scholarly journals Potential Key Genes Associated with Stroke types and its subtypes: A Computational Approach

2021 ◽  
Author(s):  
Gourab Das ◽  
Pradeep Kumar
Keyword(s):  
Stroke Risk ◽  
Diagnostic Marker ◽  
Small Vessel Disease ◽  
Large Artery ◽  
Human Genes ◽  
Gene Database ◽  
Key Genes ◽  
Toast Classification ◽  
Ncbi Gene Database ◽  
Gene Symbols

AbstractTo investigate prospective key genes and pathways associated with the pathogenesis and prognosis of stroke types along with subtypes. Human genes using genome assembly build 38 patch release 13 with known gene symbols through NCBI gene database (https://www.ncbi.nlm.nih.gov/gene) were fetched. PubMed advanced queries were constructed using stroke-related keywords and associations were calculated using Normalized pointwise mutual information (nPMI) between each gene symbol and queries. Genes related with stroke risk within their types and subtypes were investigated in order to discover genetic markers to predict individuals who are at the risk of developing stroke with their subtypes. A total of 2,785 (9.4%) genes were found to be linked to the risk of stroke. Based on stroke types, 1,287 (46.2%) and 376 (13.5%) genes were found to be related with IS and HS respectively. Further stratification of IS based on TOAST classification, 86 (6.6%) genes were confined to Large artery atherosclerosis; 131 (10.1%) and 130 (10%) genes were related with the risk of small vessel disease and Cardioembolism subtypes of IS. Besides, a prognostic panel of 9 genes signature consisting of CYP4A11, ALOX5P, NOTCH, NINJ2, FGB, MTHFR, PDE4D, HDAC9, and ZHFX3 can be treated as a diagnostic marker to predict individuals who are at the risk of developing stroke with their subtypes.

Abstract TP159: Correlation Between Arterial Stiffness And The Severity Of Acute Cerebral Infarction

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
YEONG-BAE LEE ◽  
Joo-Hwan Park ◽  
Eunja Kim ◽  
Ki-Tae Kim ◽  
Ju Kang Lee ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Arterial Stiffness ◽  
Acute Ischemic Stroke ◽  
Pulse Wave ◽  
Small Vessel Disease ◽  
Large Artery ◽  
Significant Difference ◽  
Initial Severity ◽  
Artery Disease ◽  
Toast Classification

Arterial stiffness is an independent predictor of cardiovascular disease and stroke and can be evaluated by measuring pulse wave velocity(PWV) between 2 sites in the arterial tree, with a higher PWV indicating stiffer arteries. Recent studies have demonstrated that arterial stiffness is associated with intracranial large artery disease and the severity of cerebral small vessel disease. The aim of this study is to clarify whether pulse wave velocity value predict initial severity of acute ischemic stroke. We enrolled consecutive patients with acute ischemic stroke. Demographic factors, laboratory data, brain imaging, neurological exam and arterial stiffness measured by brachial ankle PWV (baPWV) were evaluated on admission in all subjects. The subtype of acute ischemic stroke was classified according to the TOAST classification. All patients were categorized into two groups based on the initial severity of stroke, indicated by modified Rankin Scale(mRS). Severe group was defined as a mRS ≥ 3 at admission. Unpaired student’s t-test or Mann-whitney U-test were used to compare maximal and meanbaPWV values between two groups. We enrolled 78 patients. According to the TOAST classification, the etiology of stroke was large artery disease (LAD) in 34 patients, small vessel disease (SVD) in 23 patients, and other subtypes in 12 patients. There were 28 patients with good outcome and 41 patients with poor outcome. The maximal and mean baPWV values were significantly increased in inpatients with high mRS score (2120.17± 527.75, 1999.21 ± 437.46) compared with those with low mRS score (1751.96 ± 363.49, 1723.14 ± 353.02)(p=0.001, p=0.007). In patients with SVD subtype, there was significant difference in maximal and mean baPWVvalues between two groups (p=0.030, p=0.047), whereas there was no significant difference in baPWV in patients with LAD subtype (p=0.141, p=0.172). The main finding of our study is that arterial stiffness indicated by baPWV is associated with the initial severity of acute ischemic stroke. Because initial stroke severity is strongly associated with functional outcome of stroke, this findings suggest that measurement of baPWV may predict long-term outcome in patients with stroke especially in those with TOAST classification confirmed as SVD.

