Cerebrospinal Fluid Analysis in Multiple Sclerosis Diagnosis: An Update

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) with brain neurodegeneration. MS patients present heterogeneous clinical manifestations in which both genetic and environmental factors are involved. The diagnosis is very complex due to the high heterogeneity of the pathophysiology of the disease. The diagnostic criteria have been modified several times over the years. Basically, they include clinical symptoms, presence of typical lesions detected by magnetic resonance imaging (MRI), and laboratory findings. The analysis of cerebrospinal fluid (CSF) allows an evaluation of inflammatory processes circumscribed to the CNS and reflects changes in the immunological pattern due to the progression of the pathology, being fundamental in the diagnosis and monitoring of MS. The detection of the oligoclonal bands (OCBs) in both CSF and serum is recognized as the “gold standard” for laboratory diagnosis of MS, though presents analytical limitations. Indeed, current protocols for OCBs assay are time-consuming and require an operator-dependent interpretation. In recent years, the quantification of free light chain (FLC) in CSF has emerged to assist clinicians in the diagnosis of MS. This article reviews the current knowledge on CSF biomarkers used in the diagnosis of MS, in particular on the validated assays and on the alternative biomarkers of intrathecal synthesis

Definition of the upper reference limit of glycated albumin in blood donors from Italy

Glycated Albumin (GA) has been proposed as a short-term indicator of glycemic homeostasis. The aim of this study is to describe the distribution of GA in a large sample of blood donors from Italy to evaluate whether demographic features, namely age and sex, could influence GA levels and define specific reference limits. The study included 1334 Italian blood donors. GA was measured using an enzymatic method (quantILab Glycated Albumin, IL Werfen, Germany). The upper reference limit (URL) was calculated using the non-parametric percentile method. A modest, although significant, increase of GA was observed in relation to age (p14.5% presented a mean age of 48.4±12.2 years, 66.7% were males and the mean glucose was 6.88±2.5 mmol/L. GA in Caucasians shows a similar increasing trend at older ages documented in other ethnicities. The definition of the URL in this population could be useful for both clinical studies, which will clarify the role of GA for diagnosing and monitoring diabetes, and will encourage the introduction of GA in clinical practice

Non-skeletal activities of vitamin d: From physiology to brain pathology

Vitamin D is a secosteroid hormone regulating the expression of almost 900 genes, and it is involved in the regulation of calcium and phosphate metabolism, immune response, and brain development. Low blood vitamin D levels have been reported in patients affected by various diseases. Despite a large amount of literature data, there is uncertainty surrounding the role of vitamin D as a serum biomarker in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Indeed, the lack of internationally recognized 25(OH)D3 reference measurement procedures and standard materials in the past led to unstandardized serum total 25(OH)D3 results among research and clinical care laboratories. Thus, most of the literature studies reported unstandardized data, which are of little use and make it difficult to draw conclusions of the role of vitamin D in AD and PD. This review summarizes the extra-skeletal actions of vitamin D, focusing its role in immunomodulation and brain function, and reports the issue of lacking standardized literature data concerning the usefulness of vitamin D as a biomarker in AD and PD

Association between homocysteinemia and metabolic syndrome in patients with cardiovascular disease

Abstract BACKGROUND: This is an observational study undertaken in aim to evaluate the association between metabolic syndrome (MS) and high homocysteinemia (HHcy) in relation with cardiovascular disease (CVD). METHODS: The study involved 126 subjects with angiographically documented CVD and 65 healthy subjects. MS has been diagnosed according to the ATP III criteria and plasma homocysteine concentration has been evaluated. RESULTS: In patients with CVD the prevalence of MS and HHcy is 17.4% and 25.4% respectively; MS coexists with HHcy in 67.2% of patients; analogous results can be observed among men and women. HHcy and MS are associated with CVD (OR 2.53, 95% CI 1.95-12.43 and OR 5.74, 95% CI 2.67-12.34 respectively) but the presence of the two conditions gives rise to a stronger increase in CVD risk (OR 13.11, 95% CI 5.27-32.06). CONCLUSIONS: Our data suggest that HHcy and MS could work together in increasing CVD risk

Prevalence and risk of new-onset diabetes mellitus after COVID-19: a systematic review and meta-analysis

AimsAfter the acute phase of SARS-CoV-2 infection, the onset of glycemic impairment and diabetes have been reported. Nevertheless, the exact burden of glycemic impairment and diabetes after COVID-19 has not been clearly described.Materials and methodsElectronic search was run in Pubmed (MEDLINE), Web of Science, Scopus, and ClinicalTrial.org for reports published from database inception to September 2022. We included observational studies reporting quantitative data on diabetes prevalence or its onset in subjects with a history of SARS-CoV-2 infection from at least 60 days. Risk of bias was assessed by the JBI’s critical appraisal checklist. Random effect model was used to calculate pooled data. The review protocol was registered on PROSPERO (CRD42022310722).ResultsAmong 1,630 records screened, 20 studies were included in the analysis. The mean or median age of participants ranged from ~ 35 to 64 years, with a percentage of males ranging from 28% to 80%. Only two studies were considered at low risk of bias. The estimate of diabetes prevalence, calculated on a total of 320,948 participants pooled with 38,731 cases, was 16% (95%CI: 11-22%). The estimate of proportion of incident cases of diabetes was 1.6% (95%CI: 0.8-2.7%). Subgroup analysis showed that previous hospitalization increased the prevalence of diabetes and the proportion of incident cases.ConclusionDiabetes is common in individuals who have experienced SARS-CoV-2 infection, especially if they required hospitalization. This data may be helpful to screen for diabetes and manage its complications in individuals who experienced COVID-19.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022310722, identifier CRD42022310722

