Platelet Surface CD62p and Serum Vitamin D Levels are Associated with Clopidogrel Resistance in Chinese Patients with Ischemic Stroke

Background: To explore the association of platelet activation markers, vitamin D, and antiplatelet drugs resistance in ischemic stroke patients. Methods: A total of 230 patients with ischemic stroke were enrolled in this study. Platelet aggregation, platelet activation marker (CD62p), and vitamin D were measured after 7-14 days of dual antiplatelet treatment (aspirin?+?clopidogrel). All individuals were divided into a drug resistance group and a drug sensitive group according to the platelet maximum aggregation rate induced by antagonist adenosine diphosphate or arachidonic acid. Results: In this study, the prevalence of aspirin resistance was low (1.2%), while the prevalence of clopidogrel resistance (CR) was 24.8%, so we focused on CR. The percentage of CD62p on activated platelet [(25.74 ± 4.61) versus (12.41 ± 3.93), P < .001] and the prevalence of hypertension [93.0% (53) versus 79.8% (138), P?=?.021] in CR group were significantly higher than those in clopidogrel sensitive (CS) group, while the vitamin D concentration [(8.96 ± 4.41) versus (13.9 ± 4.84) ng/mL, P?=?.003] in CR group was significantly lower compared with the CS group. No significant difference was found in soluble P-selectin between these 2 groups [(56.2 ± 16.13) versus (54.2 ± 14.87) ng/mL, P?=?.258], neither in calcium [(2.29 ± .12) versus (2.33 ± .13) mmol/L, P?=?.821]. Logistic regression analysis showed that hypertension (odds ratio [OR] = 5.348, 95% confidence intervals [CI] 1.184-23.350, P?=?.026), expression of platelet CD62p (OR?=?1.095, 95% CI 1.052-1.201, P?=?.018) and vitamin D level (OR?=?.832, 95% CI .763-.934, P?=?.005) were associated with CR in ischemic stroke patients. Conclusions: CR in ischemic stroke patients is associated with several independent predictors, including increased platelet activation marker CD62p, decreased vitamin D level, and hypertension.     

缺血性脑卒中和短暂性脑缺血发作患者氯吡格雷抵抗及其影响因素分析

目的观察北方汉族人群缺血性脑卒中及短暂性脑缺血发作(TIA)患者氯吡格雷抵抗的发生率,并分析可能相关的影响因素。方法共入选104例接受氯吡格雷75 mg·d-1治疗的动脉粥样硬化性脑梗死及TIA患者,于治疗前及治疗后第7天,应用比浊法检测腺苷二磷酸诱导的血小板聚集率。以血小板聚集率下降≤10%为划界,分为氯吡格雷抵抗(CR)组37例(35.58%)和非氯吡格雷抵抗(NCR)组67例(64.42%)。采集两组患者的病史及临床资料,进行统计学分析。结果 CR组合并2型糖尿病和高血压病的患病率高于NCR组(分别P=0.024,P=0.008);CR组血清胆固醇水平和体重指数(BMI)高于NCR组(分别P=0.040,P=0.013)。多因素Logistic回归分析提示BMI≥28 kg/m2与氯吡格雷抵抗可能具有相关性(OR=3.600,95%CI:1.110~11.678,P=0.033)。结论 BMI≥28 kg/m2可能为缺血性脑卒中及TIA患者发生氯吡格雷抵抗的危险因素     

Meta-analysis of APOE ε2/ε3/ε4 polymorphism and cerebral infarction

The risk of cerebral infarction (CI) is contributed to the combination of environmental influences and genetic factors. The Apolipoprotein E (APOE) gene polymorphism as a risk factor in CI has been suggested, but direct evidence from genetic association studies remains inconclusive even in Chinese population. The purpose of this study was to identify association between the APOE ε2/ε3/ε4 polymorphism and the development of CI. Published relevant case–control studies were collected from electronic databases. Data were combined using odds ratio (OR) with 95 % confidence interval (CI). Totally, 29 studies published from 1997 to 2012, involving 2,737 CI cases and 2,689 controls in Chinese population were subjected to final analysis. The pooled results suggested that CI subjects carrying ε4 allele had an increased risk for CI (ε4 vs. ε3: OR = 2.50, 95 % CI 1.98–3.16, P < 0.001, ε4 carriers vs. E3E3 genotype: OR = 2.82, 95 % CI 2.16–3.67, P < 0.001), compared with those carrying ε3 allele. However, carriers of APOE ε2 allele had no significant increased risk for CI, compared with those carrying ε3 allele. Potential publication bias was observed in the genetic model of ε4 versus ε3, but the results might not be affected deeply by the publication bias. Using the trim and fill method, the adjusted risk estimate for ε4 allele versus ε3 allele was attenuated but remained significant (OR = 2.00, 95 % CI 1.59–2.53, P < 0.001), suggesting the stability of our results. Taken together, our study suggests that APOE ε4 allele is associated with an increased risk of developing CI in Chinese population.     

