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Multiple Sclerosis (MS) is a progressive autoimmune disease affecting the central nervous system, causing communication disruptions between the brain and the body. Early and accurate detection of MS lesions in brain Magnetic Resonance Imaging (MRI) scans is crucial for effective treatment. This paper proposes MSNet, a deep learning-based approach for automatic detection and diagnosis of MS lesions from MRI images, leveraging Convolutional Neural Networks (CNNs) for precise lesion identification and classification. Our methodology involves a comprehensive analysis of MRI datasets, including preprocessing steps such as normalization and lesion segmentation. We propose a novel CNN architecture tailored for MS lesion detection, achieving an accuracy rate of 98.2 % on the test dataset. By incorporating advanced image recognition techniques, our system classifies MS lesions from diverse brain pathologies present in MRI images. The model also highlights MS lesions within the MRI images, aiding neuroradiologists in accurate diagnosis and treatment planning. This study contributes significantly to improving MS diagnosis by providing a reliable and automated tool for lesion detection and classification.

Balo concentric sclerosis is considered a fulminant demyelinating disease that is characterized by the formation of specific concentric foci in the white matter of the brain that resemble sawing trees. This article describes the clinical case of a patient who has come with complaints of weakness and stiffness in the lower limbs, more in the left leg, a feeling of stiffness and tension in the left hand, the inability to walk without aids. Taking into account the complaints, the clinical picture and the pre-test: laboratory examination of blood and liquor, magnetic resonance imaging (MRI) of the brain and thoracic spine with contrast, the patient was diagnosed with multiple sclerosis, secondary-spineprogressive current (Balo variant), reliable according to the 2017 McDonald Criteria. The following is a literature review describing the pathogenesis, clinical profile, diagnostic approaches and treatment options for the disease.

In recent decades, there has been an increase in the incidence of autoimmune diseases (AID) among adults and children. The immunopathogenesis of AID is based on an imbalance between autoaggressive and regulatory cells (Tregs), which is regulated by metabolic signaling pathways and the cytokine microenvironment. Understanding the mechanisms of immunometabolism opens up new possibilities for the treatment of patients with AID. The aim was to evaluate the activity of lymphocyte dehydrogenases associated with OXPHOS and glycolysis, depending on the level of proinflammatory and anti-inflammatory cytokines in children with AID.324 children with AID were examined: 80 – Crohn’s disease (CD), 53 – ulcerative colitis (UC), 89 – psoriasis (PS), 66 – multiple sclerosis (MS), 36 – autoimmune hepatitis (AIH). Activity of mitochondrial dehydrogenases (succinate dehydrogenase (SDH) and glycerol-3-phosphate dehydrogenase (GFDH)) were evaluated by immunocytochemical method using flow cytometry. The level of cytokines (CС) in blood sera was determined by multiplex analysis.In each studied group of children, CС with the highest values in exacerbation and remission of the disease were identified. The maximum values of CС were in patients with exacerbation: CD, UC, PS, MS – IL-23; AIH – IL-27. Evaluation of cytokine complexes associated with cells showed significant differences between patients in exacerbation/remission: CD, UC and PS – M1(IL-1+IL-6+TNFα), cTh1(IFNγ+IL-12p70+TNFβ+IL-2), cTh2 (IL-4+IL-5+IL-10+IL-13+IL-17E/IL-25+IL-33), cTh17 (IL-1β+IL-6+IL-17A+IL-17F+IL-21+IL-22+IL-23); MS – M1, cTh1, cTh2; AIH – cTh2. SDH activity in AID remission differed between pathologies in CD4+ cells, Th17 and Tregs. In exacerbation of AID, there were differences in Tregs between patients with UC and PS. The highest GPDH activity in exacerbation was observed in CD4+ lymphocytes, Th17 and Tregs in CD. The ratio of SDH/GPDH in T-lymphocytes in children with CD in exacerbation and remission was lowest and significantly lower than in UC, PS, MS, AIH and apparently healthy children. In the group of children with a low SDH/GPDH ratio, the levels of CCL20/MIP3α, IFNγ, IL-12p70, IL-13, IL-17A, IL-1β, and TNFα were significantly increased. Conclusions. Informative cytokine complexes were identified in children with AID. The relationship between the metabolic activity of lymphocytes and the level of circulating cytokines is shown.

Up to 50% of patients with multiple sclerosis (MS) are affected by depression.Objective: to develop a multifactorial model of predictors of depression in MS, considering sociodemographic, clinicopsychopathological and clinicofunctional characteristics.Material and methods. 157 patients with MS and depression were analyzed. The control group consisted of 100 MS patients without depression. The observation period was 10 years. The following scales were used: Beck, MFI-20, Spielberger-Hanin, visual analogue scale (VAS) for pain, PASAT test, EDSS. We performed an MRI scan, and identified significant stressful events, the type of MS, clinically isolated and radiologically isolated syndromes, concomitant diseases and the use of MS disease-modifying treatments (DMTs). The diagnosis of depression was made according to the ICD-10 criteria. Multivariate models were developed using analysis of variance and multiple linear regression equation.Results. A multifactorial model of predictors for the development of depression with a high multiple correlation value (r=0.85) was proposed. Factors with pronounced influence on the development of depression were: high rate of progression of MS (Beta=0.879), highly active course of MS (Beta=0.876), asthenia 89.6±1.1 points on the MFI-20 scale with an increase of 1.48% per year (Beta=0.784). Significant factors were: localization of lesions in the frontal, temporal regions of the right hemisphere (Beta=0.742), reactive anxiety 56±2.64 points on the SpielbergerKhanin scale with an increase of 1.89 % per year (Beta=0.682), increase in the area of lesions in the brain by 1.83 % per year (Beta=0.618), multiple lesions in the brain (Beta=0.591). Statistically significant predictors with less influence on the development of depression were: female gender, secondary education, living alone, significant stressful events in the past, autoimmune diseases, depression before the development of MS, depression in close relatives, pain syndrome (6–8 points on VAS). Cognitive impairment, increase in PASAT score of 2.87% per year, body mass index with an increase of 1.61% per year, clinically isolated and radiologically isolated syndromes before the development of MS, age of onset of MS, age of onset of depression, disability indicator according to EDSS, type of MS, comorbidity and medication use are not predictors of depression in MS.Conclusion. A high rate of MS progression, a very active course of MS, an increase in asthenia on the MFI-20 scale, localization of lesions in the frontal and temporal regions of the right hemisphere and an increase in reactive anxiety were identified as important predictors of depression in MS.

Objective: to determine the sensitivity and specificity of simultaneous analysis of the central vein sign (CVS) and the concentration of free kappa chains (FKC) in cerebrospinal fluid (CSF) in the diagnosis of multiple sclerosis (MS).Material and methods. Eighty patients participated in the study. The main group comprised 54 patients who had been diagnosed with MS according to the 2017 McDonald criteria. The comparison group comprised 26 patients with other diseases of the central nervous system. An enzyme-linked immunosorbent assay was used to determine the concentration of FKC in the CSF. MRI of the brain was performed in all patients. The total and relative number of lesions with CVS were calculated.Results. An increased level of FKC in the CSF and a higher frequency of lesions with CVS were found in the group of MS patients compared to the control group (p

An imbalance in the production of proand anti-inflammatory cytokines plays an important role in the pathogenesis of multiple sclerosis (MS) and chronic neuroborreliosis (CNB).Objective: to perform a comparative analysis of cytokine production in patients with MS and CNB in order to evaluate the differential diagnostic potential of a multiplex assay of the concentration of the most important cytokines.Material and methods. Fifty-seven patients participated in the study. The group of patients with relapsing-remitting MS consisted of 36 individuals (12 men and 24 women), median age – 38.5 [28.0; 48.50] years, MS duration – 9.5 [3.5; 12.5] years. Clinical reactivation of persistent herpesvirus infection (PHVI) was present in 18 (50%) patients. The group of patients with CNB comprised 21 patients (4 men and 17 women) aged 59.0 [52.0; 67.0] years with a disease duration of 2.5 [1.0; 4.0] years. 18 healthy donors were analyzed as controls. The concentrations of 15 cytokines in blood serum: interleukin 1β (IL1β), IL4, IL6, IL10, IL17A, IL17F, IL21, IL22, IL23, IL25, IL31, IL33, interferon γ (IFNγ), tumor necrosis factor α (TNFα), soluble CD40 ligand (sCD40L) were determined by xMAP multiplex technology using reagents produced by Bio-Rad (USA).Results. A significant increase in the levels of IL10 and IL33 (p