Abstract 34: Improvement In Etiological Identification In Tia And Minor Stroke Using The Causative Classification Of Stroke.

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Jamsheed A Desai ◽  
Ahmad Abuzinadah ◽  
Oje Imoukhuede ◽  
Jayesh Modi ◽  
Manya L Bernbaum ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Relative Increase ◽  
Classification Systems ◽  
Minor Stroke ◽  
Large Artery ◽  
Stroke Treatment ◽  
Minor Ischemic Stroke ◽  
Undetermined Etiology ◽  
Toast Classification

Background: classification of Transient Ischemic attacks (TIA) and minor stroke is challenging, as there is no classification systems developed specifically for the TIA and minor stroke patient population. Hypothesis: We hypothesize that the newly developed Causative Classification System (CCS) and the Atherosclerosis Small Vessel Disease Cardiac Source Other Source (ASCO) classification would reduce the proportion of patients classified as cause undetermined compared with The Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification in a large prospectively evaluated TIA and Minor stroke population. Methods: Using published algorithms for TOAST, CCS, and ASCO, a single rater classified the etiology in patients presenting with a high-risk TIA (weakness or speech disturbance lasting ≥ 5minutes) or minor ischemic stroke (National Institute of Health Stroke Scale score ≤ 3) who underwent CT/CTA and subsequent MRI as part of the CATCH study. Results: 419 patients with TIA or Minor stroke were classified using TOAST, CCS, and ASCO. The proportion of patients with an undetermined etiology was 51.3% (215/419) with TOAST. This was significantly reduced by both CCS 36% (151/419, p< 0.001) and ASCO 41% (172/419, p< 0.001). CCS was also less likely to have an undetermined etiology as compared to ASCO (36% versus 41%, p = 0.024). When compared with TOAST, there was a 23.9% (95%CI:18.1- 29.7, P< 0.001) and 17.4% (10.1- 24.7, P< 0.001) reduction in the proportion of patients assigned to the undetermined group using CCS and ASCO respectively. The 8.5 % reduction in the undetermined group between CCS and ASCO was also statistically different P=0.031). Compared with ASCO1, CCS increased the assignment of patients to large artery disease (relative increase 7.4% {4.3-10.4}, P< 0.001) and Cardio-embolism/cardio-aortic categories (relative increase 8.1% {4.6-11.5}, P< 0.001). Conclusions: Both CCS and ASCO were superior to TOAST in assigning fewer patients to an undetermined etiology category. CCS was superior to ASCO at reducing the proportion of patients with undetermined etiology. This was largely driven by increased assignment in the large artery and Cardio-aorto embolic categories.

Comparison Study of ASCO and TOAST Classification System in Chinese Minor Stroke Patients

2019 ◽  
Vol 47 (1-2) ◽  
pp. 95-100 ◽  
Author(s):  
Xiao-Yu Xin ◽  
Lin Cheng ◽  
Zhao Yang ◽  
Yu Zhang ◽  
Li-Li Zeng ◽  
...  
Keyword(s):  
Classification System ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Minor Stroke ◽  
Large Artery ◽  
Stroke Patients ◽  
Vessel Disease ◽  
Small Artery Occlusion ◽  
Toast Classification ◽  
The Impact

