Long-Term Outcomes in Patients with Anemia And Cerebral Venous Thrombosis

Background

Anemia is associated with unfavorable functional outcome in ischemic and hemorrhagic stroke. However, the relationship between anemia and prognosis in patients with cerebral venous thrombosis (CVT) has not been studied.

Methods

Consecutive CVT patients were retrospectively identified from November 2011, through January 2017. Anemia was defined according to the World Health Organization criteria (non-pregnant female hemoglobin level?<?120 g/L, pregnant female?<?110 g/L and male?<?130 g/L), which was further classified as mild, moderate, and severe anemia according to hemoglobin concentration, and as microcytic, normocytic, and macrocytic anemia according to mean corpuscular volume. Unfavorable outcome was defined as modified Rankin Scale (mRS) of 3–6. Factors such as age, sex, coma, malignancy, intracerebral hemorrhage, and straight sinus and/or deep CVT involved, premorbid mRS were adjusted to evaluate the relationship between anemia and prognosis in CVT patients.

Results

A total of 238 CVT patients were included, among whom 73 patients (30.67%) were diagnosed with anemia. Multivariate logistic regression analysis showed that patients with anemia had a higher risk of mRS of 3–6 (OR?=?3.62; 95% CI, 1.45–9.01; P?=?0.006) and mortality (OR?=?5.46; 95% CI, 1.90–15.70; P?=?0.002). Subgroup analysis showed that severe anemia was independently associated with mRS of 3–6 (OR?=?8.80; 95% CI, 1.90–40.81; P?=?0.005) and mortality (OR?=?9.82; 95% CI, 1.81–53.25; P?=?0.010). Similarly, microcytic anemia increased the risk of mRS of 3–6 (OR?=?4.64; 95% CI, 1.48–14.52; P?=?0.008) and mortality (OR?=?9.68; 95% CI, 2.61–35.91; P?=?0.001). In addition, our study also revealed that lower hemoglobin level, evaluated as a continuous variable, was inversely associated with mRS of 3–6 (OR?=?0.98; 95% CI, 0.96–0.99; P?=?0.007) and mortality (OR?=?0.97; 95% CI, 0.95–0.99; P?=?0.005).

Conclusions

Anemia was a significant and independent predictor of unfavorable functional outcome in patients with CVT.

     

Methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to epilepsy

Background

Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism was reported as risk factor for multiple diseases due to its role in conversion of homocysteine to methionine. The aim of the present meta-analysis was to find out the validity of association of C677T polymorphism with epilepsy susceptibility.

Methods

Pubmed, Science Direct, Springer Link and Google Scholar, databases were searched for relevant studies up to January, 31, 2018. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed using five genetic models. All statistical analysis was done by MetaAnalyst and Mix programs.

Results

Except recessive model, significant association was found between MTHFR C677T polymorphism and epilepsy risk in other four genetic models (T vs C: OR?=?1.29, 95% CI?=?1.08–1.52, p?=?0.004; TT vs CC: OR?=?1.48, 95% CI?=?1.19–1.82, p?=?0.0003; TT + CT vs CC: OR?=?1.20, 95% CI?=?1.05–1.38, p?=?0.008; TT vs CT + CC: OR?=?1.35, 95% CI?=?1.11–1.62, p?=?0.002). Similarly, in the subgroup analysis based on ethnicity, significant association was found in Asian (T vs C: OR?=?1.85; 95% CI?=?1.15–2.99; p?=?0.03) and Caucasian populations (TT vs CC: OR?=?1.38; 95% CI?=?1.10–1.1.73; p?=?0.005). No evidence of heterogeneity and publication bias was detected in present meta-analysis.

Conclusion

In conclusion, results of present meta-analysis suggested that 677T allele of MTHFR is significantly increases the epilepsy susceptibility.

     

Clinical Value of Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratio After Aneurysmal Subarachnoid Hemorrhage

Background

Inflammation and thrombosis are associated with the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH) and neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are emerging as novel inflammatory markers in stroke. We aimed to identify the association of NLR and PLR with delayed cerebral ischemia (DCI) and 3-month outcome after aSAH.