Objective: to look for differences in the transcriptome profiles in mononuclear blood cells of a group of patients with radiologically isolated syndrome (RIS) who developed symptoms of multiple sclerosis (MS) in the following three years of observation and a group of patients with RIS who did not develop MS during this period.Material and methods. The study included 19 patients with RIS (9 men and 10 women), six of whom developed symptoms of MS during the three-year follow-up period. The transcription profiles of blood mononuclear cells were compared between the groups of patients with RIS who developed or did not develop MS symptoms during this period. The work was conducted in the format of a prospective study; the time of blood collection was taken as the reference point. Full transcriptome profiling was performed using RNA sequencing on an MGISEQ-200 platform. Differential gene expression analysis was performed using the DESeq2 package for the R programming language. Subsequent analysis involved constructing a network of interactions between the protein products of the detected differentially expressed genes based on data from the STRING database, identifying a cluster of interacting proteins, and analyzing the enrichment of this cluster by participants in pathways annotated in the KEGG database.Results. The expression of 146 genes differed significantly (p1) in the studied groups of patients with RIS: in patients with subsequent manifestation of MS symptoms, the expression of 67 genes was lower and expression of 79 genes was higher than in patients without MS symptoms. The decrease in expression of two of the 67 genes (ADGRG7 and LGALS9C) remained significant even after correction for multiple comparisons (padj=2.17⋅10-11 and padj=6.19⋅10-6, respectively). Analyzing the network of interactions between the protein products of the differentially expressed genes allowed the identification of a cluster of 12 genes: APBB2, CCL4, CCL4L2, CDH2, DAZL, FOSB, H2BC17, JUN, KLF4, KLF5, MAPK8IP1, SYCE1; it is over-represented by components of the Toll-like receptor signaling pathway.Conclusion. The transcriptome profiles of blood mononuclear cells differ in groups of patients with RIS who did or did not develop MS symptoms during the three-year follow-up period. The decrease in the expression level of ADGRG7 and LGALS9C genes detected in this study as a sign of rapid conversion of RIS to MS needs to be confirmed in independent samples.

Multiple sclerosis (MS) is a chronic autoimmune disease of the nervous system of a predominantly progressive nature. In addition to diseasemodifying drug therapy of MS patients require physical rehabilitation, including tele-rehabilitation (TeleRBT).Objective: to evaluate the efficacy of TeleRBT in MS patients as one of the rehabilitation stages during the 2020–2021 coronavirus pandemic.Material and methods. The study involved 36 patients diagnosed with MS who completed a TeleRBT course. The course included 10 lessons of 60 minutes each over 10 days with a two-day break. Various questionnaires and scales were used to assess efficacy, and neurological status was also assessed.Results. In the group of patients who participated in TeleRBT, the level of disability on the EDSS scale did not change; walking function improved: the time to walk 25 feet decreased from 9.77±6.74 to 8.85±5.26 s (p=0.016), tolerance to physical activity increased: 6 minute walking distance without rest increased from 246.02±145.60 to 261.58±118.55 m (p=0.02), the speed of information processing in PASAT test improved from 31.92±18.35 to 43.12±21.39 (p

SinnoVex is a drug from the group of bioanalogues of interferon beta-1a for intramuscular administration, which has moderate efficacy in reducing clinical exacerbations of multiple sclerosis (MS), which is most pronounced in the initial treatment of relapsing-remitting MS (RRMS) with low or moderate disease activity.Objective: to analyze the experience with the use of the drug SinnoVex in several parallel studies in the Russian population of patients with RRMS.Material and methods. We analyzed the results of three retrospective post-marketing clinical trials, in which we compared the efficacy and safety of the use of interferon beta-1a for once-weekly intramuscular administration under the trade name SinnoVex in the treatment of the Russian population of patients with RRMS with other MS disease-modifying treatments (DMTs), in particular with high-dose interferons beta-1a and interferons beta-1b for subcutaneous administration. The total number of patients who received therapy with SinnoVex was 235 subjects. The efficacy of the therapy was assessed using the following indicators: average annual frequency of exacerbations, MRI activity, achievement of the NEDA-3 indicator. The safety of the therapy was evaluated based on the occurrence of adverse events (AEs) and their severity as well as the frequency of discontinuation of the drug.Results. Based on the results of the studies presented, no statistically significant differences in the clinical efficacy or tolerability of the intramuscularly administered SinnoVex preparation compared to other drugs of the interferon beta group were found. The spectrum and severity of AEs were in line with expectations; no unexpected AEs were observed.Conclusion. Among the important advantages of the drug are the relatively rare intramuscular injections and rare local skin AEs after injections, which significantly increase the benefit of the drug in young patients. In this regard, SinnoVex is most commonly used as an initial drug as part of an escalation approach to the treatment of RRMS and then needs to be replaced by more highly effective firstor second-line DMTs if efficacy is insufficient.

Search for agents for the add-on therapy of multiple sclerosis (MS) that can enhance the effect of first-line MS disease-modifying therapy (DMTs) is a very current issue. Such a boost is needed to reduce the need to switch to second-line DMTs, whose pathogenetic therapy leads to severe side effects in many cases. Curcumin, a natural polyphenol, has immunoregulatory properties and a favorable safety profile. At the same time, micellar forms of curcumin can increase its bioavailability.Objective: to investigate the effect of the micellar form of curcumin on clinical parameters in MS patients receiving first-line DMTs.Material and methods. MS patients (n=40) receiving interferon-β (IFNβ) therapy who showed a suboptimal response were randomly divided into two groups, one group received additional therapy (dietary enrichment for 6 months) with curcumin in micellar form, the second group did not receive dietary curcumin. At the beginning and end of the study, the disease activity (clinical and radiological), the degree of disability on the EDSS scale, the severity of chronic fatigue on the MFIS scale, the quality of life on the SF-36 scale and the level of cytokines (interleukin 6 and IFNγ) in the blood plasma were determined. Adverse events were also recorded during the observation period and the safety of the therapy was assessed based on the results of general and biochemical blood tests.Results. In the group of patients whose diet was enriched with curcumin, quality of life indicators improved both in the physical component (from 50.2±6.4 to 52.5±6.8; p=0.03) and in the psychological component (from 42.9±15.9 to 45.6±15.5; p=0.02). In the group receiving curcumin, the proportion of patients with exacerbations over 6 months also decreased – from 45 to 9 % (p=0.01). After 6 months of dietary enrichment, lower plasma levels of IFNγ were observed in patients receiving curcumin than in the group without dietary enrichment. No adverse events were noted during the observation period.Conclusion. The preliminary results allow us to consider micellar forms of curcumin, which have an acceptable tolerability and safety profile, as a potential additional method to increase the efficacy of first-line DMTs in MS patients with suboptimal response to IFNβ.

In multiple sclerosis (MS), the development and introduction of disease-modifying treatments (DMTs) into clinical practice can improve treatment outcomes. Interferon beta drugs are commonly used as DMTs. Among these drugs, sampeginterferon beta-1a (Tenexia®) was recently approved – an innovative original development of BIOCAD that is the next pegylated interferon beta-1a in its class. Clinical observations of patients with relapsing-remitting MS who received Tenexia® are presented. In the first clinical observation, the patient initially received glatiramer acetate as DMT, which led to exacerbations and an increase in neurological disturbances. The patient was switched to treatment with Tenexia®, during which no exacerbations and no increase in neurological disturbances were observed. In the second observation, the patient, who had been suffering from MS for 11 years, did not receive any DMTs. A year ago, the drug Tenexia® was prescribed as a DMT for the first time, with no exacerbations, no increase in neurological disturbances or negative changes on MRI during treatment. In the third observation, a patient suffering from MS for 5 years was initially prescribed teriflunomide as DMT, with exacerbations and an increase in neurological disturbances noted during the treatment. The patient was switched to Tenexia®, which led to a stable remission. The presented observations reflect the positive experience with the use of the drug sampeginterferon beta-1a in real-life clinical practice.

Multiple sclerosis (MS) is a chronic autoimmune disorder that manifests itself in progressive neurodegeneration causing a broad spectrum of cognitive deficits in the patients. Cognitive impairment being an essential component of the clinical picture of the disease come in a variety of manifestations and significantly lower the MS patients’ quality of life. This paper reports contemporary views on the prevalence and pathogenesis of cognitive impairment; the data of original studies involving patients with multiple sclerosis are provided.