The SIRT2 Polymorphism rs10410544 and Risk of Alzheimer’s Disease: A Meta-analysis

Previous studies have reported an association between human sirtuins’ single-nucleotide polymorphisms (SNPs) and Alzheimer’s disease (AD) susceptibility in the apolipoprotein E (APOE) ε4-negative population, although the findings are inconsistent. To obtain a more precise estimation of this relationship, we conducted a meta-analysis to assess the association between the rs10410544 C/T polymorphism of SIRT2 and the risk of AD with APOE ε4 status. We searched all relevant PubMed publications and included three studies in our meta-analysis involving a total of 1,794 patients and 2,054 control subjects. Odds ratios (ORs) with 95 % confidence intervals (CIs) were employed to evaluate the association of the SIRT2 SNP with AD susceptibility, and we analyzed the extracted data stratified by the APOE ε4-carrying status. Overall, the results show that the SIRT2 SNP is associated with human AD risk in the comparison models (T vs. C: OR 1.140, 95 % CI 1.034–1.258; TC vs. CC: OR 1.178, 95 % CI 1.019–1.361; TT + TC vs. CC: OR 1.197, 95 % CI 1.043–1.373). In the stratified analyses, the European population had a significantly increased risk of AD (T vs. C: OR 1.110, 95 % CI 1.002–1.229), and we also observed a significant association in the APOE ε4-negative population (T vs. C: OR 1.165, 95 % CI 1.025–1.324; TT + TC vs. CC: OR 1.222, 95 % CI 1.022–1.461). This meta-analysis indicates that the presence of the SIRT2 SNP with APOE ε4-negative status contributes to the development of AD in humans Epidemiological studies of larger sample sizes are warranted to confirm this hypothesis.     

缺血性卒中患者平均血小板体积水平与氯吡格雷抵抗的相关性分析

目的观察缺血性卒中患者的氯吡格雷抵抗(clopidogrel resistance,CR)与血小板平均体积(mean platelet volume,MPV)的关系。方法连续入组2013年3月~2014年1月期间在广州医科大学附属第三医院神经内科住院的缺血性卒中患者150例,所有患者均服用氯吡格雷75 mg/d,于用药前、用药物后10~14 d后应用比浊法测定血小板聚集率的变化,依据结果分为CR组和氯吡格雷敏感(clopidogel sensitivity,CS)组,对两组的一般资料、危险因素及MPV水平进行比较,同时采用多因素Logistic回归分析来确定MPV水平与CR的相关性。结果纳入的150例患者中,有44例(29.33%)发生CR,CS组106例。单因素分析中,CR组糖尿病、既往短暂性脑缺血发作(transient ischemic attack,TIA)病史及总胆固醇水平等均高于CS组(P值分别为0.001、0.001和0.004);CR组MPV水平高于CS组[(9.55±0.40)fl vs(9.28±0.35)fl,P0.001]。而在多因素Logistic回归分析中显示,MPV水平[比值比(odds ratio,OR)10.555,95%可信区间(confidence interval,CI)2.524~44.134,P=0.001]、总胆固醇(OR 1.561,95%CI 1.051~2.318,P=0.027)、既往TIA(OR 6.537,95%CI 2.475~17.262,P=0.000)、糖尿病(OR 7.632,95%CI 2.620~22.228,P=0.000)与CR相关。结论 MPV水平是CR发生的独立危险因素之一,作为CR的预测与筛查工具有一定的价值。     

Intravenous thrombolysis for ischemic stroke in the golden hour: propensity-matched analysis from the SITS-EAST registry

