The relationship between homocysteine, cognition and stroke subtypes in acute stroke

BACKGROUND: Elevations in plasma homocysteine (Hcy) have been associated with an increased risk of stroke and dementia. The mechanisms underlying these associations remain poorly understood. OBJECTIVES: This study examines the relationships between Hcy, cognition, and stroke subtype. We hypothesize that: 1) Hcy levels are inversely related to cognition, 2) Hcy levels are unrelated to stroke subtype, and 3) stroke subtype affects cognition. METHODS: We studied 169 consenting patients admitted for acute stroke during a 4 month period. Blood was drawn for Hcy levels and the Mini-Mental State Examination (MMSE) was administered within 9 days of admission. The Oxfordshire Community Stroke Project Classification was used to characterize stroke subtypes. Correlation between Hcy and MMSE scores was examined as was the relationships between Hcy and stroke subtype, and between stroke subtypes and MMSE scores. RESULTS: A significant inverse correlation between Hcy levels and MMSE scores was demonstrated (r=-0.243, p=0.001). MMSE scores also differed according to the type of stroke, with Total or Partial Anterior Circulation Infarcts (TACI/PACI) scoring lowest (F=8.77, df=2, p<0.001). Hcy levels did not differ between the various stroke subtypes (F=0.21, df=2, p=0.81). Multivariate linear regression analysis showed that age, education, and stroke subtype, but not Hcy, were independent predictors of acute MMSE scores. CONCLUSIONS: In this study sample, there was an inverse relationship between Hcy and cognition in acute stroke patients. However, Hcy was not an independent predictor for cognition in acute stroke after other factors such as stroke subtype and patient age were taken into account. These results suggest that during the acute stage of stroke, stroke subtype is a more important factor in determining cognition than Hcy levels.     

Plasma endothelin-1 levels neither increase nor correlate with neurological scores, stroke risk factors, or outcome in patients with ischemic stroke

BACKGROUND AND PURPOSE: Endothelins (ETs) are potent vasoconstrictors and may play a role in the pathophysiology of several diseases. Limited and controversial data exist on their role in human ischemic stroke. We planned a prospective, observational, and longitudinal clinical study to test whether ET-1 levels increase in various phases of ischemic stroke and whether the ET-1 levels correlate with neurological scores, stroke etiology, stroke risk factors, or final outcome. METHODS: We measured plasma ET-1 levels with a sandwich-enzyme immunoassay method in 101 consecutive patients with ischemic stroke on admission and 1 week, 1 month, and 3 months after stroke and in 101 sex- and age-matched control subjects. At each sampling, the patients underwent a complete neurological evaluation. All stroke risk factors were recorded, an array of laboratory tests were performed, and the subtype of ischemic stroke was determined. The patients were contacted 3 years later for prognostic determination. RESULTS: ET-1 levels in patients (2.4+/-1.3 pg/mL on admission, 2.2+/-1.4 pg/mL at 1 week, 2.1+/-1.4 pg/mL at 1 month, and 2.1+/-1.2 pg/mL at 3 months) were not different from those of the control subjects (2.2+/-0.9 pg/mL) at any time point. No correlation was found between the ET-1 levels and stroke etiology, stroke risk factors, stroke recurrence risk, age, sex, or neurological scores, except that ET-1 levels correlated with the use of warfarin and with body mass index. CONCLUSIONS: Plasma ET-1 levels were normal in patients with ischemic stroke. Our findings cannot exclude a role of ETs in the pathophysiology of ischemic stroke because plasma levels might not accurately reflect intracerebral concentrations, but they also do not support the occurrence of a major plasma ET-1 level increase at any phase of stroke. Our patient population is the largest ever reported in whom ET-1 levels were measured, but it consisted of mild and moderately ill patients with stroke due to the study design, of which the aim was long-term observation, which excludes severely ill patients.     

