<Emphasis Type="Italic">TLR4</Emphasis> polymorphisms affect stroke risk and inflammatory response in Chinese ischemic stroke patients

This study aimed to evaluate the association of the toll-like receptor 4 (TLR4) polymorphisms rs1927914, rs10759932, and rs11536889 with susceptibility to ischemic stroke (IS) and the serum levels of inflammatory cytokines. A total of 816 IS patients and 816 control subjects were genotyped using Sequenom MassARRAY technology. The serum levels of interleukin 1 beta (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNFα) were measured by enzyme-linked immunosorbent assay. rs1927914 was significantly associated with male IS patients in the additive model [odds ratio (OR) = 0.81; 95% confidence interval (CI) = 0.67–0.99; P = 0.039] and in the allele model (OR = 0.81; 95% CI = 0.66–0.99; P = 0.037). In the dominant model, rs10759932 was significantly associated with the serum TNFα level of the male IS patients [regression coefficient (β) = 0.15; 95% CI = 0.01–0.29; P _adj = 0.042]. This polymorphism was also correlated with the serum IL-8 level of female IS patients in the additive model (β = 0.24; 95% CI = 0.25–0.43; P _adj = 0.021) and in the recessive model (β = 0.65; 95% CI = 0.11–1.11; P _adj = 0.026). The TLR4 gene rs1927914 polymorphism was associated with susceptibility to IS in males. Moreover, the rs10759932 polymorphism may affect inflammatory response in IS patients.     

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.     

Risk factors for unprovoked epileptic seizures in multiple sclerosis: a systematic review and meta-analysis

The role of different factors in influencing the risk of seizures during multiple sclerosis (MS) is not known. To perform a systematic review and meta-analysis of risk factors for epilepsy during MS. Pubmed, Google scholar, and Scopus databases were searched. Articles published in English (1986–2016) were included. Nine studies were included (3 retrospective cohort and 6 case–control) enrolling 2845 MS patients (217 with epilepsy; 7.6%). MS patients with epilepsy had a younger age at onset compared to MS patients without seizures (difference in means = ?5.42 years, 95% CI ?7.19 to ?3.66, p < 0.001). Mean EDSS value at inclusion tended to be higher in patients with epilepsy, without reaching statistical significance (difference in means = 0.45, 95% CI ?0.01 to 0.91, p = 0.054). No differences were observed in sex distribution (OR = 0.94, 95% CI 0.51–1.72, p = 0.83) and clinical form (OR = 1.03, 95% CI 0.33–3.21, p = 0.96). Two studies evaluated presence and number of cortical lesions as a risk factor for epilepsy in MS using different MRI techniques: in one study, cortical lesions were more frequently observed in patients with epilepsy (OR = 7.06, 95% CI 2.39–20.8; p < 0.001). In the other, cortico-juxtacortical lesions were more frequently observed in patients with epilepsy (OR = 2.6, 95% CI 1.0–6.5; p = 0.047). Studies about risk factors for epilepsy during MS are heterogeneous. Compared to MS patients without seizures, patients with epilepsy have an earlier MS onset and a higher EDSS score after similar disease duration. Clinical form of MS and sex do not predict the appearance of seizures.     

Depression and Smoking Cessation: Evidence from a Smoking Cessation Clinic with 1-Year Follow-Up

Background

Smoking is more prevalent among people with depression. Depression may make cessation more difficult and cessation may affect depression symptoms.

Purpose

The aims of this study were to assess the associations between (1) baseline depression and 1-year smoking abstinence and (2) abstinence and change in depression.

Methods

Observational study using data collected routinely in a smoking cessation clinic in the Czech Republic from 2008 to 2014. Aim 1: N = 3775 patients; 14.3% reported mild and 15.4% moderate/severe baseline depression levels measured using Beck’s Depression Inventory (BDI-II). Logistic regressions assessed if depression level predicted 1-year biochemically verified abstinence while adjusting for patient and treatment characteristics. Aim 2: N = 835 patients abstinent at 1 year; change in depression was analysed using Chi-square statistics, t test and mixed method analyses of variance.

