[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.

[Treatment of a spastic increase of muscle tone in multiple sclerosis with botulinum toxin]. / Korrektsiia spasticheskogo povysheniia myshechnogo tonusa pri rasseiannom skleroze s ispol'zovaniem botulinoterapii.

The article presents data of the reviews, consensus and recommendations on the use of botulinum toxin type A (BTA) in multiple sclerosis (MS) patients with spasticity syndrome. It presents the results of randomized clinical trials that confirm the efficacy and favorable safety profile of dysport in treatment of MS patients. The complex approach to spasticity therapy and rehabilitation in MS is discussed.

[Clinical guidelines for the use of dimethyl fumarate in relapsing-remitting multiple sclerosis]. / Klinicheskie rekomendatsii po primeneniiu preparata dimetilfumarat pri remittiruiushche-retsidiviruiushchem rasseiannom skleroze.

Multiple sclerosis is a chronic demyelinating and neurodegenerative disease of the central nervous system, in which autoimmune inflammation and oxidative stress play essential pathogenetic roles. Activation and infiltration of immune cells in brain tissues, lipid peroxidation products, mitochondrial dysfunction, defective antioxidant protection, and many other pathological factors result in demyelination, axonal injury and death, and apoptosis of oligodendrocytes and neurons, all of which causes constant progression of the disease. The new oral agent for the treatment of relapsing-remitting multiple sclerosis (RRMS), dimethyl fumarate (DMF), helps change the pathogenetic mechanisms of the disease, thus decreasing the rate of exacerbations, slowing down disease progression, and reducing the risk of radiological progression of the disease.

[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.

[Disease-modifying drugs in pediatric patients with multiple sclerosis]. / Preparaty, izmenyayushchie techenie rasseyannogo skleroza, u detei i podrostkov.

The vast majority of therapies are being evaluated and introduced for the treatment of adult multiple sclerosis (MS). A role of these drugs in the management of pediatric MS has yet to be defined both in Russia and in the whole world. Despite the fact that today the study of new drugs in the pediatric population have included in routine practices of the big pharmaceutical agencies, such as FDA and EMA, recommendations for the treatment of pediatric patients with MS are based not so much on a long period of systematic clinical research, but on professional consensus of international expert associations, in particular, the International pediatric multiple sclerosis study group (IPMSSG). The clinical trials include the small number of patients which is not comparable to those conducted in adults. Therefore, there is a need for study designs for assessment of efficacy and safety of the drugs for MS treatment in children and adolescents. The authors present the IPMSSG concept on the treatment of pediatric MS taking into account peculiarities of the Russian legislation and experience of national experts.

[A comparison analysis of the use of intravenous ß-interferon-1a 30 mcg and subcutaneous ß-interferon-1a 44 mcg in routine clinical practice of treatment in patients with multiple sclerosis]. / Sravnitel'nyi analiz rezul'tatov primeneniya v povsednevnoi klinicheskoi praktike dlya lecheniya rasseyannogo skleroza preparatov ß-interferon-1a 30 mkg dlya vnutrimyshechnogo vvedeniya i ß-interferon-1a 44 mkg dlya podkozhnykh in''ektsii.

OBJECTIVE: to compare the results of treatment of multiple sclerosis (MS) with genfaxon, cinnovex and rebif. MATERIAL AND METHODS: The drugs were used in the treatment of 80 patients of the Moscow West administrative okrug during 2014-2015. Thirty patients were treated with genfaxon, 20 with cinnoVex and 30 with the original drug rebif. RESULTS AND CONCLUSION: Twenty-five percent of patients treated with cinnoVex were withdrawn from the study due to the non-efficacy (mean frequency of relapses was the same before and after treatment). A significant decrease of relapses was noted in patients treated with genfaxon. The high frequency of side-effects was the major problem in the treatment withgenfaxon. Due to this reason, some patients stopped treatment.A significant decrease of relapses was noted in patients treated with rebif though aversive effects were frequent during the first year of treatment. The effects of biosimilars found in this study are in line with earlier reports. Therefore, the increase of the quality of interferon-beta-1a biosimilars used for MS treatment is needed.

[Dopamine receptor agonists: new forms and new possibilities in the treatment of Parkinson's disease].