The prevalence of multiple sclerosis (MS) is steadily increasing not only due to rising incidence, but also due to improvements in diagnosis and treatment. Accordingly, there is growing interest in improving the quality of life (QL) of chronic patients, for the assessment of which general scales are used, as well as scales developed specifically for MS. In this work, we analyzed publications devoted to assessing the quality of life of MS patients using the nonspecific SF-36 scale for the period from 2018 to 2023. Data were assessed on all eight scales: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, emotional state and mental health. The usefulness of the SF-36 questionnaire has been shown in the management of patients with MS by a general practitioner for a comprehensive assessment of QL dynamics during treatment and in planning of further treatment and rehabilitation measures. However, the ambiguity of numerous QL studies results in MS obtained using the SF-36 questionnaire requires continued research and improvement of the instrument itself.

Introduction: Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system accompanied by neurodegeneration contributing to cognitive dysfunction. Cognitive impairment occurs in 40%-65% of patients with MS and can manifest even in the early stages of the disease.Objective: To evaluate cognitive dysfunction features in patients with MS.Materials and methods: The study included patients with MS (n=30; age, 40.8±9.74 years; disease duration, 9.67±6.96 years; Expanded Disability Status Scale [EDSS] score, 4.76±2.11) and healthy individuals (n=30; age, 40.3±12.24 years). Cognitive impairment was assessed using the Montreal Cognitive Assessment Scale (MoCA) and the Paced Auditory Serial Addition Test (PASAT).Results: Cognitive impairment in the group of MS patients was found in 73.3% of the cases. The mean MoCA, PASAT-3, and PASAT-2 scores of MS patients were 13.56%, 24.31%, and 29.48% lower than those in the control group, respectively. In women, the cognitive level in MS patients remains higher than in men. Analysis of the PASAT-3 and PASAT-2 results in MS patients did not reveal any statistically significant differences between the groups of patients aged 18-35 years and those aged 36-44 years and the groups of patients aged 18-35 years and those aged 45-59 years. The results of the MoCA and hearing tests in patients with higher and secondary education were not statistically significant. We found an inverse relationship between EDSS and PASAT-2 (R= −0.49; P< .05), EDSS and PASAT-3 (R= −0.37; P< .05). The most severe cognitive impairment was observed with high EDSS (7.5-9).Conclusions: We have identified features of cognitive functions in MS. Follow-up and therapy of MS patients require cognitive dysfunction assessment using appropriate scales.

The article provides an analysis of modern methods of treatment of secondary progressive multiple sclerosis (SPMS). The only drug that has proven its effectiveness in all types of SPMS (with exacerbations and without exacerbations) is siponimod. Clinical trials of this drug have proven its efficacy and safety in this type of MS. If the drug is included in the list of high-cost technologies, this modern method of treating SPMS can be made available to all patients who need it.

Purpose: to identify the intraretinal hyperreflective foci (HRF), their specific characteristics, localization features and correlations with the duration of the disease, type of course and previous episodes of optic neuritis (ON) in multiple sclerosis (MS) patients using a high-resolution OCT scanning protocol. Materials and methods. The study included 160 patients (318 eyes) divided into 8 groups, i.e. Group 1: 44 eyes (13.84 %) — MS onset without a history of ON; Group 2: 30 eyes (9.43 %) — debut of MS with ON; Group 3: 56 eyes (17.61 %) — relapsing-remitting MS (RRMS) lasting ≤ 10 years without ON; Group 4: 38 eyes (11.95 %) — RRMS lasting ≤ 10 years with ON; Group 5: 49 eyes (15.41 %) — RRMS lasting ˃ 10 years without ON; Group 6: 37 eyes (11.63 %) — RRMS lasting ˃ 10 years with ON; Group 7: 34 eyes (10.69 %) — secondary progressive MS (SPMS) without ON; Group 8: 30 eyes (9.43 %) — SPMS with ON. Results. HRF were identified in all groups, at the levels of both the outer nuclear layer (ONL) and the inner nuclear layer (INL). Their number increased depending on the duration, type of course, and the presence of ON history. The thickness of the inner layers of the retina corresponded to the average normative indicators in the group with the onset of MS without ON. In the SPMS group after ON, a decrease in the total thickness of ganglions retinal cells layer (GCL) and the inner plexiform layer (IPL) was noted, showing minimal values of both avGCL + IPL (65.83 ± 8.27 μm) and avRNFL (76.37 ± 6.94 μm). High inverse correlations were revealed between avGCL + IPL and the amount of GRF at the levels of ONL and INL (-0.82 and -0.85, respectively, p = 0.01). Conclusions. The presence and quantity of HRF can be considered as a prognostic non-invasive biomarker associated with the duration of MS and the history of ON, allowing one to visualize the penetration of microglia activated by immune cells into the unmyelinated part of the central nervous system, helpful in elucidating their role in the pathogenesis and progression of the disease.

Among rather rare but extremely interesting and important conditions, myelitis stands apart due to its complexity and diversity of clinical manifestations. In this article, in addition to the well-known data on this group of diseases, we present the results of the analysis of eight cases of myelitis, which may serve as a starting point for the development of more effective and streamlined strategies in diagnosis and treatment. It may also contribute to deeper understanding of difficult cases in neurological practice.

CD3+CD20+T lymphocytes are a population of T cells that, along with standard T cell markers, express the atypical membrane molecule CD20 (a traditional B cell marker). These cells were identified not so long ago and are currently being actively studied. Normally, they constitute up to 3-5% of the CD3+T cell compartment in human peripheral blood, and are also found in primary and secondary lymphoid organs, cerebrospinal fluid, brain tissue and liver. In healthy individuals, CD3+CD20+T cells are heterogeneous and contain a lower proportion of CD4+ cells, but produce higher levels of GM-CSF, IFNγ, IL-17, TNFα, IL-4, IL-10, adhesion molecules and chemokine receptors than CD3+CD20-T cells, indicating a highly activated proinflammatory phenotype with properties potentially promoting their pathogenic infiltration into the CNS. Recent studies have established the pathogenic behavior of CD3+CD20+T cells in a wide range of diseases, including hematological and non-hematological CD20+T cell malignancies and HIV, as well as autoimmune pathologies, in particular multiple sclerosis, a disabling inflammatory neurodegenerative disease that is accompanied by damage to the myelin sheath nerve fibers. CD20 positive T cells are detected in patients with multiple sclerosis in the peripheral blood, cerebrospinal fluid (occur at a frequency similar to that of B cells and show a correlation with disease severity) and white matter of the brain. CD20 positive T lymphocytes in the peripheral blood of patients with multiple sclerosis have been shown to produce high levels of IFNγ and IL-17А, which are two proinflammatory cytokines involved in the pathogenesis of this disease. It is possible that CD20+T cells represent a separate subpopulation of Th17 cells, the so-called Th1-polarized Th17, which are the product of redifferentiation of Th17 cells into Th1 and combine the phenotypic characteristics of both populations. And the expression of CD20 T cells may be a valuable marker that determines the target subpopulation of such pathogenic T cells, as well as serve as a target for therapy of autoimmune diseases.

Background. Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease, which is characterized by the inevitable disability of patients in the long term, which determines the relevance of this problem. Currently, active improvements are being made in the methods of diagnosing multiple sclerosis, which include the use of the central vein sign in magnetic resonance imaging (MRI) as a neuroimaging biomarker of MS with high sensitivity and specificity.Aim of study. Determination of the possibility of assessing the central vein sign (CVS) according to MRI data as a potential diagnostic biomarker of MS.Object and methods. An open single-center prospective study of brain MR data was conducted in 55 patients with a verified diagnosis of MS (EDSS 1.0-6.5) aged 19 to 72 years. MR-images were obtained on a tomograph with a magnetic field induction force of 3.0 T. Patients underwent MRI of the brain according to the standard protocol: T2-VI, FLAIR, T1-VI (before and after administration of contrast agent), SWI. A comprehensive statistical analysis and evaluation of the obtained MRI data was performed using the Statistica 12 program.Result. During the evaluation of MR-tomograms, all patients with a verified diagnosis in the foci of MS were found to have CVS. In 14.5 % of patients, CVS was detected in 10-30 % of foci, in 61.8 % of patients in 30-60 %, in 23.6 % of patients, from 60 to 95 % was detected. Accordingly, 52.7 % of patients overcame the threshold value of 45 % required for the differential diagnosis of MS from other conditions.Conclusion. The use of CVS in MRI helps to solve the problem of differential diagnosis of MS from other demyelinating diseases when using its threshold criterion – the percentage of foci containing central veins.