Results

Rate of abstinence was lower for patients with mild (32.5%, OR = 0.68; 95% CI: 0.54 to 0.87, p = 0.002) and moderate/severe depression (25.8%; OR = 0.57, 95% CI: 0.45 to 0.74, p < 0.001) compared with patients without depression (40.5%).Across abstinent patients, the majority with baseline depression reported lower depression levels at follow-up. Overall mean (SD) BDI-II scores improved from 9.2 (8.6) to 5.3 (6.1); t(834) = 14.6, p < 0.001. There were significant main effects of time (F(1832) = 880.8, p < 0.001, partial η² = 0.51) and baseline depression level (F(2832) = 666.4, p < 0.001, partial η² = 0.62) on follow-up depression and a significant depression * time interaction (F(2832) = 296.5, p < 0.001, partial η² = 0.42).

Conclusions

In this effective smoking cessation clinic, depression at the start of treatment predicted reduced smoking abstinence 1 year later. Patients abstinent from smoking experienced considerable improvement in depression.

     

Prevalence and Associated Factors of Depression Among Post-Stroke Patients in Bangladesh

To assess the prevalence of depression and its associated factors among patients with stroke in Bangladesh. We conducted a cross-sectional study among 164 post-stroke patients attending two hospitals in Dhaka city between January and June 2011. Depression was measured using the Hamilton Depression Rating Scale. Factors associated with depression were analyzed using multivariate logistic regression. Results: The prevalence of depression was 70 and 32 % had severe depression. The mean ± sd age of the participants was 58.91 ± 7.03 years. Multivariate regression analysis revealed that factors significantly associated with depression were living in a joint family (OR = 13.5, 95 % CI = 1.3–145.7, p = 0.032), those unable to perform daily activities by themselves (OR = 14.9, 95 % CI = 2.0–108.1, p = 0.008) and those with comorbid dysphasia (OR = 9.5, 95 % CI = 1.0–86.9, p = 0.046) and hypertension (OR = 5.2, 95 % CI = 2.3–15.4, p = 0.012). Depression is a significant health problem among post-stroke patients in Bangladesh. This leads to careful management of depression for social support to achieve better patient outcome.     

Etiologic spectrum and functional outcome of the acute inflammatory myelitis

Clinical, neuroimaging, and laboratory features are not specific enough to establish the etiological diagnosis of the acute inflammatory myelitis (AIM). Longitudinally extensive transverse myelitis (LETM) seen on magnetic resonance imaging (MRI) has been associated with a poor functional prognosis. The aim of this study was to assess the functional outcomes of a first AIM event comparing patients with LETM vs. no LETM on MRI and to report the differential diagnosis. Clinical, radiological, biochemical aspects were collected, and Winner–Hughes Functional Disability Scale (WHFDS) was performed after 3 and 6 months. Centromedullary lesions were associated with LETM, lateral lesions with partial lesion (PL), and brain MRI lesions with multiple sclerosis and acute encephalomyelitis disseminated. LETM patients were associated with a worse functional outcome as the need of a wheelchair after 3 and 6 months (OR = 7.61 p = 0.01; OR 4.8 p = 0.04, respectively), a walker or cane (OR = 11.0 p = 0.002, OR = 4.3 p = 0.03, respectively). In addition, we found a correlation between LETM and acute complete transverse myelitis and PL with acute partial transverse myelitis (83.3 and 90.9%, respectively; p < 0.0001). In conclusion, AIM is a heterogeneous syndrome from an etiological point of view and LETM patients had worse functional prognosis compared with PL after 3 and 6 months.     

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.     

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.     