Main mechanisms of action of dopamine receptor agonists, efficacy of their use according to the results of earlier clinical trials and possible side-effects are discussed. The authors present their experience of prescription of rotigotine transdermal system in an open study of 30 patients with Parkinson's disease. The duration of the study was 8 weeks. There was a significant improvement of both motor and nonmotor (pain sensations, sleep, mood). The effective dose for treatment of initial stages was 4-6 mg daily and for the full-blown stage - 6-8 mg daily. The tolerability was good.

[Epstein-Barr virus in the pathogenesis of multiple sclerosis (a review)]. / Virus Épshteina-Barr v patogeneze rasseiannogo skleroza (obzor).

Multiple sclerosis is now regarded as a disease, which is based on genetic predisposition. Trigger mechanism are various exogenous factors. The Epstein-Barr virus is thought to be a trigger. This report provides information about possible mechanisms of the influence of the Epstein-Barr virus on the development of multiple sclerosis.

[Clinical epidemiology of multiple sclerosis in Moscow. Сlinical demo-graphic characteristics in population of one region of Moscow]. / Klinicheskaia épidemiologiia rasseiannogo skleroza v Moskve. Sovremennye kliniko-demograficheskie osobennosti na primere populiatsii odnogo iz okrugov goroda.

The changes in clinical features of multiple sclerosis (MS) are noted worldwide which can be explained by diagnosis improvement and DMT implementation. Epidemiological studies of 2008-2012 in the North-West Administrative District of Moscow noted the higher proportion of women among patients of MS (M:F=1:2.61), longer duration of the disease (mean 14.3±10.6 years, maximum - 53 years) and life expectancy of patients (44.3±12.7 years, the maximum age - 77 years). The percentage of patients with secondary progressive course of MS increased (35%). In addition, MS onset before 16 years old was diagnosed more often (5.66% of cases) and late onset MS was identified in 4.04% of the cases. Up to 45.9% of MS patients have moderate and expressed disability (group 1 and 2 disability).

[Oral disease modifying therapy of multiple sclerosis: the current view]. / Primenenie tabletirovannykh preparatov dlia lecheniia rasseiannogo skleroza: sovremennoe sostoianie problemy.

The review includes data on experimental and clinical studies of new oral methods of multiple sclerosis (MS) disease modifying therapy (DMT). The mechanisms of action, results of clinical trials of stages II and III with the data on their clinical and MRI-efficacy, tolerability and safety of fingolimod, dimethylfumarate (BG-12), teriflunomide and laquinimod are included. The risk management plans for possible side-effects of every product and the peculiarities of their use in individually selected MS treatment are discussed.

[The activation of the type I interferon signaling pathway in multiple sclerosis patients treated with russian analogue of Β-interferon-1b: transcriptome profiling data]. / Aktivatsiia signal'nogo puti interferonov tipa I u bol'nykh rasseiannym sklerozom pod vozdeistviem rossiiskogo analoga Β-interferona-1b (po dannym transkriptsionnogo profilirovaniia).

Implementation of the analogues of Β-interferon (Β-IFN), produced by recombinant strains of E. coli (Β-IFN-1b), for internal use in the Russian Federation for the treatment of multiple sclerosis (MS), implies a verification of their action at the transcriptome level in order to confirm the activation of the main signaling pathways involved in IFNb mechanism of action. In this work, the analysis is carried out for Infibeta (Generium, Russia). Using genome-wide transcriptional profiling with ILLUMINA HT-12 microarray, the differentially expressed genes in peripheral blood mononuclear cells of MS patients upon administration of Infibeta were studied. Comparison of gene expression levels in treatment-naive MS patients prior to first Β-IFN administration and 10 hours after it, identified 490 genes with significantly changed expression level, where 191 genes were up-regulated and 299 genes were down-regulated. Among the involved genes are those coding the components of the inflammatory system, innate and adaptive immunity, apoptosis, signal transduction, transcription, translation, degradation. Using gene set analysis, we confirmed the involvement of type I interferon signaling pathway genes and interferon-inducible genes in a patient's individual response to drug. Thus, the transcriptome profiling analysis allows concluding that the mechanism of action of Infibeta immunomodulatory drug is equal to that described for the original Β-IFN drugs.

[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.