Natural anticoagulants (antithrombin III, protein C, and protein S) in patients with mild to moderate ischemic stroke

BACKGROUND AND PURPOSE: The role of the natural anticoagulants, antithrombin III (AT III), protein C (PC), and protein S (PS), in patients with mild to moderate ischemic stroke remains uncertain. We aimed to find out whether their levels in peripheral blood correlated with the severity of neurological deficit or can predict clinical outcome and recurrence. METHODS: We studied AT III, PC, and free PS levels in 55 consecutive patients likely to survive the study period on admission, 1 week, 1 month and 3 months after a first-ever ischemic stroke. Sex- and age-matched controls were studied once. All patients underwent a full neurological examination and blood sampling at each study time point; comprehensive stroke risk factors were recorded, and the etiology of the ischemic stroke was determined. All patients were contacted 3 years later for possible recurrent ischemic events. RESULTS: AT III level was found to be significantly lower at all time points after stroke; PC level was significantly increased on admission and normal at subsequent measurements, and PS level was normal on admission but significantly decreased later. The levels of the natural anticoagulants did not correlate with the etiology of stroke, any stroke risk factor, or neurological scores, except that the AT III level on admission showed significant correlation with stroke severity and disability at 3 months. Natural anticoagulant levels did not predict recurrence of ischemic stroke. CONCLUSIONS: The measurements of the level of AT III, PC, or PS did not deliver useful information for management of patients with mild or moderate ischemic stroke, expect that AT III level on admission might predict outcome.     

脑出血患者血清脑源性神经营养因子与痴呆的相关性分析

目的探讨脑出血患者血清脑源性神经营养因子(BDNF)与痴呆的相关性。方法选取180例脑出血患者,出院后6个月根据认知功能评分分为血管性认知功能障碍组(VCI)60例,其中血管性痴呆组(VD)22例,非痴呆型血管性认知功能障碍组(VCIND)38例;对照组为无认知障碍者120例。入院后及出院后6个月采用酶联免疫吸附法(ELISA)检测血清BDNF水平,分析其与认知功能障碍的相关性。采用ROC曲线分析BDNF对VCI发生的预测价值。结果VCI组年龄、NIHSS评分、出血量、出血部位、Hcy水平及BDNF水平与对照组比较差异有统计学意义(P<0.05)。多因素分析示高龄、NIHSS评分高、大量出血、脑叶出血、Hcy水平升高及BDNF水平降低是脑出血患者发生VCI的危险因素(P<0.05)。出院时6个月VCIND组与对照组MMSE评分、BDNF水平均高于入院时(P<0.05)。出院后6个月VD组BDNF水平高于入院时(P<0.05)。出院后6个月3组MMSE评分比较差异有统计学意义(P<0.05),两两比较,VD组与VCIND组MMSE评分低于对照组(P<0.05),VD组MMSE评分低于VCIND组(P<0.05)。入院时及出院后6个月3组BDNF水平比较差异有统计学意义(P<0.05),两两比较,入院时及出院后6个月VD组与VCIND组BDNF水平均低于对照组(P<0.05),VD组BDNF水平低于VCIND组(P<0.05)。出院后6个月BDNF水平与MMSE评分呈正相关(P<0.05)。BDNF预测VD及预测VCIND的AUC面积分别为0.749、0.704,均>0.7,灵敏度分别为84.2%、85.9%,特异度分别为80.9%、80.6%。结论脑出血患者血清BDNF水平与出血后VCI的发生相关,随着BDNF水平的降低,VCI严重程度随之增加,且入院后血清BDNF水平可以预测VCI的发生,特别是VD发生的标记物之一,临床上血清BDNF水平低的患者需引起重视。     

血清同型半胱氨酸、纤维蛋白原、胱抑素C水平与急性脑梗死患者NIHSS评分的相关性分析

目的 探讨入院时血清同型半胱氨酸（homocysteine，Hcy）、纤维蛋白原（fibrinogen，FIB）和胱抑素C （cystatin-C，Cys-C）水平与急性脑梗死患者NIHSS评分的关系。 方法 回顾性纳入2014年1月-2018年11月于任丘康济新图医院神经内科住院的急性脑梗死患者，依 据入院时NIHSS评分分为轻型组（NIHSS评分＜7分）、中型组（7分≤NIHSS评分＜15分）、重型组（NIHSS 评分≥15分）。比较三组间血清Hcy、FI B、Cys-C水平差异，进一步用Spearman相关分析评估血清Hcy、 FI B、Cys-C水平与NIHSS评分的关系。 结果 共纳入4468例患者，中位年龄65.00（65.00～72.00）岁，男性2765例（61.88%）。轻型组3943 例（88.25%），中型组441例（9.87%），重型组84例（1.88%）。三组间血清Hcy（P＜0.001）、FI B（P ＜0.001）、Cys-C（P =0.035）水平比较，整体差异有统计学意义；进一步两两比较发现，轻型组血清 Hcy、FI B和Cys-C水平均低于中型组和重型组。Spearman相关分析发现，血清Hcy（r =0.770，P＜0.001）、 FI B（r =0.440，P =0.003）、Cys-C（r =0.580，P＜0.001）水平与急性脑梗死患者NIHSS评分呈正相关。 结论 急性脑梗死患者血清Hcy、FI B、Cys-C水平与NIHSS评分呈正相关。     