As there are scarce data regarding the outcomes of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) within 60 min from symptom onset (“golden hour”), we sought to compare outcomes between AIS patients treated within [GH(+)] and outside [GH(?)] the “golden hour” by analyzing propensity score matched data from the SITS-EAST registry. Clinical recovery (CR) at 2 and 24 h was defined as a reduction of ≥10 points on NIHSS-score or a total NIHSS-score of ≤3 at 2 and 24 h, respectively. A relative reduction in NIHSS-score of ≥40% at 2 h was considered predictive of complete recanalization (CREC). Symptomatic intracranial hemorrhage (sICH) was defined using SITS-MOST criteria. Favorable functional outcome (FFO) was defined as a mRS-score of 0–1 at 3 months. Out of 19,077 IVT-treated AIS patients, 71 GH(+) patients were matched to 6882 GH(?) patients, with no differences in baseline characteristics (p > 0.1). GH(+) had higher rates of CR at 2 (31.0 vs. 12.4%; p < 0.001) and 24 h (41 vs. 27%; p = 0.010), CREC at 2 h (39 vs. 21%; p < 0.001) and FFO (46.5 vs. 34.0%; p = 0.028) at 3 months. The rates of sICH and 3-month mortality did not differ (p > 0.2) between the two groups. GH(+) was associated with 2-h CR (OR: 5.34; 95% CI 2.53–11.03) and CREC (OR: 2.38; 95% CI 1.38–4.09), 24-h CR (OR: 1.88; 95% CI 1.08–3.26) and 3-month FFO (OR: 2.02; 95% CI 1.15–3.54) in multivariable logistic regression models adjusting for potential confounders. In conclusion, AIS treated with IVT within the GH seems to have substantially higher odds of early neurological recovery, CREC, 3-month FFO and functional improvement.     

Symptomatic carotid stenosis and stroke risk in patients with transient ischemic attack according to the tissue-based definition

Background and Purpose: Symptomatic carotid stenosis (sCS), a common cause of transient ischemic attack (TIA), is correlated with higher stroke risk. We investigated the frequency and associated factors of sCS in patients with TIA and the association between sCS and stroke risk following TIA. Methods: Over a three-year period (2011–2013), 861 consecutive patients with TIA, who were admitted to the Department of Neurology at the University of Lübeck, Germany, were included in a monocenter study and prospectively evaluated. Diagnosis of TIA was in accordance with the tissue-based definition (transient neurological symptoms without evidence of infarction by brain imaging). Results: Of 827 patients (mean age, 70 ± 13.2 years; 49.7% women), 64 patients (7.7%; 95% confidence interval [CI], 5.9%–9.7%) exhibited sCS and 3 patients (0.3%) showed an occlusion of the corresponding internal carotid artery. Logistic regression revealed that sCS was associated with male sex (odds ratio [OR], 2.7; 95% CI, 1.2–3.6; p = 0.012), amaurosis fugax (OR, 8.1; 95% CI, 3.4–19–4; p < 0.001), unilateral weakness (OR, 3.4; 95% CI, 1.9–6.1; p < 0.001), symptom duration less than 1 h (OR, 2.0; 95% CI, 1.1–3.4; p = 0.019) and previous stroke (OR, 2.7; 95% CI, 1.5–4.7; p = 0.001). During hospitalization (mean, 6.6 days), five patients (0.6%; 95% CI, 0.1%–1.2%) suffered from stroke. The stroke risk was higher in patients with sCS than in those without sCS (6.3% vs. 0.1%; p < 0.001), whereas the recurrent TIA risk (2.6%) did not differ between the groups (4.7% vs. 2.5%; p = 0.29). Conclusion: SCS appears to be associated with a higher risk of stroke in patients with TIA defined according to the tissue-based definition.     

