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.

Val66Met polymorphism is associated with decreased likelihood for pediatric headache and migraine.

Background: Migraine is a complex multifactorial disorder and its pathogenesis still remains unclear. Evidence suggests the involvement of the activated trigeminovascular pathway, in which BDNF seems to play an important role. Therefore, BDNF polymorphisms are promising candidate susceptibility factors.Aim: BDNF rs6265 functional polymorphism was analyzed in order to determine its possible association with pediatric headache and migraine risk.Methods: The research included 120 consecutive pediatric patients who were diagnosed with headache and 120 healthy controls. The diagnosis was in compliance with the International Classification of Headache Disorders. Blood samples were collected from all participants and genotyped for rs6265.Results: BDNF rs6265 was significantly associated with decreased headache risk, particularly in the dominant model [Odds Ratio, OR (95% confidence interval, C.I.): 0.47 (0.26-0.85), p = 0.011] and the log-additive model [OR (95% C.I.): 0.48 (0.28-0.82), p = 0.0053]. During the sensitivity analysis, the associations were also maintained among patients with migraine.Conclusions: This is the first study to reveal a significant association of this BDNF variant with headache risk. Additionally, Val66Met was also for the first time related to decreased childhood migraine risk.

Risk Factor Genes in Patients with Dystonia: A Comprehensive Review.

Background: Dystonia is a movement disorder with high heterogeneity regarding phenotypic appearance and etiology that occurs in both sporadic and familial forms. The etiology of the disease remains unknown. However, there is increasing evidence suggesting that a small number of gene alterations may lead to dystonia. Although pathogenic variants to the familial type of dystonia have been extensively reviewed and discussed, relatively little is known about the contribution of single-nucleotide polymorphisms (SNPs) to dystonia. This review focuses on the potential role of SNPs and other variants in dystonia susceptibility. Methods: We searched the PubMed database for peer-reviewed articles published in English, from its inception through January 2018, that concerned human studies of dystonia and genetic variants. The following search terms were included: "dystonia" in combination with the following terms: 1) "polymorphisms" and 2) "SNPs" as free words. Results: A total of 43 published studies regarding TOR1A, BDNF, DRD5, APOE, ARSG, NALC, OR4X2, COL4A1, TH, DDC, DBH, MAO, COMT, DAT, GCH1, PRKRA, MR-1, SGCE, ATP1A3, TAF1, THAP1, GNAL, DRD2, HLA-DRB, CBS, MTHFR, and MS genes, were included in the current review. Discussion: To date, a few variants, which are possibly involved in several molecular pathways, have been related to dystonia. Large cohort studies are needed to determine robust associations between variants and dystonia with adjustment for other potential cofounders, in order to elucidate the pathogenic mechanisms of dystonia and the net effect of the genes.

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.

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.

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.