In March 2020, oral cladribine was licensed in Russian Federation for the treatment of adult patients with highly active relapsing multiple sclerosis as defined by clinical or imaging features. Three years after the introduction into the Russian market, practical aspects in the use of cladribine tablets we evaluated, including data from real-world studies and the experience gained in the own routine clinical practice. Early initiation of cladribine therapy, use of cladribine in treatment naïve patients and patients with suboptimal response to previous disease-modifying therapy, use of cladribine as the treatment of choice in patients with suboptimal response to platform disease-modifying therapy and washout period while switching to cladribine from other disease-modifying therapy. During the discussion thirteen neurologists from federal and regional centers experienced in multiple sclerosis diagnosis and therapy were asked to answer several questions regarding the practical use of cladribine tables and come to consensus opinion. Consent was reached if at least 75% of the experts agreed on a particular statement. The experts agreed on the possibility to switch patients to cladribine from platform disease-modifying therapy in case of MRI activity or neutralizing antibodies in the absence of relapses activity to achieve better disease control, potential cladribine effects on progression independent of relapses, washout period reduction while switching from natalizumab to cladribine. Consensus opinion will help to manage practical questions regarding cladribine usage.

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare or underdiagnosed autosomal-recessive mitochondrial disease that sometimes mimics progressive multiple sclerosis (MS). Difficulties in diagnosing LBSL are due to the possibility of the onset of the disease in adulthood, and the nonspecific clinical picture in the form of slowly progressive neurological symptoms (pyramidal, cerebellar, sensory and cognitive impairments) without the involvement of other organs and systems characteristic of mitochondrial pathology. However, a notable feature of LBSL is its pathognomonic magnetic resonance imaging of the white matter of the brain and spinal cord, which allows a reliable diagnosis when certain criteria are met. Currently, there are no drugs registered for the specific treatment of LBSL, however, correct diagnosis is necessary to complete the epidemiological data, and to prevent the prescription of drugs with side effects that worsen the quality of life of patients. The number of clinical publications about LBSL is small, both in Russian and foreign publications, and therefore each identified case is of great interest. The article presents a brief review of the literature and a case report of a patient with the adult-onset LBSL, who received disease modifying therapy of multiple sclerosis for a long time. The patient’s main problems were progressive lower paraparesis and ataxia. To make clinicians more aware, we have reviewed the difficulties in differential diagnosis between LBSL and MS, we provided detailed medical history, neurological status, and magnetic resonance imaging findings.

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.

OBJECTIVE:To evaluate the severity and frequency of infusion reactions (IR) in patients with highly active relapsing-remitting multiple sclerosis (MS) In Russian population receiving alemtuzumab therapy.MATERIAL AND METHODS:In retrospective study, we analyzed data from 50 patients with highly active relapsing-remitting multiple sclerosis (MS) from six Regional MS Centers in the Russian Federation who received two courses of alemtuzumab between 2018 and 2022.RESULTS:Among all IRs, the most frequently reported were hives-like rashes, which were registered in 27 people, mostly of mild severity (70.6%). Headaches were the second most common IR, observed in 17 patients (34%). When comparing the group of patients who underwent music therapy (MT) with those who received alemtuzumab therapy without MT, no statistically significant difference was found in the frequency and severity of IRs.CONCLUSION:All patients experienced IRs of varying degrees of severity. A decrease in the score on the EDSS disability scale was noted. MT did not affect the occurrence or severity of IRs.

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.

Purpose. The aim of the study was to investigate changes in iron distribution in the brain of patients with multiple sclerosis (MS) using magnetic resonance imaging (MRI) technique – quantitative susceptibility mapping (QSM) – in comparison with clinical data.Materials and methods. Three groups of patients were included in this prospective study: 47 patients with relapsing-remitting MS (RRMS), 20 patients with secondary progressive MS (SPMS) and 39 healthy controls. For all patients we collected clinical data, including history of present illness (H&P) and disability degree, and performed brain MRI followed by QSM maps obtaining and assessing relative magnetic susceptibility in subcortical structures.Results. We found an increase in magnetic susceptibility in the heads of the caudate nuclei and in putamen in patients with SPMS as compared to RRMS. At the same time, a decrease in magnetic susceptibility in the thalamic pulvinar was detected in patients with MS in the long term, but a sharp hyperintensity in conjunction with decreasing volume was observed in some patients.Conclusion. Increased magnetic susceptibility on the QSM in subcortical structures of the brain, reflecting iron content, is more typical for patients with SPMS, which may indicate the prognostic value of these changes.

