Search

Multiple Sclerosis (MS) is an immune-mediated and neurodegenerative disease of central nervous system. Relapsing-remitting (RR)-MS occurring with acute attacks and remissions, is the most common clinical type of MS. There are different strategies applied in first-line treatment of RR-MS patients such as interferon-beta (IFN-beta) and glatiramer acetate. In this study, activating and inhibitory receptor expressions and interleukin (IL)-22 levels of NK cells were investigated in RR-MS patients with or without IFN-beta therapy. Activating receptor expression and IL-22 levels of NK cells were increased in RR-MS patients under IFN-beta therapy. Elevated NK cells with activating profile and increased IL-22 under IFN-beta therapy suggest that IFN-beta treatment might direct NK cells toward a pro-inflammatory status.

Multiple sclerosis (MS), is a chronic inflammatory disease of central nervous system with unclear etiology. Relapsing-remitting (RR)-MS is the most frequent subtype of disease. Natural Killer (NK) cells have roles in cytotoxicity and immune regulation by cytokine secretions, with uncertain contribution to MS pathogenesis. This study aimed to explore contribution of NK cells to MS pathogenesis. Percentages of CD3(-)CD16(+)CD56(+) total NK cells, CD3(-)CD16(+)CD56(dim) and CD3(-)CD16(-)CD56(bright) NK cell subsets, NK cytotoxicity and intracellular IFN-gamma, IL-10 and IL-22 levels were investigated in patients with RR-MS and clinically isolated syndrome (CIS) as well as healthy subjects. Decreased IFN-gamma and increased IL-22 production might have detrimental effects on the clinical course of RR-MS. Impaired cytotoxicity is correlated with disease duration in RR-MS. These findings support the possible contribution of NK cells to RR-MS immuno-pathogenesis. (C) 2018 Published by Elsevier Inc.

Boz, Cavit/0000-0003-0956-3304; Altintas, Ayse/0000-0002-8524-5087; YUCEYAR, NUR/0000-0003-4590-6423; Sevim, Serhan/0000-0002-0518-3374; Efendi, Husnu/0000-0002-9143-3893, WOS: 000502098900008, PubMed: 31473488, Background: Fingolimod and teriflunomide are commonly used in the treatment of relapsing-remitting multiple sclerosis (RRMS). These have not been compared in controlled trials, but only in observational studies, with inconclusive results. Comparison of their effect on relapse and disability in a real-world setting is therefore needed. Objectives: the objective of this study was to compare the efficacy of fingolimod and teriflunomide in reducing disease activity in RRMS. Methods: This multicenter, retrospective observational study was carried out with prospectively collected data from 15 centers. All consecutive RRMS patients treated with teriflunomide or fingolimod were included. Data for relapses, Expanded Disability Status Scale (EDSS) scores and brain magnetic resonance imaging (MRI) scans were collected. Patients were matched using propensity scores. Annualized relapse rates (ARR), disability accumulation, percentage of patients with active MRI and treatment discontinuation over a median 2.5-year follow-up period were compared. Results: Propensity score matching retained 349 out of 1388 patients in the fingolimod group and 349 out 678 in the teriflunomide group for final analyses. Mean ARR decreased markedly from baseline after 1 and 2 years of treatment in both the fingolimod (0.58-0.17 after 1 year and 0.11 after 2 years, p < 0.001) and teriflunomide (0.56-0.29 after 1 year and 0.31 after 2 years, p < 0.001) groups. Mean ARR was lower in fingolimod-treated patients than in those treated with teriflunomide at years 1 (p = 0.02) and 2 (p = 0.004). Compared to teriflunomide, the fingolimod group exhibited a higher percentage of relapse-free patients and a lower percentage of MRI-active patients after 2.5-year follow-up. Disability worsening was similar between the two groups. Patients were less likely to discontinue fingolimod than teriflunomide (p < 0.001). Conclusion: Fingolimod was associated with a better relapse control and lower discontinuation rate than teriflunomide. the two oral therapies exhibited similar effects on disability outcomes.

In patients with multiple sclerosis (MS) intensive efforts are directed at identifying biomarkers in bodily fluids related to underlying disease mechanisms, disease activity and progression, and therapeutic response. Besides MR imaging parameters cerebrospinal fluid (CSF) biomarkers provide important and specific information since changes in the CSF composition may reflect disease mechanisms inherent to MS. The different cellular and protein-analytical methods of the CSF and the recommended standard of the diagnostic CSF profile in MS are described. A brief update on possible CSF biomarkers that might reflect key pathological processes of MS such as inflammation, demyelination, neuroaxonal loss, gliosis and regeneration is provided.

Mutations in Notch3 gene are responsible for the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). It is a late onset neurological disorder recognized by recurrent strokes and dementia. We describe here the clinical and molecular findings of three unrelated Turkish families with CADASIL syndrome. Two of the families were identified to have the same mutation, p.R110C (c.C328T), located in exon 3 of the Notch3 gene. Interestingly, the phenotypic expression of the disease in these two families was markedly different in severity and age of onset implicating additional genetic and/or non-genetic modulating factors involved in the pathogenesis. In addition, we identified the novel p.C201R (c.T601C) mutation in exon 4 of the Notch3 gene in a proband of the third family with two consecutive stroke-like episodes and typical MRI findings. Mutations described here cause an odd number of cysteines in the N-terminal of the EGF domain of Notch3 protein, which seems to have an important functional effect in the pathophysiology of CADASIL. The phenotypic variability in families carrying the same molecular defect as presented here makes the prediction of prognosis inconceivable. Although DNA analysis is effective and valuable in diagnosing approximately 90% of the CADASIL patients, lack of genotype-phenotype correlation and prognostic parameters makes the presymptomatic genetic counseling very difficult.