缺血性卒中/TIA患者抗栓药物的使用及影响因素分析：中国七城市门诊连续病例的横断面调查

目的 评估中国缺血性卒中(IS)或短暂性脑缺血发作（TIA）患者应用抗血栓药物（包括抗血小板药物和抗凝药物）的现况，并分析其影响因素。方法 采用横断面研究方法，调查2006年7月1日至8月15日期间，中国主要城市二、三级医院神经内科门诊连续IS或TIA患者近期的抗血栓药物使用情况。22家医院参加调查，总计2384例卒中患者连续入选；有3家不符合中心入选标准被除外，最后19家医院的资料被采用，总计有2283例卒中患者的数据纳入分析中。结果 2283例卒中患者中，使用阿司匹林者占71.9％，使用阿司匹林+氯吡格雷占4.2％，使用氯吡格雷者占7.3％，各种抗血小板药物合计例数占75.6％。伴心房颤动的81例卒中患者中，使用华发林者占17.3％。医疗保险[比值比（OR）1.473，95%可信区间（CI）1.088～1.994]、公费医疗（OR 1.632，95%CI 1.029～2.589）、月均收入≥500元以上（OR 2.136，95%CI 1.508～3.026）、高血压（OR 1.463，95%CI 1.159～1.847）和脂代谢紊乱（OR 1.499，95%CI 1.187～1.893）是卒中患者接受抗血小板药物的促进因素。患者年龄≥75岁（OR 0.701，95%CI 0.498～0.988）及改良的Rankin评分4～5分（OR 0.684，95%CI 0.486～0.965）是用药的阻碍因素。结论 中国大城市二、三级医院IS和TIA患者的抗血栓治疗现状不容乐观，各类抗血栓药物应用的比例较低，为改善以上状况，亟待探索有效的改进模式，缩短临床实践与指南间的差距。     

Cognitive reserve and neuropsychological functioning in older HIV-infected people

Progress in treatments has led to HIV+ patients getting older. Age and HIV are risk factors for neurocognitive impairment (NCI). We explored the role of cognitive reserve (CR) on cognition in a group of virologically suppressed older HIV+ people. We performed a multicenter study, consecutively enrolling asymptomatic HIV+ subjects ≥60 years old during routine outpatient visits. A comprehensive neuropsychological battery was administered. Raw test scores were adjusted based on Italian normative data and transformed into z-scores; NCI was defined according to Frascati criteria. All participants underwent the Brief Intelligence Test (TIB) and the Cognitive Reserve Index (CRI) questionnaire as proxies for CR. Relationships between TIB, CRI, and NCI were investigated by logistic or linear regression analyses. Sixty patients (85 % males, median age 66, median education 12, 10 % HCV co-infected, 25 % with past acquired immunodeficiency syndrome (AIDS)-defining events, median CD4 cells count 581 cells/μL, median nadir CD4 cells count 109 cells/μL) were enrolled. Twenty-four patients (40 %) showed Asymptomatic Neurocognitive Impairment. At logistic regression analysis, only CRI (OR 0.94; 95 % CI 0.91–0.97; P?=?0.001) and TIB (OR 0.80; 95 % CI 0.71–0.90; P?<?0.001) were associated with a lower risk of NCI. Higher CRI and TIB were significantly correlated with a better performance (composite z-score) both globally and at individual cognitive domains. Our findings highlight the role of CR over clinical variables in maintaining cognitive integrity in a virologically suppressed older HIV-infected population. A lifestyle characterized by experiences of mental stimulation may help to cope aging and HIV-related neurodegeneration.     

Aspirin platelet reactivity on platelet function and clinical outcome in minor stroke or transient ischemic attack

ObjectiveWhether aspirin platelet reactivity affects platelet function and clinical outcomes with different antiplatelet therapies in patients with mild stroke or transient ischemic attack (TIA) remains unclear. We conducted a subgroup analysis of the PRINCE trial.Materials and methodsPatients with mild stroke or TIA were randomized into aspirin+ticagrelor, or aspirin+clopidogrel groups; aspirin reaction units (ARU) were measured at the baseline and after 7 ± 2 days to assess response to treatment. High on-treatment platelet reactivity (HPR) was defined as ≥550 ARU (poor response to aspirin). The platelet functions of ticagrelor and clopidogrel were measured using the VerifyNow P2Y₁₂ assay for P2Y₁₂ reaction units (PRU); HPR to P2Y₁₂ was defined as >208 PRU (poor response to P2Y₁₂). Clinical outcomes included stroke and clinical vascular and bleeding events after 90 days.ResultsAmong 628 enrolled patients, 69 (11%) were poor aspirin responders. After 7 ± 2 days, the proportion of poor P2Y₁₂ responders for ticagrelor versus clopidogrel significantly reduced in poor (2.6% versus 27.4%) and good (14.3% versus 29.4%) aspirin responders. There were significant interactions between treatment groups, and between treatment groups and aspirin platelet reactivity for poor P2Y₁₂ responders (P = 0.01). After 90 ± 7 days, there were no significant interactions between treatment groups and aspirin platelet reactivity for new stroke risk (good aspirin responders: 5.5% versus 8.8%, hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.32 to 1.16; P = 0.13; poor aspirin responders: 8.6% versus 8.8%, HR: 0.97, 95% CI: 0.20–4.81; P = 0.97; P for interaction = 0.60). Major bleeding was less frequent in poor than good aspirin responders (ticagrelor/aspirin: 0.4%/0%; clopidogrel/aspirin: 1.4%/0%).ConclusionsIn patients with minor stroke or TIA, clopidogrel, and particularly ticagrelor, decreased platelet function in poor versus good aspirin responders. The poor platelet reactivity of aspirin could not sufficiently reduce the risk of recurrent stroke with ticagrelor or clopidogrel; however, HPR (poor aspirin response) may have a protective effect on clinically relevant major bleeding.     