Objective: to determine the sensitivity and specificity of method of determining the concentration of immunoglobulin free light chains (FLCs) in cerebrospinal fluid (CSF) in the diagnosis and differential diagnosis of multiple sclerosis (MS).Material and methods. 80 patients participated in the study. The main group consisted of 54 patients diagnosed with MS according to the 2017 McDonald criteria. The comparison group (n=26) comprised patients with other diseases of the nervous system. An enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of FLCs (kappa- and lambda-chains) in the CSF.Results. In the group of patients with MS, an increase in the concentration of free kappa-chains (к-FLCs) in the CSF was found compared to the comparison group (p

The discovery of antibodies against aquaporin-4 (AQP4) and against myelinoligodendrocyte glycoprotein (MOG) confirmed the existence of two disease entities distinct from multiple sclerosis (MS) — neuromyelitis optica spectrum disorders (NMOSD) and myelinoligodendrocyte glycoprotein-associated disease (MOGAD). Demyelinating optic neuritis (ON) can be either idiopathic (iDON) or a manifestation of MS, NMOSD (AQP4-ON) or MOGAD (MOG-ON).Objective: to determine the clinical features of ON and to evaluate the diagnostic value of optical coherence tomography (OCT) in demyelinating diseases of the central nervous system.Material and methods. The study included 43 patients with demyelinating ON who were divided into three groups according to the underlying disease (NMOSD, MOGAD and MS/iDON). We assessed visual acuity (VA) in the acute phase and analyzed VA and average values of retinal nerve fiber layer thickness (RNFL) and retinal ganglion cell complex (RGC) thickness using OCT data 6 months after the onset of ON.Results. ON was observed in the onset of the disease in 75% of NMOSD patients, 62% of MOGAD patients and 86% of MS/iDON patients. In the MOGAD and NMOSD groups, bilateral ON was predominantly observed. In 65% of patients with MOGAD (MOG-ONr), a recurrent course of ON was observed. VA was significantly lower in patients with AQP4-ON in acute phase and comparable to the MOG-ONr group in the long-term phase. VA in the onset of MOG-ON with a single episode was comparable to that of MS/iDON (p=0.2), but recovery was less pronounced (p=0.03). The most significant thinning of the RNFL and RGC complex was observed in the AQP4-ON and MOG-ONr groups. In AQP4-ON and MOG-ON groups, restoration of VA up to 0.5 and higher was observed significantly more frequently in the group of patients receiving pulse therapy with glucocorticoids (p=0.018).Conclusion. The study showed the most pronounced structural and functional disturbances in the long-term phase of AQP4-ON and MOG-ONr. MOG-ON was characterized by a high frequency of relapses with the influence of this factor on VA and thinning of the retinal layers in the long-term.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection with severe brain damage caused by the JC-virus, against the background of immunosuppressive conditions. The diagnosis of PML is complex and includes: the clinical picture, neuroimaging data, the presence of JC-virus DNA in samples of cerebrospinal fluid or brain tissue. HIV-associated PML is difficult to diagnose. In patients with multiple sclerosis, an increase in the incidence of PML is associated with the use of natalizumab. Increasing alertness towards the development and detection of PML makes it possible to achieve a favorable outcome.

The aim. To investigate plasma levels of main coagulation and fibrinolytic factors in MS patients with and without COVID-19 history. Materials and methods. A total of 127 participants were enrolled in this study, including 97 MS patients and 30 healthy controls (HC). Patients with MS were divided into two groups: MS+Covid group (n=41) – patients with MS, who had a laboratory-verified diagnosis of COVID-19 in the past 3-6-month period and MS group (n=56) – patients with MS, who did not suffer from COVID-19 previously. Determination of plasma levels of prothrombin, plasminogen, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), protein C (PC), soluble thrombomodulin (TM) was performed by means of enzyme-linked immunosorbent assay. Spectrophotometric techniques were used to determine concentrations of fibrinogen, soluble fibrin monomeric complexes (SFMC) as well as plasminogen activity and inhibitory potential of α-2-antiplasmin. Results. The MS group was characterized by elevated levels of plasma prothrombin, fibrinogen, D-dimer, SFMC, soluble TM compared to HC, while PC concentration did not differ between MS and HC groups. Plasma plasminogen level as well as plasma level of the potential plasmin activity were significantly decreased in MS patients compared to HC group. The plasma tPA level was significantly reduced while plasma PAI-I level was significantly increased in MS patients compared to HC. Patients of MS group had an increased level of plasma α-2-antiplasmin activity compared with HC group. To note, most of studied parameters did not differ between two MS groups, except protein C, soluble thrombomodulin levels and plasma α-2-antiplasmin activity. Conclusions. The results of our study showed that MS patients have got altered hemostasis parameters; however, further study is necessary to find out the relationship between particular components of coagulation and fibrinolytic systems and pathophysiology of MS. Additionally, our findings demonstrated that a SARS-CoV-2 infection had a limited effect on hemostasis parameters in MS patients, causing changes in only a few parameters, including thrombomodulin and protein C levels as well as α-2-antiplasmin activity.

BACKGROUND: Non-contrast magnetic resonance perfusion can identify areas of cerebral perfusion changes in patients with multiple sclerosis, even in the absence of focal lesions [1]. This technique offers several advantages, including non-invasiveness [2] and a short data collection time, which allows for repeated examinations and dynamic monitoring without contrast loading on the patient. The use of contrast-free magnetic resonance perfusion in patients with multiple sclerosis may prove to be a valuable diagnostic, management, and evaluation tool for the disease course. Nevertheless, the quantitative assessment of perfusion in multiple sclerosis remains a relatively understudied area in clinical practice [3]. The application of the developed algorithm for postprocessing of non-contrast MR perfusion data allows for the assessment of specific areas of interest and the estimation of absolute perfusion values in milliliters per 100 grams per minute. AIM: The study aims to develop an algorithm and investigate cerebral perfusion changes by non-contrast magnetic resonance perfusion in patients with multiple sclerosis compared with controls. MATERIALS AND METHODS: The study population comprises patients with multiple sclerosis (n=15) and a control group (n=15). The methodology employed in this study is magnetic resonance imaging on a 3.0T Philips Ingenia machine, using the basic study protocol (T1- and T2-weighted images, FLAIR, DIR, and CE_T1) and supplemented with pseudo-continuous arterial spin labeling (pCASL). The statistical analysis employed nonparametric methods. RESULTS: The quantitative processing of non-contrast perfusion data presents significant challenges. To address this, an algorithm was developed, which incorporates the use of the following software: Radiant, MatLAB, FSL (BASIL), MriCroGL, PyCharm. The perfusion in a group of conditionally healthy volunteers, without consideration of liquor-containing spaces and cerebral vessels, was isolated and co-registered with the atlas of T1-weighted images. The average perfusion was found to be 52.8±1.32 mL/(100 g×min), which is consistent with the findings of leading studies worldwide and reflects the efficacy and quality of the algorithm [4, 5]. Furthermore, within the context of the study, values for the demyelination focus [9.7 ± 5.4 mL/(100 g×min)] and for the visually intact white matter of the cerebral hemispheres [46.1 ± 1.7 mL/(100 g×min)] were obtained in the group of patients with multiple sclerosis. Moreover, a diffuse decrease in perfusion indices in visually intact regions of the cerebral hemispheres relative to the control group was revealed. This finding is also widely reported in the scientific literature [6]. CONCLUSIONS: The application of the developed algorithm for the analysis of pseudo-continuous arterial spin labeling in patients with multiple sclerosis allows for the assessment of perfusion in both the focus of demyelination and in the visually intact white matter of the cerebral hemispheres. It was demonstrated that in visually intact areas of the cerebral hemispheres, there is a diffuse decrease in perfusion indices (on average by 13%) relative to the results of the control group. This observation indicates that the use of the pseudo-continuous arterial spin labeling method allows for the suspicion of the appearance of foci before their clinical and morphological verification on other routine sequences.

Inflammatory processes accompanied by damage to the cell bodies of neurons are combined into the group of neuroinflammation. At the molecular, cellular and tissue levels, neuroinflammation serves as a sanogenetic response to a variety of injuries, including post-traumatic conditions and neurodegeneration. However, inflammatory changes in long-lived cells such as neurons inevitably trigger a range of adverse effects. As a result, prognosis often depends on the severity of neuroinflammation. In this work, we review the spectrum of biomarkers involved in two key mechanisms of neuroinflammation: immune-mediated and mechanical injury, that have a potential clinical application: cytokines, neurospecific proteins and their proteolysis products, markers of oxidative stress, matrix metalloproteinases and endocrine parameters. Over the past decades, a significant pool of data on neuroinflammation biomarkers has been accumulated and continues to grow, but no consensus has been reached on the actual gradation of their clinical significance. Applied branches of medicine require further systematization of information on biomarkers of neuroinflammation for effective prognostic decisions.

