[Neurofilament light chain: a diagnostic potential for multiple sclerosis]. / Neirofilament legkikh tsepei: diagnosticheskie vozmozhnosti pri rasseyannom skleroze.

OBJECTIVE: To evaluate the influence of disease activity, the degree of patient disability and pathogenetic therapy on the concentration of neurofilament light chain (NFL) in the blood serum of patients with multiple sclerosis (MS). MATERIAL AND METHODS: One hundred and fourteen patients (84 women and 30 men) with definite MS were examined. The concentration of NFL in the blood serum of patients with MS was determined by enzyme immunoassay. The level of NFL was analyzed depending on the characteristics of the course and activity of the demyelinating process, the severity of neurological disorders as well as disease modifying drugs (DMDs). RESULTS: An NFL level equal to or greater than 4201 pg/ml was found to be associated with a higher risk of developing a clinical exacerbation in the next 4 months. In patients with progression of disability over the next 2 years, the initial concentration of NFL was significantly higher than in the group with a stable EDSS score. The NFL level (4943 pg/ml and higher), which may be a predictor of increased disability in the next two years, was established. CONCLUSION: The study demonstrates the possibility of using serum NFL levels as a diagnostic marker of possible exacerbation, as well as predicting disability in patients with MS.

[Homocysteine and markers of endothelial dysfunction in multiple sclerosis]. / Gomotsistein i markery endotelial'noi disfunktsii pri rasseyannom skleroze.

OBJECTIVE: To identify hyperhomocysteinemia and to assess its possible association with the course and other markers of endothelial damage in multiple sclerosis. MATERIAL AND METHODS: Analysis of blood serum for homocysteine, for the content of adhesion molecules sPECAM-1, matrix metalloproteinase 9, blood plasma test for von Willebrand factor antigen in patients with multiple sclerosis. The values of these indicators were analyzed depending on the course and activity of the demyelinating process, the severity of neurological disorders, as also depending on the therapy received. RESULTS: Hyperhomocysteinemia was found in more than half of patients with multiple sclerosis. A significantly higher homocysteine level was found in male patients, and hyperhomocysteinemia was associated with the activity of the process in patients with highly active multiple sclerosis. CONCLUSION: The results of the study suggest a possible association of hyperhomocysteinemia with high process activity and disease progression, as well as with mechanisms of neurodegeneration. Determination of homocysteine concentration may be one potential marker for predicting the course of the disease.

[Effect of different groups of first line DMT on endothelial damage in multiple sclerosis]. / Vliyanie razlichnykh grupp PITRS pervoi linii na povrezhdenie endoteliya pri rasseyannom skleroze.

INTRODUCTION: Vascular changes, including destabilization of the blood-brain barrier, are common pathological signs in multiple sclerosis (MS). There are prerequisites, which indicate the direct effects of disease modifying therapy (DMT) on the state of the vascular wall and reduce the damage to the endothelium in MS. AIM OF THIS STUDY: Was to identify and evaluate the relationship of endothelial dysfunction in patients with multiple sclerosis with used DMT. MATERIALS AND METHODS: The study included 85 patients with a reliable diagnosis of MS according to the McDonald criteria of 2010 (56 women, 29 men) aged from 17 to 62 years (average age 36.3±1.2 years). All patients underwent a comprehensive clinical and neurological examination, laboratory tests (blood serum analysis for the content of adhesion molecules sICAM-1, sPECAM-1, sE-selectin, sP-selectin, for the content of homocysteine and matrix metalloproteinase 9 (MMR-9) by ELISA; blood plasma analysis for Von Willebrand factor antigen (vWf) by ELISA).The results of the study indicate a decrease of endothelial damage in MS during interferon therapy. Its also allow the use of indicators such as von Willebrand factor antigen, sPECAM-1, sE-selectin levels as potential markers of the effectiveness of DMT.

[Registry-based comparison of multiple sclerosis epidemiology trend data in 1999 and 2019: the case of Yaroslavl]. / Dinamika osnovnykh epidemiologicheskikh pokazatelei rasseyannogo skleroza po rezul'tatam sravneniya registrov patsientov 1999 i 2019 gg. v Yaroslavle.

OBJECTIVE: To compare the epidemiological indicators of multiple sclerosis (MS) in Yaroslavl when comparing the 1999 and 2019 registers to study the pathomorphism of the disease in this territory. MATERIAL AND METHODS: During the work, the data of the 1999 and 2019 registers were used, including the age of the debut, the date of diagnosis, the form of the disease, clinical characteristics, the treatment received and its duration. In 1999, 257 patients living in the city of Yaroslavl (155 women and 102 men) were included in the MS registry with a reliable diagnosis of MS according to Poser's criteria with confirmation according to neuroimaging data. In 2019, 479 people living in the territory of Yaroslavl (342 women and 137 men) were included in the register with a diagnosis of MS based on the criteria of MacDonald 2005, 2010, 2017. As of 01.01.19, 970 patients (530 women and 440 men) were included in the patient register of the Yaroslavl region. RESULTS AND CONCLUSION: Clinical and epidemiological review of Yaroslavl MS Registry data in 1999 and 2019 showed significant changes in disease pattern. The prevalence rate increased from 42.6 to 78.5 cases per 100,000 people. The morbidity rate rose from 1.58 to 3.28 cases per 100,000 people. The reasons for the increase are improvement in the diagnostic quality, new diagnostic criteria and the true growth of prevalence and morbidity. The use of disease modifying drugs (DMDs) has extended «the time to EDSS 3,0¼ by 4 years, «the time to EDSS 6,0¼ by 5-8 years.