Reversal of Coagulopathy Using Prothrombin Complex Concentrates is Associated with Improved Outcome Compared to Fresh Frozen Plasma in Warfarin-Associated Intracranial Hemorrhage

Background

There are no studies demonstrating that prothrombin complex concentrates (PCC) improves outcome compared FFP in patients with warfarin-associated intracranial hemorrhage.

Methods

A prospective, observational study was conducted of patients who received PCC (Bebulin VH), FFP, or PCC + FFP. All groups received vitamin K 10 mg IV. INR reversal (<1.4), adverse events (venous thromboembolism, myocardial infraction, pulmonary edema), major hemorrhage (new or worsened intracranial hemorrhage, anemia requiring transfusion or GI bleed), and 3-month functional outcome were compared between the groups using Chi squared and logistic regression analysis.

Results

Of 64 patients, PCC alone was used in 16 (mean dose 48 IU/kg), FFP alone in 25 (mean dose 12.5 ml/kg), and PCC + FFP in 23 (median doses 47.4 IU/kg and 11.4 ml/kg, respectively). INR correction occurred in 88, 84, and 70 %, respectively. There were no differences in time to INR correction or adverse events between the groups, but FFP alone was associated with more major hemorrhage after administration (52 %, OR 5.0, 95 % CI 1.6–15.4, P = 0.006) and PCC with less (6 %, OR 0.1, 95 % CI 0.01–0.8, P = 0.033). After adjusting for age, admission GCS, initial INR, and bleed type, the use of PCC was associated with a lower risk of death or severe disability at 3-months (adjusted OR 0.02, 95 % CI 0.001–0.8, P = 0.039), while FFP alone was associated with a higher risk (adjusted OR 51.6, 95 % CI 1.2–2163.1, P = 0.039).

Conclusions

PCC adequately corrected INR without any increase in adverse events compared to FFP and was associated with less major hemorrhage and improved 3-month outcomes in patients with warfarin-associated intracranial hemorrhage.     

Combined clopidogrel–aspirin treatment for high risk TIA or minor stroke does not increase cerebral microbleeds

Abstract

Objectives:

To study whether Clopidogrel–Aspirin combined treatment for high risk transient ischaemic attack (TIA) or minor stroke results in increased number of lesions associated with anti-thrombotic cerebral haemorrhage or cerebral micro-bleeds (CMB) than aspirin alone treatment.

Methods:

The patients recruited in CHANCE test in our hospital participated in this study. We made a comparison between treatments Aspirin–Clopidogrel combined group and the Aspirin alone group in the numbers of CMB and subsequent cerebral haemorrhages. In addition, we analysed the association between the increased numbers of CMB and subsequent intracerebral haemorrhages. All 129 patients with high risk TIA with microbleeds or minor stroke within 24?hours after the onset (average age 65.9?±?9.3, 48.7% were male patients) were divided randomly into two groups: (1) 67 patients were given combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300?mg, then 75?mg per day for 90?days, plus aspirin at a dose of 75?mg per day for the first 21?days);(2) the rest patients were given aspirin treatment (75?mg per day for 90?days). All participants received open-label aspirin at a clinician-determined dose of 75–300?mg on the first day.

Results:

The CMB were found in 52.7% of all patients in both groups. There was no siginificant difference between the Aspirin group and the Aspirin–clopidogrel treated group, though the latter showed some slight increase in CMB (Odds ratios (OR)?=?1.16, 95% confidence intervals (CI) =?0.54–2.47, P?=?0.71). But the numbers of CMB were remarkably associated with the number of primary existing CMB (OR?=?6.46, 95%CI 2.57–16.23, P?<?0.001), especially that of primary existing CMB ≥?3.In addition, the increasing numbers of CMB associated with primary CMB lesions, which located in corticosubcortical area (CSC) (OR?=?4.69, 95%CI 1.51–14.53, P?=?0.007).

