Association between Helicobacter pylori infection and Guillain-Barré Syndrome: A meta-analysis.

BACKGROUND: Helicobacter pylori (H pylori) is a Gram-negative bacterium, considered to trigger autoimmune gastrointestinal disorders. This pathogen has also been linked to the autoimmune sequelae in extra-gastrointestinal diseases and peripheral neuropathies. Guillain-Barré syndrome (GBS) is a serious autoimmune demyelinating disorder of peripheral nerves, usually with a post-infectious onset. About 30% of cases of GBS attributed to by Campylobacter jejuni, so, H pylori, could be also involved. Growing evidence suggests the likely involvement of H pylori infection in the development of GBS. The aim of the current study was to therefore estimate the prevalence of H pylori antibodies in GBS. METHODS: A search of the literature was performed, using the PUBMED database, until December 2018. Data were extracted from six case-control studies, and a stratification analysis was conducted according to cerebrospinal fluid (CSF) or serum detection material. RESULTS: Among 29 records found, 6 studies met in the inclusion criteria for the meta-analysis. In the CSF subgroup, 105 participants were involved (40 GBS patients and 65 controls), while the serum subgroup included 325 participants (152 GBS and 173 controls). Data were combined using a fixed-effects model. Anti-H pylori IgG were significantly more prevalent in GBS patients compared to controls, in both CSF (95% CI: 9.66-186.56, OR: 42.45, Pz < .00001) and serum (95% CI: 1.30-4.11, OR: 2.31, Pz: .004) subgroups. CONCLUSION: The present meta-analysis showed a strong association between GBS and the presence of H pylori antibodies, especially in CSF, thereby suggesting a role of H pylori infection in the pathophysiology of GBS.

Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder, caused by, so far, unknown pathogenetic mechanisms. There is no doubt that pro-inflammatory immune-mediated mechanisms are pivotal to the pathogenicity and progression of the disease. In this review, we highlight the binary role of microglia activation in the pathophysiology of the disorder, both neuroprotective and neuromodulatory. We present how the expression of several cytokines implicated in dopaminergic neurons (DA) degeneration could be used as biomarkers for PD. Viral infections have been studied and correlated to the disease progression, usually operating as trigger factors for the inflammatory process. The gut-brain axis and the possible contribution of the peripheral bowel inflammation to neuronal death, mainly dopaminergic neurons, seems to be a main contributor of brain neuroinflammation. The role of the immune system has also been analyzed implicating a-synuclein in the activation of innate and adaptive immunity. We also discuss therapeutic approaches concerning PD and neuroinflammation, which have been studied in experimental and in vitro models and data stemming from epidemiological studies.

Burnout Evaluation and Potential Predictors in a Greek Cohort of Mental Health Nurses.

BACKGROUND: Job burnout is one of the most serious occupational health hazards, especially, among mental health nurses. It has been attributed among others to staff shortages, health service changes, poor morale and insufficient employee participation in decision-making. AIM: The aim of this study was to measure burnout among mental health nurses, investigate relations between burnout and organizational factors and examine potential predictors of nurses' burnout. Specifically, this study aimed to investigate whether role conflict, role ambiguity, organizational commitment and subsequent job satisfaction could predict each of the three dimensions of burnout. DESIGN/METHODOLOGY/APPROACH: During current cross sectional, the survey was administered to 232 mental health nurses, employed in four private psychiatric clinics in the region of Larissa, Thessaly, Greece in May 2015. Our findings were based on the responses to 78 usable questionnaires. Different statistical analyses, such as correlation analyses, regression analyses and analyses of variance were performed in order to explore possible relations. FINDINGS: High emotional exhaustion (EE) accounted for 53.8% of the sample, while high depersonalization (DP) and high personal accomplishment (PA) accounted for 24.4% and 25.6%, respectively. The best predictors of burnout were found to be role conflict, satisfaction with workload, satisfaction with training, role ambiguity, satisfaction with pay and presence of serious family issues. PRACTICAL IMPLICATIONS: These findings have implications for organizational and individual interventions, indicating that mental health nurses' burnout could be reduced, or even prevented by team building strategies, training, application of operation management, clear instructions and psychological support.

Musculoskeletal Pain Due to Wheelchair Use: A Systematic Review and Meta-Analysis.

