NOTCH3 cysteine-altering variant is an important risk factor for stroke in the Taiwanese population

Neurology ◽  
2019 ◽  
Vol 94 (1) ◽  
pp. e87-e96 ◽  
Author(s):  
Yi-Chung Lee ◽  
Chih-Ping Chung ◽  
Ming-Hong Chang ◽  
Shuu-Jiun Wang ◽  
Yi-Chu Liao
Keyword(s):  
Risk Factor ◽  
Ischemic Stroke ◽  
Clinical Manifestations ◽  
White Matter Lesions ◽  
Reference Population ◽  
Important Risk Factor ◽  
Vessel Occlusion ◽  
Asian Populations ◽  
Modifying Factors ◽  
Increased Risk

ObjectiveTo test the hypothesis that the prevalence and clinical effect of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) have been underestimated in Asian populations.MethodsThe Taiwan Biobank, containing 1,517 Taiwanese genome sequences, was queried for pathogenic NOTCH3 cysteine-altering mutations. NOTCH3 mutations identified in the reference population were genotyped in 7,038 stroke- and dementia-free individuals and 800 patients with ischemic stroke. NOTCH3 genotyping, clinical manifestations, and the severity of white matter lesions on MRI were compared between the 2 groups.ResultsThree cysteine-altering NOTCH3 variants (p.R544C, p.C853Y, and p.C884Y) were identified from the Taiwan Biobank. We confirmed that the NOTCH3 p.R544C mutation was present in a significant number of individuals in Taiwan, including 60 of the 7,038 healthy controls (0.9%), 17 of the 800 patients with ischemic stroke (2.1%), and 16 of the 245 patients with small vessel occlusion (SVO) stroke (6.5%). The other 2 cysteine-altering mutations were rarely detected. After adjusting for vascular risk factors, harboring the p.R544C variant resulted in a 3.40-fold increased risk for overall stroke and an 11.05-fold increased risk for SVO stroke (p = 0.0001 and 3.9 × 10−10, respectively). Three symptom-free individuals carrying the p.R544C mutation had extensive leukoencephalopathy typical of CADASIL at age 59, 66, and 67, suggesting that p.R544C-related CADASIL could remain subclinical at advanced age.ConclusionThe NOTCH3 p.R544C variant is an important risk factor for SVO stroke in Taiwan. Phenotypic variation among individuals carrying a NOTCH3 mutation indicates the existence of disease-modifying factors in CADASIL.

MO765CENTRAL VEIN STENOSES IN HD PATIENTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Aleksei Zulkarnaev ◽  
Andrey Vatazin ◽  
Vadim Stepanov ◽  
Ekaterina Parshina ◽  
Mariya Novoseltseva
Keyword(s):  
Risk Factor ◽  
Vascular Access ◽  
Dwell Time ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Cox Proportional Hazards ◽  
Important Risk Factor ◽  
Central Vein ◽  
Increased Risk ◽  
The Mean