[Side-effects of glucocorticosteroids in multiple sclerosis: a case report of a patient with global amnesia]. / Pobochnye éffekty terapii gliukokortikosteroidami pri rasseiannom skleroze: opisanie klinicheskogo sluchaia s global'noi amneziei

Pulse-doses of corticosteroids are actively used in the treatment of multiple sclerosis relapses. Short pulse-treatment is usually well-tolerated by patients though side-effects may be observed. We described a rare case of transient global amnesia after the pulse-treatment with corticosteroids. A complex examination excluded other causes of amnesia.

[Unified assessment of adverse events of multiple sclerosis disease modifying drugs]. / Unifikatsiia otsenki pobochnykh éffektov terapii preparatami, izmeniaiushchimi techenie rasseiannogo skleroza.

One of the important components of effective treatment оf multiple sclerosis is adherence to therapy and long-term patient compliance, as well as timely detection and correction of adverse events. Using disease modifying drugs (DMD) in general medical practice is very different from that in clinical trials, in particular, there is no uniform approach to identify the adverse events of therapy. The authors developed a form of the Adverse events of DMD questionnaire, and checked its reliability and validity.

[Effects of ecological characteristics of place of residence on the incidence, prevalence and risk of multiple sclerosis in the Republic North Ossetia - Alania]. / Ékologicheskie kharakteristiki mesta prozhivaniia i risk razvitiia rasseiannogo skleroza v Respublike Severnaia Osetiia - Alaniia.

Objective. To study the relationship between characteristics of place of residence and epidemiological indicators of multiple sclerosis (MS) in the Republic North Ossetia - Alania. Material and methods. We present the data on the effects of environmental characteristics of place of residence on the incidence, prevalence and risk of MS. Data of 110 MS patients and matched controls have been analyzed. Results. Ecological characteristics of place of residence of MS patients differ significantly from those of controls. The prevalence and incidence of MS increase in patients who have moved from presumably pollution free areas to the places with high population density and plant facilities. Conclusion. MS is thought to be a disease caused by the interaction of genetic susceptibility and environmental factors. Risk factors are intoxication with heavy metal and chemical compounds and living in environmentally disadvantaged areas.

[An analysis of an effect of infectious diseases and diet factors on the risk of multiple sclerosis in the population of the Republic North Ossetia - Alania]. / Analiz vliianiia nekotorykh vneshnikh faktorov na risk razvitiia rasseiannogo skleroza v populiatsii Respubliki Severnaia Osetiia - Alaniia.

Objective. To carry out the first in the Republic North Ossetia - Alania clinical epidemiological study of environmental risk factors for multiple sclerosis (MS) in the indigenous population. Material and methods. We have analyzed results of a questionnaire survey of 110 patients with MS and 110 matched controls. Results. We have identified statistically significant differences between the type of diet of MS patients and controls in different age periods, as well as the most significant infectious risk factors for MS. Conclusion. MS is a chronic autoimmune disease caused by the interaction of genetic and environmental factors. Among the environmental factors, infectious diseases and type of diet play the most important role.

[Asthenia, emotional disorders and quality of life of patients with multiple sclerosis]. / Asteniia, émotsional'nye rasstroistva i kachestvo zhizni u patsientov s rasseiannym sklerozom.

Objective. The evaluation of the dynamics of asthenia, chronic fatigue syndrome, emotional disorders and quality of life of patients with multiple sclerosis (MS) and to explore the possibility of using idebenon (noben) in treatment of these impairments. Material and methods. We studied 35 patients, 18 men and 17 women, with MS (mean age 36.4±8.86 years, mean disease duration 10.33±6.07 years); 83% of patients had remitting type and others - secondary progressive type. Along with neurological examination, we used the Modified Fatigue Impact Scale (MFIS 21), the Hospital Anxiety and Depression Scale and a quality of life questionnaire (EQ5D). Patients had marked asthenia and chronic fatigue at baseline. The old age of the patients and duration of MS and its severity according to EDSS predicted the higher levels of asthenia, chronic fatigue and anxiety with depression and lower quality of life on EQ5D. All patients received noben in dosage 90 mg daily (30 mg 3 times a day) during 6 months. Results and conclusion. Idebenon (noben) reduced the severity of chronic fatigue syndrome, asthenia and depression in MS patients. The dose used in the study may be regarded as the optimal dose that provides best efficacy with minimal side-effects.