Background: Multiple Sclerosis (MS) is a multifactorial disease whose pathogenesis is the result of interaction among genetic, epigenetic, and environmental factors. Among these, a role for vitamin D ...hypovitaminosis has emerged in recent decades. Vitamin D levels are influenced by both environmental and genetic factors. Single nucleotide polymorphisms (SNPs) in genes codifying for molecules involved in vitamin D metabolism have been associated with an increased risk of developing MS. However, few studies assessed the association of such SNPs with the severity of the disease. The aim of this observational study was to evaluate the potential association among vitamin D status, MS severity, and vitamin D-related SNPs, alone or in combination. Methods: In a cohort of 100 MS patients, we genotyped 18 SNPs in the following genes: NAD synthetase 1, CYP2R1, vitamin D binding protein, vitamin D receptor, Retinoid X Receptor-α, KLOTHO, CYP24A1, and CYP27A1. Serum 25(OH)D3 levels were measured by high-performance liquid chromatography. Genotyping was performed by real-time polymerase chain reaction or PCR-RFLP. Results: We did not find any association between SNPs, alone or in combination, and MS severity. Conclusion: In this study, we make an initial evaluation of the possible influence of several SNPs in vitamin D-related genes on MS severity.
Regulatory T cells (Tregs) alterations have been implicated in the pathogenesis of Multiple Sclerosis (MS). Recently, a crucial role of the X-Linked Forkhead Box P3 (FoxP3) for the development and ...the stability of Tregs has emerged, and FOXP3 gene polymorphisms have been associated with the susceptibility to autoimmune diseases. The expression of Foxp3 in Tregs is regulated by the transcription factor GATA binding-protein 3 (GATA3) and vitamin D
. The aim of this retrospective case-control study was to investigate the potential association between FOXP3 and GATA3 genetic variants, Vitamin D
, and MS risk.
We analyzed two polymorphisms in the FOXP3 gene (rs3761547 and rs3761548) and a polymorphism in the GATA3 gene (rs3824662) in 106 MS patients and 113 healthy controls. Serum 25(OH)D3 was also measured in all participants.
No statistically significant genotypic and allelic differences were found in the distribution of FOXP3 rs3761547 and rs3761548, or GATA3 rs3824662 in the MS patients, compared with controls. Patients that were homozygous for rs3761547 had lower 25(OH)D3 levels.
Our findings did not show any association among FOXP3 and GATA3 SNPs, vitamin D
, and MS susceptibility.
Background
Sleep disorders are common in patients with multiple sclerosis and have a bidirectional interplay with fatigue and depression.
Objective
To evaluate the effect of treatment with oral ...dimethyl fumarate on the quality of sleep in relapsing-remitting multiple sclerosis.
Methods
This was a multicentre observational study with 223 relapsing-remitting multiple sclerosis subjects starting treatment with dimethyl fumarate (n=177) or beta interferon (n=46). All patients underwent subjective (Pittsburgh Sleep Quality Index) and objective (wearable tracker) measurements of quality of sleep. Fatigue, depression, and quality of life were also investigated and physical activity was monitored.
Results
Patients treated with dimethyl fumarate had significant improvement in the quality of sleep as measured with the Pittsburgh Sleep Quality Index (p<0.001). At all-time points, no significant changes in Pittsburgh Sleep Quality Index score were observed in the interferon group. Total and deep sleep measured by wearable tracker decreased at week 12 with both treatments, then remained stable for the total study duration. Depression significantly improved in patients treated with dimethyl fumarate. No significant changes were observed in mobility, fatigue and quality of life.