Natalizumab reduces serum pro-angiogenic activity in MS patients

Angiogenesis has been implicated in the pathobiology of multiple sclerosis (MS). Osteopontin exerts a pro-angiogenetic effect and is increased in body fluid of MS patients. To evaluate the effect of 1 year natalizumab treatment on serum pro-angiogenic activity and on plasma osteopontin levels in relapsing (RR) MS patients. Ten RRMS patients scheduled for natalizumab treatment were enrolled and evaluated at baseline and after 1-year natalizumab treatment. Pro-angiogenic activity was assessed by a chick embryo chorioallantoic membrane assay (CAM), osteopontin levels were evaluated by an enzyme-linked immunosorbent assay. Plasma and serum samples of 10 treatment-naïve RRMS and 10 healthy controls (HCs) were used as controls of baseline evaluations. Both treatment-naïve and natalizumab scheduled RRMS patients had higher baseline vessel density (22.0?±?3.9 and 22.5?±?2.6, p?<?0.0001) and higher osteopontin levels (65.7?±?24.3 ng/ml and 65.9?±?16.6 ng/ml, p?=?0.019 and p?=?0.029, respectively) than HCs (9.0?±?2.2; 48.5?±?7.8 ng/ml, respectively). Baseline osteopontin levels and vessel density were significantly correlated (rs?=?0.373, p?=?0.043). After 1 year of treatment, the number of vessels and the osteopontin levels, were significantly reduced (11.9?±?2.1, p?<?0.005; 49.3?±?20.0 ng/ml, p?=?0.028). Our results suggest that natalizumab could exert its anti-inflammatory properties also by inhibiting the angiogenetic mechanisms in RRMS patients.     

The Validation Study of Neurofilament Heavy Chain and 8-hydroxy-2′-deoxyguanosine as Plasma Biomarkers of Clinical/Paraclinical Activity in First and Relapsing-Remitting Demyelination Acute Attacks

Although current evidence mainly suggests immunopathogenesis of demyelination and neurodegeneration in multiple sclerosis (MS), there are results which document the importance of other factors, such as oxidative stress and its mediated injuries. The oxidative stress intensity in axonal damage during acute demyelination is little known. We performed this study as a cross-sectional biomarker validation study in order to evaluate the parameters of axonal damage (phosphorylated neurofilaments heavy chain (pNF-H)) and oxidative stress (8-hydroxy-2′-deoxyguanosine (8-OHdG)) in plasma of patients with initial and relapsing-remitting demyelination attacks, defined as clinically isolated syndrome (CIS) and relapsing-remitting multiple sclerosis (RRMS); and the correlations between these parameters and biological (index of blood brain barrier (BBB) permeability), clinical (index of disease progression), and radiological (T₁-Gd-enhancing lesion volume) activities of disease. Both parameters were increased in CIS and RRMS compared to control subjects (p < 0.05). The positive correlations were observed between 8-OHdG values and index of BBB permeability, clinical severity of disease, and demyelinated brain lesion volume, in CIS group (r > 0.50; p < 0.05). Similar correlations were obtained between pNF-H values and the above parameters, as well as the index of disease progression, in RRMS group (r > 0.30; p < 0.05). There was a significant correlation between values of 8-OHdG and pNF-H only in CIS group, r = 0.52, p < 0.05. While the plasma values of 8-OHdG reflect the degree of acute demyelination in CIS, pNF-H values reflect that in RRMS. The obtained results must be reevaluated in similar prospective studies related to their prognostic values.     