Objective: to evaluate the efficacy of a comprehensive rehabilitation program on functional independence in daily life, exercise tolerance and quality of life (QoL) in patients with relapsing-remitting multiple sclerosis (RRMS) in remission.Material and methods. 38 patients with RRMS were analyzed (33 women and 5 men; age – 41.6±7.7 years; EDSS – 4.0 [3.5; 5.0] points, duration of MS – 8.0 [3.0; 21.0] years). The patients received comprehensive rehabilitation in a hospital for 2.5 weeks. The examination was carried out before and after the rehabilitation program. Independence in daily activities was assessed using the Functional Independence Scale, the Get Up and Go Test and the Berg Balance Scale. Exercise tolerance was determined using a cardiopulmonary exercise test (CPET) on a cycle ergometer. The following parameters were measured: oxygen consumption during exercise (VO2 peak oxygen uptake), percentage from the predicted VO2 peak (% pred VO2 peak) and maximal workload in metabolic units (MET). Walking speed was measured according to the Davis protocol in the SMART-D laboratory (Italy). QoL was determined using the SF-36 questionnaire, which assesses physical functioning (PF), general health (GH), vital activity (VT) and social functioning (SF). Cognitive functioning was assessed using the Montreal Cognitive Scale (MoCA) and depression using the Beck Depression Inventory (BDI). Results. After completion of the rehabilitation course, there was a significant increase in VO2 peak (from 18.8±3.8 to 20.4±4.3 ml/kg/min), % pred VO2 peak (from 59±13 to 63±14%), maximal workload (from 5.4±1.2 to 5.8±1.2 MET), maximal heart rate (from 140±14 to 147±13) and walking speed (from 0.84±0.29 to 0.97±0.28 m/s). At the same time, despite an improvement the patients did not reach the age- and gender adjusted reference values for exercise tolerance. QoL indicators also increased, reaching or exceeding the populational values obtained for the Russian population: PF – from 45 to 52.2; GH – from 51 to 52; VT – from 45 to 50; SF – from 62.5 to 75. The number of points on the BDI also decreased significantly (from 9 to 6), and the increase on the MoCA scale had tendency to significant difference (p=0.064). Conclusion. A comprehensive rehabilitation program in patients with RRMS in remission helps to increase exercise tolerance and improve functional independence and QoL.

Objective: to determine the specificity and sensitivity of the central vein sign (CVS) for the diagnosis of multiple sclerosis (MS). Material and methods. We analyzed 76 patients. The main group consisted of 40 patients with a confirmed diagnosis of MS according to the McDonald criteria, 2017. The comparison group included 20 patients with migraine and 16 patients with cerebral microangiopathy. All patients underwent a standardized MRI scan of the brain, including 3D FLAIR and SWI modes. The total number of T2/FLAIR hyperintense lesions in the brain and the number of lesions with CVS were calculated. Results. In the group of MS patients, the total and relative number of lesions with CVS was higher than in the comparison group (p

Introduction. Beta interferons are effective and safe agents for the treatment of relapsing-remitting multiple sclerosis (RRMS). PEGylated interferons have been developed in order to increase patient adherence. Direct comparisons of the efficacy and safety of PEGylated interferons have not yet been conducted. Our objective was to evaluate the efficacy and safety of SamPEG-IFN-β1a versus PEG-IFN-β1a in adult patients with RRMS. Materials and methods. We conducted a systematic search of randomized clinical trials (RCTs) using the PubMed, Embase and eLIBRARY.RU databases. Efficacy was assessed based on the proportion of patients with disease relapses and the annualized relapse rate (ARR) during the 1st and the 2nd years of treatment. Safety was assessed by the number of patients with adverse events (AEs), serious AEs (SAEs), and any AEs that led to the treatment discontinuation. We conducted pairwise matching-adjusted indirect comparison (MAIC) to assess comparative efficacy of PEGylated IFNs. To evaluate the efficacy, hypotheses of non-inferiority of SamPEG-IFN-β1a to PEG-IFN-β1a and superiority of SamPEG-IFN-β1a over PEG-IFN-β1a were tested. Results. Based on results of the systematic review, four articles were selected wherein the results of phase 3 clinical trial of PEG-IFN-β1a and phase 2–3 clinical trial of SamPEG-IFN-β1a were described. In PEG-IFN-β1a group (n = 512) the agent was administered once every 2 weeks, in SamPEGIFN-β1a group (n = 114) the agent was administered at a dose of 240 μg. The analysis results confirmed the hypothesis of SamPEG-IFN-β1a non-inferiority to PEG-IFN-β1a in efficacy, while SamPEG-IFN-β1a superiority over PEG-IFN-β1a in efficacy was not confirmed. The hypothesis of SamPEG-IFN-β1a superiority over PEG-IFN-β1a in safety was also confirmed based on a significantly lower incidence of SAEs and any AEs that led to treatment discontinuation. Conclusions. The proportion of patients with relapses and the ARR in 1 year and in 2 years of therapy indicates that SamPEG-IFN-β1a is non-inferior to PEG-IFN-β1a in efficacy. SamPEG-IFN-B1a demonstrated a more favourable safety profile than PEG-IFN-B1a as showing less odds of SAEs and AEs leading to treatment discontinuation.

Relevance. Demyelinating diseases of the central nervous system and multiple sclerosis, in particular, make their debut at a young age and can lead to profound disability and death within a few years. In the last decade, there has been an increase in the number of cases of demyelinating diseases in Russia and in the world, which necessitates an in-depth study of these pathologies. Goal. To study the dynamics and features of the formation of morbidity, prevalence and mortality from demyelinating diseases of the central nervous system, including multiple sclerosis in various population groups in the Russian Federation. Materials and methods. The study design is a descriptive retrospective epidemiological study (continuous). The data was sampled from the forms of the federal state statistical observation on the distribution of the deceased by gender, age groups and causes of death of Rosstat (FSN S-51), as well as from the statistical collections of the Federal State Budgetary Institution "Central Research Institute of the Ministry of Health of the Russian Federation "Morbidity of the population" from 2009 to 2021. Results. The analysis of the data showed that in 2009-2021 in Russia there was an increase in idiopathic inflammatory demyelinating diseases (IDD) and multiple sclerosis (MS) among the adult population and adolescents aged 15 to 17 years. There is no tendency to increase or decrease the incidence among children under 14 years of age. The highest average long–term incidence rates of IDD and MS among adults are observed in the Ufa region (7.13 ± 0.27 and 5.31 ± 0.23 per 100 thousand adults, respectively), among children under 14 - IDD in the Central Federal District (1.88 ± 0.18 per 100 thousand contingent) and MS in the Central Federal District and Volga Federal District (0.22 ± 0.07 per 100 thousand contingent). Among children from 15 to 17 years of age, the highest incidence of IDD is noted in the Northwestern Federal District (4.41 ± 1.10 per 100 thousand contingent) and the Ural Federal District (4.40 ± 1.09 per 100 thousand contingent), RS – in the Central Federal District (2.67 ± 0.51 per 100 thousand contingent). IDD and MS are the least common among all age groups in the Far Eastern Federal District. Over the period from 2000 to 2020, there has been a decrease in MS mortality in the Russian Federation by 34%, from 0.72 to 0.48 per 100,000 population. The average annual mortality rate from MS among men was 0.4 ± 0.021 cases per 100 thousand of the contingent, among women 0.5 ± 0.023 cases per 100 thousand of the contingent. Conclusion. The increase in the incidence of demyelinating diseases and MS, in particular, is an important medical and social problem. These pathologies significantly reduce the quality of life and shorten the duration of work, due to the development of persistent disability in the young population. The study showed the uneven distribution of the disease across the territories of the Russian Federation, which in the future will improve the logistics of drug delivery and the provision of medical personnel, which confirms the relevance of constant and in-depth study of the epidemiology of idiopathic inflammatory demyelinating diseases in Russia.

The research was aimed at analyzing modern algorithms for diagnosing lesions in multiple sclerosis on MRI images. Multiple sclerosis is a severe disease of the central nervous system and ranks first among the causes of disability in patients of young working age. In connection with the development of computer vision and machine learning technologies, the relevance of using these technologies for medical diagnostics is growing. Such approaches are necessary for the effective development and implementation of diagnostic systems using artificial intelligence. Modern algorithms and models for lesion segmentation were selected and implemented. Material and methods. The paper presents CV features of diagnosing multiple sclerosis on MRI images, existing data sets: ISBI-2015, MSSEG-2016, MSSEG-2021; existing algorithms and models for lesion segmentation: U-Net, nnU-Net, TransUnet, TransBTS, UNETR, Swin UNETR. Results and discussion. The architectures and models of nnU-Net, UNETR, Swin UNETR were trained and compared at ISBI2015 with various parameters and loss functions. Four MRI sequences were used: T2-WI, T2-FLAIR, PD, MPRAGE. Lesion segmentation was approved by certified experienced neuroradiologists. Conclusions. The approaches described in the paper including data processing, model training, and results analysis, focused on the selection and development of high-quality computer vision algorithms for identifying multiple sclerosis lesions in MRI images. Identification and segmentation of demyelination foci is a necessary step for diagnosing the disease, as well as for calculating and interpreting more meaningful indicators of disease severity and progression.

