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.
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