Peginterferon beta-1a reduces the evolution of MRI lesions to black holes in patients with RRMS: a post hoc analysis from the ADVANCE study

The presence of chronic black holes, i.e., chronic lesions that are hypointense on T1-weighted images and are indicative of more severe tissue injury, has been increasingly utilized as a surrogate marker of therapeutic outcome in multiple sclerosis. The ADVANCE study was a 2-year, double-blind, pivotal trial evaluating the safety and efficacy of subcutaneous peginterferon beta-1a 125 mcg in 1512 patients with relapsing–remitting multiple sclerosis (RRMS). This report describes the correlation of clinical outcomes with the evolution of acute lesions into chronic black holes in ADVANCE, and the efficacy of peginterferon beta-1a in reducing this evolution. Treatment with peginterferon beta-1a significantly reduced the mean number of new/enlarging T2-weighted (NET2) lesions (0.76 vs. 1.03 from week 24, p = 0.0037; 0.44 vs. 0.99 from week 48, p < 0.0001) and new gadolinium-enhancing (Gd+) lesions (0.15 vs. 0.32 from week 24, p < 0.0001; 0.09 vs. 0.19 from week 48) that evolved into chronic black holes by 2 years. Patients with NET2 or Gd+ lesions at 24 weeks that evolved into chronic black holes showed significantly worse clinical outcomes, including a greater proportion with 12-week (14.9 vs. 8.4%; p = 0.0167) and 24-week (12.3 vs. 7.0%; p = 0.0333) confirmed disability worsening and higher mean annualized relapse rate (0.62 vs. 0.43; p = 0.0118), compared with patients with lesions that did not evolve into black holes. The correlation was independent of treatment. Reduced risk of evolution of new lesions into chronic black holes with peginterferon beta-1a treatment suggests potential to reduce long-term disability in RRMS by preventing irreversible tissue damage.     

Metabolic syndrome is associated with increased risk of short-term post-procedural complications after carotid artery stenting

The risk factors for post-procedural events after carotid artery stenting (CAS) have not been well established. The aim of this study was to investigate the association between metabolic syndrome (MetS) and the risk of post-CAS complications. A total of 358 consecutive patients who underwent CAS were enrolled in this prospective study. Patients’ demographic data, clinical characteristics, and complications after CAS within 30 days were recorded. Logistic regression analysis was performed to identify possible risk factors for post-procedural complications after CAS. The incidence of complications after CAS within 30 days was 7.0%. Logistic regression analysis identified the following as independent risk factors for 30-day transient ischemic attacks, stroke, myocardial infarction, and death after CAS: metabolic syndrome (OR = 2.31, 95% CI 1.91–3.01, P = 0.004), diabetes (OR = 2.24, 95% CI 1.74–2.76, P = 0.026), symptomatic patient (OR = 1.73, 95% CI 1.23–3.05, P = 0.011), and age (OR = 1.87, 95% CI 1.35–2.57, P = 0.042). Among the components of MetS, central obesity (OR = 2.21, 95% CI 1.24–2.63, P = 0.006), low high-density lipoprotein cholesterol (HDL-C) (OR = 1.66, 95% CI 1.34–2.27, P = 0.022), and high fasting plasma glucose (OR = 2.32, 95% CI 1.85–2.74, P = 0.003) were associated with increased risk of 30-day complications after CAS. This present study suggests that patients with metabolic syndrome have significantly increased risk of complications after CAS within 30 days. Moreover, MetS patients with central obesity, high fasting plasma glucose, or low HDL-C have significantly increased risk of complications after CAS within 30 days.     

Associations between high callous–unemotional traits and quality of life across youths with non-conduct disorder diagnoses

