Homogeneity of large and small vessel disease over time: Arguments from a study on recurrent stroke in 998 patients with first cerebral infarct

Background: Data on subtype and location of recurrent stroke after a first cerebral infarct may be relevant for prognosis and for understanding progression of the vascular disease underlying stroke subtypes over time. Therefore, we studied 30-day case fatality, stroke subtype, and stroke location in first and recurrent stroke, accounting for stroke subtype. Methods: We conducted a cross-sectional follow-up of 998 patients with first cerebral infarct registered in a hospital-based stroke registry. Results: After a follow-up of 691 ± 521 (SD) days, there were 138 (13.8%) first recurrent strokes, 84 (61%) of which had computed tomography. Recurrent stroke was of the same subtype as the first stroke in 27 (57%) of 339 lacunar, 38 (83%) of 435 atherothrombotic, and 33 (94%) of 224 cardioembolic cerebral infarcts. The annual stroke recurrence rate was about 7% for the whole group. Logistic regression analysis showed lacunar first stroke and hypertension as independent predictors for recurrent lacunar stroke, and atherothrombotic first stroke type for recurrent atherothrombotic stroke. Stroke recurrences that were of the same type as the first stroke occurred in the same brain area as the first stroke in 70% of lacunar and 79% of atherothrombotic cases. This was more frequent when compared with nonsimilar recurrence types: odds ratio (OR) 4.38, 95% confidence interval (CI) 1.09–15.79; and OR 5.63, 95% CI 1.38–22.92, respectively. Only 33% of cardioembolic recurrent strokes occurred in the same area. The 30-day case fatality in index and recurrent stroke was, respectively, 2% and 14% (OR 7.90, 95% CI 2.78–22.48) for lacunar, 10% and 26% (OR 3.27, 95% CI 1.62–6.60) for atherothrombotic, and 23% and 31% (OR 1.47, 95% CI 0.55–3.93) for cardioembolic index infarcts. Conclusions: The annual stroke recurrence rate after a first brain infarcts is about 7%. Early case fatality after recurrent stroke is higher than after first stroke, with marked differences between stroke subtypes. Progression of small and large vessel disease, and the brain area of their location, are rather homogeneous over time.     

GWAS-Supported <Emphasis Type="Italic">CRP</Emphasis> Gene Polymorphisms and Functional Outcome of Large Artery Atherosclerotic Stroke in Han Chinese

Elevated C-reactive protein (CRP) levels increase the risk of poor functional disability in patients with ischemic stroke (IS). This study aimed to investigate the association between CRP gene polymorphisms and 3-month functional disability of large artery atherosclerotic (LAA) stroke in Han Chinese. Patients with first-ever LAA IS were prospectively enrolled in Nanjing Stroke Registry Program between August 2013 and October 2015. Five single-nucleotide polymorphisms (SNPs) (rs876537, rs2794520, rs3093059, rs7553007 and rs11265260) in CRP gene related to CRP levels in Asian by genome-wide association study were genotyped. The functional outcome at 3 months after the index stroke was assessed by the modified Rankin scale. Associations between genotypes and functional outcome of LAA IS were analyzed with logistic regression model. A total of 690 eligible patients (507 males) were evaluated. SNPs rs11265260 (multivariate-adjusted, p?=?0.022), rs2794520 (multivariate-adjusted, p?=?0.036) and rs3093059 (multivariate-adjusted, p?=?0.027) were significantly associated with elevated CRP in acute IS. Two SNPs, rs3093059 (dominant model: adjusted OR 2.49; 95% CI 1.55–4.00; recessive model: adjusted OR 3.67; 95% CI 1.22–11.03) and rs11265260 (dominant model: adjusted OR 2.51; 95% CI 1.56–4.02; recessive model: adjusted OR 4.70; 95% CI 1.63–13.56) independently predicted 3-month poor outcome of first-ever LAA IS, after adjusting for covariates. In addition, haplotype analysis indicated that haplotype GCTGC (adjusted OR 1.76; 95% CI 1.05–2.95; p?=?0.031) increased the poor outcome risk. SNPs rs3093059 and rs11265260 in CRP gene may influence the 3-month functional outcome of first-ever LAA IS in Han Chinese.     

