Relationship between Methylenetetrahydrofolate Reductase C677T Homozygous Mutation and Cerebral Small Vessel Disease Subtypes

Background: Neuroimaging detects cerebral small vessel disease (CSVD) subtypes, including infarction, asymptomatic lacunes, cerebral microbleeds, white matter hyperintensities (WMHs), and enlarged perivascular space. Methylenetetrahydrofolate reductase (MTHFR) plays an essential role in the metabolism of folic acid and homocysteine. The purpose of this study was to investigate the relationship between the MTHFR C677T mutation and CSVD subtypes.Methods: A total of 144 patients with acute ischemic stroke who visited the Korea University Guro Hospital between April 2020 and August 2020 were retrospectively reviewed. After excluding 24 patients, due to missing laboratory, clinical, or imaging information, a total of 120 patients were analyzed.Results: Among the 120 participants, 25% were included in the MTHFR C677T homozygous mutation group, which had significantly lower folic acid levels (6.24±4.21 ng/mL vs. 8.24±4.21 ng/mL, p=0.03) and higher total homocysteine levels (17.09±14.07 μmol/L vs. 9.65±3.19 μmol/L, p<0.01). Using multiple logistic regression analysis, the homozygous mutation (adjusted odds ratio [aOR]=4.29; 95% confidence interval [CI]=1.16–15.90) and age (aOR=1.06; 95% CI=1.01–1.11) were independently associated with moderate to severe WMHs. Additionally, moderate to severe WMHs were more frequent in the homozygous mutation group (86.7% vs. 66.7%, p=0.01). In a detailed analysis, the homozygous mutation group showed a significantly higher rate of moderate to severe periventricular WMH (PWMH) (86.7% vs. 65.6%, p<0.01).Conclusion: The MTHFR C677T homozygous mutation was positively correlated with moderate to severe PWMH subtypes of CSVD.

Download Full-text

Association of Serum Interleukin-34 and Insulin Resistance with Cognitive Impairment in Patients with Cerebral Small Vessel Disease

Current Neurovascular Research ◽

10.2174/1567202618666211110113323 ◽

2021 ◽

Vol 18 ◽

Author(s):

TianTian Jiang ◽

Yong Zhou ◽

Dongmei Zhang ◽

Zhiyong Cao ◽

Laifang Bian ◽

...

Keyword(s):

Insulin Resistance ◽

Cognitive Impairment ◽

Roc Curve ◽

Small Vessel Disease ◽

Multiple Logistic Regression Analysis ◽

Serum Levels ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

Tyg Index

Objective: Insulin resistance (IR) is a key pathological process during the development of cerebral small vessel disease (CSVD) and vascular cognitive impairment (VCI). The triglyceride-glucose in-dex(TyG index) is considered as a novel marker of insulin resistance and can represent peripheral tissue insulin sensitivity. Interleukin-34(IL-34) is a cytokine of the short-chain helical hematopoietic cytokine family and recent studies have shown that it's serum levels may represent an important biomarker for atherosclerosis. Here, we aimed to investigate whether the TyG index and serum IL-34 levels were re-lated to VCI in patients with CSVD. Method: This study included a total of 280 CSVD patients. TyG index, clinical baseline data, and fast-ed venous blood for quantification serum levels of IL-34 were acquired within 24 hours of admission. Multiple logistic regression analysis was applied to analyze the association between potential risk fac-tors and VCI, and receiver operator characteristic(ROC) curve was used to evaluate the diagnostic value of IL-34, TyG index, and their combination for detecting VCI. Results: Among all included CSVD patients, 166 patients (59.3%) were diagnosed with VCI based on the cognitive function scale (MOCA). After adjusting for confounding factors, serum IL-34 levels and TyG index were independently associated with VCI (P<0.05). Using ROC curve analysis, the optimal thresholds for identification of VCI based on serum IL-34 levels and TyG index were 41.57pg/ml (area under the curve (AUC): 0.723; sensitivity 76.5%; specificity 64%) and 3.94(AUC:0.727; sensitivity 72.3%; specificity 62.3%), respectively. Conclusion: This study demonstrated that IL-34 and TyG index are closely associated with VCI in CSVD patients and may represent clinical therapeutic targets for CSVD.

Download Full-text

Association of MTHFR C677T Genotype With Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype

Stroke ◽

10.1161/strokeaha.115.011545 ◽

2016 ◽

Vol 47 (3) ◽

pp. 646-651 ◽

Cited By ~ 29

Author(s):

Loes C.A. Rutten-Jacobs ◽

Matthew Traylor ◽

Poneh Adib-Samii ◽

Vincent Thijs ◽

Cathie Sudlow ◽

...

Keyword(s):

Ischemic Stroke ◽

Small Vessel Disease ◽

Mthfr C677t ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

Disease Subtype

Download Full-text

Effects of rosuvastatin in combination with nimodipine in patients with mild cognitive impairment caused by cerebral small vessel disease

Panminerva Medica ◽

10.23736/s0031-0808.18.03475-4 ◽

2020 ◽

Vol 61 (4) ◽

Author(s):

Junling Zhang ◽

Nannuan Liu ◽

Chaoqun Yang

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease

Download Full-text

Faculty Opinions recommendation of Blood brain barrier breakdown as the starting point of cerebral small vessel disease? - New insights from a rat model.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718270093.793491297 ◽

2014 ◽

Author(s):

Mark Fisher ◽

Rachita Sumbria

Keyword(s):

Blood Brain Barrier ◽

Rat Model ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Brain Barrier ◽

Small Vessel ◽

Vessel Disease ◽

Starting Point ◽

Barrier Breakdown ◽

Blood Brain Barrier Breakdown

Download Full-text

Cerebral small vessel disease or intracranial large vessel atherosclerosis may carry different risk for future strokes

Stroke and Vascular Neurology ◽

10.1136/svn-2019-000305 ◽

2020 ◽

Vol 5 (2) ◽

pp. 128-137

Author(s):

Huimin Chen ◽

Yuesong Pan ◽

Lixia Zong ◽

Jing Jing ◽

Xia Meng ◽

...