INTRODUCTION: Wheelchair users are at a high risk of experiencing non-neuropathic pain of musculoskeletal origin as a result of being wheelchair-bound. The aim of this systematic review was to establish the prevalence of musculoskeletal pain in wheelchair users that is attributable to wheelchair use, and to describe the different pain syndromes and discuss risk factors and management options. METHODS: After a systematic MEDLINE search, we identified 40 papers eligible for inclusion. RESULTS: The pooled prevalence of musculoskeletal pain at any location was 50% (95% CI 33-67%). The most common pain syndrome was shoulder pain (pooled prevalence 44%, 95% CI 36-52%). Wheelchair users were 5.8 times as likely to suffer from shoulder pain as controls (95% CI 2.7-12.2, p < 0.0001). Other pain syndromes included neck, elbow, wrist, hand and low back pain. Older age and increased duration of wheelchair use were the most significant determinants of pain in wheelchair users. CONCLUSIONS: Musculoskeletal pain as a result of wheelchair use is very common amongst wheelchair users. Management of pain should follow national and international guidelines. Optimal adjustment of seating position may prevent pain, and is important to be taken into consideration.

Regulation of microRNA in systemic lupus erythematosus: the role of miR-21 and miR-210.

miRNAs are small non-coding RNA molecules that participate through silencing in post-transcriptional regulation of gene expression. Recent studies have highlighted the importance of microRNAs (miRNAs) as regulators of both the innate and the adaptive immune response. There are emerging data regarding the role of miRNAs in patients with Systemic Lupus Erythematosus (SLE). One of the main stimuli for the induction of miR-21 is hypoxia. Moreover, the expression and function of miR-210 is directly related to the activity of "hypoxia inducible factor-1a" (HIF-1a). The aim of the study is to examine the regulation of miR-21 and mir-210 in patients with SLE based on the hypothesis that cellular hypoxia may have an important role in SLE pathogenesis. Plasma, PBMC and urine samples will be collected from patients with SLE and normal controls. miR expression will be studied with real-time PCR. Functional experiments will examine the effect of miR-21 and miR- 210 on HIFa and ERK1/2 και PI3K/AKT signalling pathways. The study will provide novel data regarding the expression and the role of miR-21 and miR-210 in patients with SLE. The results of the study will contribute to a better understanding of miR network regulation in SLE in order to ultimately identify molecules that can be used in clinical practice as diagnostic or prognostic markers, treatment response markers, or even as potential future therapeutic targets.

Prevalence of C9orf72 hexanucleotide repeat expansion in Greek patients with sporadic ALS.

A total of 178 consecutive patients with definite sALS without frontotemporal dementia (FTD) were enrolled in this study, after complete clinical evaluation. A Repeat-Primed Polymerase Chain Reaction (RP-PCR) protocol was applied to detect the G4C2 repeats expansions. In the studied sALS patients, 5.06% (n = 9) carried the C9orf72 mutation. Among carriers, 2/3 of them were females and spinal onset accounted for 78% and bulbar for 22%, while the mean age of onset was about 60 years. Our study showed that the prevalence of C9orf72 repeat expansion in Greek sALS patients is similar to the overall frequency of the mutation in European populations. The pathogenic mutation remains a promising biomarker for genetic testing and targeted treatment.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy revisited: Genotype-phenotype correlations of all published cases.

OBJECTIVE: The aim of this study was to evaluate the correlation between the various NOTCH3 mutations and their clinical and genetic profile, along with the presentation of a novel mutation in a patient. METHODS: Here, we describe the phenotype of a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) harboring a novel mutation. We also performed an extensive literature research for NOTCH3 mutations published since the identification of the gene and performed a systematic review of all published cases with NOTCH3 mutations. We evaluated the mutation pathogenicity in a great number of patients with detailed clinical and genetic evaluation and investigated the possible phenotype-genotype correlations. RESULTS: Our patient harbored a novel mutation in the NOTCH3 gene, the c.3084 G > C, corresponding to the aminoacidic substitution p.Trp1028Cys, presenting with seizures as the first neurologic manifestation. We managed to find a correlation between the pathogenicity of mutations, severity of the phenotype, and age at onset of CADASIL. Significant differences were also identified between men and women regarding the phenotype severity. CONCLUSIONS: The collection and analysis of these scarce data published since the identification of NOTCH3 qualitatively by means of a systematic review and quantitatively regarding genetic profile and pathogenicity scores, highlight the significance of the ongoing trend of investigating phenotypic genotypic correlations.