Abstract Background and Aims The prevalence of central vein stenosis (CVS) in patients on hemodialysis (HD) is difficult to be assessed directly. This is mainly caused by the variety of clinical signs and the high frequency of asymptomatic CVS. Aim: to assess the frequency of occurrence of various CVS forms in HD patients. Method The retrospective observational study is based on the results of treatment of 1865 HD patients who underwent diagnostic and therapeutic procedures on vascular access in our center. In case of vascular access dysfunction, patients were examined according to a local protocol: ultrasound of the peripheral (to exclude lesion of peripheral AVF segments) and central veins (over the available length), followed with CT-angiography or percutaneous angiography, if necessary. Results AVF/AVG dysfunction was observed in 29.4% of patients (549 of 1865). 211 patients were diagnosed with CVS. The prevalence of CVS was 11.3% (211 of 1865) among all HD patients and 38.4% (211 of 549) in patients with AVF dysfunction. Among patients with CVS, 37% (78 of 211) had vein lesions without clinical symptoms or with minimal manifestations (a tendency to decrease KT/V). The prevalence of asymptomatic CVS was 4.2% (78 of 1865) in the general population of HD patients and 14.2% (78 of 549) in patients with AVF dysfunction. In case of asymptomatic CVS it was detected by an ultrasound examination during CVC implantation (N=38), during unsuccessful attempts to implant CVC (N=29), in the case of recurrent AVF thrombosis without underlying peripheral segments lesion (N=9) or during echocardiography (N=2). The prevalence of asymptomatic CVS among patients without AVF dysfunction was 5.9% (78 of 1316). True prevalence of subclinical CVS among HD patients without obvious signs of AVF dysfunction may vary widely. A total of 48.8% (103 of 211) of all CVS cases were treated. At the same time, in 10.7% (11 of 103) of cases, patients did not present symptoms of CVS, and surgery was performed due to recurrent AVF thrombosis without damage of the peripheral parts of AVF. Patients with clinically manifest CVS who received endovascular interventions had a significantly higher risk of AVF loss compared to patients with asymptomatic CVS: HR=2.566 [95% CI 1.706; 3.86], log rank p<0.0001. However, patients with an asymptomatic CVS had a higher risk of AVF function loss compared to the general HD population (HR=2,051 [95% CI 1,243; 3,384], log rank p= 0.0004) – fig. 1. The use of CVC is a known risk factor of CVS development. We analyzed the relationship of CVS risk with multiply CVC placements and catheter dwell time using the Cox proportional hazards regression model (fig. 2). In the univariate model, a greater No of CVCs as well as longer time in place increased the risk of CVS. In the multivariate model (χ2=105.516, df=2, p<0.0001), catheter dwell time was no longer associated with an increased risk of CVC, while the mean number of inserted catheters remained an important risk factor. Conclusion The prevalence of both symptomatic and asymptomatic forms of CVS in HD patients is high. Patients with vascular access dysfunction should be carefully examined to identify the asymptomatic CVS. The mean No of catheterizations is a more important risk factor of CVS than longer catheter dwell time.

scholarly journals Complex method of the prognosis of tick-born neuroinfections

2008 ◽  
Vol 7 (5-2) ◽  
pp. 420-423
Author(s):  
A. V. Subbotin ◽  
V. A. Semyonov ◽  
I. Yu. Torshin ◽  
O. A. Gromova ◽  
Ye. V. Fyodorova ◽  
...  
Keyword(s):  
Immune Response ◽  
Risk Factor ◽  
Catalytic Activity ◽  
Rna Viruses ◽  
Clinical Manifestations ◽  
Important Risk Factor ◽  
Biochemical Data ◽  
Complex Method ◽  
Gene Coding ◽  
Tick Borne Encephalitis

Here, we propose a method of forecasting the development of the heavy forms of the tick-borne encephalitis using diagnostic tables. The method is based on evaluation of the patients with syndrome of endogenous intoxication using immunological and biochemical data along with evaluation of the clinical manifestations. We also propose an advanced form of the method that includes data based on the genotype of OAS1 — the gene, coding oligonucleotidesynthetase needed for immune response to RNA viruses. OAS1 genotype is an important risk factor since the differences in catalytic activity of OAS1 isoenzymes result in different susceptibility to the virus of the tick-borne encephalitis.

Abstract WP24: Arterial Tortuosity is a Potent Determinant of Safety in Endovascular Therapy for Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
David S Liebeskind ◽  
Geoffrey P Colby ◽  
Nils H Mueller-Kronast ◽  
M A Aziz-Sultan ◽  
Richard P Klucznik ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Therapy ◽  
Mechanical Thrombectomy ◽  
Cerebral Arteries ◽  
Vessel Occlusion ◽  
Systematic Analysis ◽  
Arterial Tortuosity ◽  
Increased Risk ◽  
Multivariate Prediction ◽  
Arterial Anatomy