Background: Precise subtype classification based on underlying pathophysiology is important to prevent recurrent attack in minor stroke patients. A newly developed Atherosclerosis, Small vessel disease, Cardiac source, Others (ASCO) phenotypic classification system aims to characterize patients using different grades of evidence for stroke subtypes. However, this system has not been specifically applied to minor stroke population. In our study, the impact of using the newer ASCO criteria on minor stroke etiologies was investigated, and compared with that of Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. Methods: Consecutive patients with minor ischemic stroke (NIHSS ≤3) were assessed and subtyped by the ASCO and TOAST systems. Stroke etiologies were presented and compared. The McNemar test and k statistic were used to analyze the difference and concordance between the 2 algorithms, respectively. Results: A total of 604 first-ever minor stroke patients were analyzed in the present study. Using TOAST classification, large artery atherosclerosis was the most frequent subtype (281, 46.5%), followed by small artery occlusion category (165, 27.3%). When ASCO was applied, 37 different profiles of stroke etiologies were identified. Using grade 1 of evidence, atherosclerosis (A1) was the most frequent subtype (308, 51.0%), followed by small vessel disease (S1, 178, 29.5%). Under consideration of grades 1 and 2, 239 (39.6%) patients were classified into more than 1 category. The ASCO system revealed determined etiologies in 104 of the 137 patients classified to cause undetermined subtype by TOAST classification. Good to very good accordance was observed between ASCO grade 1 and TOAST schemes across etiologic subtypes (κ = 0.719–0.832) except cause undetermined category (κ = 0.470). Conclusion: Application of ASCO decreased the proportion of patients assigned to cause undermined category compared to TOAST system. Comprehensive characteristics of ASCO system might be helpful in the personalized therapy or secondary prevention for individual patients in the future.

Phenotypic ASCO Characterisation of Young Patients with Ischemic Stroke in the Prospective Multicentre Observational sifap1 Study

2015 ◽  
Vol 40 (3-4) ◽  
pp. 129-135 ◽  
Author(s):  
Marc E. Wolf ◽  
Ulrike Grittner ◽  
Tobias Böttcher ◽  
Bo Norrving ◽  
Arndt Rolfs ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Small Vessel Disease ◽  
Age Groups ◽  
Cryptogenic Stroke ◽  
Young Patients ◽  
Lower Grade ◽  
Large Artery ◽  
Evidence Grade ◽  
Grade 3 ◽  
Toast Classification

Background: The prospective, multinational European ‘Stroke in Young Fabry Patients' (sifap1) study collected 4,467 patients with acute ischemic cerebrovascular events aged 18-55 years. Initially, aetiologic subtyping was performed using the TOAST classification; however, recently the phenotypic ASCO classification was presented and might be more useful to identify stroke aetiologies in young patients with a wide set of different causes. ASCO is a classification system divided in four etiologic categories (Atherosclerosis, Small vessel disease (SVD), Cardiac embolism, Other cause) with different grades of severity (1-3) and aims to characterise patients in a more comprehensive way. Methods: We determined the ASCO score for each patient, according to prospectively collected data using the study protocol. The distribution of aetiologies was analysed with regard to concomitant causes, cryptogenic stroke and different age groups. Results: A potentially causal aetiology (grade 1) was detected in 29.3% of 4,467 patients. Merging grades 1 and 2, a suspected aetiology was found in 54.1%. In 8.6% of patients concomitant aetiologies were identified. Most common causes were cervical arterial dissection and persistent foramen ovale, but there was also a high prevalence of large artery atherosclerosis and SVD especially in older patients of this collective. About 50% of patients had more than one finding with a lower grade of evidence (grade 3). In 14% final classification of strictly cryptogenic stroke was made. Conclusions: This is the largest study to date, using the ASCO characterisation of ischemic stroke aetiologies. ASCO classification provides first evidence that many young patients presenting with acute stroke have concomitant stroke aetiologies associated with a substantial atherosclerosis risk profile. ASCO could be integrated in clinical routine and registry data banks, as well as large clinical trials to improve stroke documentation.