Conclusion
In patients with relapsing-remitting multiple sclerosis, the treatment with dimethyl fumarate was associated with improvements in patient-reported quality of sleep. Further randomised clinical trials are needed to confirm the benefits of long-term treatment with dimethyl fumarate.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by John Cunningham Virus (JCV). We report four PML cases in immunocompromised ...patients, respectively treated with (1) Natalizumab, (2) Rituximab, (3) autologous stem-cell transplantation, and (4) Tacrolimus. All patients underwent neurological examination, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), JCV-DNA research on biological samples, and lymphocytes subpopulation study. All cases presented with motor, behavioural, and cognitive disorders. Visual, sensitive, and cerebellar deficits developed in three cases. MRI revealed widespread progressive demyelinating areas with active borders; three patients presented contrast enhancement. One patient developed inflammatory reconstitution syndrome (IRIS). At MRS, all cases presented decreased N-acetyl-aspartate (NAA) and three cases showed increased choline (Cho). In one patient, plasma and urine tested positive for JCV-DNA, while cerebrospinal fluid (CSF) analysis confirmed JCV in two patients. The fourth patient had a low JCV-DNA blood titer and brain biopsy showed subacute necrosis. Two patients had abnormal lymphocyte subpopulations. Three patients underwent therapy with Mirtazapine, one of whom received Mefloquine in add-on. No clinical response was registered. Clinical onset, MRI and MRS were highly suggestive of PML in all patients, despite three cases presented contrast enhancement. In three cases JCV-DNA detection in biological samples confirmed the diagnosis. The fourth patient fulfilled diagnosis of “presumptive PML”. Our data confirm the importance to complete the diagnostic workup despite the presence of findings not completely consistent with classical PML. We hypothesize that atypical characteristics could due to the clinical conditions leading to PML.
•Four cases of PML in iatrogenic immunocompromised patients.•Clinical presentation was typical for PML.•Diagnostic findings were not completely consistent with classical PML.•Atypical findings do not exclude diagnosis when clinical data are highly suggestive.•It is necessary to improve the diagnostic and therapeutic management of patients.
Multiple sclerosis (MS) is an autoimmune and degenerative disorder of the central nervous system (CNS) that causes a progressive loss of motor and cognitive performances. Moreover, since the earlier ...phases, axonal loss as well as neuronal degeneration and a failure of oligodendrocytes to promote myelin repair have been demonstrated. In previous studies, it has been shown that the treatment of rat neuronal primary cultures with serum from MS patients can be toxic for neurons. Here we report a pilot investigation showing that CSF from patients contains extracellular vesicles (EVs) able to induce cell death in rat cultured astrocytes. Although these data are still preliminary, they suggest at least two notable considerations: i) EVs can be instrumental to pathology, and their concentration in CSF might be proportional to MS severity; ii) astrocytes can be part of the degenerative process. As a consequence, we propose that cultured astrocytes can be used as a model to study the toxicity of EVs from patients affected by MS at different stages. In addition, we suggest that EVs and their cargoes might be used as biomarkers of MS severity.
Because of the imprecision of the ecological impacts and the frequent lack of quantitative information, fuzzy theory provides a useful approach to the environmental impact evaluation. In this paper, ...the environmental parameters are defined through fuzzy numbers. By considering the quality of the global component as derived from primitive environmental components, for these primitive components the quality is generally derived from their fuzzy physical parameters. Suitable operators are proposed in order to estimate the global environmental component quality as a function of environmental primitive components quality that can decrease or increase the environmental quality. Also in fuzzy form the magnitude of the plant impact factor that strikes the environmental components is esteemed. This magnitude is a function of environmental parameters that can be fuzzy, as fuzzy can be the relation between these parameters and the magnitude of the impact factor. Therefore, through the matrix method, the total environmental impact (T.E.I.) in fuzzy terms is calculated, as in fuzzy form, the percentage of impact on every environmental component is calculated. A criterion is proposed in order to compare fuzzy T.E.I. for various sceneries. This criterion is based on a ranking method that considers the grade of prudence of the decision-maker and the acceptable risk. Finally, a case study is reported as an explanation of the method.