Multiple sclerosis (MS) is one of the most common causes of disability in young people of working age. The prevalence of this disease has increased significantly in recent years and today amounts to more than 2 900 000 people worldwide. The transition from relapsing-remitting MS to secondary progressive MS is observed in 25 % of cases within 10 years the disease duration, and with further time the proportion of patients with secondary progressive MS increases. Despite the importance of preventing patient disability, today the diagnosis of secondary progressive MS is established retrospectively, which makes the issue of identifying early markers of disease progression extremely relevant. The most promising diagnostic markers allow the differentiation of progressive MS with a sensitivity of up to 87 % and a specificity of up to 90 %. This review will consider the most promising clinical, instrumental and biological signs of early progression of MS.

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, which is based on inflammatory demyelination and neurodegeneration. Over the course of the COVID-19 pandemic, there has been a perception that the virus has an effect on the course of immune processes. The questions of whether the frequency of autoimmune diseases, including the nervous system, and their course has changed have been discussed. Aim of the study was to assess the clinical and epidemiological characteristics of MS during the COVID-19 pandemic from 01.01.2020 to 01.01.2023 in Novosibirsk. In the course of our work, we studied the incidence of MS and the features of the clinical picture of the debut of MS associated with COVID-19 infection. Material and methods. The study included 628 patients with MS living in Novosibirsk with the onset of the disease in the period before the pandemic from 01.01.2017 to 12/31/2019 (341 patients) and during the pandemic from 01.01.2020 to 01.1.2023 (287 patients). Results. The incidence rates of MS in Novosibirsk were calculated, it was 7.1 7.6 6.4 7.38 6.92 and 3.2 per 100 thousand population in 2017, 2018, 2019, 2020, 2021 and 2020, respectively. The average incidence of MS in the study period before the pandemic was 7.03 per 100 thousand population, during the pandemic – 5.83 per 100 thousand population (critical value of the Student’s t-test = 1.972, with a significance level of a = 0.05). When analyzing the association of clinical manifestations of the onset of MS with COVID-19, it was found that coordination disorders were observed in patients with moderate infection more often than in patients with mild infection (p < 0.05; odds ratio 0.410, 95% confidence interval 0.162–1.035). No statistically significant correlation of clinical manifestations with the severity of infection was shown for patients with primary progressive MS, however, the predominance of the multi-focal nature of disease after a more severe course of COVID-19 was noted (40 %). After the first clinical demyelinating episode in the group of patients with relapsing-remitting MS, the chances of complete recovery in patients with mild infection are 2.8 times higher than in patients with moderate infection (p < 0.05). Conclusions. Thus, as a result of the conducted study, the effect of COVID-19 on the change in the incidence of MS was not revealed. In the process of analyzing the clinical features of MS during the pandemic, it was found that COVID-19 infection can contribute to an unfavorable course of MS with worse recovery of neurological deficits after episodes of exacerbations, which leads to the accumulation of disability of patients.

Introduction: Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system, marked by inflammation, demyelination, and neurodegeneration. It severely impacts quality of life with symptoms like spasticity, pain, and cognitive impairment. Conventional treatments often fail, necessitating alternative therapies. Purpose: This review evaluates the efficacy and safety of cannabis extracts in treating MS, enhancing understanding of their benefits and limitations. State of knowledge: Studies suggest that cannabinoids may alleviate MS symptoms, particularly spasticity and pain. Clinical trials have shown significant reductions in muscle stiffness and pain, along with improved sleep quality. Meta-analyses, by Whiting et al. and Cochrane, support these findings but highlight the risk of side effects, which may limit long-term use. Additionally, research on animal models and in vitro studies indicate that cannabinoids may have neuroprotective and immunomodulatory properties, potentially reducing neuroinflammation and demyelination. Conclusion: Cannabinoids exhibit potential as a complementary therapy for managing MS symptoms, especially spasticity and pain. However, evidence is mixed, with some studies showing limited efficacy and considerable risk of side effects. More long-term, high-quality studies are needed to fully understand the therapeutic potential and safety profile of cannabinoids in MS treatment. Despite the challenges, the growing availability and changing legal status of medical cannabis suggest it could be a viable option for some patients, provided its use is carefully monitored and adapted to individual needs.

Introduction Multiple sclerosis (SM) is the most common chronic inflammatory-demyelinating disease of the Central Nervous System. In its course, a multifocal damage is done to a nervous tissue - myelin sheaths surrounding axons become disintegrated. This process leads to a dysfunction of the electrical impulses passage along nerve fibers which occurs as various symptoms that hinder the functioning of the patients. Aim of the study This review aims to summarize treatment methods of relapsing-remitting type of multiple sclerosis (RRMS). Following information will be presented: groups of medications, mechanism of its action, its most important side effects and its effectiveness. Material and method This review presents the current state of knowledge about relapsing-remitting type of multiple sclerosis (RRMS) treatment - it is based on Pubmed database and was carried out using keywords concerning the issues of multiple sclerosis. Cited articles were selected in order to base on up-to-date investigation results. Summary A wide range of therapeutic options let neurologists treat their patients accurately, but the basic knowledge about each substance should be assimilated to choose the best individual therapy. Patients suffering from multiple sclerosis differ from each other and a personal approach is needed to implement appropriate treatment as soon as possible. Early start allows patients to not to lose their everyday functioning areas, as the neurodegenerative process is stopped at the initial stage. If some changes in brain tissue structure are permanently done, neurologists should know the options of symptomatic treatment to alleviate a patient's suffering.

Multiple sclerosis (MS) is a chronic, demyelinating disease that leads to disability. Understanding the etiology of MS contributes to the development of pathogenetic methods of treatment, and the search for informative biomarkers of the effectiveness of treatment will allow the patient to adjust therapy in time. The aim of this work was to determine informative cytokines and cytokine profiles to predict the effectiveness of IFN-β1a therapy in children with MS.Materials and methods. 66 children with MS aged 16 [14.2–17.5] years who are on INFß-1a therapy were examined: group 1 — patients with exacerbation of MS (with active foci of demyelination by MRI), n = 34; group 2 — patients in remission of MS (without active foci), n = 32. The content of cytokines in the blood serum of patients was assessed using the multiplex panel Human Th17 Magnetic Bead Panel.Results: There was a significant increase in cytokine concentrations in patients with exacerbation of MS compared with children in remission: IL5, IL6, IL9, IL12p70, IL17E/IL25, IL21, IL28A, GM-CSF, TNFß. Threshold values for IL9 (AUC = 0,785), IL6 (AUC = 0,750), TNFß (0,740), IL28A (AUC = 0,744) were obtained above which it is possible to predict an exacerbation of MS in patients: IL9 — 3.9 pg/ml (Sn — 70.6, Sp — 71.9), IL6 — 4.0 pg/ml (Sn — 70.6, Sp — 68.8), TNFß — 6.6 pg/ml (Sn — 70.6, Sp — 71.9), IL28A — 243.0 pg/ml (Sn — 70.6, Sp — 71.9). Cytokine profiles associated with T-lymphocytes and their functions were evaluated using z-score.Conclusions. For the first time, an increase in cytokine levels was demonstrated in children with active foci of demyelination compared to patients in remission of MS. An increase in proinflammatory cytokines and cytokine profiles associated with Th1 and Th17, as well as with Th2 and Th22 has been shown. The use of threshold values for IL9, IL6, TNFβ, IL28A will help predict the development of exacerbation in patients with MS.

Over the past decade, the scientific research has shown that the community of microorganisms that inhabit the gut, known as the gut microbiota, is closely linked to human health and disease, in part as a result of its influence on the systemic immune responses. The accumulated evidence suggests that these effects on the immune system are significant in neuroinflammatory diseases such as multiple sclerosis, and that modulation of the gut microbiota may be a potential therapeutic target in these conditions. In recent years, more and more studies have been appearing devoted to the role of microbiota in the development of various pathological processes in the central nervous system, including multiple sclerosis, through the brain-gut axis. In this regard, the question of finding ways to influence the microbiome is interesting. In addition to the existing attempts through the use of probiotics and fecal microbiota transplantation, of particular interest is the search for other ways of influencing the microbiome, including the effect of multiple sclerosis modifying therapies on the microbiota’s composition. The purpose of this review is to summarize the current evidence investigating the effects of disease-modifying treatment on the gut microbiome.

