[Clinical and epidemiological aspects of neuromyelitis optic spectrum diseases in the russian population]. / Kliniko-epidemiologicheskie aspekty zabolevanii spektra optikoneiromielita v rossiiskoi populyatsii.

OBJECTIVE: To present clinical and epidemiological aspects of neuromyelitis optica spectrum disorders (NMOSD) in the Russian Federation. MATERIAL AND METHODS: We studied 142 patients who met diagnostic criteria of 2015 for NMOSD. Sex, age at disease onset, presence or absence of aquaporin-4 immunoglobulin G antibodies (AQP4-IgG), mail clinical symptoms, oligoclonal IgG, therapy for the treatment of exacerbations and prevention of exacerbations, compliance with 2006 diagnostic criteria were assessed. RESULTS: The prevalence of women is 4.26:1, the most frequent age at disease onset is 18-29 years (36% of cases). The laboratory aspects of the disease are characterized and approaches to the treatment and prevention of exacerbations of NMOSD in patients of the Russian population are evaluated. Approaches to diagnostics are compared depending on the applied diagnostic criteria (34% of patients do not meet neuromyelitis optica 2006 diagnostic criteria). A prognosis for the prevalence of NMOSD in the Russian population has been proposed: 0.45-4.21/100000. CONCLUSION: This is the first published data on clinical and epidemiological characteristics of NMOSD in the Russian Federation.

[Monoclonal antibody therapies for rapidly progressive and highly active multiple sclerosis in the era of the COVID-19 pandemic]. / Terapiya monoklonal'nymi antitelami bystroprogressiruyushchego i vysokoaktivnogo rasseyannogo skleroza v epokhu pandemii COVID-19.

As the COVID-19 pandemic continues, reducing the risk of infection for immunocompromised patients remains an important issue. Patients with aggressive multiple sclerosis (MS) require immunosuppressive therapy in order to control the overactive autoimmune response. Preliminary international and national trials demonstrate that older age, higher disability status and progressive MS are generally associated with a more severe clinical course of COVID-19. However, uncertainty remains about the effect of disease-modifying therapies on the COVID-19 clinical presentation. In this article, we pay special attention to monoclonal antibodies used for immune reconstitution therapy, which results in significant changes to the T-cell and/or B-cell repertoire. Based on the published data from registries in different countries, we attempted to estimate the benefits and risks of these therapies in a complicated epidemiological setting.

C9orf72 Gene Expression in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We studied the expression of C9orf72 gene in pathologies associated with hexanucleotide repeats expansion in this gene: frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The study included 7 patients with hexanucleotide repeats expansion in the C9orf72 gene and 9 patients of the control group. The expression of C9orf72 mRNA was evaluated in blood leukocytes by real-time PCR. Methylation of CpG-sites in C9orf72 promotor region was evaluated by DNA sequencing after bisulfite conversion. A 2-fold decrease in the C9orf72 gene expression was found in patients with hexanucleotide repeats expansion in comparison with controls, though the difference did not reach statistical significance due to small sample size. The highest expression was shown for ALS in comparison with FTD and FTD-ALS phenotype. A trend to inverse correlation between C9orf72 mRNA level and promoter methylation of this gene as well as between mRNA level and age of disease onset was demonstrated.

[Experience in designing an electronic multiple sclerosis registry]. / Opyt sozdaniya elektronnogo registra patsientov s rasseyannym sklerozom.

OBJECTIVE: To develop an electronic registry of patients with MS in the Russian Federation and to analyze the collected epidemiological and clinical data. MATERIALS AND METHODS: Patients aged 18 and older with definite multiple sclerosis were included in the study. We designed a specialized electronic individual registration form (registry) to gather information about study participants. This paper presents data collected in the project between September 25, 2017 and March 25, 2020. RESULTS: We collected information on 2728 patients. This paper presents the results of data analysis from the registry of MS patients, including demographic, clinical and epidemiological characteristics, the type and timing of treatment received. Based on the data obtained, certain issues with primary diagnosis of multiple sclerosis and delayed initiation of disease-modifying therapy can be highlighted, which contribute to the transition of the disease to a secondary progressive course and disability increase.

Effect of Mutations in SOD1 and C9orf72 Genes on Autophagy in Lymphomonocytes in Myotrophic Lateral Sclerosis.

Insoluble protein inclusions accumulate in somatic cells in amyotrophic lateral sclerosis. The most common gene mutations associated with this pathology are SOD1 and C9orf72. Protein aggregates can be removed from cells by autophagy. We studied the relationship between the presence of genetic abnormalities in the SOD1 and C9orf72 genes and changes in autophagy in lymphomonocytes in amyotrophic lateral sclerosis. The study included 85 patients with amyotrophic lateral sclerosis and 15 healthy volunteers. Genetic analysis for the presence of mutations in the SOD1 and C9orf72 genes and detection of autophagy marker LC3 in lymphomonocytes were performed. In amyotrophic lateral sclerosis, autophagy activation in lymphomonocytes was found. We also obtained evidence that protein product of the mutant C9orf72 gene can disturb the late stages of autophagy.