Abstract Objective To assess the association between diabetes preceding Parkinson's disease (PD) and PD. Methods PD individuals were matched to PD free individuals randomly selected from people in ...the same municipality as the cases. Occurrence of diabetes preceding PD onset among cases and controls was assessed through a structured questionnaire. Information regarding current and past medical treatment and other variables was also collected. We used univariate and multivariate logistic models to calculate crude and adjusted odds ratios (OR). Covariates are adjusted for included education, smoking habit, alcohol and coffee consumption. Results 318 PD individuals (165 women, 153 men) and 318 matched controls were included in the study. PD patients had a mean age at interview of 66.7 years. Mean age at PD onset was 60.8 years and mean PD duration 5.9 years. We found an inverse association between PD and diabetes preceding PD onset in all groups stratified by gender, age at PD onset, body mass index (BMI), smoking habit, alcohol and coffee consumption. Multivariate analysis yielded the same findings after controlling for the variables (adjusted OR 0.4; 95% CI, 0.2–0.8). Conclusions Our findings provide additional support for a potential link between diabetes and PD.
Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. At present, the molecular mechanisms causing the initiation, development and progression of ...MS are poorly understood, and no reliable proteinaceous disease markers are available. In this study, we used an immunoproteomics approach to identify autoreactive antibodies in the cerebrospinal fluid of MS patients to use as candidate markers with potential diagnostic value. We identified an autoreactive anti-transferrin antibody that may have a potential link with the development and progression of MS. We found this antibody at high levels also in the serum of MS patients and created an immunoenzymatic assay to detect it. Because of the complexity and heterogeneity of multiple sclerosis, it is difficult to find a single marker for all of the processes involved in the origin and progression of the disease, so the development of a panel of biomarkers is desirable, and anti-transferrin antibody could be one of these.
Cognitive impairment may occur at any time during the course of multiple sclerosis (MS), and it is often a major cause of disability in patients with the disease. The APOE-epsilon4 allele is the ...major known genetic risk factor for late onset familial and sporadic Alzheimer's Disease (AD), and it seems to be implicated in cognitive decline in normal elderly persons.
To investigate the clinical and genetic variables that can be associated with the cognitive decline in patients with MS.
Five-hundred and three patients with clinically definite MS underwent a battery of neuropsychological tests and, according to the number of failed tests, were divided into cognitively normal and impaired. All patients were genotyped for APOE gene polymorphisms.
Fifty-six percent of MS patients showed, to different extents, cognitive impairment. Cognitive decline was predominant in men and was associated with disease duration, Kurtzke Expanded Disability Status Scale (EDSS) score, a low level of education, and, interestingly, the epsilon4 allele of the APOE gene. By contrast, cognitive impairment in women was independent of any investigated variable.
The findings demonstrate that clinical and genetic factors play a role in men affected by MS developing cognitive impairment.
A better understanding of the epidemiological impact of suicidal ideation after stroke is required to identify subjects needing personalised interventions.
The aim of this meta-analysis was to ...estimate rates and correlates of suicidal ideation among stroke survivors.
We searched via Ovid, Medline, Embase and PsycInfo from database inception until August 2016. Predefined outcomes were (1) rates of suicidal ideation based on random-effects pooled proportion and (2) relevant sociodemographic and clinical correlates, using random-effects odds ratio (OR) or standardised mean difference (SMD) for categorical and continuous variables, respectively.
Fifteen studies and 13 independent samples, accounting for 10 400 subjects, were included in meta-analyses. The pooled proportion of suicidal ideation among stroke survivors was 11.8% (7.4% to 16.2%), with high heterogeneity across studies (I
=97.3%). Current (OR=11.50; p<0.001) and past (OR=6.96; p<0.001) depression, recurrent stroke (OR=1.77; p<0.001), disability (SMD=0.58; p=0.01) and cognitive impairment (SMD=-0.22; p=0.03) were all associated with suicidal ideation. Moreover, suicidal ideation was less likely in stroke survivors who were married (OR=0.63; p<0.001), employed (OR=0.57; p=0.02) and had higher education levels (OR=0.55; p=0.002).
Despite some limitations, this meta-analysis shows that about one out of eight stroke survivors has suicidal ideation. Thus, there is enough evidence to support the use of routine screening and early interventions to prevent and treat suicidal ideation after stroke, especially among subjects carrying specific correlates.
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