Keyword(s):

Regression Models ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Arterial Stenosis ◽

Small Vessel ◽

Minor Stroke ◽

Bleeding Events ◽

Stroke Outcomes ◽

Vessel Disease ◽

Increased Risk

BackgroundThe effect of cerebral small vessel disease (CSVD) and intracranial arterial stenosis (ICAS) on stroke outcomes remains unclear.MethodsData of 1045 patients with minor stroke or transient ischaemic attack (TIA) were obtained from 45 sites of the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. We assessed the associations of burdens of CSVD and ICAS with new strokes and bleeding events using multivariate Cox regression models and those with modified Rankin Scale (mRS) scores using ordinal logistic regression models.ResultsAmong the 1045 patients, CSVD was present in 830 cases (79.4%) and ICAS in 460 (44.0%). Patients with >1 ICAS segment showed the highest risk of new strokes (HR 2.03, 95% CI 1.15 to 3.56, p=0.01). No association between CSVD and the occurrence of new strokes was found. The presence of severe CSVD (common OR (cOR) 2.01, 95% CI 1.40 to 2.89, p<0.001) and >1 ICAS segment (cOR 2.15, 95% CI 1.57 to 2.93, p<0.001) was associated with higher mRS scores. Severe CSVD (HR 10.70, 95% CI 1.16 to 99.04, p=0.04), but not ICAS, was associated with a higher risk of bleeding events. Six-point modified CSVD score improved the predictive power for bleeding events and disability.InterpretationCSVD is associated with more disability and bleeding events, and ICAS is associated with an increased risk of stroke and disability in patients with minor stroke and TIA at 3 months. CSVD and ICAS may represent different vascular pathologies and play distinct roles in stroke outcomes.Trial registration numberNCT00979589

Download Full-text

Lenticulostriate artery combined with neuroimaging markers of cerebral small vessel disease differentiate the pathogenesis of recent subcortical infarction

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x21992622 ◽

2021 ◽

pp. 0271678X2199262

Author(s):

Shuai Jiang ◽

Tian Cao ◽

Yuying Yan ◽

Tang Yang ◽

Ye Yuan ◽

...

Keyword(s):

Magnetic Resonance ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

Branch Atheromatous Disease ◽

Lenticulostriate Artery ◽

Subcortical Infarction

Recent subcortical infarction (RSI) in the lenticulostriate artery (LSA) territory with a non-stenotic middle cerebral artery is a heterogeneous entity. We aimed to investigate the role of LSA combined with neuroimaging markers of cerebral small vessel disease (CSVD) in differentiating the pathogenic subtypes of RSI by whole-brain vessel-wall magnetic resonance imaging (WB-VWI). Fifty-two RSI patients without relevant middle cerebral artery (MCA) stenosis on magnetic resonance angiography were prospectively enrolled. RSI was dichotomized as branch atheromatous disease (BAD; a culprit plaque located adjacent to the LSA origin) (n = 34) and CSVD-related lacunar infarction (CSVD-related LI; without plaque or plaque located distal to the LSA origin) (n = 18). Logistic regression analysis showed lacunes (odds ratio [OR] 9.68, 95% confidence interval [CI] 1.71–54.72; P = 0.010) and smaller number of LSA branches (OR 0.59, 95% CI 0.36–0.96; P = 0.034) were associated with of BAD, whereas severe deep white matter hyperintensities (DWMH) (OR 0.11, 95% CI 0.02–0.71; P = 0.021) was associated with CSVD-related LI. In conclusion, the LSA branches combined with lacunes and severe DWMH may delineate subtypes of SSI. The WB-VWI technique could be a credible tool for delineating the heterogeneous entity of SSI in the LSA territory.

Download Full-text

Genotype–phenotype correlations of heterozygous HTRA1-related cerebral small vessel disease: case report and systematic review

Neurogenetics ◽

10.1007/s10048-021-00646-5 ◽

2021 ◽

Author(s):

Haohan Zhang ◽

Xiaoming Qin ◽

Yingying Shi ◽

Xinya Gao ◽

Fengyu Wang ◽

...

Keyword(s):

Systematic Review ◽

Case Report ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

Disease Case

Download Full-text

Total Cerebral Small Vessel Disease Score and Anthropometric Indices: A Population-Based Study in Older Adults of Amerindian Ancestry

European Neurology ◽

10.1159/000517915 ◽

2021 ◽

pp. 1-4

Author(s):

Oscar H. Del Brutto ◽

Robertino M. Mera

Keyword(s):

Older Adults ◽

Small Vessel Disease ◽

Brain Magnetic Resonance Imaging ◽

Population Based ◽

Cerebral Small Vessel Disease ◽

The Body ◽

Small Vessel ◽

Population Based Study ◽

Vessel Disease ◽

Ordinal Logistic Regression Model

A total of 590 older adults of Amerindian ancestry living in rural Ecuador received anthropometric measurements and a brain magnetic resonance imaging to estimate the total cerebral small vessel disease (cSVD) score. A fully adjusted ordinal logistic regression model, with categories of the total cSVD score as the dependent variable, disclosed significant associations between the waist circumference, the waist-to-hip, and the waist-to-height ratios – but not the body mass index (BMI) – and the cSVD burden. Indices of abdominal obesity may better correlate with severity of cSVD than the BMI in Amerindians. Phenotypic characteristics of this population may account for these results.

Download Full-text