EXPRESS: Evolving Ischemic Stroke Subtypes in 15 years: A hospital-based observational study

2021 ◽  
pp. 174749302110059
Author(s):  
Yiu Ming Bonaventure Ip ◽  
Lisa Au ◽  
Yin Yan Anne Chan ◽  
Florence Fan ◽  
Hing Lung Ip ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Recurrence Rate ◽  
Small Vessel Disease ◽  
Mainland China ◽  
Cardioembolic Stroke ◽  
Large Artery ◽  
Risk Factor Control ◽  
Stroke Subtypes ◽  
Artery Disease ◽  
Ischemic Attack

Background: Depicting the time trends of ischemic stroke subtypes may inform healthcare resource allocation on etiology-based stroke prevention and treatment. Aim: To reveal the evolving ischemic stroke subtypes from 2004 to 2018. Methods: We determined the stroke etiology of consecutive first-ever transient ischemic attack or ischemic stroke patients admitted to a regional hospital in Hong Kong from 2004 to 2018. We analyzed the age-standardized incidences and the 2-year recurrence rate of major ischemic stroke subtypes. Results: Among 6940 patients admitted from 2004 to 2018, age-standardized incidence of ischemic stroke declined from 187.0 to 127.4 per 100,000 population (p<0.001), driven by the decrease in large artery disease (43.0 to 9.67 per 100,000 population (p<0.001)) and small vessel disease (71.9 to 45.7 per 100,000 population (p<0.001)). Age-standardized incidence of cardioembolic stroke did not change significantly (p=0.2). Proportion of cardioembolic stroke increased from 20.4% in 2004-2006 to 29.3% in 2016-2018 (p<0.001). 2-year recurrence rate of intracranial atherothrombotic stroke reduced from 19.3% to 5.1% (p<0.001) with increased prescriptions of statin (p<0.001) and dual anti-platelet therapy (<0.001). In parallel with increased anticoagulation use across the study period (p<0.001), the 2-year recurrence of AF-related stroke reduced from 18.9% to 6% (p<0.001). Conclusion: Etiology-based risk factor control might have led to the diminishing stroke incidences related to atherosclerosis. To tackle the surge of AF-related strokes, arrhythmia screening, anticoagulation usage and mechanical thrombectomy service should be reinforced. Comparable preventive strategies might alleviate the enormous stroke burden in mainland China.

scholarly journals Online database for brain cancer-implicated genes: exploring the subtype-specific mechanisms of brain cancer

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Min Zhao ◽  
Yining Liu ◽  
Guiqiong Ding ◽  
Dacheng Qu ◽  
Hong Qu
Keyword(s):  
Brain Cancer ◽  
Differential Expression Analysis ◽  
Survival Rates ◽  
Brain Regions ◽  
Solid Base ◽  
Cancer Subtypes ◽  
Human Genes ◽  
Subtype Identification ◽  
Genetic Mechanisms ◽  
Gene Database

Abstract Background Brain cancer is one of the eight most common cancers occurring in people aged 40+ and is the fifth-leading cause of cancer-related deaths for males aged 40–59. Accurate subtype identification is crucial for precise therapeutic treatment, which largely depends on understanding the biological pathways and regulatory mechanisms associated with different brain cancer subtypes. Unfortunately, the subtype-implicated genes that have been identified are scattered in thousands of published studies. So, systematic literature curation and cross-validation could provide a solid base for comparative genetic studies about major subtypes. Results Here, we constructed a literature-based brain cancer gene database (BCGene). In the current release, we have a collection of 1421 unique human genes gathered through an extensive manual examination of over 6000 PubMed abstracts. We comprehensively annotated those curated genes to facilitate biological pathway identification, cancer genomic comparison, and differential expression analysis in various anatomical brain regions. By curating cancer subtypes from the literature, our database provides a basis for exploring the common and unique genetic mechanisms among 40 brain cancer subtypes. By further prioritizing the relative importance of those curated genes in the development of brain cancer, we identified 33 top-ranked genes with evidence mentioned only once in the literature, which were significantly associated with survival rates in a combined dataset of 2997 brain cancer cases. Conclusion BCGene provides a useful tool for exploring the genetic mechanisms of and gene priorities in brain cancer. BCGene is freely available to academic users at http://soft.bioinfo-minzhao.org/bcgene/.