Research regarding callous–unemotional (CU) traits in non-conduct disorder (CD) diagnoses is sparse. We investigated the presence of high CU traits and their associations with quality of life (QoL) in a clinically referred sample of youths with non-CD diagnoses. Parents of 1018 children referred to a child and adolescent psychiatric clinic and rated their child’s CU traits and QoL. Experienced clinicians derived DSM-IV-TR diagnoses based on systematic clinical evaluations of these children. High CU traits compared to low CU traits were present in 38.5 % of the sample, and more often in boys than girls (69.4 vs. 30.6 %, p = .004), and were associated with more police contacts (12.2 vs. 3.5 %, p < .001). Logistic regression analyses revealed that those with diagnoses of autism spectrum disorder (odds ratio; OR = 1.61; 95 % CI 1.24–2.09; p < .001) and disruptive behavior disorder not otherwise specified/oppositional defiant disorder (OR = 4.98; 95 % CI 2.93–8.64; p < .001), but not attention-deficit/hyperactivity disorder (OR = 1.01; 95 % CI .79–1.31; p = .94), were more likely to have high than low CU traits. Those with anxiety/mood disorders were more likely to have low than high CU traits (OR = .59; 95 % CI .42–82; p = .002). In all diagnostic groups, high CU compared to low CU traits were associated with significantly lower QoL, while controlling for gender, age, and comorbidity. As such, high CU traits significantly modify QoL in non-CD disorders.     

Cerebrospinal fluid levels of free fatty acid associated with ischemic stroke recurrence and functional outcome

The aim of this study was to evaluate the association between cerebrospinal fluid (CSF) levels of free fatty acid (FFA) and functional outcome and stroke recurrence in patients with ischemic stroke. In a prospective study, CSF levels of FFA were measured using an enzyme cycling method on admission in 217 consecutive patients with first-ever ischemic stroke. Clinical information was collected. Functional outcome and stroke recurrence were evaluated at 1-year follow-up. Multivariate analyses were performed using logistic regression models. The CSF FFA level was obtained in all patients with a median value of 0.22 (IQR 0.12–0.33) mmol/l. At admission, 89 patients (41.0 %) had a minor stroke (NIHSS < 5). In these patients, the median FFA level was lower than that observed in patients with moderate-to-high clinical severity (0.16 vs 0.27 mmol/l, p < 0.001). Patients with unfavorable outcomes and stroke recurrence had significantly higher FFA CSF levels on admission (all p < 0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that CSF FFA ≥ 0.33 mmol/l (third quarters) was an independent predictor of functional outcome (OR = 2.825; 95 % CI 1.502–5.313, p = 0.001) and stroke recurrence (OR = 7.862; 95 % CI 3.248–19.031, p < 0.0001). Our results demonstrate that high FFA SCF levels were independently associated with both the poor functional prognosis and stroke recurrence in patients with ischemic stroke.     

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.     

Serum uric acid levels and freezing of gait in Parkinson’s disease

Uric acid (UA) is a natural antioxidant and iron scavenger in the human body, which has been hypothesized to exert an anti-oxidative effect in Parkinson’s disease (PD). This study aimed to investigate the relationship between serum UA levels and freezing of gait (FOG) in PD. A total of 321 Chinese PD patients with fasting serum UA evaluated were included in the cross-sectional study. Demographics, clinical features, and therapeutic regimen were collected. The Unified PD Rating Scale (UPDRS) III and Hoehn and Yahr (H and Y) stage were used to evaluate the severity of disease, and the Frontal Assessment Battery (FAB) and Montreal Cognitive Assessment (MoCA) scales were used to assess the cognitive function. Patients with FOG showed lower proportion of male, longer disease duration, lower body mass index, lower concentrations of serum UA, higher total levodopa equivalent daily dosage, higher UPDRS III score, greater median H and Y stage, lower scores of FAB and MoCA, and higher frequencies of motor fluctuation, dyskinesia, falls, and festination compared to patients without FOG (P < 0.05). The binary logistic regression model indicated that high UPDRS III score (OR = 1.049, P < 0.001), fluctuation (OR = 2.677, P = 0.035), dyskinesia (OR = 6.294, P = 0.003), festination (OR = 3.948, P < 0.001), falls (OR = 7.528, P < 0.001), and low serum UA levels (OR = 0.990, P < 0.001) were associated with FOG. Our study suggests that low serum UA concentration is associated with the occurrence of FOG in PD.     

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.     