Conclusions:

For the treatment of high-risk TIA or minor stroke patients, the clopidogrel–aspirin treatment did not increase the number of CMB than Aspirin alone. It appears that the extent of CMB was associated with the extent of existing CMB occurred in previous stroke, which was mostly located in cortical, subcortical zone.     

Association of VEGF gene polymorphisms with sporadic Parkinson’s disease in Chinese Han population

Recent evidence indicates that vascular endothelial growth factor (VEGF) is capable of protecting dopaminergic (DA) neurons. Parkinson’s disease (PD) is a progressive neurodegenerative disease caused by the degeneration of nigrostriatal dopaminergic neurons. To evaluate the role of VEGF single nucleotide polymorphisms (SNPs) and haplotypes in PD, we performed a case–control study including 400 PD patients and 400 healthy-matched controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) analysis and DNA sequencing were used to detect the rs699947, rs2010963 and rs3025039 polymorphisms of the VEGF gene in cases and controls. Our study revealed that T allelic frequency of rs3025039 polymorphism was significantly higher in PD subjects (OR 1.497, 95 % CI 1.099–2.040, P = 0.013) than that in controls. Significant association for rs3025039 could be found in additive model (TT vs. CT vs. CC: OR 1.489, 95 % CI 1.018–2.177, P = 0.040) and dominant model (TT + CT vs. CC: OR 1.538, 95 % CI 1.068–2.216, P = 0.021). Subgroup analyses performed by gender suggested that this association could be found in male, but not in female. Moreover, it also demonstrated a significant association in the subgroup of late-onset PD (LOPD). However, for rs699947 and rs2010963 polymorphisms, genotype or allele frequencies did not differ between groups. No significant association could be found between rs699947 and rs2010963 polymorphism and PD risk. None of the observed haplotypes showed significant association with PD. Therefore, these results suggested that the VEGF gene might be associated with risk of developing sporadic PD in Han Chinese and the rs3025039 polymorphism may be a risk factor for sporadic PD.     

Short-term risk and predictors of stroke after transient ischemic attack

BackgroundTransient ischemic attack (TIA) is a marker of stroke, especially in the early phase following this event. The aims of this study are to determine the short-term risk of stroke and to evaluate the independent predictors of stroke in patients with TIA who are hospitalized within 48 hours after symptom onset.MethodsDuring a 36-month period (beginning in November 2007), 3554 patients (mean age: 70.5 ± 13 years; 49.9% female; mean NIHSS score: 1.4 ± 2.5) from 15 hospitals suffering from TIA were prospectively evaluated.ResultsOf the 3554 patients, 43 (1.2%) suffered from stroke during hospitalization (6.5 ± 4.3 days). We identified the following independent predictors for stroke after TIA: male sex (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.3–5; P = 0.008), age ≥ 65 years (OR, 4.7; 95% CI, 1.4–15; P = 0.01), hyperlipidemia (OR, 2.4; 95% CI, 1.2–4.8; P = 0.015), and dysarthria (OR, 2; 95% CI, 1.1–5.0; P = 0.038).ConclusionPatient characteristics (male sex, age, and hyperlipidemia) and TIA symptom (dysarthria) may be useful in defining stroke after TIA in patients who were hospitalized with TIA.     

Prior medical conditions and the risk of amyotrophic lateral sclerosis

Sporadic amyotrophic lateral sclerosis (ALS) is believed to be a complex disease in which multiple exogenous and genetic factors interact to cause motor neuron degeneration. Elucidating the association between medical conditions prior to the first symptoms of ALS could lend support to the theory that specific subpopulations are at risk of developing ALS and provide new insight into shared pathogenic mechanisms. We performed a population-based case–control study in the Netherlands, including 722 sporadic ALS patients and 2,268 age and gender matched controls. Data on medical conditions and use of medication were obtained through a structured questionnaire. Multivariate analyses showed that hypercholesterolemia (OR 0.76, 95 % CI 0.63–0.92, P = 0.006), the use of statins (OR 0.45, 95 % CI 0.35–0.59, P = 1.86 × 10^?9) or immunosuppressive drugs (OR 0.26, 95 % CI 0.08–0.86, P = 0.03) were associated with a decreased risk of ALS. Head trauma was associated with an increased ALS susceptibility (OR 1.95, 95 % CI 1.11–3.43, P = 0.02). No association was found with autoimmune diseases, cancer, psychiatric disorders or cardiovascular diseases, or survival. The lower frequency of hypercholesterolemia and less use of statins in ALS patients indicate a favorable lipid profile prior to symptom onset in at least a subpopulation of ALS. Prior head trauma is a risk factor for ALS and the significantly lower use of immunosuppressive drugs in ALS patients could suggest a protective effect. The identification of specific subpopulations at risk for ALS may provide clues towards possible pathogenic mechanisms.     