Multiple sclerosis (MS) is an autoimmune inflammatory neurodegenerative disease of the central nervous system. The disease is characterized by a heterogeneous clinical course, which is reflected in the fact that there are various types, such as relapsing-remitting MS (RRMS), primary and secondary progressive MS (PPMS and SPMS, respectively). Currently, there is an active search for MS biomarkers capable of predicting and assessing disease progression with high sensitivity and specificity, which would be of great benefit in determining treatment tactics and evaluating their efficacy. MicroRNAs (miRNAs) are short (21–25 nucleotides) non-coding RNA molecules that are primarily involved in post-transcriptional regulation of gene expression. miRNAs play an essential role in tissue development, homeostasis, immune system regulation, and immune cell maturation; they are also involved in the pathophysiology of MS. In addition, high hopes are pinned on miRNAs as disease biomarkers, mainly due to their stability and ability to be released from cells into the extracellular space and circulate there for a long time. The review considers published data on miRNAs in different types of MS. In the future, changes in their levels may be used to create a panel of prognostic markers for disease progression. Studies of miRNAs levels in both circulating fluids (plasma, serum, cerebrospinal fluid) and brain tissue of MS patients were reviewed. Based on the aggregated data from the studies reviewed, it can be confirmed that the accumulated data are quite sufficient to recognize that regulatory miRNAs molecules are involved in the pathophysiological mechanisms of MS progression. However, there is still a long way to go to establish a panel of circulating miRNAs that predict the rate of progression of MS.

У статті подано клінічне спостереження пацієнтки з діагнозом «Harding-синдром — поєднання спадкової оптичної нейропатії Лебера і розсіяного склерозу». Обговорюється сучасне уявлення про патогенез.

Currently, the use of anticoagulants is a mandatory component of the complex therapy of COVID-19. Regarding the choice of drugs and their dosages, there is no consensus yet. Increasing doses reduces the risk of thrombosis, but at the same time increases the risk of bleeding, which is a common event in severe COVID-19. This makes it relevant to study alternative options for thromboprophylaxis. The aim of this study was to compare the efficacy and safety of oral sulodexide and dabigatran etexilate in patients with COVID-19. Sulodexide demonstrated the same clinical efficacy as dabigatran in the treatment of patients with a degree of lung damage not higher than CT-2, while the relief of the initially existing coagulopathy occurred significantly faster, and there was no excessive increase in thrombin time, characteristic of dabigatran.

The pathogenesis of multiple sclerosis (MS), a chronic disease of the CNS, includes autoimmune and neurodegenerative components. In most cases, patients develop relapsing-remitting MS (RRMS), while 10–15% of patients develop primary progressive MS (PPMS), which differs from RRMS in the mechanisms of the pathological process, some demographic, and some clinical characteristics. These differences may be explained by the epigenetic regulation of gene expression in PPMS including DNA methylation as one of the key epigenetic processes. The features of DNA methylation in various cell populations in PPMS patients remain understudied. The goal of this study is to identify differentially methylated CpG sites (DMSs) of the genome of CD4+ T lymphocytes, which characterize PPMS. The study included eight treatment-naïve PPMS patients and eight healthy controls. Genome-wide analysis of DNA methylation of CD4+ T lymphocytes was performed using high-density DNA microarrays. We have identified 108 DMSs, which distinguish PPMS patients from healthy controls. In PPMS patients 81% of the DMSs are hypermethylated . More than a half of the identified DMSs are located in known genes in CpG islands and adjacent regions, which indicates a high functional significance of these DMSs in PPMS development. Analysis of the overrepresentation of DMS-containing genes in the main biological processes demonstrates their involvement in the regulation of cell adhesion to the extracellular matrix and the development of the immune response, i.e., antigen processing and presentation, and development of the immune system. Genome-wide analysis of DNA methylation in CD4+ T lymphocytes of PPMS patients indicates the involvement of this epigenetic process in the immunopathogenesis of the disease. These results may help better understand the pathogenesis of this severe form of MS.

One of the target areas for the development of the Russian pharmaceutical industry at present is the development of next-in-class drugs medicines. These are original, patent-protected drugs that act on known biological targets, improved or modified in structure and mechanism of action compared to existing, successfully proven medicine. The article presents the results of an expert council on the management of patients with multiple sclerosis and the place of new original medicines of the JSC BIOCAD company (SamPEG-IFN-β1a and divozilimab) in multiple sclerosis therapy algorithm.

У цій статті наведено клінічний випадок агресивної форми розсіяного склерозу — варіант Марбурга. Обговорюються питання діагностики й можливі варіанти терапії відповідно до міжнародних опублікованих даних.