Association of Endothelin-converting Enzyme-1b C-338A Polymorphism with Increased Risk of Ischemic Stroke in Chinese Han Population

Endothelin-converting enzyme-1b (ECE-1b) C-338A is a polymorphism located in ECE-1 gene promoter, which has been reported to correlate with the risk of carotid atherosclerosis. We conducted a hospital-based case–control study of 309 patients with ischemic stroke and 309 controls matched on age and gender. The frequencies of ECE-1b-338 CC, CA, and AA genotypes in cases (45.0, 40.4, and 14.6 %) were significantly different from those of controls (53.1, 39.1, and 7.8 %, χ ²?=?8.519, P?=?0.014), respectively. Compared with C carriers, A alleles showed correlation with a 42 % increased risk of ischemic stroke (adjusted odds ratio (OR)?=?1.42, 95 % CI?=?1.11–1.81). After adjustment for potential risk factors, the AA genotype still kept positive correlation with ischemic stroke (OR?=?1.78; 95 % CI?=?1.06–3.54). In stratified analyses, the significant association of the A allele with ischemic stroke was observed in female subjects (adjusted OR?=?1.64, 95 % CI?=?1.17–2.89) and the subjects with age ≥64 years old (adjusted OR?=?2.09, 95 % CI?=?1.38–3.23). The present study suggested that the C-338A polymorphism of the ECE-1b gene was associated with an increased risk of ischemic stroke in the Chinese Han 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.     

Genetic Polymorphisms in Pre-microRNAs and Risk of Ischemic Stroke in a Chinese Population

Ischemic stroke is considered to be a complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. MicroRNAs participated in various physiopathological processes; common single-nucleotide polymorphisms (SNPs) in pre-miRNAs have been shown to be associated with susceptibility to several human diseases. We evaluated the associations of the hsa-mir-196-a2/rs11614913 T/C, hsa-mir-146a/rs2910164 C/G, and hsa-mir-499/rs3746444 A/G polymorphisms in pre-miRNAs with the risk of ischemic stroke in a Chinese population. The three polymorphisms were identified in 296 ischemic stroke patients and 391 healthy controls using polymerase chain reaction–restriction fragment length polymorphism. The frequency of the allele G of hsa-mir-499/rs3746444 A/G showed significant association with ischemic stroke when compared with controls (OR?=?1.509, 95%CI?=?1.151–1.978, P?=?0.003). Increased ischemic stroke risks were associated with rs3746444 A/G genotypes in different genetic model (homozygote comparison: P?=?0.045, OR?=?2.084, 95%CI?=?1.019–4.262; heterozygote comparison: P?=?0.024, OR?=?1.489, 95%CI?=?1.063–2.087; dominant genetic model: P?=?0.007, OR?=?1.563, 95%CI?=?1.135–2.153). Similar results were obtained by adjusted fully risk factors. However, we failed to find any association between the alleles and genotypes of rs2910164 C/G and rs11614913 T/C SNPs and ischemic stroke, respectively (p?>?0.05). The present study provided evidence that hsa-mir-499/rs3746444 A/G polymorphism might be associated with a significantly increased risk of ischemic stroke in a Chinese population, indicating that the common genetic polymorphism in pre-microRNAs contributed to the pathogenesis of ischemic stroke.     

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.     

