TNF and sTNFR1/2 plasma levels in ALS patients

The involvement of the immune system has been hypothesized in the pathogenesis of amyotrophic lateral sclerosis (ALS). In this study a significantly higher level of TNF-alpha and its soluble receptors, TNF-R1 and TNF-R2, has been found in plasma of patients affected by the sporadic form of ALS compared to normal subjects. The genetic analysis of the polymorphisms of TNF-alpha, TNF-R1 and TNF-R2 showed no statistically significant differences in alleles and genotype frequencies between patients and controls. These data suggest a participation of the immune system in response to as far unknown intracellular signals.     

Use of nutritional devices in Cornelia de Lange syndrome: Data from a large Italian cohort

Cornelia de Lange syndrome (CdLS) is a genetic condition characterized by intellectual disability, peculiar facial dysmorphisms, multiorgan malformations, and growth problems. Majority cases of CdLS are caused by mutations in genes of Cohesin pathway. Although feeding problems are a well‐known feature, no specific data have been published about the use of nutritional devices. We analyzed use, type, time of introduction, and duration of nutritional devices in 73 CdLS patients. In total, 29/73 (40%) used a device; nasogastric tube (NGT) in 28/73 (38%) and percutaneous endoscopic gastrostomy (PEG) in 7/73 (10%). NGT was placed during the first days/weeks of life. 19/28 (68%) maintained it for less than 3 months, 7/28 (25%) for a period between 3 and 12 months, while 2/28 (7%) for more than 1 year. PEG was placed within the first year in 4/7 (57%) and removed in two patients after 4 years These data have been matched with a wide number of genetic and clinical variables. Presence of upper limb malformations is positively correlated with the need of a device. From the opposite side, the use of a device positively correlates with a more severe prognosis as regard growth, intellectual development and disease severity. Our data show that nutritional devices are frequently used by CdLS patients, also if the majority of them (93.1%) succeed with time in achieving a normal oral nutrition. Finally, the need, the type of device used and the duration of NGT or/plus PEG can be considered a further sign of worse prognosis of the disease itself.     

Gut microbiota dysbiosis in Parkinson disease: A systematic review and pooled analysis

Background and purpose

The role of the gut microbiome in the pathogenesis of Parkinson disease (PD) is under intense investigation, and the results presented are still very heterogeneous. These discrepancies arise not only from the highly heterogeneous pathology of PD, but also from widely varying methodologies at all stages of the workflow, from sampling to final statistical analysis. The aim of the present work is to harmonize the workflow across studies to reduce the methodological heterogeneity and to perform a pooled analysis to account for other sources of heterogeneity.

Methods

We performed a systematic review to identify studies comparing the gut microbiota of PD patients to healthy controls. A workflow was designed to harmonize processing across all studies from bioinformatics processing to final statistical analysis using a Bayesian random-effects meta-analysis based on individual patient-level data.

Results

The results show that harmonizing workflows minimizes differences between statistical methods and reveals only a small set of taxa being associated with the pathogenesis of PD. Increased shares of the genera Akkermansia and Bifidobacterium and decreased shares of the genera Roseburia and Faecalibacterium were most characteristic for PD-associated microbiota.

Conclusions

Our study summarizes evidence that reduced levels of butyrate-producing taxa in combination with possible degradation of the mucus layer by Akkermansia may promote intestinal inflammation and reduced permeability of the gut mucosal layer. This may allow potentially pathogenic metabolites to transit and enter the enteric nervous system.     

Celiac disease prevalence and predisposing-HLA in a cohort of 93 Williams-Beuren syndrome patients

Williams-Beuren syndrome is considered to be at increased risk for celiac disease, as for recent literature data and celiac disease guidelines, despite pathogenic mechanisms are still unclear. Our study analyzed the prevalence of autoimmune disorders, HLA DQ2 and/or DQ8 haplotypes, of transglutaminase antibodies and of diagnosis of celiac disease in a cohort of 93 Williams-Beuren syndrome's patients (mean age 21.26 years). Our study showed an increased prevalence of celiac disease equal to 10.8% (10/93 patients). We did not find a significant different frequency of predisposing HLA in subjects with Williams-Beuren syndrome compared to literature data in the general population (49.5% vs. 42.9%, with p > .1), nor a susceptibility to autoimmunity. This suggests that the increased prevalence of celiac disease in Williams-Beuren syndrome cannot be ascribed to HLA haplotype and may be related to other factors that still need to be identified in these patients.     

Rock around DYRK1A: Ethnic diversity,clinical challenges

DYRK1A-related intellectual disability is a recently described syndrome characterized by microcephaly, global developmental delay, impaired speech development, and distinctive facial features, which let to define it as a recognizable syndrome. Here we report four new patients of different ethnicity, broadening the clinical phenotype of the condition and highlighting how ethnic influences in the facial appearance could make it less recognizable.