Stroke Risk of Asymptomatic Intra- and Extracranial Large-Artery Disease in Apparently Healthy Adults

2006 ◽  
Vol 22 (4) ◽  
pp. 263-270 ◽  
Author(s):  
Wakoh Takahashi ◽  
Tomohide Ohnuki ◽  
Michiru Ide ◽  
Shigeharu Takagi ◽  
Yukito Shinohara
Keyword(s):  
Stroke Risk ◽  
Healthy Adults ◽  
Large Artery ◽  
Artery Disease ◽  
Apparently Healthy

Abstract T P153: Women and Men with Ischemic Stroke in SiGN Have Different Subtype Distributions and Risk Factors

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Kathryn M Rexrode ◽  
Braxton D Mitchell ◽  
Kathleen A Ryan ◽  
Steven J Kittner ◽  
Hakan Ay ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Stroke Risk ◽  
Cardioembolic Stroke ◽  
Relative Distribution ◽  
Large Artery ◽  
Stroke Risk Factors ◽  
Stroke Subtypes ◽  
Small Artery Occlusion ◽  
Ischemic Stroke Risk

Introduction: The relative distribution of stroke risk factors, as well as ischemic stroke subtypes, in women compared with men is not well described. Hypothesis: We hypothesized that the distribution of ischemic stroke risk factors and subtypes would differ by sex, with a later onset in women and greater proportion of comorbidities. Methods: The NINDS Stroke Genetics Network (SiGN) consortium was established to evaluate genetic risk factors for ischemic stroke. A total of 23 separate studies performed Causative Classification of Stroke (CCS) typing using standardized criteria on ischemic stroke cases and contributed data on risk factors. We compared the distribution of ischemic stroke risk factors and CCS phenotypes between men and women with ischemic stroke. Results: Of the 16,228 ischemic strokes in SiGN, 8005 (49.3%) occurred in women. Median age at stroke was older in female than male stroke cases (73 vs. 66 years) (p=<0.0001). Among stroke cases, women were more likely than men cases to have hypertension or atrial fibrillation and less likely to have diabetes or coronary artery disease, or to smoke (p <0.003 for all). The distribution of stroke subtypes also differed by sex, with women less likely than men to have large artery infarction and small artery occlusion, and more likely to have cardioembolic stroke and undetermined stroke due to incomplete work-up (p values all <0.0001; see Table). Results were similar when the distribution of stroke subtypes was examined for those <70 years and ≥70 years, except for cardioembolic stroke remaining more common only among women ≥70. Conclusions: In this large group of carefully phenotyped ischemic strokes, the distribution of ischemic stroke subtypes and risk factor profiles differ significantly by sex. Evaluation of the causes of these differences may highlight areas for improved prevention and risk reduction in both genders.

scholarly journals Hypoxia Inducible Factor 1-α in Acute Ischemic Stroke: Good Predictor for Clinical Outcome

2019 ◽  
Author(s):  
Lisda Amalia ◽  
Yeremia Tatang ◽  
Henny Anggraini Sadeli ◽  
Ida Parwati ◽  
Ahmad Rizal ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Small Vessel Disease ◽  
Hypoxia Inducible Factor ◽  
Rank Test ◽  
Large Artery ◽  
Stroke Treatment ◽  
Nihss Score ◽  
Hypoxia Inducible Factor 1 ◽  
Angiogenesis Process