[Diagnostic value of antibodies to myelin oligodendrocyte glycoprotein in demyelinating diseases of the central nervous system]. / Diagnosticheskoe znachenie antitel k mielin-oligodendrotsitarnomu glikoproteinu pri demieliniziruiushchikh zabolevaniiakh tsentral'noi nervnoi sistemy.

AIM: To evaluate the diagnostic value of MOG-IgG antibodies in multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). MATERIAL AND METHODS: Twenty-nine patients with definitive MS according to the criteria of McDonald, 2010 (21 with relapse-remitting MS and 8 with secondary progressive MS), 7 patients with ADEM confirmed by clinical and instrumental data and 27 healthy volunteers were included in the study. Serum MOG-IgG levels were evaluated in all patients. MOG-IgG levels in the cerebrospinal fluid (CSF) were evaluated in 22 cases with MS, 6 cases with ADEM, and 8 healthy volunteers using ELISA. RESULTS AND CONCLUSIONS: Serum MOG-IgG levels are significantly higher in patients with MS and ADEM compared to the control group. No statistically significant differences in the serum MOG-IgG levels were found between MS and ADEM groups. When analyzing the level of MOG-IgG in CSF, no statistically significant between-group differences were obtained. The sensitivity and specificity of the determination of MOG-IgG in serum in patients with MS are 75,8% and 92.59%, respectively. MOG-IgG is detected in serum and CSF in patients with demyelinating diseases that indicates its pathogenetic significance in the development of MS and ADEM. Serum MOG-IgG may be a valuable biomarker for demyelinating diseases. Further research in a large population of patients is required.

[Leptomeningeal B-cell follicles in multiple sclerosis: a role in the pathogenesis and prognostic value]. / Éktopicheskie limfoidnye V-kletochnye follikuly pri rasseiannom skleroze: rol' v patogeneze zabolevaniia i prognosticheskaia znachimost'.

B-lymphocytes play an important role in the development and maintenance of the inflammatory process in multiple sclerosis. Recently special attention has been paid to cell formations that are found in the meninges in patients with multiple sclerosis - the so-called leptomeningeal follicle-like structures that contain not only B-lymphocytes, but also other immunocompetent cells, creating a special environment for clonal expansion, selection and further proliferation of B-lymphocytes. Magnetic resonance imaging (MRI) of the brain with gadolinium-based contrast agents reveals local subarachnoid space contrasting that corresponds to the accumulation of the contrast agent by large lymphoid follicles. This phenomenon is called leptomeningeal contrast enhancement and according to some literature data, its severity correlates with the rate of progression of the disease and functional disability. The review presents the available literature on leptomeningeal follicle-like B-cell structures, as well as prospects of using leptomeningeal contrast enhancement on MRI as a potential biomarker for predicting disease severity in patients with multiple sclerosis.

[The application of high-frequency and iTBS transcranial magnetic stimulation for the treatment of spasticity in the patients presenting with secondary progressive multiple sclerosis]. / Primenenie transkranial'noi magnitnoi stimulyatsii v lechenii sindroma spastichnosti pri vtorichno-progredientnom rasseyannom skleroze.

Spasticity is considered to be a common manifestation of multiple sclerosis. Muscle relaxants are not sufficiently effective; more than that, some of them often cause a variety of adverse reactions. Transcranial magnetic stimulation (TMS) can be a promising new tool for the treatment of spasticity. The objective of the present study was to compare the effectiveness of the two TMS protocols: rhythmic (high-frequency) TMS (rTMS) and stimulation with the theta bursts (iTBS) in terms of their ability to reduce spasticity in the patients presenting with multiple sclerosis. PATIENTS AND METHODS: Twenty two patients with secondary-progressive multiple sclerosis were pseudo-randomized into two groups: those in the first (high-frequency) group received the treatment with the use of rTMS therapy at a frequency of 10 Hz; the patients of the second group, underwent stimulation with the theta bursts (iTBS). All the patients received 10 sessions of either stimulation applied to the primary motor area (M1) of both legs. The effectiveness of TMS protocols was evaluated before therapy and after 10 sessions of stimulation based on the Modified Ashworth scale (MAS), the expanded disability status scale (EDSS), and the Kurtzke functional scale (Kfs). In addition, the patients were interviewed before treatment, after 10 rTMS sessions, immediately after and within 2 and 12 weeks after the completion of the treatment using questionnaires for the evaluation of spasticity (SESS) , fatigue, and dysfunction of the pelvic organs (severity of defecation and urination disorders), fatigue. RESULTS: The study has demonstrated a significant reduction in spasticity in the patients of both groups at the end of the TMS protocol based on the MAS scale. There was no significant difference between the outcomes of the two protocols. Both had positive effect on the concomitant «non-motor¼ symptoms (fatigue, dysfunction of the pelvic organs). CONCLUSION: High-frequency transcranial magnetic stimulation (10 sessions of rTMS therapy at a frequency of 10 Hz) and stimulation with the theta-bursts applied to the M1 area in both legs can be an effective alternative treatment of spasticity in the patients with secondary-progressive multiple sclerosis. Further research is needed to detect more accurately the differences between the outcomes of the two stimulation protocols and the development of indications for their application on an individual basis.