Relevance of early cervical cord volume loss in the disease evolution of clinically isolated syndrome and early multiple sclerosis: a 2-year follow-up study

Upper cervical cord area (UCCA) atrophy is a prognostic marker for clinical progression in longstanding multiple sclerosis (MS). The objectives of the study were to quantify UCCA atrophy and evaluate its impact in clinically isolated syndrome (CIS) and relapsing–remitting MS (RRMS); to compare converting CIS patients with stable CIS, and to study changes of UCCA and brain white matter (WM) and grey matter (GM) at 2-year follow-up. 110 therapy-naive patients including 53 CIS [6 ± 6 months after symptom onset (SO)] and 57 early RRMS (SO: 12 ± 9 months) underwent sagittal 3D-T1w brain MR (3T). Mean UCCA (C1–C3 level), WM and GM, disability status (EDSS), pyramidal and sensory functional scores, motoric fatigue were assessed at baseline (BL), 12 and 24 months. Volumes were compared with 34 age- and gender-matched healthy controls to assess atrophy. RRMS (78.1 ± 8.7 mm², p = 0.011) and converting CIS (77.3 ± 8.0 mm², p = 0.046) presented with baseline UCCA atrophy, when compared with controls (82.7 ± 5.2 mm²), but not stable CIS (82.6 ± 7.4 mm², p = 0.998). Baseline WM was reduced in RRMS (509.3 ± 25.7 ml vs. controls: 528.4 ± 24.1 ml, p = 0.032). Baseline UCCA correlated negative with muscular weakness and fatigability in all patients and RRMS. EDSS exceeding 3 was associated with lower baseline UCCA. Longitudinal atrophy rates were higher in UCCA than in brain volumes. Early cervical cord atrophy in CIS and RRMS was confirmed and may represent a potential new risk marker for conversion from CIS to MS. Baseline atrophy and atrophy change rates were higher in UCCA compared to WM and GM, suggesting that cervical cord volumetry might become an additional MRI marker relevant in future clinical studies in CIS and early MS.     

Functional neuroimaging in migraine

Migraine can be accompanied by some gastrointestinal (GI) disorders. In this study, we aimed to investigate the relationship between migraine and tension-type headache (TTH) and different lower and upper GI disorders as well as non-alcoholic fatty liver (NAFLD) and cholelithiasis. This cross-sectional study included 1574 overweight and obese participants who were referred to the Obesity Research Center of Sina Hospital, Tehran, Iran. The diagnosis of migraine and TTH was made by an expert neurologist based on the international classification of headache disorders-III β (ICHD III β). GI disorders, including irritable bowel syndrome (IBS), constipation, heartburn, dyspepsia, non-alcoholic fatty liver (NAFLD), and cholelithiasis, were diagnosed by a gastroenterology specialist. The overall mean age of participants was 37.44 ± 12.62. A total of 181 (11.5%) migraine sufferers (with and without aura) and 78 (5%) TTH subjects were diagnosed. After adjusting for potential confounders by multivariable regression models, migraine had significant association with IBS (OR = 5.16, 95% CI = 2.07–12.85, P = 0.000), constipation (OR = 3.96, 95% CI = 2.25–6.99, P = 0.000), dyspepsia (OR = 4.12, 95% CI = 2.63–6.45, P = 0.000), and heartburn (OR = 5.03, 95% CI 2.45–10.33, P = 0.000), while the association between migraine and NAFLD was marginally significant (OR = 2.03, 95% CI = 0.98–4.21, P = 0.055). Furthermore, the prevalence of NAFLD (OR = 2.93, 95% CI 1.29–6.65, P = 0.010) and dyspepsia (OR = 4.06, 95% CI = 2.24–7.34, P = 0.000) was significantly higher in TTH patients than the headache-free group. These findings show an association between GI disorders and primary headaches especially migraine and are, therefore, of value to the management of migraine and TTH. Further studies should investigate the etiology of the relationship between all subtypes of primary headaches and GI disorders.