Purpose: to study significant functional and structural changes in the retina and the intraocular section of the optic nerve in multiple sclerosis (MS) patients and analyze how they are interrelated with electrophysiological changes in the visual analyzer.Materials and methods. The study included 44 patients (88 eyes): group 1 (26 eyes) with MS duration ≤ 5 years and no history of optic neuritis (ON); group 2 (30 eyes) with MS duration from 6 to15 years and no history of ON; and group 3 (32 eyes) with MS duration ≤ 15 years with a history of ON. All patients underwent a complete ophthalmological examination and optical coherence tomography and had visually evoked potentials (VEP) and static automated perimetry registered.Results. A decrease in functional and structural parameters progressing with the duration of MS was revealed. In particular, best corrected visual acuity (BCVA) fell to 0.860 ± 0.075, the photosensitivity index MD maximally fell to -3.78 ± 0.95 dB, the strength of the P100 wave amplitude dropped to 7.84 ± 2.98 μV, the latency index of VEP rose to 124.21 ± 1.36 ms, the thickness of GCL + IPL fell to 65.69 ± 7.85 μm, and RNFL thickness averagely fell a low as to 80.25 ± 8.81 μm. When analyzing the topography of GCL + IPL decrease by sectors, the maximum value was revealed in the upper temporal segment (67.63 ± 7.89 μm). Sectoral changes in RNFL arranged in descending order of thickness showed the following sequence: lower upper nasal temporal. As the disease progressed, structural and functional changes were accompanied by an increase in the depth and a decrease in the thickness of the lamina cribrosa, with a maximum value revealed in the group with prior ON (239.00 ± 11.93 μm). Strong correlations were found in all study groups between (1) ave. GCL + IPL and ave. RNFL (r = 0.69; 0.64; 0.88, p < 0.03), (2) ave. GCL+IPL and BCVA (r = 0.86; 0.75; 0.78, p < 0.05), (3) MD and ave GCL + IPL (r = 0.52; 0.69; 0.71, p < 0.03), and (4) MD and ave. RNFL (r = 0.67; 0.61; 0.66, p < 0.05), as well as between the parameters of the lamina cribrosa and the markers under study.Conclusion. Significant functional and structural changes in the retina and the optic nerve were detected, correlating with the duration of the disease and with the clinical features of the course of multiple sclerosis. The presence of ON in history was accompanied by more pronounced changes, which can be considered as an important additional aggravating factor of the disease.

Histologically, chronic demyelinating lesions in multiple sclerosis (MS) have been shown to include inactive lesions that do not change over time and active or “smouldering" lesions that tend to enlarge over time and are surrounded by pro-inflammatory activated microglial cells that are loaded with iron. To identify “smouldering" foci of demyelination and assess the “latent” inflammatory process in the brain, MRI sequences sensitive to the detection of substances with paramagnetic properties, including iron, must be used. They include an innovative technique such as quantitative susceptibility mapping (QSM).Objective: to identify, using MRI different types of chronic demyelination foci in MS, based on iron distribution and the degree of damage (myelination) in their structure.Material and methods. The patterns of iron distribution in demyelinating lesions in 90 MS patients were investigated using QSM. In addition, two lesions with different iron distribution patterns were randomly selected on the QSM map for each patient, in which the magnetic transfer ratio (MTR), indirectly reflecting the degree of myelination, was calculated. The identified changes were also compared with visualization of lesions in standard MRI modes (T1 MPRAGE, T2 FLAIR).Results. Despite the predominantly identical visualization in T2 FLAIR mode, chronic foci of demyelination show different patterns on the QSM maps, which is due to the peculiarities of iron distribution: some foci are not detected on QSM, while others are visualized either in the form of a homogeneous or a ring-shaped pattern. When comparing QSM data with MTR, it was found that MTR indicators were highest in non-visualized lesions (demyelination is minimal), while damage was most pronounced in lesions with ring-shaped iron distribution.Conclusion. Different patterns of iron distribution in demyelination foci compared to the degree of myelination in these foci according to MTR were identified using QSM, which is of great importance for the evaluation of latent inflammation and the development of the neurodegenerative process in MS.

A joint conclusion of the Russian-Belarusian Expert Council “New opportunities in the treatment of patients with multiple sclerosis” on the organization of medical care, diagnosis and treatment of multiple sclerosis (MS) and other autoimmune diseases is presented. 12 neurologists from different medical institutions in Russia and Belarus took part in the work of the Council. In the conclusions of the Council, special attention was paid to two new Russian original drugs, modifying the course of MS. The place of these drugs in the healthcare system of these countries was determined. Sampeginterferon beta-1a itself is an effective and safe drug of first choice (first-line treatment) for relapsing remitting MS. Divozilimab is a highly effective and safe second-line treatment indicated for rapidly progressive and highly active MS, even when substituted for a firstor second-line treatment in relapsing remitting and secondary progressive (with exacerbations) MS. The experts emphasized how promising the use of these drugs is in the complex treatment of MS.

Currently, more than 15 molecules are already approved for the treatment of multiple sclerosis, and sometimes physicians encounter problems selecting a drug for therapy when considering patients with the initial equivalent characteristics. When selecting a drug, it is important to consider not only the efficacy and safety of the drug, but also the possibility of further therapy after discontinuation of the initially selected drug. This paper discusses the results of clinical trials on the efficacy and safety of ofatumumab and its potential advantages over other anti-CD20 agents.

An increase in the incidence of multiple sclerosis (MS) has been reported over the last decade, possibly due to environmental factors. The purpose of this review article is to summarize current advances in the understanding of the gut-brain axis, which mediates the link between the central nervous system and the gut microbiome. It also summarizes the clinical findings from numerous studies investigating the effects of diseasemodifying therapies on the gut microbiome in patients with MS.

Autoimmune diseases are characterized by dysregulation of immune responses and damage to healthy body tissues. Their complete cure remains elusive, and existing therapies are often accompanied by side effects. Recent studies have shown a signifi cant role of disturbances in the composition of the microbiome in the development of autoimmune reactions. Moreover, modulation of the microbiome through various therapeutic interventions represents a promising direction in the framework of complex therapy of the underlying disease. Extracellular vesicles, in particular exosomes, transport biologically active substances between cells, and a number of studies have shown their therapeutic effect in autoimmune diseases. However, the role of extracellular vesicles in modulating the microbiome remains poorly understood, and further research is needed to better understand their impact on the pathogenesis of autoimmune diseases and associated microbiome changes, as well as to develop new treatment strategies. The presented literature review, based on a study of English-language sources, examines the importance of the microbiota of different loci of the human body (intestines, skin, oral cavity) in the development of autoimmune diseases such as multiple sclerosis, psoriasis and Sjögren’s disease. The role of extracellular vesicles in modulating the microbiome during autoimmune diseases therapy is discussed.

Pilates exercise method, characterized by its holistic approach, underscores core stability, strength, and flexibility, coupled with meticulous muscle control, optimal posture, and focused attention on breathing. Widely embraced in both general and clinical fitness realms, this study aims to evaluate the integration of Pilates into physical therapy practices for patients with neurological disorders. Existing studies indicate the potential efficacy of Pilates in diverse rehabilitation contexts. However, neurological disorders, specifically multiple sclerosis (MS) and Parkinson's disease (PD), have been the primary focus. While systematic reviews and meta-analyses suggest Pilates as a plausible option in physiotherapy for PD and MS patients, a paucity of research on this subject necessitates a comprehensive review of recent original studies. Analysis of gathered data suggests that Pilates, when incorporated, may yield benefits for patients with various neurological disorders. Consideration of Pilates as a supplementary element to physical activity for those with PD and MS emerges as a reasonable proposition. The study also encourages contemplation of Pilates in rehabilitation research across a broader spectrum of neurological disorders. Subsequent investigations, incorporating relevant considerations, will contribute to a nuanced understanding of Pilates' potential benefits and its comparative advantages over traditional interventions for neurological disorders.

Purpose: to study the prevalence of various chronic infections, the frequency of their reactivation and characteristic associations of microorganisms in patients with optic neuritis of various etiologies.Material and methods. 13 patients with optic neuritis (ON) and 12 patients with ON and multiple sclerosis were tested for a broad range of infectious agents in their blood serum.Results. All patients were shown to have mixed infections; 64 % of them had an association of 4 or more infectious agents. The patients of both groups were infected with Epstein-Barr virus (100 %), Cytomegalovirus (92 %) and Herpex simplex viruses (92 %) types 1 and/or 2 with serological signs of their reactivation. The combination of Herpes virus reactivation, Toxoplasma and urogenital infection was more often detected in patients with demyelinating ON. In patients with multiple sclerosis, a mutual correlation was detected: the higher the degree of infection (combination of 5 or more pathogens), the lower the visual acuity at the onset of the disease (p < 0.05) and the less favourable the vision prognosis.Conclusion. Possibly, mixed infection may play an important role in the pathogenesis of ON, including that of demyelinating etiology, as a trigger or an aggravating factor.