Background: Subarachnoid hemorrhage (SAH) associated with vessel injury during endovascular therapy for acute ischemic stroke is a known complication. Arterial anatomy may predispose to increased risk of SAH and technical safety, yet factors such as clot location, arterial size and tortuosity have not been explored. We examined these anatomical factors with respect to SAH during thrombectomy. Methods: Arterial anatomy at the site of occlusion and mechanical thrombectomy during device deployment was detailed by the STRATIS core lab. Luminal diameters, arterial branching and segmental tortuosity were measured. Arterial tortuosity was quantified using the distance factor metric (DFM). Statistical analyses included descriptives of arterial anatomy, with univariate and multivariate modeling to predict SAH. Results: Arterial tortuosity in each segment from the proximal cerebral arteries to the site of occlusion was quantified in 790 subjects treated with mechanical thrombectomy in STRATIS. Cumulative arterial tortuosity to the site of vessel occlusion was greater in distal lesions (Table 1). SAH was clearly linked with more distal thrombectomy (p=0.017), with 19.0% of distal M2, 16.7% of M3, 7.3% of distal M1, 5.8% of proximal M2, 2.4% of distal ICA and 2.1% of proximal M1. Multivariate prediction of SAH revealed that arterial diameter was unrelated to SAH (p=0.30) when accounting for tortuosity, whereas the presence of tortuosity tripled the risk of SAH (OR 3, p<0.05). Conclusions: This novel systematic analysis of arterial tortuosity and angiographic anatomy during mechanical thrombectomy establishes tortuosity as a determinant of SAH, providing insight for future techniques and innovative device designs.

scholarly journals RNF213 variation, a broader role in neurovascular disease in Caucasian and Japanese populations

2020 ◽  
Author(s):  
Oswaldo Lorenzo-Betancor ◽  
Patrick R. Blackburn ◽  
Luca Farrugia ◽  
Alexandra I. Soto-Beasley ◽  
Ronald L. Walton ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Genome Wide Association Study ◽  
Ring Finger ◽  
Missense Variant ◽  
Genetic Mutation ◽  
Caucasian Population ◽  
Young Onset ◽  
Asian Populations ◽  
Increased Risk ◽  
D Values

AbstractMoyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease that predominantly affects East Asian populations. The major genetic mutation associated with MMD in Asian populations is the p.R4810K substitution in Ring Finger Protein 213 (RNF213). Interestingly, variants in the RNF213 gene have also been implicated in intracranial aneurysms (IA) in French-Canadian population, suggesting that variation in this gene may play a broader role in cerebrovascular phenotypes. In a recent genome-wide association study (GWAS) in a Caucasian population, variants rs6565653 and rs12601526 in the Solute Carrier Family 26 Member 11 (SLC26A11) gene, which is less than 10kb away from RNF213, showed a suggestive association with young onset ischemic stroke. We propose that the signal could be tagging an association with common variation in the RNF213 gene. We analyzed the linkage disequilibrium (LD) pattern in the SLC26A11-RNF213 gene region and we observed a high LD between variants in this region based on D’ values. We show that SLC26A11 rs6565653 variant tags RNF213 rs12944088, a missense variant that is more common among subjects with IA than in healthy individuals. Given the fact that rs6565653 tags several RNF213 variants, it is highly likely that some of these tagged variants modify the risk of suffering stroke. The LD analyses suggest that the SLC26A11 signal from the young onset ischemic stroke GWAS performed in a Caucasian population is also tagging variation at the RNF213 loci, supporting the hypothesis that RNF213 variation may result in a variety of neurovascular disorders including an increased risk and/or worse prognosis following ischemic stroke in Caucasian population.

Migraine, stroke, and the heart

2020 ◽  
pp. 98-109
Author(s):  
Simona Sacco ◽  
Antonio Carolei
Keyword(s):  
Risk Factor ◽  
Migraine Attack ◽  
Patent Foramen Ovale ◽  
Heart Diseases ◽  
Clinical Manifestations ◽  
Vascular Events ◽  
Increased Risk ◽  
Genetically Determined ◽  
Relationship Of ◽  
The Relationship

Accumulating data have linked migraine to cerebrovascular and heart diseases. The relationship between migraine and stroke is complex and bidirectional. A stroke, either ischaemic or haemorrhagic, may produce symptoms mimicking a migraine attack; a migraine attack may mimic a stroke; migraine may be directly associated with an ischaemic stroke (migrainous infarction); migraine may represent a risk factor for stroke; several diseases, mostly genetically determined, include among their clinical manifestations attacks of migraine and stroke; lastly, migraine has been associated with subclinical infarct-like brain lesions and white matter hyperintensities. The risk of cardiac vascular events in migraineurs varies greatly among studies, ranging from a lower-than-average to a moderately increased risk as suggested by the most recent data. Initial evidence also suggested an association between migraine and patent foramen ovale, but this possibility has been recently challenged. The mechanisms underlying the relationship of migraine with cerebrovascular and cardiovascular diseases are still cryptic and rather complex. In migraineurs, a heightened vigilance toward some comorbid risk factor is warranted together with caution in prescribing oral contraceptives.