The need to review the guidelines for the management of patients with multiple sclerosis using multiple sclerosis disease modifying drugs has become acute enough since the beginning of 2020 following the outbreak of the COVID-19 pandemic caused by a novel coronavirus SARS-CoV-2. Immunosuppressive drugs were also specifically addressed, as it is during administration of these drugs that the more severe course of COVID-19 disease was expected. Both the Russian and foreign teams published results of their research works. This article presents a retrospective analysis of the incidence rates of COVID-19 in patients with multiple sclerosis after selective immunosuppressive therapy with alemtuzumab and a clinical case when a patient was infected with coronavirus in the first days following the last infusion of the therapy course without clinical manifestations of the infectious disease. The author discusses the mechanisms underlying such a favourable outcome due to the CD52 lymphocyte depletion leading to the reduction of risks of developing hyperimmune reactions that underlie severe complications of COVID-19, and analyses previously published works of our foreign colleagues on the same theme. The review of the accumulated works and personal experience suggest that it is the CD52 lymphocyte depletion that makes it possible to avoid the cytokine storm and, as a result, the more severe course of COVID-19. Amidst the COVID-19 pandemic, during the prescription of multiple sclerosis disease modifying drugs, it should be borne in mind that patients should have access to all types of modern therapy and that the benefits should outweigh the sum of possible risks.

The article presents the results of the discussion of the use of anti-B-cell therapy in multiple sclerosis (MS). These cells play a significant role in immunoregulation in MS, not only by producing antibodies to myelin antigens after transformation into plasma cells, but also by presenting the antigen to T cells, producing activation cytokines, and forming laminar follicles. The article provides an expert consensus statement on different drugs of this class in the MS treatment. In addition, the possibilities of determining the disease prognosis for the initially correct treatment choice are highlighted. Undoubtedly, there is a need for confirmation of the MS diagnosis, possible stratification of patients into different risk groups, and evaluation of the response to therapy. Potential additional research methods included evoked potentials and optical coherence tomography, baseline vitamin D3 level as a prognostic marker of the disease course, neurofilament levels in serum and cerebrospinal fluid to confirm neuron damage. However, it takes much time to study, determine the methodology, reference values, and develop a single standard approach to identify and implement a biomarker, which should then be implemented in routine clinical practice.

Neuromyelitis optica spectrum disorders (NMOSDs) are autoimmune inflammatory disorders accompanied by central nervous system damage, widespread immunemediated demyelination, and axonal damage, involving mainly the optic nerves, spinal cord, and area postrema. The diagnostic capabilities, administration and routing of patients, and therapeutic approaches to this disease need to be improved. During several expert councils held in 2019–2021 in different regions of the Russian Federation, we discussed multiple issues related to various aspects of medical care for patients with NMOSDs. As a result, the experts developed further steps necessary to improve the medical care to these patients: to write and publish clinical guidelines for the diagnosis and treatment of NMOSDs; to consider the possibility of optimizing the NMOSDs diagnostic program including the aquaporin-4 antibodies (AQP4-IgG) testing; to evaluate the implementation of a set of measures aimed at including the corresponding laboratory investigations into the system of state guarantees (together with the institutions of the Ministry of Health of Russia), if there is clinical and economic feasibility; to include the issues of timely NMOSDs evaluation in educational programs initiated by the scientific medical community, in order to raise awareness of primary care neurologists in relation to the clinical and neuroimaging signs of probable NMOSDs; to assess the possibility of introducing routing schemes for patients with NMOSDs at the regional level; to work out a decision on the collection of NMOSDs epidemiological and clinical data in the Russian Federation.

The COVID-19 pandemic was announced in 2020, and many professional medical societies had to review their algorithms for the management of high-risk patients. In addition to risk factors such as overweight, age over 65 years, cardiovascular disease, diabetes mellitus, and bronchial asthma, other chronic diseases should also be emphasized, taking into account possible immunosuppressive therapy. This publication presents two clinical cases of COVID-19 infection in patients with multiple sclerosis treated with ocrelizumab. During the course of the disease, both patients developed a cytokine storm and were treated with IL-6 blockers. Both cases ended with recovery and a subsequent return to anti-B-cell therapy. Given the mechanism of action of ocrelizumab, there are higher risks of infectious complications, including with COVID-19, but mortality is not higher than the population average. The information published to date may serve as a reason to consider the use of extended dosing intervals to minimize the possible risks of COVID-19 infection, which are probably highest in the first months after infusion.

Alemtuzumab (Lemtrada) is a recombinant humanized IgG1 kappa monoclonal antibody to the surface cell glycoprotein, a CD52 differentiation cluster. The drug is approved for use in more than 65 countries, including the Russian Federation. The drug is one of the most effective methods of treating patients with aggressive multiple sclerosis, but the risk management plan should be followed. The safety profile of the drug includes infusion-associated reactions, thyroid dysfunction, immune cytopenia, acute cardiovascular events, infections, and other autoimmune diseases. This publication provides updated practical recommendations for the use of the drug and ensuring the safety of patients treated with alemtuzumab.