Multiple sclerosis (MS) is a socially significant immune-mediated disease, characterized by demyelination, axonal transection and oligodendropathy in the central nervous system. Inflammatory demyelination and neurodegeneration lead to brain atrophy and cognitive deficit in up to 75% of the patients. Cognitive dysfunctions impact significantly patients' quality of life, independently from the course and phase of the disease. The relationship between pathological brain findings and cognitive impairment is a subject of intensive research. Summarizing recent data about prevalence, clinical specificity and treatment of cognitive disorders in MS, this review aims to motivate the necessity of early diagnosis and complex therapeutic approach to these disturbances in order to reduce the social burden of the disease.

Multiple sclerosis (MS) is associated with cytokine imbalance and high rate (40-70%) of cognitive impairment. The objective of this study is to investigate the relationship between serum concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-17A, IL-18, IL-10, and cognitive performance in patients with relapsing-remitting MS (RRMS). Methods The study comprised 159 patients with RRMS (mean age 40.08 ± 8.48 years) in remission phase and 86 age-, gender-, and education-matched healthy controls. Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities test (SDMT), and Isaacs test were used for assessment of working memory, attention, visuo-perceptual abilities, information processing speed, and executive functions. Serum cytokine concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Results Patients had significantly increased serum concentrations of TNF-alpha and IL-17A and decreased levels of IL-10 compared to the controls (p < 0.05). Negative correlation was found between serum TNF-alpha and SDMT score in patients with disease evolution longer than 10 years (r = -0.258 p = 0.033); PASAT and SDMT scores were in negative correlation with concentration of IL-17A (r = -0.229 p = 0.004; r = -0.166 p = 0.041). Cognitive impairment was established in 46.5% (n = 74) of the patients. Cognitively impaired patients had significantly higher serum IL-17A than cognitively preserved individuals (p = 0.007). Multiple linear regression analysis revealed IL-17A as a significant predictor of cognitive performance in RRMS patients. Conclusion The results from this study suggest that pro-inflammatory cytokines IL-17A and TNF-alpha simultaneously with decreased IL-10 are involved in cognitive deterioration in RRMS.

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system characterised with a complex system of interactions between proinflammatory and anti-inflammatory cytokines in its course. Aim: The aim of the present study was to investigate the serum levels of cytokines TNF-α, IFN- γ, IL- 4 and IL- 10 in female patients with MS and healthy individuals, the changes occurring in the relapse and remission phases of the disease and their correlation with the severity of the neurological deficit. Patients and methods: Thirty-five women with relapsing-remitting MS were examined. The patients’ age ranged between 18 and 50 years and MS was verified clinically and by magnetic resonance imaging according to the McDonald criteria. Thirteen of the patients were treated with interferon-β-1b. The serum concentrations of TNF-α, IFN- γ, IL- 4 and IL- 10 were determined twice - in relapse and in remission - using an enzyme-linked immunosorbent assay (EL ISA). The control group consisted of 35 age-matched healthy females. Results: The comparison of cytokine serum concentrations during the two phases of the disease showed significant elevation of the TNF-α serum levels in the relapse phase and of IL- 4 - in the remission phase. The comparison between the patients and the healthy control subjects demonstrated statistically significant lower concentrations of TNF-α in remission patients and higher concentrations of IL- 10 in relapse patients. The patients with interferon-β-1b treatment showed different profile of cytokine secretion from the patients without interferon-β-1b treatment. Interferon-β-1b-treated patients showed significantly lower serum levels of TNF-α and IFN- γ during the relapse phase and higher TNF-α and IL- 10 serum levels during the remission phase compared with the untreated patients. Conclusions: Serum levels of TNF-α and IL- 4 objectively reflect the immune response during relapse and remission of the disease. The severity of neurological deficit as estimated with the expanded disability status scale (EDSS ) does not depend on the serum levels of TNF-α, IL- 10 and IFN- γ in the two phases of MS.