Risk of Surgery and Anesthesia for Ischemic Stroke

2000 ◽  
Vol 92 (2) ◽  
pp. 425-425 ◽  
Author(s):  
Gilbert Y. Wong ◽  
David O. Warner ◽  
Darrell R. Schroeder ◽  
Kenneth P. Offord ◽  
Mark A. Warner ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Ischemic Stroke ◽  
High Risk ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Independent Risk Factor ◽  
Index Date ◽  
Stroke Index ◽  
Increased Risk

Background The goal of this study was to determine if the combination of surgery and anesthesia is an independent risk factor for the development of incident (first-time) ischemic stroke. Methods All residents of Rochester, MN, with incident ischemic stroke from 1960 through 1984 (1,455 cases and 1,455 age- and gender-matched controls) were used to identify risk factors associated with ischemic stroke. Cases and controls undergoing surgery involving general anesthesia or central neuroaxis blockade before their stroke/index date of diagnosis were identified. A conditional logistic regression model was used to estimate the odds ratio of surgery and anesthesia for ischemic stroke while adjusting for other known risk factors. Results There were 59 cases and 17 controls having surgery within 30 days before their stroke/index date. After adjusting for previously identified risk factors, surgery within 30 days before the stroke/index date (perioperative period) was found to be an independent risk factor for stroke (P&lt;0.001; odds ratio, 3.9; 95% confidence interval, 2.1-7.4). In an analysis that excluded matched pairs where the case and/or control underwent surgery considered "high risk" for stroke (cardiac, neurologic, or vascular procedures), "non-high-risk surgery" was also found to be an independent risk factor for perioperative stroke (P = 0.002; odds ratio, 2.9; 95% confidence interval, 1.5-5.7). Conclusion Our results suggest that there is an increased risk of ischemic stroke in the 30 days after surgery and anesthesia. This risk remains elevated even after excluding surgeries (cardiac, neurologic, and vascular surgeries) considered to be high risk for ischemic stroke.

scholarly journals Risk Stratification Tool for Ischemic Stroke: A Risk Assessment Model Based on Traditional Risk Factors Combined With White Matter Lesions and Retinal Vascular Caliber

2021 ◽  
Vol 12 ◽  
Author(s):  
Lu Zhao ◽  
Bin Jiang ◽  
Hongyang Li ◽  
Xiufen Yang ◽  
Xiaoyue Cheng ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Risk Factor ◽  
Ischemic Stroke ◽  
White Matter ◽  
White Matter Lesions ◽  
Traditional Risk Factor ◽  
Assessment Model ◽  
Risk Assessment Model ◽  
Retinal Vascular Caliber ◽  
Traditional Risk Factors

Objective: This study aims to establish a risk assessment model based on traditional risk factors combined with the Fazekas classification of white matter lesions and retinal vascular caliber for screening the patients at high risk of ischemic stroke.Methods: This study included 296 patients (128 cases of ischemic stroke and 168 cases in the normal control group). The basic data of the patients were collected. Color fundus photography was performed after pupil dilation, and the retinal vascular caliber was measured using semiautomated vascular measurement software (IVAN Software, Sydney, Australia). The severity of white matter lesions (WML) on cranial nuclear magnetic fluid-attenuated inversion recovery images were assessed using the Fazekas scale. Moreover, logistic regression analysis was used to establish different risk assessment models for ischemic stroke. The effects of models were evaluated through the receiver operating characteristic (ROC) curve and the Delong test compared area under the curve.Results: The sensitivity and specificity of models 1 (the traditional risk factor model), 2 (the retinal vascular caliber model), 3 (the WML model), and 4 (the combined the traditional risk factor, WML and central retinal artery equivalent (CRAE) model) were 71 and 55%, 48 and 71%, 49 and 67%, and 68 and 68.5% with areas under the curve of 0.658, 0.586, 0.601, and 0.708, respectively. The area under the receiver operating characteristic curve in models 1, 2, 3, and 4 showed statistically significant differences. Moreover, no statistical significance exists in the pairwise comparison of other models.Conclusion: The risk assessment model of ischemic stroke combined with Fazekas grade of WML and CRAE is superior to the traditional risk factor and the single-index model. This model is helpful for risk stratification of high-risk stroke patients.

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