Methods

Two hundred and forty-seven patients diagnosed with aSAH within 24 h of symptoms onset were enrolled. Clinical, neuroradiological, laboratory, and follow-up data were collected from electronic database. Functional outcome was assessed by modified Rankin Scale. Admission NLR, PLR, and combined NLR-PLR associated with outcomes were evaluated by logistic regression analysis, and we used receiver operating characteristic curves to detect the overall predictive accuracy of these markers.

Results

Fifty-five (22.3 %) patients had unfavorable outcome and 47 (19 %) developed DCI. Both NLR and PLR were correlated with WFNS grade (ρ = 0.35[p < 0.001], ρ = 0.28[p < 0.001]) and modified Fisher grade (ρ = 0.25[p = 0.001], ρ = 0.28[p = 0.003]) and independently related to DCI (OR 2.18, 95 %CI 1.51–3.15, p = 0.016; OR 2.21, 95 %CI 1.61–3.32, p = 0.008) and functional outcome (OR 1.89, 95 %CI 1.52–3.17, p = 0.015; OR 1.77, 95 %CI 1.48–3.21, p = 0.018) at 3 months after aneurysm repair. They had comparable predictive ability in DCI occurrence (area under the curve [AUC] 0.65, 95 %CI 0.55–0.74, p = 0.002; AUC 0.68, 95 %CI 0.60–0.76, p < 0.001) and poor outcome (AUC 0.70, 95 %CI 0.63–0.77, p < 0.001; AUC 0.65, 95 %CI 0.58–0.72, p = 0.001). However, combination of the two indexes showed a better predictive value than each alone (AUC 0.73, 95 %CI 0.66–0.81, p < 0.001 for DCI; AUC 0.76, 95 %CI 0.70–0.83, p < 0.001 for poor outcome).

Conclusions

NLR and PLR as novel inflammatory biomarkers are independent predictors of DCI development and functional outcome after acute aSAH. When combined together, they may help to identify high-risk patients more powerfully.

     

Association of CD1 and FcγR gene polymorphisms with Guillain–Barré syndrome susceptibility: a meta-analysis

CD1 and immunoglobulin G Fc receptor (FcγR) genes have been proposed to be involved in the pathogenesis of Guillain–Barré syndrome (GBS). However, results of different studies are conflicting. This meta-analysis aimed to systematically examine the association between CD1 and FcγR gene polymorphisms and GBS. A comprehensive literature search through PubMed, EmBase, ScienceDirect, and Cochrane Library was performed to identify all eligible studies. The strength of association was assessed by pooled odds ratios (ORs) and corresponding 95% confidence intervals (95% CI) in allelic, dominant, recessive, homozygous and heterozygous genetic models. Four case–control studies about polymorphisms of exon 2 in CD1A and CD1E genes and GBS risk and five studies (six cohorts) about FcγR gene polymorphisms and GBS risk were included in this meta-analysis. The association between exon 2 of CD1E gene polymorphism and GBS was marginally significant in Caucasians in allelic model (OR?=?1.193, 95% CI?=?1.001–1.423, P?=?0.049). FcγRIIA gene polymorphism was significantly associated with GBS risk in Caucasians under allelic model (OR?=?1.553, 95% CI?=?1.018–2.368, P?=?0.041) and dominant model (OR?=?1.320, 95% CI?=?1.027–1.697, P?=?0.030). However, no significant association was found between polymorphisms in exon 2 of CD1A, FcγRIIIA and FcγRIIIB genes and GBS susceptibility. This meta-analysis suggested that FcγRIIA gene polymorphism may contribute to GBS risk in Caucasians and revealed a certain trend toward significance in the association of exon 2 of CD1E gene with GBS in Caucasians. Further studies with larger sample size are required to validate these results.     

Association of the rs1611115 polymorphism in DBH gene with Parkinson’s disease: a meta-analysis

A meta-analysis was performed to assess the association between the dopamine beta-hydroxylase (DBH) rs1611115 genetic polymorphism and Parkinson’s disease (PD). A comprehensive search was conducted to identify all case–control or cohort studies. The fixed or random effect-pooled measure was selected on the basis of a homogeneity test among studies. Heterogeneity among studies was evaluated using the I². We performed sensitivity analyses to evaluate the robustness of the results. Publication bias was estimated using Egger’s linear regression test. Five case–control studies corresponded to the inclusion criteria comprising 3926 patients and 3542 controls which were included in the present meta-analysis. Our meta-analysis showed no significant association between DBH rs1611115 genetic polymorphism and risk of PD in the codominant (REM, OR?=?1.017, 95%CI?=?0.854–1.210), dominant (REM, OR?=?0.989, 95%CI?=?0.826–1.185), and recessive (REM, OR?=?1.007, 95%CI?=?0.657–1.542) models. Moreover, in the subgroup analysis based on region (Asia and Europe), no significant associations were observed in Asia or Europe. This meta-analysis suggests that the DBH rs1611115 genetic polymorphism might not be associated with PD.     