Body mass index in patients with Multiple Sclerosis: a meta-analysis.

Background: The impact of nutrition and diet on the etiology of Multiple Sclerosis (MS) has been evaluated through a number of studies. Only a limited number reported findings on the association between body mass index (BMI) and MS. We systematically assessed whether BMI differs between MS patients and healthy individuals. Methods: The PubMed database was searched for available studies assessing the relationship between BMI and MS until April 2018. Random effects models were applied for evaluating the association of mean BMI between MS, relapsing-remitting MS (RRMS) patients, females, or males with MS, and their respective healthy control groups. Results: We included 25 studies. The mean BMI of MS patients during the course of the disease and RRMS patients was significantly different from the mean BMI of their healthy counterpart individuals [standardized mean difference (SMD) (95% confidence interval (CI)): -0.25 (-0.44, -0.06), PZ = 0.01 and SMD (95%): -0.27 (-0.54, -0.01), PZ = 0.04, respectively]. The mean BMI of females with MS was significantly differentfrom that of corresponding healthy females [SMD (95% CI): -0.52 (-0.96, -0.07), PZ = 0.02]. Moreover, the mean BMI was significantly different between males with MS and healthy males [SMD (95% CI): -0.75 (-1.33, -0.18), PZ = 0.01]. Conclusions: Statistically significantly lower mean BMI was revealed in the overall MS patients' group during the MS course than in healthy controls. The same difference was revealed in all parts of the meta-analysis demonstrating a significantly lower BMI in patients with RRMS, in females, and in males with MS, when compared to their respective healthy individuals.

Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options.

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by focal or diffuse inflammation, demyelination, axonal loss and neurodegeneration. Brain atrophy can be seen in the earliest stages of MS, progresses faster compared to healthy adults, and is a reliable predictor of future physical and cognitive disability. In addition, it is widely accepted to be a valid, sensitive and reproducible measure of neurodegeneration in MS. Reducing the rate of brain atrophy has only recently been incorporated as a critical endpoint into the clinical trials of new or emerging disease modifying drugs (DMDs) in MS. With the advent of easily accessible neuroimaging softwares along with the accumulating evidence, clinicians may be able to use brain atrophy measures in their everyday clinical practice to monitor disease course and response to DMDs. In this review, we will describe the different mechanisms contributing to brain atrophy, their clinical relevance on disease presentation and course and the effect of current or emergent DMDs on brain atrophy and neuroprotection.

AQP4 tag SNPs in patients with intracerebral hemorrhage in Greek and Polish population.

BACKROUND: A relatively small number of genetic variants are implicated to pathophysiology of intracerebral hemorrhage (ICH). Aquaporin-4 (AQP4) has been reported to be implicated in the pathophysiological processes of ICH development. OBJECTIVE: To examine the role of AQP4 gene region polymorphisms on the ICH risk. METHODS: A total of 250 Greek and 193 Polish patients with primary ICH and 250 and 322 respective controls were enrolled, forming two independent cohorts in order to validate any significant effect. With logistic regression analyses, 7 AQP4 tag single nucleotide polymorphisms (SNPs) were examined for association with ICH risk, lobar/non-lobar ICH risk, and 6-month disability after ICH. Cox regression analysis was applied in order to the effect of AQP4 SNPs on ICH age of onset be tested. Correction for multiple comparisons was applied. RESULTS: Multivariate logistic regression analysis showed that rs3875089 in the Greek cohort and rs3763043, rs335931 in the Polish cohort had a significant influence on the risk of ICH, lobar and non-lobar ICH. Regarding the age of onset, rs3875089 in the Greek cohort and rs3763043, rs11661256 in the Polish cohort were found to significantly alter the age of onset of ICH and its subtypes. However, all of the above associations did not survive the Bonferroni correction (p-value >0.007). Finally, AQP4 tag SNPs were not found to have any significant effect on long-term disability after ICH. CONCLUSIONS: In conclusion, the present study provides an indication that AQP4 gene variants may affect susceptibility to primary ICH and may influence the ICH age of onset.

