A. N. Boiko

Neuroprotective Therapy with Citicoline (Ceraxon) in Patients with Ischemic Stroke

The dynamics of neurological symptoms were assessed using the Scandinavia Stroke Scale and functional disease outcomes with the Barthel index and modified Rankin scale in 89 patients during the acute period of ischemic stroke of moderate severity, whose treatment included citicoline (Ceraxon) i.v. and p.o. The results were compared with those from a reference group (52 patients) selected in terms of clinical and demographic parameters, who received similar treatment without citicoline. By discharge from hospital (days 21–24 of illness), there was significantly (p < 0.05) greater recovery in the study group. The efficacy of citicoline was significantly (p < 0.05) greater in patients aged less than 70 years and when citicoline was given in the first hours of illness.

Клинические рекомендации по применению препарата диметилфумарат при ремиттирующе-рецидивирующем рассеянном склерозе

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.

Efficacy and Tolerance of Glatiramer Acid (Copaxone) on Long-Term Use: 10 Years of Experience at the Moscow City Multiple Sclerosis Center

We summarize here 10 years of experience of using glatiramer acetate (Copaxone) in 74 patients with active remitting multiple sclerosis (MS). Significant decreases in the frequency of disease exacerbation over all 10 years were noted. Disease severity on the EDSS was stable and increased significantly only by the tenth year of observations. Positive stable clinical dynamics were independent of disease severity at the moment of treatment initiation. Tolerance of glatiramer acetate was good, allowing us to come close to controlling the course of MS – 64.8% of patients had no more than one exacerbation in 10 years, while 71.6% showed no or minimal progression of disease (up to 1 point on the EDSS scale). These observations lead to the conclusion that 10 years of treatment with Copaxone allows disease development to be controlled in many patients.

Characteristics of the formation of chronic fatigue syndrome and approaches to its treatment in young patients with focal brain damage

Chronic fatigue is among the manifestations of focal brain lesions. It is most often encountered in multiple sclerosis (MS) and patients with the sequelae of traumatic, inflammatory, and vascular brain damage (encephalopathies). The aim of the present work was to study the mechanisms of formation of this syndrome in 50 patients with focal brain lesions of different origins (in the inactive stage) and to assess the possibility of correcting it using the combined agent Fezam (2 capsules t.i.d. for one month), which contains piracetam and cinarrizine. In patients with encephalopathies, chronic fatigue syndrome was directly associated with the severity of depression. Patients with MS showed changes in the value-sense sphere. Neuropsychological testing showed that the psychological and personality components played a greater role in the origins of chronic fatigue in patients with encephalopathies than in those with MS. Fezam significantly decreased the severity of chronic fatigue, particularly in patients with MS; in the second group (non-MS patients) this was accompanied by a decrease in the severity of depression. Mild side effects (in six patients — 12%) consisted generally of sleep disturbances. These results indicate that Fezam should be used in the treatment of chronic fatigue in patients with focal brain lesions; in encephalopathies it should be combined with psychoactive agents.

Atypical Multiple Sclerosis – Baló’s Concentric Sclerosis: Two Case Reports and a Review

We present two case reports of patients with diagnoses of Baló’s concentric sclerosis. The characteristics of the pathogenesis of this disease are considered in relation to the differential diagnosis against other types of multiple sclerosis and potential therapeutic tactics are discussed.

Dendritic Cells in Multiple Sclerosis

This review presents data on the main functions of dendritic cells (DC) and their structure and stages of development. The role of DC in maintaining immunological tolerance is discussed, as it their role in the development of autoimmune diseases. The involvement of DC in the immunopathogenesis of multiple sclerosis (MS) is considered, along with their therapeutic potential in these cases.

Polymorphic Variants of Immune Response Genes as a Risk Factor for the Development of Primary Progressive Multiple Sclerosis

Objectives. To analyze the involvement of immune response genes in the pathogenesis of primary progressive multiple sclerosis (PPMS). Materials and methods. A representative cohort of 111 ethnically Russian patients with PPMS took part in a multicenter study. The involvement of immune system genes in the pathogenesis of PPMS was analyzed by investigating the associations of variants of cytokines genes and genes involved in antigen processing and presentation by antigen-presenting cells with the disease. Results and conclusions. Carriership of the IL4 genotype (rs2243250)*C/C and CLEC16A (rs6498169)*G/G was found to have a positive association with the development of PPMS in Russian patients. The association described in studies of other populations, HLA-DRB1*15 with a high risk of developing this form of MS, was confirmed.