Association between <Emphasis Type="Italic">FGF20 rs12720208</Emphasis> gene polymorphism and Parkinson’s disease: a meta-analysis

Previous studies have claimed the association of rs12720208 polymorphism in the fibroblast growth factor 20 (FGF20) gene with the increased risk of Parkinson’s disease (PD), but results from the published data were controversial. The aim of our present meta-analysis was to estimate the overall association between FGF20 rs12720208 polymorphism and the risk of PD. Case–control studies with sufficient data evaluating the association between rs12720208 C/T polymorphism and PD susceptibility were systematically identified in PubMed, OVID, SinoMed, Chinese National Knowledge Infrastructure (CNKI) up to July 10, 2015. A total of 3402 PD patients and 3739 controls from seven case–control studies were collected for this meta-analysis. The pooled odds ratio (OR) with its 95 % confidence interval (CI) was calculated to assess the genetic association between FGF20 rs12720208 polymorphism and the risk of PD. In this study, no enough proof was found to prove the association in any genetic models with random-effects model (CT+TT vs. CC: OR = 1.147, 95 % CI: 0.883–1.489, P = 0.304; TT vs. CC+CT: OR = 1.754, 95 % CI: 0.878–3.505, P = 0.112; T vs. C: OR = 1.169, 95 % CI = 0.919–1.487, P = 0.204; TT+CC vs. CT: OR = 0.906, 95 % CI = 0.694–1.182, P = 0.466). Our results suggest that there is no sufficient evidence to support the association between rs12720208 polymorphism and PD risk. Studies with larger sample size across diverse populations and subgroup analyses are necessary in the future.     

Relative Telomere Length and Stroke Risk in a Chinese Han Population

This study aimed to further understand the role of relative telomere length (RTL) in susceptibility to stroke and investigate the association regulator of telomere elongation helicase 1 (RETL1) gene polymorphisms and RTL. RTL was measured using the real-time quantitative polymerase chain reaction (qPCR) from 300 stroke patients and 299 healthy controls. Genotyping was performed using the Sequenom MassARRAY platform. The results indicated that stroke patients had significantly shorter median RTL than controls (P?<?0.001). Compared with the longer RTL (≥?0.766), the shorter RTL (<?0.766) was significantly increased the risk of stroke (odds ratio [OR]?=?8.44, 95% confidence interval [CI] 5.42–13.14, P?<?0.001). The RTL was categorized into tertiles, we found that the shorter RTL (0.515–1.366) (OR?=?16.27, 95% CI 7.72–34.29, P?<?0.001) and lowest RTL (<?0.515) (OR?=?30.63, 95% CI 14.27–65.75, P?<?0.001) were significantly increased stroke risk compared with the highest RTL (>?1.366). Stratified analysis showed that the shorter RTL was also significantly increased the risk of stroke compared with the longer RTL in male, age <?60 years and ≥?60 years, except the female participants. In addition, individuals with the genotypes AA (rs2297441) and GG (rs6089953) have shorter telomeres than the genotypes GG (P?=?0.031) and AA (P?=?0.032), respectively. Our results suggested that shorter RTL was associated with an increased risk of stroke. The association was found between the genotypes AA (rs2297441) and GG (rs6089953) and shorter RTL in case group. Further studies in larger sample size and biological functional assays are warranted to validate our findings.     