Cyclooxygenase 2 Genetic Polymorphism May Increase the Risk of Developing Leukoaraiosis in Chinese

Cyclooxygenase-2 (COX-2) is a key enzyme involved in the conversion of arachidonic acid into prostaglandins, which are important mediators of inflammation. To clarify the role of inflammation in the pathogenesis of cerebral small vessel disease (SVD), we investigate the possible modulating effect of the functional COX-2 polymorphisms -1195G?>?A (rs689466) and -765G?>?C (rs20417) on the risk for development of cerebral SVD in a Chinese population. Genomic DNA of 116 patients with lacunar infarction (LI), 334 patients with leukoaraiosis (LA) and 450 control subjects was genotyped for the COX-2 -1195G?>?A and -765G?>?C polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. Distribution of genotypes and haplotypes in patients and controls were compared. The genotype distribution of the -765G?>?C polymorphism was not different between the patients with LI or LA and the control group. The 1195A allele carriers was identified independently to be related with LA (adjusted OR?=?1.41, 95 % confidence interval (CI)?=?1.09–2.10, P?=?0.03) but not associated with LI. The linkage disequilibrium analysis showed that -1195G?>?A and -765G?>?C SNPs are moderate linkage disequilibrium in this study population (D′?=?0.70, r ²?=?0.16). Compared with G-1195-G-765 haplotype, the haplotype of A-1195-G-765 showed significantly increased the risk of LA (OR?=?1.24, 95 % CI?=?1.10–1.55, P?=?0.04) but not LI. In conclusion, we found that -1195G?>?A polymorphism and A-1195-G-765 haplotype of COX-2 were associated with susceptibility to LA in a Chinese population.     

Cyclooxygenase-2 Genetic Polymorphism and Stroke Subtypes in Chinese

Background

Cyclooxygenase-2 (COX-2) catalyzes the formation of prostaglandins that contribute to the inflammation in atherosclerosis. The aim of the present study was to investigate the relationship between two polymorphisms (?1195G>A and -765G>C) in the COX-2 gene and subtypes of ischemic stroke in a Chinese population.

Methods

Genomic DNA of 224 patients with large artery atherosclerosis (LAA), 329 patients with small vessel occlusion (SVO), and 450 controls were genotyped for the COX-2 1195G>A (rs689466) and -765G>C (rs20417) polymorphisms using polymerase chain reaction–restriction fragment length polymorphism. Chi-square test and logistic regression analysis were performed for association analysis.

Results

The frequencies of variant allele with -1195G>A and -765G>C polymorphisms were 0.46 and 0.22, respectively. The -1195GA genotype and 1195A allele carriers were identified independently to be related with ischemic stroke (adjusted OR?=?1.51, 95 % CI: 1.09–2.10, P?=?0.02; OR?=?1.45, 95 % CI: 1.06–1.97, P?=?0.02) and SVO (adjusted OR?=?1.57, 95 % CI: 1.07–2.30, P?=?0.02; OR?=?1.50, 95 % CI: 1.05–2.16, P?=?0.03). In contrast, the 1195G>A polymorphism was not associated with LAA. No relationship between the -765G>C polymorphism and risk of either ischemic stroke was observed. The linkage disequilibrium analysis showed that -1195G>A and -765G>C SNPs are moderate linkage disequilibrium in this study population (D′?=?0.72, r ²?=?0.16). Compared with G-1195-G-765 haplotype, the haplotype of A-1195-G-765 showed significant increased risk of ischemic stroke (OR?=?1.27, 95 % CI: 1.05–1.54, P?=?0.02) and SVO (OR?=?1.27, 95 % CI: 1.02–1.58, P?=?0.03) but not LAA.

Conclusions

In conclusion, we found that -1195G>A polymorphism and A-1195-G-765 haplotype of COX-2 were associated with susceptibility to ischemic stroke in a Chinese population. The effects were confined to SVO among the stroke subtypes rather than to LAA.     