Abstract Background. Stroke is the third leading causes of death and can cause severe disability. Ischemic stroke has a higher prevalence compared to hemorrhage stroke. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor which maintains cellular homeostasis in response to hypoxia. It can trigger apoptosis while stimulating angiogenesis process and decrease neurological deficit after an ischemic stroke. However, this protein complex has not been widely investigated. Objective. Here, we examined the potential of HIF-1α as a marker for neuroplasticity process after ischemic stroke. Methods. Serum HIF-1α were measured in acute ischemic stroke patients. National Institute of Health Stroke Scale (NIHSS) were assessed on the admission and discharge day (between days 7 and 14). To classify the ischemic stroke, we used (Trial of Org 10172 in Acute Stroke Treatment) TOAST criteria. Statistical significances were calculated with Spearman rank test. Results. A total of 58 patients, 31 with large artery atherosclerosis LVD and 27 with small vessel disease (SVD) were included in this study. HIF-1α level in LVD group was (mean ± SD) 0.5225 ± 0.2459 mg/L and in SVD group was 0.3815 ± 0.121 mg/L. HIF-1α was higher (p = 0.004) in LVD group than in SVD group. The initial NIHSS score in LVD group was (mean ± SD) 15.46 ± 2.61 and discharge NIHSS score was 13.31 ± 3.449. Initial NIHSS score in SVD group was 6.07 ± 1.82 and the discharge NIHSS was 5.703 ± 1.7055. In LVD group, HIF-1α was correlated significantly with initial NIHSS (p = 0.0000) and discharge NIHSS (p = 0.0000, r = 0.93). This was also the case for SVD. We found a significant correlation between the level of HIF-1α with initial NIHSS (p = 0.0000) and discharge NIHSS (p = 0.0383) in SVD group (r = 0.94). Conclusion. HIF-1α has a strong correlation with NIHSS and it may be used as the predictor of acute ischemic stroke outcome.

Abstract TP124: 90-Day Disability Outcomes and Stroke Etiology: An ALIAS 2 Secondary Analysis

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Eric D Goldstein ◽  
Vivek K Reddy ◽  
Stephanie Lyden ◽  
Jennifer J Majersik ◽  
Adam de Havenon
Keyword(s):  
Univariate Analysis ◽  
Secondary Analysis ◽  
Large Artery ◽  
Logistic Regression Models ◽  
Stroke Etiology ◽  
Disability Outcome ◽  
Toast Classification ◽  
Iv Tpa ◽  
Toast Criteria

Background: Acute ischemic stroke (AIS) treatment remains a leading cause of global morbidity and mortality despite advancements in therapeutic options. Cardioembolic AIS had previously been associated with the greatest long-term disability and mortality. Our aim is to provide an updated perspective of 90-day disability outcomes with regard to stroke etiology. Methods: This is a secondary analysis of the ALIAS 2 trial. The primary outcome was the 90-day mRS. Stroke etiology was defined based on TOAST criteria. Spearman’s Rho is used to determine correlation between etiology and mRS. Univariate and multivariate logistic regression models are fit to a binary stratification of our outcome (mRS 0-1 vs 2-6). Results: A total of 776 patients were enrolled between 2009 and 2012 with a mean (SD) age of 64.7 (12.7) years. The median (IQR) NIHSS was 11 (8, 17) with 55.3% being male, 76.7% white, and 89.7% having received IV TPA. Large artery atherosclerosis (LAA) (201/776, 25.9%), cardioembolism (271/776, 34.9%) and cryptogenic (196/776, 25.3%) were the most common AIS etiologies. The 90-day mRS had significant differences by TOAST category (rho = 0.013, p<0.001). Individuals with LAA had the highest mean 90-day mRS (Figure 1). LAA was associated with lower odds of good outcome in both univariate analysis (OR 0.68, 95% CI 0.48-0.96) and in a multivariate model (OR 0.66, 95% CI 0.45-0.97) adjusted for age, NIHSS, diabetes, hypertension, hyperlipidemia, sex, white race and administration of IV TPA. Conclusion: Our secondary analysis revealed that AIS with a NIHSS greater than 8 of LAA origin purported a worse 90-day disability outcome. This data may serve to remind clinicians that AIS from LAA may yield comparable or greater disability than cardioembolic AIS. Figure 1: Mean 90-day disability outcome based on TOAST classification. LAA purported worse mean disability outcomes compared to other grouped etiologies.

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