Long non-coding RNA <Emphasis Type="Italic">H19</Emphasis> and <Emphasis Type="Italic">MALAT1</Emphasis> gene variants in patients with ischemic stroke in a northern Chinese Han population

Objectives Long non-coding RNAs (lncRNAs) have been identified as key regulators in the development of atherosclerosis, which is a major cause of ischemic stroke. However, to date, there are no reports on the association between lncRNA gene variation and the risk of ischemic stroke. Therefore, we assessed the association between H19 and MALAT1 gene polymorphisms and susceptibility to ischemic stroke in a northern Chinese Han population. Methods In our study, we genotyped four genetic variations in lncRNA-H19 and -MALAT1 (rs217727, rs2251375, rs619586, and rs3200401) in a case–control study of 567 ischemic stroke patients and 552 control subjects. Results We found that the TT genotype of the rs217727 polymorphism within H19 was significantly associated with increased risk of ischemic stroke in our northern Chinese Han population (odds ration (OR)?=?1.519, 95% confidence interval (CI)?=?1.072–2.152, p?=?0.018). Stratified analysis based on stroke subtype revealed that the increased risk was more evident in small vessel ischemic stroke (OR?=?1.941, 95% CI?=?1.260–2.992, p?=?0.02). Individuals with the TT genotype had a 1.941 times higher risk of small vessel ischemic stroke when compared with the subjects of CC?+?CT. These correlations remained after adjusting for confounding risk factors of stroke (OR?=?1.913, 95% CI?=?1.221–2.998, p?=?0.005). However, there was no significant association between H19 rs2251375 or MALAT1 rs3200401 and ischemic stroke in either total population analysis or subgroup analysis. Conclusion In conclusion, our findings suggest that the H19 rs217727 gene polymorphism contributes to small vessel ischemic stroke susceptibility in the Chinese Han population and may serve as a potential indicator for ischemic stroke susceptibility.     

Obstructive sleep apnea and cerebral white matter change: a systematic review and meta-analysis

Obstructive sleep apnea (OSA) can cause sleep fragmentation and intermittent hypoxemia, which are linked to oxidative stress. White matter changes (WMCs) representing cerebrovascular burden and are at risk factor for oxidative ischemic injury. The current study explores the mutual relationships between OSA and WMCs. We performed a systematic review of electronic databases for clinical studies investigating OSA and WMCs. Random-effects models were used for pooled estimates calculation. A total of 22 studies were included in the meta-analysis. The results revealed a significantly higher prevalence rate of WMCs [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.52–2.80, p?<?0.001] and significantly higher severity of WMCs (Hedges’ g?=?0.23, 95% CI 0.06–0.40, p?=?0.009) in the patients with OSA than in controls. Furthermore, the results revealed a significantly higher apnea–hypopnea index (Hedges’ g?=?0.54, 95% CI 0.31–0.78, p?<?0.001) and significantly higher prevalence rate of moderate-to-severe OSA (OR 2.86, 95% CI 1.44–5.66, p?=?0.003) in the patients with WMCs than in controls, however there was no significant difference in the prevalence rate of mild OSA between the patients with WMCs and controls (OR 0.71, 95% CI 0.20–2.54, p?=?0.603). OSA was associated with a higher prevalence and more severe WMCs, and the patients with WMCs had an increased association with moderate-to-severe OSA. Future large-scale randomized controlled trials with a longitudinal design are essential to further evaluate treatment in patients with OSA.     

Factors influencing the clinical expression of intermediate CAG repeat length mutations of the Huntington’s disease gene

Our aim is to elucidate the clinical variables associated with the development of manifest HD in patients with intermediate CAG repeat lengths. 2,167 participants were seen throughout 44 research sites in the United States, Canada or Australia over a five-year natural history observational study (2006–2011) (Trial # NCT00313495). The Chi-square test and a generalised linear model were used to examine the differences in demographics and cognitive tests among three groups of CAG repeat length. The mixed model was then used to examine the time effect on cognitive assessments by CAG groups. No patient with CAG repeat length 27–35 developed manifest HD, whereas three patients with 36–39 did. Total motor score, maximal chorea score and maximal dystonia score were significantly different at baseline (p < 0.001) for each measure between those patients with a repeat length 27–35 versus those 36–39; as were total functional assessment, independence scale and total functional capacity (p < 0.001). Being aged 65 years or more (OR 5.81, 95 % CI 0.37–90.58, p = 0.02) and smoking (OR 13.99, 95 % CI 2.03–96.44, p = 0.007) were related to manifest HD in patients with CAG 36–39; those with an associated university degree or higher education were less frequently diagnosed as manifest HD (OR 0.10, 95 % CI 0.02–0.54, p = 0.007). Age, smoking and lower education achievement were found to be significantly associated with higher odds of manifest HD in patients with intermediate CAG repeat length mutations.     

