, hospitalization expenses and clinical outcomes between two groups of different TOAST subtypes were compared. Good clinical outcome was defined as a modified Rankin Score (mRS) of 0-2. Results Compared to control group, the lengths of stay for ACI patients in pathway group were significantly shorter (P=0.004) while those with good clinical outcomes were significantly higher (P=0.002). Furthermore, the lengths of stay for large artery atherosclerosis (LAA) subtype patients in pathway group were shorter (P=0.000), both total hospital charges and medication costs were significantly reduced (P=0.044, 0.036) while those with good clinical outcome were significantly higher (P=0.002); the differences among other four subtypes of small artery occlusion (SAO), cardioembolism (CE), stroke of other etiology (SOE) and stroke of undetermined etiology (SUE) were not statistically significant. Conclusion The implementation of clinical pathway may offer more benefits to LAA subtype ACI patients than other subtypes. Key words: Cerebrovascular Accident; Clinical pathways; Prognosis

Long‐term risk of recurrent vascular events after young stroke: The FUTURE study

Long-term data on recurrent vascular events after young stroke are limited. Our objective was to examine the long-term risk of recurrent vascular events after young stroke. We prospectively included 724 consecutive patients with a first-ever transient ischemic attack (TIA), ischemic stroke, or intracerebral hemorrhage (ICH), aged 18 to 50 years, admitted to our hospital between January 1, 1980 and November 1, 2010. Outcomes were (1) stroke; (2) myocardial infarction or cardiac or peripheral arterial revascularization procedures; or (3) composite event of these, whichever occurred first. After a mean follow-up of 9.1 years (standard deviation = 8.2, range = 0-31.0), 142 patients (19.6%) had at least 1 recurrent vascular event. Cumulative 20-year risk of stroke was 17.3% (95% confidence interval [CI] = 9.5-25.1) after TIA, 19.4% (95% [CI] = 14.6-24.3) after ischemic stroke, and 9.8% (95% CI = 1.0-18.7) after ICH. Cumulative 20-year risk of any vascular event was 27.7% (95% CI = 18.5-37.0) after TIA and 32.8% (95% CI = 26.7-38.9) after ischemic stroke. Age and male sex were associated with other arterial events, but not with stroke. Among TOAST (Trial of Org 10172 in Acute Stroke Treatment) subtypes, adjusted for age, sex, and decennium of inclusion, atherothrombotic stroke, cardioembolic stroke, and lacunar stroke were associated with recurrent stroke (hazard ratio [HR] = 2.72, 95% CI = 1.34-5.52; HR = 2.49, 95% CI = 1.23-5.07; and HR = 2.92, 95% CI = 1.45-5.88, respectively). Patients with young stroke remain at substantial risk of recurrent vascular events for decades, suggesting that the underlying disease that caused stroke at a young age continues to put these patients at a high risk for vascular disease throughout their lives.

TOAST subtypes: its influence upon doctors&amp;rsquo; decisions of antihypertensive prescription at discharge for ischemic stroke patients

AimTo investigate the influence of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtypes in doctors’ decisions to use antihypertensive prescriptions at discharge for ischemic stroke patients in a real-world setting.MethodsUsing the China National Stroke Registry, we analyzed data from 12,063 hospitalized patients who had been diagnosed with ischemic stroke. The cause of ischemic stroke was classified according to the TOAST criteria. The information about the prescription of antihypertensive medication at discharge was extracted from medical records. Multivariate logistic regression was used to assess the impact of TOAST subtypes on the prescription of antihypertensive medication at discharge.ResultsMultivariate analysis showed that, compared with large artery atherosclerosis patients with moderate (<70%) stenosis, large artery atherosclerosis patients with severe (≥70%) stenosis or patients with stroke of undetermined etiology were less likely to be prescribed antihypertensive medication at discharge (odds ratio [OR], 0.72; 95% confidence interval [CI]: 0.59–0.88; OR, 0.71; 95% CI: 0.64–0.79), while patients with small artery occlusion were more likely to be prescribed antihypertensives (OR, 1.50; 95% CI: 1.33–1.69).ConclusionThe TOAST subtype is an important determinant of the prescription of antihypertensive medication for ischemic stroke patients at discharge in normal clinical practice.

Decreased plasma decorin levels following acute ischemic stroke: Correlation with MMP-2 and differential expression in TOAST subtypes

Accumulating evidence suggests that extracellular matrix (ECM) remodeling plays a significant role following acute ischemic stroke (AIS). Decorin (DCN) is a well-recognized molecule present in the ECM; however, the role of DCN in AIS remains unknown. The present study aimed to investigate whether plasma concentrations of DCN are altered in patients following an AIS and whether they are correlated with matrix metalloproteinase-2 (MMP-2) levels and other laboratory and clinical variables. Plasma concentrations of DCN were assessed in 102 patients with AIS (less than 7 days) and 120 control subjects using ELISA assays. The correlation between DCN concentrations and MMP-2 levels, Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtypes, stroke severity and risk factors were evaluated. The expression of DCN was significantly decreased in patients with AIS (P<0.001), particularly in the large-artery atherosclerosis (LAAS) group. The levels of DCN were positively correlated with MMP-2 (R=0.332; P<0.001), thus MMP-2 is an independent predictor of DCN concentration (P<0.001). DCN levels below 8,500 pg/ml had sensitivity and specificity values of AIS of 79.4 and 62.8%, respectively and DCN below 8,500 pg/ml was associated with AIS (OR=4.8; 95% CI: 2.1-11.1; P<0.001) following adjustment for potential confounders. In conclusion, for the first time, a reduction in DCN was detected in patients following AIS and these altered plasma concentrations were correlated with MMP-2. Larger studies are required to further investigate whether DCN is involved in the pathogenesis of ischemic stroke.