Impact of serum uric acid,albumin and their interaction on Parkinson’s disease

The study aimed to investigate the correlation between Parkinson’s disease (PD) and serum levels of uric acid (UA), albumin and their interaction. A cross-sectional study was conducted to evaluate the relationship of serum UA, albumin with PD. A total of 96 PD patients and 108 healthy controls were recruited at Huai’an First People’s Hospital, Nanjing Medical University. Baseline data included age, gender, body mass index (BMI), disease duration, Hoehn and Yahr scale (H&Y) stage, serum UA and albumin levels. The levels of serum UA and albumin were significantly lower in PD patients than those in controls (P = 0.001; P = 0.000). Serum albumin levels were strikingly different in H&Y group (P = 0.004). Multivariable logistic regression showed that the levels of serum UA (P = 0.001, adjusted OR 0.993, 95% CI 0.988–0.997) and albumin (P = 0.000, adjusted OR 0.513, 95% CI 0.425–0.620) were independent risk factors in PD. The receiver operating characteristic (ROC) curve analyses showed that the area under curve (AUC) for serum UA and albumin was 0.669 (95% CI 0.594–0.744) and 0.883 (95% CI 0.835–0.931), respectively. The combination of serum albumin and UA improved the AUC to 0.898 (95% CI 0.854–0.942). Serum UA and albumin levels significantly decreased in PD patients and were independent risk factors for PD. More studies are needed to confirm our findings.     

A Quantitative Assessment of the Association Between 1425G/A Polymorphism in PRKCH and Risk of Stroke

Previous studies suggested an association between 1425G/A polymorphism in PRKCH and stroke risk, but the results were inconsistent. To obtain a more precise estimation, we carried out a meta-analysis to analyze the effect of 1425G/A SNP in PRKCH on stroke risk. We searched PubMed, ISI Web of Science, Chinese Biomedical Database, China National Knowledge Infrastructure and WANFANG Data for all eligible case–control studies through April 2014. The odds ratios (ORs), together with the 95 % confidence intervals (CIs), were calculated to evaluate the strength of association between 1425G/A SNP and stroke risk. Overall, seven eligible studies involving a total of 4,574 cases and 5,471 controls were included in our meta-analysis. The results showed that the variant genotypes of 1425G/A polymorphism in PRKCH were significantly associated with a higher risk of stroke in all genetic models (GA vs. GG: OR 1.35, 95 % CI 1.24–1.47, P < 0.001; AA vs. GG: OR 1.50, 95 % CI 1.24–1.82, P < 0.001; GA/AA vs. GG: OR 1.37, 95 % CI 1.26–1.49, P < 0.001; AA vs. GA/GG: OR 1.35, 95 % CI 1.12–1.62, P = 0.002; A vs. G: OR 1.29, 95 % CI 1.21–1.39, P < 0.001). In the subgroup analysis, significantly increased risks were also observed for ischemic stroke, larger sample size (>1,000) and population-based studies. The result of our meta-analysis indicated that the 1425G/A SNP in PRKCH may contribute to susceptibility of stroke, especially for ischemic stroke.     

Association between G2385R and R1628P polymorphism of LRRK2 gene and sporadic Parkinson’s disease in a Han-Chinese population in south-eastern China

The G2385R and R1628P polymorphisms of the leucine-rich repeat kinase 2 (LRRK2) gene have been reported to be associated with Parkinson’s disease (PD), but no data are available on Han-Chinese population of south-eastern China. This study aimed to investigate whether G2385R and R1628P variants are associated with sporadic PD in this population. Total 1,060 subjects were enrolled; including 550 unrelated healthy controls and 510 patients with sporadic PD. Genotyping of polymorphisms was performed by PCR–restriction fragment length polymorphism analysis. All variant samples were sequenced for further confirmation. The results showed that the A allele of the G2385R variant was significantly enriched in sporadic PD patient group (4.8 %) when compared with control group [1.1 %; odds ratio (OR) 4.58, 95 % confidence interval (CI) 2.42–8.65, P < 0.01]. However, no significant difference in the frequency of the C allele of R1628P polymorphism variant was observed between cases and controls (2.8 vs. 1.7 %, OR 1.67, 95 % CI 0.93–2.99, P = 0.08). In conclusion, this study provides the first evidence that G2385R polymorphism is a risk factor for sporadic PD in Han-Chinese population of south-eastern China.     