Genetic Analysis of the Leucine-Rich Repeat and lg Domain Containing Nogo Receptor-Interacting Protein 1 Gene in Essential Tremor

Variants in the leucine-rich repeat and lg domain containing nogo receptor-interacting protein 1 gene (LINGO1) have been identified to be associated with the increased risk of essential tremor (ET), especially among Caucasians. To explore whether the LINGO1 gene plays a role in ET susceptibility, we performed a systematic genetic analysis of the coding region in the LINGO1 gene. Four nucleotide variants have been genotyped, including three known variants (rs2271398, rs2271397, and rs3743481), and a novel G→C transition (ss491228439). Extended analysis showed no significant difference in genotypic and allelic distributions between 151 patients and 301 control subjects for these four variants (all P?>?0.05). However, further sex-stratified analysis revealed that the C allele of rs2271397 and ss491228439 contributed the risk of ET in female (P?=?0.017, OR?=?2.139, 95 % CI 1.135?~?4.030 for rs2271397 and P?=?0.038, OR?=?1.812, 95 % CI 1.027?~?3.194 for ss491228439). Haplotype analysis indicated that A465-C474-C714 haplotype was significantly associated with increased risk of ET in female (P?=?0.041, OR?=?1.800, 95 % CI 1.020?~?3.178). Our results indicate that the LINGO1 variants are associated with ET in Chinese Han female patients.     

Serum levels of homocysteine at admission are associated with post-stroke depression in acute ischemic stroke

The primary purpose of this study was to assess the serum levels of homocysteine (HCY) at admission to the presence of post-stroke depression (PSD). From September 2014 to December 2015, first-ever acute ischemic stroke patients within the first 24 h after stroke onset were consecutively recruited and followed-up for 3 months. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for depression. By the time of 3 month after stroke, 238 had finished the follow-up and included in our study. Totally, 65 out of the 238 patients were diagnosed as depression (27.3%; 95% CI 19.6–35.4%). The results showed significantly higher HCY levels in patients with depression [21.4 (IQR 16.5–23.4) mmol/L vs. 14.1 (IQR 11.2–18.5) mmol/L, P < 0.0001) at admission than patients without depression. In multivariate logistic regression analysis, HCY was an independent predictor of PSD with an adjusted OR of 1.07 (95% CI 1.01–1.22; P = 0.013). Based on the ROC curve, the optimal cut-off value of serum HCY levels as an indicator for prediction of PSD was projected to be 16.5 mmol/L, which yielded a sensitivity of 82.5% and a specificity of 63.6%, with the area under the curve at 0.745 (95% CI 0.672–0.818; P < 0.0001). An increased risk of PSD was associated with serum HCY levels ≥16.5 mmol/L (adjusted OR 6.13, 95% CI 3.32–14.16; P < 0.001) after adjusting for above-recorded confounders. Elevated serum levels of HCY at admission were associated with depression 3-month after stroke, suggesting that these alterations might participate in the pathophysiology of depression symptoms in stroke patients.     

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.

     

Alcohol consumption and the risk of stroke among hypertensive and overweight men

High blood pressure and overweight are risk factors for stroke. The aim of the present study was to examine the association between alcohol consumption and the risk of stroke according to the level of blood pressure and body weight. This study is a population-based sample of men with an average follow-up of 14.9 years from eastern Finland. A total of 2,599 men with no history of stroke at baseline participated. During the follow-up period, 224 strokes occurred, of which 181 were ischemic strokes. After adjustment for age, year of examination, socioeconomic status, serum LDL cholesterol, body mass index, smoking and energy expenditure of physical activity (kcal/day), there was a significant trend of an increased risk for any and ischemic stroke among hypertensive men. Hypertensive (blood pressure of over 140/90 mm Hg) men, who did not consume alcohol had a 1.72-fold (95 % CI 1.12–2.66; p = 0.014) relative risk (RR) for any stroke and a 1.90-fold (95 % CI 1.15–3.13; p = 0.012) RR for ischemic stroke. Among hypertensive men who consumed alcohol RR was 1.86-fold (95 % CI 1.20–2.89; p = 0.005) for any stroke and 2.02-fold (95 % CI 1.21–3.35; p = 0.007) for ischemic stroke. Men who did not consume alcohol with elevated BMI (≥26.4 kg/m²) had a 1.63-fold RR (95 % CI 1.11–2.40; p = 0.013) for any stroke and a 1.33-fold RR (95 % CI 0.87–2.04; p = 0.199) for ischemic stroke after adjusting for risk factors. Overweight men (≥26.4 kg/m²) who consumed alcohol had a 1.73-fold RR (95 % CI 1.18–2.54; p = 0.005) for any stroke and a 1.71-fold RR (95 % CI 1.14–2.57; p = 0.010) for ischemic stroke after being adjusted for risk factors. In conclusion, this population-based prospective study shows that hypertensive and overweight men who consumed alcohol had an increased risk for stroke.     