Safety and efficacy of Cerebrolysin in early post-stroke recovery: a meta-analysis of nine randomized clinical trials

This meta-analysis combines the results of nine ischemic stroke trials, assessing efficacy of Cerebrolysin on global neurological improvement during early post-stroke period. Cerebrolysin is a parenterally administered neuropeptide preparation approved for treatment of stroke. All included studies had a prospective, randomized, double-blind, placebo-controlled design. The patients were treated with 30–50 ml Cerebrolysin once daily for 10–21 days, with treatment initiation within 72 h after onset of ischemic stroke. For five studies, original analysis data were available for meta-analysis (individual patient data analysis); for four studies, aggregate data were used. The combination by meta-analytic procedures was pre-planned and the methods of synthesis were pre-defined under blinded conditions. Search deadline for the present meta-analysis was December 31, 2016. The nonparametric Mann-Whitney (MW) effect size for National Institutes of Health Stroke Scale (NIHSS) on day 30 (or 21), combining the results of nine randomized, controlled trials by means of the robust Wei-Lachin pooling procedure (maximin-efficient robust test), indicated superiority of Cerebrolysin as compared with placebo (MW 0.60, P?<?0.0001, N?=?1879). The combined number needed to treat for clinically relevant changes in early NIHSS was 7.7 (95% CI 5.2 to 15.0). The additional full-scale ordinal analysis of modified Rankin Scale at day 90 in moderate to severe patients resulted in MW 0.61 with statistical significance in favor of Cerebrolysin (95% CI 0.52 to 0.69, P?=?0.0118, N?=?314). Safety aspects were comparable to placebo. Our meta-analysis confirms previous evidence that Cerebrolysin has a beneficial effect on early global neurological deficits in patients with acute ischemic stroke.     

Influence of four polymorphisms in <Emphasis Type="Italic">ABCA1</Emphasis> and <Emphasis Type="Italic">PTGS2</Emphasis> genes on risk of Alzheimer’s disease: a meta-analysis

We preformed this meta-analysis to investigate the influence of ABCA1 (ATP-binding cassette sub-family A member 1) rs2422493 (C-477T), rs1800977 (C-14T), rs2066718 (V771M), and PTGS2 (Prostaglandin-endoperoxide synthase 2) rs20417 (G-765C) polymorphisms on the risk of Alzheimer’s disease (AD). Seventeen eligible case–control studies were acquired from PubMed, Embase, Alzgene, Chinese National Knowledge Infrastructure and Wanfang databases. The pooled odds ratios (ORs) with 95 % confidence intervals (95 % CI) were calculated to evaluate the association under five genetic models. Combined data indicated that ABCA1 rs2422493 polymorphism was statistically significant associated with increasing AD risk in three genetic models (allelic T vs C: OR = 1.12, 95 % CI: 1.01–1.24; homozygous TT vs CC: OR = 1.26, 95 % CI: 1.03–1.55; and recessive TT vs TC + CC: OR = 1.33, 95 % CI: 1.12–1.58) while no association was found between two other ABCA1 polymorphisms and AD susceptibility. Nevertheless, a further risk-stratification analysis showed that ApoE-ε4 carriers with any ABCA1 polymorphism suffered a much higher probability to be AD patients. Meanwhile, PTGS2 rs20417 polymorphism was linked to decreasing AD risk with a P < 0.0001 in five genetic models (e.g., allelic C vs G: OR = 0.59, 95 % CI: 0.50–0.70; homozygous CC vs GG: OR = 0.31, 95 % CI: 0.18–0.52; and heterozygous CG vs GG: OR = 0.64, 95 % CI: 0.52–0.78). In summary, our meta-analysis results showed that ABCA1 rs2422493 polymorphism was a risk factor for AD while PTGS2 rs20417 variant showed a protective effect on AD risk. In addition, ABCA1 rs2066718 and rs1800977 polymorphisms might not contribute to AD susceptibility in general population, but they should play a role on AD development when interacted with ApoE-ε4.     