H. pylori and Parkinson's disease: Meta-analyses including clinical severity.

The exact etiology of Parkinson's disease (PD) remains unclear. Some evidence supports Helicobacter pylori infection as a trigger or driving event, but detection and eradication of H. pylori are not part of PD management. The aims of this case-control study and meta-analysis were to determine (i) the prevalence of H. pylori infection in PD patients, (ii) associations between H. pylori infection and clinical status, and (iii) differences in motor status in PD patients before and after H. pylori eradication. A literature search was performed using the PubMed database. The prevalence of H. pylori infection in PD, its association with the unified Parkinson's disease rating scale (UPDRS), and the association of H. pylori eradication therapy with the UPDRS-III score were determined by calculating the odds ratios (OR) and the standardized mean differences (SMD) with 95% confidence intervals (CI). Fixed- and random-effects models were applied. Ten studies were included in the first meta-analysis (5043 PD patients, 23,449 HCs); H. pylori infection prevalence was higher in PD patients than in HCs [OR (95% CI): 1.47 (1.27, 1.70), Pz<0.00001]. In seven studies reporting UPDRS scores (150 H. pylori infected, 228 non-infected PD patients), there was a significant association between H. pylori infection and mean UPDRS scores [SMD (95% CI): 0.33 (0.12, 0.54), Pz = 0.003]. Regarding H. pylori eradication, in five studies (90 PD patients), there was a significant reduction in UPDRS-III scores after treatment [SMD (95% CI): 6.83 (2.29, 11.38), Pz = 0.003]. In conclusion, the present meta-analysis revealed a higher prevalence of H. pylori infection in PD patients suggesting that H. pylori may contribute to PD pathophysiology. In addition, the significantly lower UPDRS scores in non-infected PD patients and in patients after H. pylori eradication therapy demonstrate that the infection may deteriorate the clinical severity of the disease.

Body mass index and survival from amyotrophic lateral sclerosis: A meta-analysis.

BACKGROUND: Several studies have examined the relationship between body mass index (BMI) and survival from amyotrophic lateral sclerosis (ALS). Many indicate that low BMI at diagnosis or during follow-up may be associated with accelerated progression and shortened survival. This study systematically evaluated the relationship between BMI and survival in patients with ALS. METHODS: The PubMed database was searched to identify all available studies reporting time-to-event data. Eight studies with 6,098 patients fulfilled the eligibility criteria. BMI was considered a continuous and ordered variable. Interstudy heterogeneity was assessed by the Cochran Q test and quantified by the I2 metric. Fixed- or random-effects odds ratios summarized pooled effects after taking interstudy variability into account. Significance was set at p < 0.05. RESULTS: The ALS survival hazard ratio (HR) decreased approximately by 3% (95% confidence interval [CI]: 2%-5%) for each additional BMI unit when BMI was considered a continuous variable. When BMI was considered a categorical variable, the HRs for "normal" BMI vs "overweight" BMI and "obese" BMI were estimated to be as high as 0.91 (95% CI: 0.79-1.04) and 0.78 (95% CI: 0.60-1.01), respectively. The HR for the comparison of the "normal" BMI vs "underweight" BMI was estimated to be as high as 1.94 (95% CI: 1.42-2.65). CONCLUSIONS: BMI is significantly and inversely associated with ALS survival.

CpG Island Methylation Patterns in Relapsing-Remitting Multiple Sclerosis.

DNA methylation may predispose to multiple sclerosis (MS), as aberrant methylation in the promoter regions across the genome seems to underlie several processes of MS. We have currently determined the methylation status of eight genes in relapsing-remitting MS patients. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was used to determine the status of 31 CpG islands, located across eight genes, in 33 healthy individuals and 66 MS patients (33 in relapse and 33 in remission). The methylation levels in the examined sites ranged from 0 to 31%. Methylation positivity for RUNX3 and CDKN2A differed significantly between MS patients and healthy controls. Maximum methylation in RUNX3, CDKN2A, SOCS1, and NEUROG1 genes was significantly different between patients and controls. Roc curves demonstrated that the appropriate cut-offs to distinguish patients from healthy controls were 2% for RUNX3 (OR 3.316, CI 1.207-9.107, p = 0.024) and 3% for CDKN2A (OR 3.077, CI 1.281-7.39, p = 0.018). No difference in methylation was observed between patients in relapse and patients in remission, in any of the genes examined. Methylation patterns of RUNX3 and CDKN2A may be able to distinguish between MS patients and healthy controls, but not between MS patients in relapse and in remission. Graphical Abstract Methylation patterns of RUNX3 and CDKN2A may be able to discriminate healthy individuals from MS patients.