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.     

Epidemiology of stroke in Northern Italy: the Cerebrovascular Aosta Registry, 2004–2008

Our aim was to prospectively ascertain the incidence of first-ever stroke and ischaemic stroke subtypes, mortality, functional outcome and recurrence in Northern Italy. We identified all possible cases of stroke (1st January 2004 and 31st December 2008). Multiple overlapping sources were used. Standard definitions for incident cases, pathological types and infarction subtypes were used. Patient characteristics were identified and analysed, case-fatality was ascertained from administrative databases, and outcome was assessed in all surviving patients by modified Rankin Scale. We identified 1,326 incident strokes. The pathological diagnosis was confirmed in 94 % of cases. The incidence of first-ever stroke was 80.2 per 100,000 (95 % CI 73–87) when adjusted to world population. The incidence of embolic stroke was significantly greater in women than in men (p < 0.001) whereas the incidence of atherothrombotic stroke was significantly greater in men than in women (p < 0.001). The case-fatality of incident strokes was 9.5 % at 7 day, 16.1 % at 28 day, and 29.9 % at 1 year. Case-fatality of ischaemic stroke was lower than that of other pathological types (p < 0.0001). Hypertension was the most important risk factor, and atrial fibrillation was the most common in embolic stroke. Increasing age, female gender and embolic stroke subtypes were associated with an adverse outcome. Data on stroke incidence and case-fatality were similar to those of other high-income countries. However, differences were found in the distribution of risk factors and prognosis across the stroke types and ischaemic stroke subtypes. Gender differences in long-term functional outcomes were significant.     

Lymphocyte-to-monocyte ratio on day 7 is associated with outcomes in acute ischemic stroke

The main features of stroke-induced immunosuppression are lymphopenia and deactivation of monocytes in peripheral blood. We hypothesized that lymphocyte-to-monocyte ratio (LMR) in peripheral blood may represent the degree of stroke-induced immunosuppression. To prove this hypothesis, we evaluated whether LMR is associated with risk of post-stroke infection and clinical outcome at 3 months in patients with acute ischemic stroke. We selected patients with stroke in anterior circulation within 24 h from onset. Peripheral blood sampling for differential blood count was performed on days 1 and 7. The LMRs on days 1 and 7 were analyzed to determine associations with excellent outcomes (modified Rankin Scale of score 0–1 at 3 months). One hundred and two patients were included. The initial National Institutes of Health Stroke Scale score (adjusted odd ratio [OR] 0.89; 95% confidence interval [CI], 0.83–0.95; P = 0.001) and LMR on day 7 (adjusted OR 1.49; 95% CI, 1.09–2.02; P = 0.011) were associated with excellent outcomes. LMRs on day 1 were significantly lower in stroke patients with pneumonia (P = 0.007) and pneumonia or urinary tract infection (P = 0.012) than those without infections. LMRs on day 7 were also significantly lower in stroke patients with infection (P = 0.005 in pneumonia, P = 0.003 in urinary tract infection, and P < 0.001 in pneumonia or urinary tract infection) than those without infections. Lower LMRs on day 7 are associated with worse outcomes at 3 months after stroke onset. LMR may be a useful marker for assessing the stroke-induced immunosuppression.     