The efficacy and safety of calcitonin gene-related peptide monoclonal antibody for episodic migraine: a meta-analysis

Objective

This meta-analysis was performed to evaluate the efficacy and safety of monoclonal antibodies against calcitonin gene-related peptide (CGRP) for episodic migraine prevention.

Methods

MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched from inception to April 2018. Studies considered to be eligible were randomized controlled trials about efficacy and safety of calcitonin gene-related peptide monoclonal antibody for episodic migraine prevention.

Results

Eight randomized controlled trials involving 2292 patients were included. The outcomes of this meta-analysis presented that CGRP monoclonal antibodies for preventive treatment of episodic migraine significantly reduced the monthly migraine days from baseline [weighted mean difference (WMD)?=???1.52; 95%CI, ??1.92 to ??1.11; Z?=?7.40; P?<?0.001] and monthly acute migraine-specific medication consumption from baseline [WMD?=???1.45; 95%CI, ??2.17 to ??0.72; Z?=?3.93; P?<?0.001], as compared with placebo group. CGRP monoclonal antibodies for preventive treatment of episodic migraine significantly increased the ≥?50% reduction from baseline in migraine days per month [RR?=?1.54; 95%CI, 1.38 to1.71; Z?=?7.88; P?<?0.001]. The adverse events were similar between the CGRP monoclonal antibody group and placebo group (P?=?0.998). The outcomes of subgroup analysis showed that erenumab, galcanezumab, and fremanezumab significantly reduced the monthly migraine days from baseline and increased the ≥?50% reduction from baseline in migraine days per month. Both erenumab and fremanezumab significantly reduced from baseline.

Conclusions

Based on the results of this meta-analysis, CGRP monoclonal antibodies significantly reduced the monthly migraine days and acute migraine-specific medication. CGRP monoclonal antibodies were effective and safe for preventive treatment of episodic migraine.

     

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.     

Meta-analysis of the association between <Emphasis Type="Italic">ZNF512B</Emphasis> polymorphism rs2275294 and risk of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, appears to result from the combination of genetic and environmental factors. Whether the rs2275294 polymorphism in the ZNF512B gene influences ALS risk is controversial. We meta-analysed the association between rs2275294 and ALS risk based on evidence published in the PubMed database. Five case–control studies involving 2559 patients with sporadic ALS and 5740 controls were analysed. Based on random-effects meta-analysis, the polymorphism rs2275294 was associated with increased risk of ALS disease in an allele model (C vs. T: OR 1.222, 95%CI 1.057 to 1.414, p?=?0.007). The available evidence suggests that the ZNF512B polymorphism rs2275294 is associated with ALS risk. These results should be validated in large, well-designed studies, especially in non-Asian populations.     

Dose effects of lacosamide as add-on therapy for partial-onset seizure in adult

The objective of the study was to evaluate the dose effects of lacosamide on the efficacy and safety as adjunctive therapy for partial-onset seizure in adults. We searched online databases such as Pubmed, Embase, Cochrane Online Library, and Clinicaltrial.gov for randomized control trials. A meta-analysis was performed on RevMan 5.3 software. Four randomized control trials with 1855 patients out of 310 citations and 30 registered trials were identified. 400 mg/d was more effective than 200 mg/d [RR 1.23 (95 % CI 1.05–1.45), P = 0.01], but the 600 mg/d didn’t show more benefit than 400 mg/d [RR 1.01 (95 % CI 0.81–1.27), P = 0.90]. Increasing the dosage led to higher incidence of quitting the medication because of adverse events [400 vs. 200 mg/d RR 2.17 (95 % CI 1.15–4.11), P = 0.02; 600 vs. 400 mg/d RR 1.55 (95 % CI 1.12–2.15), P = 0.009]. Incidence of serious adverse events did not occur with the increase of dose [400 vs. 200 mg/d RR 1.26 (95 % CI 0.50–3.20), P = 0.62], [600 vs. 400 mg/d RR 0.52 (95 % CI 0.21–1.30), P = 0.16]. A dose of 400 mg/d resulted in a higher chance of dizziness [RR 1.50 (95 % CI 1.02–2.20), P = 0.04], vomiting [RR 1.73 (95 % CI 1.03–2.90), P = 0.04], and diplopia [RR 1.98 (95 % CI 1.19–3.30), P = 0.008] than that of 200 mg/d. 400 mg/d is the optimal dose for efficacy. The dose of 200 mg/d has the best safety for less occurrence of adverse events and less quitting. Current evidence suggests that a dose of 600 mg/d is unnecessary, except for particular reasons.     