Klotho and vitamin D in multiple sclerosis: an Italian study

Introduction Low vitamin D levels have been recognised as an important risk factor for autoimmune diseases, including multiple sclerosis (MS). MS is a multifactorial disease, the pathogenesis of which contributes both to genetic and environmental factors. Polymorphisms in genes codifying molecules involved in vitamin D homeostasis have been associated with hypovitaminosis D. However, the influence of polymorphisms of Klotho, which codify a protein with a pivotal role in vitamin D metabolism, have never been investigated. The aim of this study was to evaluate the association among genetic variants of Klotho, namely rs1207568 and rs9536314, serum 25(OH)D3 levels, and multiple sclerosis (both risk and disease progression). Material and methods 107 patients with MS and 133 healthy controls were enrolled in this study. Serum 25(OH)D3 levels and genotyping of Klotho SNPs were evaluated in all participants by high-performance liquid chromatography and real-time polymerase chain reaction, respectively. Results Allelic and genotypic frequencies did not differ between patients and controls. Concerning rs1207568, we found a trend toward lower serum 25(OH)D3 levels in MS patients with A allele (mutant), both in heterozygosis (AG) and in homozygosis (AA), in comparison to MS patients with G allele in homozygosis (GG) (AG + AA 20.5 ±6.3 µg/l; GG 22.5 ±7.5 µg/l, p = 0.07). Conclusions Our findings did not identify a role of Klotho in the genetic susceptibility to MS

Diet Rich in Plant Protein May Prevent Type 2 Diabetes

Purpose : The aim is to show the ideal protein quality and quantity and the dietary composition for the prevention and metabolic control of type 2 diabetes mellitus (T2DM). Introduction Although some reviews demonstrate the advantages of a diet with a higher protein intake, other reviews have observed that a diet high in carbohydrates, with low-glycaemic index carbohydrates and good fibre intake, is equally effective in improving insulin sensitivity. Methods Over 2831 articles were screened, and 24 from the last 5 years were analysed and summarised for this review, using the protein, diabetes and insulin glucose metabolic keywords in Pubmed in June 2019. Results Eleven studies demonstrate that a higher consumption of proteins has a positive effect on insulin sensitivity. A higher intake of animal protein seems to be related to an increased risk of T2DM. Four studies show that consumption of meat has a deleterious effect. Higher intake of plant protein and dairy products is associated with a modestly reduced risk. Discussion Based on the results obtained, for the prevention of T2DM and all disorders related to metabolic syndrome, no ideal dietary composition has yet been found. The advantage of plant protein sources may be related to the foods' low-glycaemic index due to the high fibre content. However, the right protein quality (animal and plant) and the quantity for T2DM prevention and metabolic control are unclear and need to be investigated with further long-term studies

Effects of EPHX1 and CYP3A4 polymorphisms on carbamazepine metabolism in epileptic patients

BACKGROUND: The aim of this study was to investigate the effect of two genetic polymorphisms in the coding regions (exon 3 and exon 4) of the EPHX1 gene, ie, 337T>C and 416A>G, respectively, on the metabolism of carbamazepine (CBZ) 10,11-epoxide (the active metabolite of CBZ) by evaluating the variation in serum CBZ 10,11-epoxide levels 4 hours after administration of the drug. Moreover, we reported the genotype frequencies of the CYP3A4*22 (rs 35599367, C>T) variant and its influence on the metabolism of CBZ. METHODS: The analysis was performed in 50 patients receiving CBZ as monotherapy. DNA was extracted from leukocytes using a commercially available kit. Serum CBZ 10,11-epoxide levels were measured by high-performance liquid chromatography. Allelic discrimination was performed using polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the difference in mean values for CBZ 10,11-epoxide levels according to genotype was performed using the Student's t-test with Statistical Package for the Social Sciences version 13 software. RESULTS: Fourteen percent of the study group were CC, 42% were CT, and 44% were TT for the EPHX1 337T>C variant. No GG homozygote was identified for the EPHX1 416A>G variant; 64% were AA and 36% were AG. When we compared serum CBZ 10,11-epoxide levels 4 hours after drug administration, we found no statistically significant difference between the 337 CC, CT, and TT genotypes. Similarly, no difference in serum CBZ 10,11-epoxide levels was found between 416A>G AA and AG. Genotype frequencies for the CYP3A4*22 (rs 35599367 C>T) allelic variant were 94% for CC and 6% for CT, with no statistically significant difference in serum CBZ 10,11-epoxide levels between these genotypes 4 hours after administration of the drug (2.6±1.3 μg/μL and 2.5±1.2 μg/μL, respectively). CONCLUSION: Although there is some evidence of involvement of these polymorphisms in enzyme activity in vitro, we found no interference with CBZ metabolism in vivo

Vitamin K deficiency bleeding leading to a diagnosis of Crohn’s Disease

We report the case of a 45 year old man who came to Emergency Room of Polyclinic for sudden onset of localized ecchymosis and widespread hematomas. He was subjected to blood count and first level investigations to assess coagulation. Based on the results, second level investigations were performed. Endoscopy of the gastrointestinal tract with histological examination revealed a diagnosis of Crohn's disease. Vitamin K deficiency causes the formation of vitamin K-dependent clotting factors that cannot perform their pro-coagulant action. Consequently, patients present with hemorrhagic manifestations. Clinical and laboratory features observed in this patient show that the deficiency of vitamin K-dependent coagulation factors may reveal a complex clinical condition such as an inflammatory bowel disease