Mortality of patients with multiple sclerosis: a cohort study in UK primary care

We aimed to estimate rates, causes and risk factors of all-cause mortality in a large population-based cohort of multiple sclerosis (MS) patients compared with patients without MS. Using data from the UK General Practice Research Database, we identified MS cases diagnosed during 2001–2006 and validated using patients’ original records where possible. We also included MS cases during 1993–2000 identified and validated in an earlier study. Cases were matched to up to ten referents without MS by age, sex, index date (date of first MS diagnosis for cases and equivalent reference date for controls), general practice and length of medical history before first MS diagnosis. Patients were followed up to identify deaths; hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox-proportional regression. MS patients (N = 1,822) had a significantly increased risk of all-cause mortality compared with referents (N = 18,211); adjusted HR 1.7 (95 % CI 1.4–2.1). Compared with referents, female MS patients had a higher but not significantly different HR for death than males; adjusted HR 1.86 (95 % CI 1.46–2.38) vs. HR 1.31 (95 % CI 0.93–1.84), respectively. The most commonly recorded cause of death in MS patients was ‘MS’ (41 %), with a higher proportion recorded among younger patients. A significantly higher proportion of referents than MS patients had cancer recorded as cause of death (40 vs. 19 %). Patients with MS have a significant 1.7-fold increased risk of all-cause mortality compared with the general population. MS is the most commonly recorded cause of death among MS patients.     

Association of <Emphasis Type="Italic">TNFSF4</Emphasis> Polymorphisms with Neuromyelitis Optica Spectrum Disorders in a Chinese Population

The tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene encodes a vital co-stimulatory molecule of the immune system and has been identified as a susceptibility locus for systemic lupus erythematosus, systemic sclerosis, and primary Sjögren’s syndrome. However, the association of TNFSF4 polymorphisms with neuromyelitis optica spectrum disorders (NMOSD), an inflammatory, demyelinating autoimmune disease of the central nervous system, has not yet been investigated. To evaluate whether TNFSF4 polymorphisms contribute to risk of NMOSD, four single-nucleotide polymorphisms (SNPs) (rs1234315, rs2205960, rs704840, and rs844648) were selected and genotyped in a cohort of 312 patients with NMOSD and 487 healthy controls. Our study showed that rs844648 was associated with an increased risk of NMOSD, according to the allelic model (OR = 1.30, 95% CI 1.06–1.59, P = 0.011, Pcorr = 0.044). Significant associations of rs844648 (OR = 1.67, 95% CI 1.17–2.38, P = 0.005, Pcorr = 0.02) and rs704840 (OR = 1.75, 95% CI 1.17–2.63, P = 0.007, Pcorr = 0.027) with NMOSD occurrence were also observed under the recessive model. Moreover, linkage disequilibrium analysis revealed two blocks within TNFSF4; in one block, the haplotype A_rs844648G_rs704840 significantly increased the risk of NMOSD, whereas G_rs844648T_rs704840 reduced the risk. This study demonstrates an association between TNFSF4 polymorphisms and susceptibility for the development of NMOSD in the Chinese population.     