急性缺血性卒中后抑郁的相关危险因素分析

目的探讨急性缺血性卒中后抑郁(PSD)的发生率及其相关危险因素。方法 185例经CT或MRI证实的急性缺血性卒中患者根据精神障碍诊断和统计手册第5版(DSM-V)标准和24项Hamilton抑郁量表(HAMD)评分分为PSD组和non-PSD组;分析PSD社会人口学资料、血管危险因素、相关生化指标、NIHSS、Barthel指数(BI)、MMSE等相关因素对PSD的影响。结果本组PSD发生率为40.54%(75例),主要以轻、中度抑郁为主;与non-PSD组比较,PSD组患者糖尿病发生率高(P=0.044),神经功能缺损程度重、日常生活活动能力差(P=0.000,P=0.001),MMSE评分降低(P=0.000),而超敏C-反应蛋白(hs-CRP)和同型半胱氨酸(Hcy)水平升高(P=0.000,P=0.006);其中BI、MMSE评分与HAMD评分呈负相关(均P0.05),而NIHSS评分、hs-CRP和Hcy与HAMD评分呈正相关(均P0.05);Logistic回归分析提示,低MMSE评分、高NIHSS评分及高hs-CRP和Hcy水平可能是急性缺血性PSD的独立危险因素。结论 PSD主要以轻、中度抑郁为主;PSD与糖尿病病史、认知功能障碍、神经功能缺损程度、hs-CRP和Hcy水平密切相关。     

Serum VEGF levels in acute ischaemic strokes are correlated with long-term prognosis

Background and purpose:  We investigated whether serum vascular endothelial growth factor (VEGF) levels in acute-stage ischaemic stroke patients with small vessel disease (SVD) or large vessel disease (LVD) are correlated with long-term prognoses, based on the difference in NIH Stroke Scale (NIHSS) scores between acute and chronic stages.
Methods:  From March 2007 to May 2008, we evaluated patients who experienced an ischaemic stroke for the first time, defined as SVD ( n  = 89) or LVD ( n  = 91) using the TOAST classification. Serum samples were taken immediately after admission (within 24 h of stroke onset) to evaluate VEGF levels. After 3 months, follow-up NIHSS scores were collected for all patients.
Results:  Serum VEGF levels in the acute stage (within 24 h of stroke onset) were higher in the LVD group than in the SVD group and were correlated with infarction volume. The increase in serum VEGF levels in the acute stage was proportional to an improved NIHSS score after 3 months. After adjustment for covariates, serum VEGF levels in the acute stage were still significantly correlated with the long-term prognosis of ischaemic stroke.
Conclusion:  Serum VEGF levels are correlated with long-term prognoses in acute ischaemic stroke patients.     