Association of MDR1 gene C3435T polymorphism with childhood intractable epilepsy: a meta-analysis

Drug-resistant epilepsy is also referred to as intractable, medically refractory, or pharmacoresistant epilepsy. Approximately, one-third of patients with epilepsy have recurrent seizures despite therapy. Multidrug resistance 1 (MDR1) gene may play a role in drug-resistance in epilepsy. To assess the association between MDR1 C3435T polymorphism and the response to anticonvulsants in childhood intractable epilepsy, we conducted a systematic review and meta-analysis. Studies were obtained from the electronic database of PubMed, Medline, Embase and CNKI up to September 2013. All the case–control association researches evaluating the role of MDR1 C3435T polymorphism in childhood epilepsy to antiepileptic drugs were identified. The odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated for comparisons of the alleles and genotypes with co-dominant (C/C vs. T/T, C/T vs. T/T), dominant (C/C + C/T vs. T/T), and recessive (C/C vs. C/T + T/T) models in overall and in ethnicity subgroups to measure the strength of genetic association. A total of 8 related studies, including 634 drug-resistant patients, 615 drug-responsive patients and 1,052 healthy controls were pooled in this meta-analysis. The allelic association of MDR1 C3435T with risk of drug-resistance was not significant (OR 1.03, 95 % CI 0.87–1.22, P = 0.73; OR 1.00, 95 % CI 0.86–1.16, P = 0.98) in overall and in the subgroup analysis by ethnicity (Asian: OR 0.95, 95 % CI 0.77–1.18, P = 0.67; Caucasian: OR 1.18, 95 % CI 0.89–1.57, P = 0.25). Neither association was found in other genetic models. Our results did not show a significant association between MDR1 C3435T polymorphism and response to anticonvulsant drugs, suggesting that this polymorphism may not be a risk factor to childhood intractable epilepsy.     

Multiple sclerosis and environmental risk factors: a case-control study in Iran

Studies have shown an increase in the incidence of MS in Iran. The aim of our study was to evaluate the relationship between environmental exposure and MS in Iran. This case-control study was conducted on 660 MS patients and 421 controls. Many environmental factors are compared between the two groups. Our findings demonstrated that prematurity ([OR = 4.99 (95% CI 1.34–18.68), P = 0.017]), history of measles and mumps ([OR = 1.60 (95% CI 1.05–2.45), P = 0.029; OR = 1.85 (95% CI 1.22–2.78), P = 0.003, respectively]), breast feeding [OR = 2.90 (95% CI 1.49–5.65), P = 0.002], head trauma in childhood ([OR = 8.21 (95% CI 1.56–43.06), P = 0.013]), vaccination in adulthood ([OR = 4.57 (95% CI 1.14–18.41), P = 0.032, respectively]), migraine ([OR = 3.50 (95% CI 1.61–7.59), P = 0.002]), family history of MS, IBD, migraine, and collagen vascular diseases ([OR = 2.73 (95% CI 1.56–4.78), P < 0.001], [OR = 3.14 (95% CI 1.460–6.78), P = 0.004; OR = 3.18 (95% CI 1.83–5.53), P < 0.001; OR = 1.81 (95% CI 1.03–3.20), P = 0.040, respectively]), stressful events ([OR = 32.57 (95% CI 17.21–61.64), P < 0.001]), and microwave exposure ([OR = 3.55 (95% CI 2.24–5.63), P ≤0.001]) were more in the MS group. Sun exposure ([OR = 0.09 (95% CI 0.02–0.38), P = 0.001]), dairy and calcium consumption ([OR = 0.44 (95% CI 0.27–0.71), P = 0.001]), diabetes mellitus ([OR = 0.11 (95% CI 0.01–00.99), P = 0.049], and complete vaccination during childhood appeared to decreased MS risk. Our results investigated many risk factors and protective factors in Iran.