Our study finds high frequency of hormonal disturbances among female patients with RRMS. Abnormally low concentrations of sex hormones are associated with higher serum levels of TNF-alpha and IFN-gamma, which could suggest suppressive effect of estradiol and progesterone on pro-inflammatory cytokine secretion.

Despite numerous attempts at codifying their language, the Pomaks in Greece, a linguistic as well as religious minority, do not generally put into writing this variety, which is considered to be a Bulgarian dialect. Up until about fifteen years ago, there was an absence of any kind of lexicographic tradition. The grammars, dictionaries etc. that appeared in Greece in the mid-1990’s can be classified as “external” codifications, since most of them were made by the majority. Over the last few years, however, an increasing minority-activism has changed the situation somewhat. Some writing has begun to emerge from the community, but the variety is still far from fitting the criteria for micro-literacy, the codification of which is difficult due to the different idiolectal varieties of the language actors, which are far away from a uniform orthographical norm as well as an alphabet. However, the publications in the minority language are seen as evidence of cultural emancipation and linguistic vitality. This article deals with the issues of language and literacy among the Pomaks in Greece and presents a case study of the ethno-linguistic orientation of the currently most productive Pomak language activist’s writings.

Cytokines of different types play an important role in multiple sclerosis (MS) pathogenesis as mediators and regulators of the immune processes in the central nervous system. The aim of the study was to determine the effect of interferon-beta and glatiramer acetate on serum concentrations of TNF-alpha and IL-17 A and their correlation with the degree of disability in clinically stable patients with relapsing-remitting MS. A cross-sectional, case-control study of 220 patients (68 treatment naïve; 152 treated with interferon-beta or glatiramer acetate) and 99 clinically healthy age-gender-body mass index-matched subjects were performed. Serum cytokine concentrations were measured during remission of the disease by means of ELISA. Treatment naïve patients showed significantly higher levels of IL-17 A than the treated individuals (p = .000109) and controls (p = .000044). Within the treated group, only patients with interferon-beta had significantly higher serum IL-17 than the controls (p = .023). TNF-alpha concentrations were significantly higher in the treated patients compared to the healthy controls (p = .000013), regardless of the type of the therapy. Treatment naïve individuals did not differ from the controls according to their serum TNF-alpha (p = .922). No correlation was found between the serum cytokine concentrations and Expanded Disability Status Scale (EDSS) score (p > .05). Serum concentrations of these cytokines could not be regarded as reliable predictors for the severity of the residual neurological deficit during disease-modifying treatment. Our data suggest that suppression of IL-17 A production as one of the mechanisms underlying the beneficial effect of first-line disease-modifying treatments is stronger in glatiramer acetate than in interferon-beta.

The changes in cognitive functions that occur with aging and in various pathological conditions are a subject of growing interest. Experimental and clinical data justify the hypothesis about the influence the immune system exerts on cognitive processes. The balance between pro-inflammatory and anti-inflammatory cytokines has been established as a necessary factor for normal cognitive functioning. Cytokine production is under strong genetic control and various single nucleotide polymorphisms (SNPs) in cytokine genes have been described. As cytokine SNPs have been demonstrated to affect the gene expression or the functional activity of the immune protein this logically led to the suggestion about the role of these polymorphisms in cognitive functioning. Studies exploring the association between different genetic variants of cytokine gene polymorphisms and cognitive abilities in healthy subjects and in demented patients show divergent results. The review of relevant literature suggests that SNPs implement their effect on cognition in large interactions with each other, as well as with many other factors, some of which still remain to be identified. This article summarizes the contemporary knowledge about the correlations between SNPs in cytokine genes and cognitive status in humans. Further research is needed to determine the precise role and the molecular mechanisms of action of the SNPs in cognitive processes.

Persistent cytokine imbalance in patients compared with controls is a marker for Th1-mediated CNS demyelination. Anti-inflammatory TGFβ1, IL4 are indicators of immune response intensity. The deficit severity does not depend on changes of the tested cytokines, but correlates with 25(OH)D levels during periods of relapse and remission.