Vitamin B12, folate, and homocysteine levels and multiple sclerosis: A meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating and disabling inflammatory disease of the central nervous system. Several factors contribute to MS pathogenesis including genetic-environmental interactions. Case-control studies suggest that there might be associations between MS and homocysteine (Hcy), vitamin B12, and folate blood levels. AIM: To meta-analyze all available data describing associations between MS and serum or plasma Hcy, vitamin B12, and folate levels. METHODS: The PubMed, MEDLINE, and EMBASE databases were searched for eligible case-control studies published until June 2017. After data extraction, separate analyses using mainly random-effects models were conducted to test for associations between MS and vitamin B12, Hcy, or folate blood levels. RESULTS: Twelve, 12, and 9 studies met the inclusion criteria for meta-analysis of MS and Hcy, vitamin B12, and folate levels, respectively. The standardized mean difference (SMD) between MS patients and controls was statistically significant for Hcy (SMD: 0.70, 95% CI: 0.06, 1.34). Stratification according to clinical pattern did not reveal significant differences between relapsing-remitting MS patients and controls (SMD: 0.30, 95% CI: -0.93, 1.54) or between secondary progressive MS patients and controls (SMD: 0.12, 95% CI: -1.65, 1.90). There were no significant differences in SMD between MS patients and healthy individuals for vitamin B12 (SMD: -0.09, 95% CI: -0.29, 0.10) or folate (SMD: -0.06, 95% CI: -0.17, 0.05). CONCLUSION: MS patients tend to have elevated Hcy blood levels compared to healthy controls. Hcy may contribute to the pathogenesis of the disease.

The Role of TOR1A Polymorphisms in Dystonia: A Systematic Review and Meta-Analysis.

IMPORTANCE: A number of genetic loci were found to be associated with dystonia. Quite a few studies have been contacted to examine possible contribution of TOR1A variants to the risk of dystonia, but their results remain conflicting. The aim of the present study was to systematically evaluate the effect of TOR1A gene SNPs on dystonia and its phenotypic subtypes regarding the body distribution. METHODS: We performed a systematic review of Pubmed database to identify all available studies that reported genotype frequencies of TOR1A SNPs in dystonia. In total 16 studies were included in the quantitative analysis. Odds ratios (ORs) were calculated in each study to estimate the influence of TOR1A SNPs genotypes on the risk of dystonia. The fixed-effects model and the random effects model, in case of high heterogeneity, for recessive and dominant mode of inheritance as well as the free generalized odds ratio (ORG) model were used to calculate both the pooled point estimate in each study and the overall estimates. RESULTS: Rs1182 was found to be associated with focal dystonia in recessive mode of inheritance [Odds Ratio, OR (95% confidence interval, C.I.): 1.83 (1.14-2.93), Pz = 0.01]. In addition, rs1801968 was associated with writer's cramp in both recessive and dominant modes [OR (95%C.I.): 5.99 (2.08-17.21), Pz = 0.00009] and [2.48 (1.36-4.51), Pz = 0.003) respectively and in model free-approach [ORG (95%C.I.): 2.58 (1.45-4.58)]. CONCLUSIONS: Our meta-analysis revealed a significant implication of rs1182 and rs1801968 TOR1A variants in the development of focal dystonia and writer's cramp respectively. TOR1A gene variants seem to be implicated in dystonia phenotype.

Deciphering the role of DNA methylation in multiple sclerosis: emerging issues.

Multiple sclerosis (MS) is an autoimmune inflammatory and neurodegenerative disease of the central nervous system that involves several not yet fully elucidated pathophysiologic mechanisms. There is increasing evidence that epigenetic modifications at level of DNA bases, histones, and micro-RNAs may confer risk for MS. DNA methylation seems to have a prominent role in the epigenetics of MS, as aberrant methylation in the promoter regions across genome may underlie several processes involved in the initiation and development of MS. In the present review, we discuss current understanding regarding the role of DNA methylation in MS, possible therapeutic implications and future emerging issues.