Aim. Analysis of own results of ocrelizumab therapy in patients with multiple sclerosis (MS) in the Voronezh region. Materials and methods. This work was a cross-sectional study based on the Voronezh Regional Clinical Hospital № 1. The study included 61 patients (34 women and 27 men) with MS with an average age of 38.5±2.6 years. All patients received ocrelizumab (Ocrevus) intravenously according to the scheme: an initial dose of 300 mg with an interval of 2 weeks, then 600 mg every 6 months. The effectiveness of therapy was assessed according to the NEDA-2 (no evidence of disease activity), NEDA-3 and NEP (no evidence of progression) criteria. Results. Ocrelizumab has shown high efficacy in stopping the progression of all considered types of MS. The NEDA-2 and NEP criteria were achieved by the patients as early as 6 months after the start of therapy. NEDA-3 criteria for highly active MS – by 12 months of therapy, for secondary progressive MS with exacerbations – by 18 months of therapy. The highest efficiency of treatment with ocrelizumab was shown in the group of patients with highly active MS, where not only the cessation of disease progression was noted, but also a significant decrease in the degree of disability according to the EDSS scale. Conclusion. It is necessary to start therapy with ocrelizumab at an earlier time: in primary progressive MS immediately after confirmation of the diagnosis, in relapsing MS – when signs of high disease activity and/or suboptimal response to the first of the drugs of disease modifying treatment appear. Timely initiation of ocrelizumab treatment may avoid severe disability in patients.

Stress disorders are a global public health problem, having a significant impact on patients and society. Chronic stress can lead to long-term consequences, including mental and physical illness. The body's first response to acute stress is characterized by the appearance of anxiety, but beyond a certain level, anxiety becomes maladaptive. Anxiety worsens the quality of life and adaptation of patients, complicates the course of comorbid pathology and its diagnosis. In the review anxiety disorders in patients with multiple sclerosis, Parkinson's disease, and chronic pain syndromes discussed. A significant deterioration in the course and prognosis of the neurological disease in combination with anxiety disorders in multimorbid patients has been shown. Treatment of anxiety includes psychotherapy, the use of antidepressants, and short courses of benzodiazepines. Neurexan® as the safe and effective drug that does not interact with other drugs and has a favorable tolerability profile can be recommended to patients with multimorbid pathologies to correct emotional disorders, reduce anxiety and improve sleep.

Relevance. Multiple sclerosis is accompanied by rapid progression of the disease, the development of early disability and a violation of the patient's quality of life. In recent years, advances in understanding the etiology and pathogenesis of this disease have led to the expansion of therapeutic approaches, it has become possible to influence the course of the disease. Objective - to study the effectiveness of the use of drugs that change the course of multiple sclerosis in patients registered at the center of multiple sclerosis of the Udmurt Republic.Materials and methods. The statistical analysis was performed on 45 patients of the neurological department of the "First Republican Clinical Hospital" of the Ministry of Health of the Udmurt Republic, diagnosed with multiple sclerosis, using immunomodulatory or immunosuppressive therapy.Results. At the beginning of the study, the group of patients using immunomodulatory therapy included 31 patients (68.89 %), the group of immunosuppressors -14 patients (31.11 %). The average time from the onset of the disease to the start of therapy was 1.64 ± 5.71 months. 42 patients (93.33 %) out of 45 included in the study started therapy with an immunomodulator. The average time from the start of therapy to inclusion in the study was 113.00 ± 47.52 months in the immunomodulatory therapy group. 11 patients (78.57 %) out of 14 taking immunosuppressive therapy at the start of the study switched to it after previous immunomodulatory therapy. 3 patients (6.67 %) out of 45 included in the study started treatment with immunosuppressive therapy. In the immunosuppressive therapy group, the duration of treatment was 62.57 ± 74.52 months. Progression of the disease from the moment of initiation of therapy to inclusion in the study was observed in 19 patients - 42.22 %. An increase in the EDSS index was recorded by an average of 1.82 ± 0.31 points. Improvement of clinical condition was observed in 6 patients - 13.33 %. A decrease in the EDSS index was recorded by an average of 0.91 ± 0.22 points. The difference in the EDSS index in the groups of immunomodulators and immunosuppressors is insignificant. There was no dependence of the patient's clinical condition on the number and activity of foci of demyelination.Conclusions. The objective clinical condition of the patient has no significant difference in the groups of immunomodulatory and immunosuppressive therapy, which suggests that the correct selection of a particular drug by the attending physician and its constant use by the patient is important in order to reduce the risks of complications, slow down the progression of the disease and preserve the quality of life of the patient.

Relevance. Multiple sclerosis is a global medical and social problem of our time. This is due to a decrease in the number of able-bodied population due to the onset of the disease in 20-40 years, steady progression, the appearance of persistent neurological symptoms and disability. Therapy with drugs that change the course of multiple sclerosis is not always effective for progressive forms of the disease. There are a large number of clinical trials of modern medicines and techniques that affect the main links of pathogenesis, aimed at combating further progression and reducing the existing neurological deficit. One of the promising and potentially effective methods is stem cell transplantation.The purpose of study. To analyze foreign publications on the use of stem cells for the treatment of multiple sclerosis: to assess the possibility, safety and prospects of using stem cell transplantation in patients with progressive multiple sclerosis resistant to standard therapy.Materials and methods. In the course of this study, foreign scientific articles were searched in the databases "Elibrary", "PubMed", "Cochrane Library". The analysis and generalization of data on the main etiopathogenetic mechanisms of multiple sclerosis development and methods of influencing them, on alternative methods of treating multiple sclerosis, properties of different types of stem cells, methods of transplantation, results of open clinical trials of stem cell transplantation in patients with multiple sclerosis.Results. Stem cell therapy can be used as an alternative method of treating progressive forms of multiple sclerosis. Several types of stem cells with individual properties and advantages were considered for clinical use. Autologous hematopoietic, mesenchymal, neuronal, embryonic and induced pluripotent stem cells are distinguished. Mesenchymal and hematopoietic stem cells have demonstrated the greatest therapeutic potential in clinical trials. The safety and good tolerability of transplantation of these cell types have been proven, but the effectiveness remains controversial. Clinical improvements were more often observed in patients of younger age, with a disease duration of less than 10, inefficiency in no more than two previous methods of treatment modifying the disease, and having a lower baseline EDSS score.Conclusion. Stem cell transplantation is indeed a promising method and can revolutionize the treatment strategy for neurodegenerative diseases. Clinically proven safety and efficacy make it possible to change the approach to therapy in relation to the progressive course of multiple sclerosis, to conduct large multicenter clinical trials to include the method in the treatment standards. The opportunity to stop the progression and prolong the relapse-free period makes it possible in the near future to eliminate the need to take drugs that change the course of multiple sclerosis, reduce their side effects on the body and return patients to their former lives. The full clinical effect of transplantation has yet to be demonstrated by further studies.

Objective. To study possible clinical markers associated with the unfavorable course of multiple sclerosis and its transition to a progressive subtype. Materials and methods. This prospective study included healthy volunteers and patients with relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS). For a comprehensive clinical evaluation, the participants completed the Timed 25-Foot Walk Test (T25-FW), Nine-Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Fatigue test, and MSProDiscuss questionnaires. Then we compared the results between the groups. Results. We found significant differences between the groups in regard to most of the tests. Furthermore, we proposed a composite clinical score (CCS) based on T25-FW, SDMT, and 9-HPT results (for both hands). Discussion. Our CCS can be a useful clinical tool to determine the most likely course of multiple sclerosis at a certain timepoint.

In solid organ recipients, post-transplant neurotoxicity of calcineurin inhibitors (CIs) can be manifested by brain and spinal cord demyelination with multiple sclerosis (MS)-like symptoms. Here are presented two case reports of neurological MS-like symptoms in the long-term post-liver transplant period with different underlying causes. CI neurotoxicity may resemble various neurological diseases, including MS. At the same time, liver transplant recipients can develop true MS regardless of the immunosuppressant use. In liver transplant recipients, adequate differential diagnosis of neurological complications avoids unnecessary medications and reverses severe neurological deficits by immunosuppressant conversion.