Papilloedema is an independent prognostic factor for POEMS syndrome

POEMS syndrome is a potentially fatal disease, and prediction of prognostic factors for POEMS syndrome is important for clinicians. Papilloedema is an early sign of the syndrome. The present study was carried out to evaluate whether papilloedema is a prognostic factor for POEMS syndrome. Between January 2003 and December 2012, 94 patients with POEMS syndrome were enrolled in this study. The patients were divided into groups with and without papilloedema. Logistic regression was performed to identify risk factors related to papilloedema. Prognostic factors were analysed with Cox proportional hazard regressions for POEMS syndrome-related prognoses, and survival curves were plotted using the Kaplan–Meier method and compared by the log-rank test. Papilloedema was found in 52.1 % of the patients with POEMS syndrome. Raised intracranial pressure [hazard ratio (HR) 3.06, 95 % confidence interval (CI) 1.24–7.41; P = 0.011] and elevated cerebrospinal fluid protein levels (HR 2.03, 95 % CI 1.07–4.51; P = 0.043) were independently associated with papilloedema. Papilloedema, decreased diffusing capacity of the lung for carbon monoxide (DLCO) and treatment with corticosteroids alone were related to poor prognosis in POEMS syndrome. In multivariate analysis, papilloedema (HR 1.58, 95 % CI 1.05–2.46; p = 0.027) and decreased DLCO (HR 2.17, 95 % CI 1.12–3.39; p = 0.023) were independent factors for POEMS syndrome-related death. Papilloedema and decreased DLCO are important prognostic factors for patients with POEMS syndrome, which can help clinicians predict the risk of mortality and provide better medical care for these patients.     

STAT4 Polymorphisms are Associated with Neuromyelitis Optica Spectrum Disorders

STAT4 plays a crucial role in the functioning of the innate and adaptive immune cells and has been identified as a susceptibility gene in numerous autoimmune disorders. However, its association with neuromyelitis optica spectrum disorders (NMOSD) remains uncertain. Here, we performed a case–control study to determine whether STAT4 contributed to the risk of NMOSD. We tested five STAT4 SNPs in 233 patients with established NMOSD and 492 healthy controls. Chi-square tests and logistic regression analyses were performed with four genetic models, including allelic, additive, dominant, and recessive models, to identify associations with NMOSD. The results of multiple test comparisons were corrected using the Benjamini and Hochberg false discovery rate (FDR–BH). After correcting for multiple test comparisons, the minor alleles of four STAT4 SNPs exhibited significant association with increased risk of NMOSD (rs7574865 T, odds ratio [OR] = 1.66, 95% confidence interval [CI] 1.32–2.08, P _corr = 0.000; rs10181656 G, OR = 1.62, 95% CI 1.29–2.03, P _corr = 0.000; rs10168266 T, OR = 1.59, 95% CI 1.27–2.00, P _corr = 0.001; and rs13426947 A, OR = 1.51, 95% CI 1.21–1.90, P _corr = 0.004). Identical results were observed in the dominant, recessive, and additive models. In contrast, the G allele of rs7601754 displayed a protective effect against NMOSD (OR = 0.53, 95% CI 0.36–0.76, P _corr = 0.006). Our study indicates that STAT4 polymorphisms are associated with the risk of NMOSD, which provides novel insights into the underlying mechanisms of this disease.     

The occurrence of seizures after ischemic stroke does not influence long-term mortality; a 26-year follow-up study

Objective

Epileptic seizures are a common complication after stroke. The relation between occurrence of seizures after stroke and long-term mortality remains elusive. We aimed to assess whether seizures in an early or late phase after ischemic stroke are an independent determinant of long-term mortality.

Methods

We prospectively included and followed 444 ischemic stroke patients with a first-ever supratentorial brain infarct for at least 2 years after their stroke regarding the occurrence of seizures. The final follow-up for mortality is from April 2015 (follow-up duration 24.5–27.8 years, mean 26.0 years, SD 0.9 years). We compared patients with early-onset seizures with all seizure-free patients, whereas the patients with late-onset seizures were compared with the 1-week survivors without any seizures. We used Cox-regression analyses to correct for possible confounding factors.

Results

Kaplan–Meier analysis showed significantly higher mortality for the patients with early-onset seizures (p?=?0.002) but after correction for known risk factors for (long term) mortality early-onset seizures had no independent influence on long-term mortality (HR 1.09; 95% CI 0.64–1.85). In patients with late-onset seizures, no significant influence from late-onset seizures on long-term mortality was found (univariate p?=?0.717; multivariate HR 0.81; 95% CI 0.54–1.20).

Conclusion

Both early-onset and late-onset seizures do not influence long-term mortality after ischemic stroke.