Effects of Catecholamines on Th17 Cells in Multiple Sclerosis

Objective. To study the possibly associations between the clinical features of multiple sclerosis(MS) and quantitative and the qualitative properties of Th17 cells and the dopamine (DA) and serum noradrenaline (NA) concentrations in patients with MS. Materials and methods. Complex neurological and immunological investigations were carried out on 43 patients with remitting MS. All patients were underwent neurological investigations including assessment of levels of disability on the EDSS scale. Serum DA and NA concentrations were determined by immunoenzyme analysis. The proportions of circulating Th-17 cells were assessed by multicolor flow cytometry. The functional activity of Th17- and Th-1 cells was assessed in terms of IL-17 and γ-interferon production by peripheral blood mononuclear cells stimulated with magnetic particles coated with anti-CD3/anti-CD28 antibodies. Results. The proportion of Th-17 cells and cytokine production in the group of MS patients in exacerbation were significantly greater than in remission and in the control group, while the DA level was lower. NA levels in MS patients were identical in exacerbation and remission but were significantly lower than in the control group. Conclusions. These data suggest that catecholamines have an inhibitory effect on Th17 cells in MS.

A Comparative Placebo-Controlled Clinical Trial of the Efficacy and Safety of Glatiramer Acetate 20 mg in Patients with Remitting Multiple Sclerosis: First-Year Study Results

Objective. To seek evidence that Timexon (BCD-063, glatiramer acetate, Biocad, Russia) and Copaxone-Teva (Teva Pharmaceuticals Ltd., Israel) have similar efficacies in patients with remitting multiple sclerosis. Materials and methods. A multicenter, double-blind, placebo-controlled, comparative, randomized, phase III study included 158 patients with confirmed diagnoses of remitting multiple sclerosis. Patients were randomized to the BCD-063, Copaxone-Teva, and placebo groups at a ratio of 2:2:1. Results and conclusions. Efficacy analysis at 48 weeks of treatment demonstrated that there were no differences between the BCD-063 and Copaxone-Teva groups in terms of MRI parameters or exacerbation frequency. Assessment of the primary endpoint (number of MRI-confirmed exacerbations per patient per year) showed that the mean number of exacerbations was 0.098361 (0.351422) in the BCD-063 group, 0.098361 (0.351422) in the Copaxone-Teva group, and 0.178571 (0.390021) in the placebo group. Assessments on the EDSS and MSFC also demonstrated that there were no differences between the BCD-063 and Copaxone-Teva groups. Both BCD-063 and Copaxone-Teva had favorable safety profiles. These data provide evidence of the therapeutic equivalence of BCD-063 (Biocad, Russia) and Copaxone-Teva, which is an important aspect for further introduction of the reproduced glatiramer acetate formulation into the treatment of multiple sclerosis.

Multiple Sclerosis Disease-Modifying Drugs in Children and Adolescents

The vast majority of drugs for the treatment of multiple sclerosis (MS) have been developed and approved for the adult patient population. The place of these drugs in the treatment of children remains undefined not only in Russia, but also throughout the world. Despite the fact that studies of new drugs in the pediatric patient population is part of the routine practice of large pharmaceutical agencies such as the FDA and the EMA, treatment recommendations FOR pediatric MS patients are based less on long-term systematized experience of clinical studies as on a professional consensus of international expert associations, particularly the International Pediatric Multiple Sclerosis Study Group (IPMSSG). Clinical trials include small numbers of patients of pediatric age, minor compared with the number of participants in adult studies. There is therefore a need to develop new assessments evidencing the efficacy and safety of drugs for the treatment of MS in children and adolescents. This article presents the views of the IPMSSG on the treatment of pediatric MS, taking account of the characteristics of the Russian legislation and experience of Russian specialists.