同型半胱氨酸及亚甲基四氢叶酸还原酶基因多态性与缺血性卒中的关系研究

目的探讨同型半胱氨酸(homocysteine,Hcy)水平及亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)基因多态性与缺血性卒中(ischemic stroke,IS)的关系,并分析Hcy与叶酸、Vit B_(12)之间的相关性。方法运用酶循环法和聚合酶链式反应(polymerase chain reaction,PCR)-芯片杂交法分别检测217例IS患者和223例对照者血浆Hcy与MTHFR C667T基因型,并对照分析两组的基因型频率和等位基因频率分布差异及血浆Hcy水平;运用免疫分析法检测两组中既往未服用过含叶酸和Vit B_(12)药物的88例IS患者和125例对照者血清叶酸、Vit B_(12)水平,并与Hcy水平进行相关性分析。结果 IS组Hcy浓度高于对照组,差异有显著性([23.95±12.13)μmol/L vs(17.31±7.20)μmol/L,t=29.61,P0.001],IS组与对照组MTHFR基因型频率CC、CT、TT型分别为14.3%、44.7%、41.0%和18.4%、48.9%、32.7%,等位基因C与T的频率分别为36.6%、63.4%和42.8%、57.2%,无显著性差异(基因型频率:χ~2=3.59,P=0.166;基因频率:χ~2=3.52,P=0.061)。MTHFR基因TT型(162例)、CT型(206例)和CC型(72例)的血浆Hcy水平分别为(25.19±12.53)μmol/L、(18.21±8.08)μmol/L和(16.65±6.90)μmol/L,其中TT型显著高于CT型和CC型,CT型显著高于CC型(P均0.001)。IS组和对照组血浆Hcy水平与Vit B_(12)呈负相关(IS组和对照组分别为r=-0.431,P0.001和r=-0.507,P0.001),与叶酸亦呈负相关(IS组和对照组分别为r=-0.489,P0.001和r=-0.446,P0.001)。结论 IS患者血浆Hcy水平较正常人偏高;MTHFR C667T基因突变、叶酸和Vit B_(12)水平降低是血浆Hcy水平升高的影响因素;MTHFR C667T基因突变可能与缺血性卒中无关。     

脑梗死后认知功能障碍患者血浆同型半胱氨酸水平及叶酸、甲钴胺的治疗作用

目的探讨脑梗死后认知功能障碍与同型半胱氨酸(Hcy)的关系,观察叶酸和甲钴胺对Hcy和认知功能的影响。方法应用荧光偏振免疫分析法测定血浆Hcy水平,比较脑梗死后认知功能障碍组患者和认知功能正常组患者Hcy水平。将脑梗死后认知功能障碍组患者按照有无接受叶酸和甲钴胺治疗随机分为治疗组和对照组,观察两组治疗前后Hcy水平及简易精神状态检查表(MMSE)分值的变化。分析Hcy与MMSE分值的相关性。结果脑梗死后认知功能障碍组患者血浆Hcy水平较认知功能正常组高;治疗组治疗后与治疗前相比,Hcy水平降低,MMSE分值升高;对照组治疗前、后Hcy水平及MMSE分值无明显变化;治疗组治疗后与对照组治疗后相比,Hcy水平降低,MMSE分值升高;脑梗死后认知功能障碍患者Hcy水平与MMSE分值呈负相关。结论脑梗死后认知功能障碍的发生和程度与血浆Hcy水平有关,联合应用叶酸和甲钴胺能改善脑梗死后认知功能障碍患者的认知功能。     

Higher Coated-Platelet Levels in Acute Stroke are Associated with Lower Cognitive Scores at Three Months Post Infarction

Background: Coated-platelets are a subset of highly procoagulant platelets observed after dual agonist stimulation with collagen and thrombin. Coated-platelet levels are increased in acute stroke compared to controls, and higher levels are associated with stroke recurrence. We examined whether coated-platelet levels measured at the time of the stroke correlate with cognitive scores at 3 months following the brain infarction. Methods: Coated-platelets were assayed in consecutive patients with nonlacunar stroke. Cognitive screening was performed using the Mini-Mental State Examination (MMSE) at 3 months after discharge. Linear regression, with adjustment for individual covariates, was used to model the association between coated-platelet levels and MMSE scores. Results: One hundred and twenty-eight patients with a mean MMSE score of 26 points (range 14-30, standard deviation [SD] 3.1) and mean coated-platelet levels of 40.9% (range 5.2-76.2, SD 13.3), completed cognitive screening. An inverse linear association was found between coated-platelet levels and MMSE score, with higher levels seen in patients with lower MMSE scores (r = ?.34, R² = .12, P < .0001). This association remained despite adjustment for potential confounding factors. In the final model, higher coated-platelet levels (coefficient ?.078, 95% confidence interval [CI]: ?.12 to ?.041, P < .0001), presence of hypertension (coefficient ?2.42, 95% CI: ?3.90 to ?.95, P = .0015), and anticoagulant use at discharge (coefficient ?1.48, 95% CI: ?2.56 to ?.39, P = .0079) were predictive of lower MMSE. Conclusions: These findings support a link between increased platelet procoagulant potential at the time of the stroke and development of cognitive impairment following cerebral infarction.