[Hyperhomocysteinemia and endothelial dysfunction in patients with cerebral vascular and autoimmune diseases]. / Gipergomotsisteinemiia i éndotelial'naia disfunktsiia pri sosudistykh i autoimmunnykh zabolevaniiakh golovnogo mozga.

Endothelial dysfunction today is recognized as one of the leading factors in the pathogenesis of diseases of the central nervous system of various etiologies. Numerous studies have shown the role of hyperhomocysteinemia in the development of endothelial dysfunction and prothrombogenic state. The most important condition in the development of multiple sclerosis (MS) is dysregulation of the blood-brain barrier (BBB) and transendothelial leukocyte migration. It has been proven that homocysteine also contributes to the damage of neurons by the mechanism of excitotoxicity and induction of apoptosis of neurons. These processes can be one of the factors of neurodegenerative brain damage, which plays a leading role in the progression of MS. This review describes the pleiotropic effect of homocysteine on these processes and its role in the pathogenesis of MS.

[Polymorphic variants of the immune response genes as risk factors for primary progressive multiple sclerosis]. / Polimorfnye varianty genov immunnogo otveta kak faktory riska razvitiia pervichno-progressiruiushchego rasseiannogo skleroza.

AIM: To analyze the involvement of immune response genes in the pathogenesis of primary progressive multiple sclerosis (PPMS). MATERIAL AND METHODS: This multicenter study included 111 patients with PPMS from the Russian ethnic group. The association of PPMS with genes of immune system was analyzed by the study of polymorphic variants of genes of cytokines and genes of antigen-presenting cells. RESULTS AND CONCLUSION: The genotypes of IL-4 (rs2243250)*C/C and CLEC16A (rs6498169)*G/G were associated with PPMS in Russians. The association between the HLA-DRB1*15 and PPMS found out in other populations was confirmed in Russians.

[The results of an open prospective study of ß-interferon biosimilars (an Yaroslavl' cohort)]. / Rezul'taty otkrytogo prospektivnogo issledovaniya bioanalogov ß-interferonov.

OBJECTIVE: to study safety and efficacy of the biosimilars of disease-modifying drugs (DMDs) in the prospective nonrandomized open long-term study of patients with multiple sclerosis in the Yaroslavl oblast (an Yaroslavl' cohort). MATERIAL AND METHODS: The study included 203 patients treated with DMD biosimilarsduring 30 months according to the instruction for using. The efficacy was assessed by the relapse frequencychanges in EDSS scores, changes of lesions on MRI T2-weighted images (T2-WI). The safety was assessed by the determination of the percentage of patients with side-effects due to the treatment. Results at baseline and month 30 visit were compared. RESULTS: There was a significant decrease in the frequency of relapses in patients treated with biosimilars compared to baseline (cinnovex by 0.03, genfaxon by 0.29, ronbetal/interferon by 0.13, infibeta by 0.36). For all biosimilars, with the exception of infibeta,EDSS scores significantly increased (cinnovex +0.31, genfaxon +0.38, ronbetal/interferon +0.66, infibeta +0.26). MRI results revealed an increase in the number of lesions in patients treated with cinnovex (+16.6%), genfaxon (+14.4%) and ronbetal (+10.6%) and a decrease of lesions on T2-WI in patients treated with infibeta (-14.5%). The most marked generalized reasponses were in the cinnovex group (flu-like syndrome - 66% of the patients), local reactions were most marked in the genfaxon group (82%). CONCLUSION: The differences between some biosimilars and original DMDs in the safety profile and efficacy suggest that attention should be drawn to the thorough study of drug effects in clinical trilas and postmarketing studiesincluding registers of patients treated with DMDs managed independently from pharmaceutical companies.

[von Willebrand factor and adhesion molecules in patients with multiple sclerosis]. / Faktor fon Villebranda i molekuly adgezii u patsientov s rasseiannym sklerozom.

Based on a role of certain adhesion molecules and vascular endothelial damage in multiple sclerosis (MS), we explored C-reactive protein, von Willebrand factor, matrix metalloproteinase-9, sICAM-1, sPECAM-1, E-selectin and P-selectin in the blood of patients. One group of the patients received pathogenic therapy. There was the increase in the level of the von Willebrand factor in patients who did not receive the therapy. The levels MMP-9 and sE-selectin were correlated with the high activity of the disease. The authors suggest the presence of the endothelial dysfunction in some patients. MMP9 and sE-selectin may be considered as potential markers of the activity of multiple sclerosis.

[Multiple sclerosis and endothelial dysfunction (a review)].

The endothelium plays an important role in the maintenance of vascular homeostasis, the tone and anatomical structure of the vascular wall. It is an essential component of the blood-brain barrier. In adverse conditions, damaged endothelium initiates many pathological processes in the human organism and plays a key role in the pathogenesis of a number of systemic diseases including multiple sclerosis. In this review, we discussed in detail the concepts of structural and functional features of a healthy endothelium and endothelial dysfunction, and present the basic theory of the damage mechanism of the blood-brain barrier and the role of endothelial cells, adhesion molecules, cerebral hypoperfusion in multiple sclerosis.

[Differential diagnosis of late-stage neuroborreliosis with affection of the central nervous system].

Chronic neuroborreliosis is an actual problem in neurology due to its under-investigation in Russia, variety of clinical forms, and the absence of well established diagnostic criteria. We present clinical and laboratory differential diagnostic criteria of chronic borrelial encephalomyelitis in comparison with multiple sclerosis. Distinguishing characteristics of Lyme encephalopathy versus vascular encephalopathy are considered. Problems and possibilities of immunological methods for identification of B. burgdorferi are discussed. The results of the antibiotic treatment of different clinical forms of neuroborreliosis with affection of the central nervous system are described.