TREM2 variants and risk of Alzheimer’s disease: a meta-analysis

Recent studies show that heterozygous variant of triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk of Alzheimer’s disease (AD) but with inconclusive results. Here, we conducted a meta-analysis to summarize and clarify the association between TREM2 variants and AD, and examined the relationship between TREM2 genetic variant and the etiology of AD. Relevant case–control studies were retrieved and collected according to established inclusion criteria. Odds ratio (OR) and 95 % confidence interval (95 % CI) were used to estimate the associations between three TREM2 variants (rs75932628, rs104894002, and rs143332484) and AD. In overall meta-analysis, the summary ORs for rs75932628, rs104894002, and rs143332484 were 2.70 [95 % CI: 2.24, 3.24; P < 0.001], 7.21 (95 % CI: 1.28, 40.78; P = 0.025), and 1.65 (95 % CI: 1.24, 2.21; P = 0.001), respectively, indicating that the TREM2 rs75932628, rs104894002, and rs143332484 may contribute to AD risk. However, sensitivity analysis showed that the results of rs104894002 and rs143332484 should be interpreted with caution, and larger sample size, particularly in different ethnicities, are needed to validate the two variants. The current meta-analysis demonstrates that TREM2 is a candidate gene for AD susceptibility, and TREM2 variant rs75932628 may be a risk factor for AD.     

Genetic association of CALHM1 rs2986017 polymorphism with risk of Alzheimer’s disease: a meta-analysis

Recent studies investigating the association of Calcium homeostasis modulator 1 (CALHM1) p.P86L polymorphism (rs2986017) with Alzheimer’s disease (AD) are controversial. Herein, we performed a meta-analysis to investigate the association between CALHM1 rs2986017 and AD risk. Literature searches of PubMed, Alzgene, and Embase were carried out up to 24 Nov 2015. The strength of the association between rs2986017 and AD was evaluated by odds ratio (OR) and 95 % confidence interval (CI). A total of 19 studies between 2008 and 2014 comprising 8777 AD cases and 8487 controls were included. Significant association of rs2986017 with AD was found in Caucasian population in allelic model (T vs. C: OR 1.13, 95 % CI 1.02–1.26, P = 0.022), and dominant model (TT + TC vs. CC: OR 1.15, 95 % CI 1.04–1.29, P = 0.018). No significant association was found in Asian population in any genetic model. Sensitivity analysis found that Dreses-Werringloer et al.’s might affect the overall result. The current meta-analysis suggested that CALHM1 rs2986017 might be associated with increased AD risk in Caucasian, but not Asian population.     

Association of GWAS-Supported Variants rs556621 on Chromosome 6p21.1 with Large Artery Atherosclerotic Stroke in a Southern Chinese Han Population

Recent genome-wide association study associated rs556621 on chromosome 6p21.1 with the risk of large artery atherosclerotic (LAA) stroke in Caucasians. However, subsequent replicate studies showed conflict results in different ethnicities. This study aimed to evaluate whether rs556621 was associated with LAA stroke in Chinese Han population. In this case–control study, 659 patients with LAA stroke and 650 healthy controls were enrolled. Associations between rs556621 genotypes and LAA stroke were analyzed with logistic regression model. Rs556621 variants were associated with increased risks of LAA stroke (codominant model: OR 1.42; 95 % CI 1.01–1.99; P = 0.010; recessive model: OR 1.40; 95 % CI 1.05–1.86; P = 0.003). When subjects were stratified by sex, TT genotype of SNP rs556621 was associated with an increased risk of LAA stroke in female when tested with recessive model (OR 2.36; 95 % CI 1.28–4.36, P = 0.006). In male subjects, however, no significant association was detected. Smoking status, sex did not significantly influence the relationship between genotypes of rs556621 and risk of LAA stroke (P _interaction = 0.140, P _interaction = 0.076). Rs556621 may play an important role in the development of LAA stroke in female Chinese of Han ethnicity. Larger studies with subjects of different ethnicities are warranted to confirm these findings.