[The effect of pregnancy on multiple sclerosis]. / Vliyanie beremennosti na rasseyannyi skleroz.

Planning for pregnancy and possibility of disease modifying treatment (DMTs) is an important question in female patients of reproductive age who suffer from multiple sclerosis (MS). The frequency of refusals to plan pregnancy is 14%. This is due to numerous concerns about the course of pregnancy, its outcomes, as well as the possible effect of DMTs on the fetus and the probability of disease transmission to a child. The article discusses immunological reactions taking place in MS patients during pregnancy, which are protective in its nature. Data for all groups of DMTs regarding pregnancy planning, possible risks of their impact on fertility and teratogenicity is presented.

The Level of Anti-Viral Antigen-Specific Antibodies to EBNA-1 in the Serum of MS Patients Does not Depend on the Severity of the Disease.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease leading to inevitable disability and primarily affecting the young and middle-aged population. Recent studies have shown a direct correlation between the risk of MS development and Epstein-Barr virus (EBV) infection. Analysis of the titer of EBV-specific antibodies among patients with MS and healthy donors among Russian population confirmed that MS is characterized by an increased level of serum IgG binding EBNA-1 (EBV nuclear antigen 1). The number of patients with elevated levels of EBNA-1-specific antibodies does not differ statistically significantly between two groups with diametrically opposite courses of MS: benign MS or highly active MS. It can be assumed that the primary link between EBV and the development of MS is restricted to the initiation of the disease and does not impact its severity.

[New opportunities in the treatment of patients with multiple sclerosis (Resolution of the Council of Experts on April 23, 2022, Moscow, JSC «BIOCAD¼)]. / Novye vozmozhnosti v terapii patsientov s rasseyannym sklerozom¼ (Rezolyutsiya soveta ekspertov 23 aprelya 2022 goda, Moskva, AO «BIOKAD¼).

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-ß1a and divozilimab) in multiple sclerosis therapy algorithm.

[Anti-Ma2 paraneoplastic autoimmune encephalitis]. / Anti-Ma2 paraneoplasticheskii autoimmunnyi entsefalit.

Paraneoplastic syndromes are a heterogeneous group of conditions affecting cancer patients, where the symptoms are not owing to the local effects of the tumor but instead owing to humoral or immunologic effects. Paraneoplastic neurological syndromes (PNS) develop in less than 1% of cancer patients and can affect any part of the nervous system. A variety of PNS phenotypes are associated with anti-Ma2 antibody, primarily encephalitis with a predominant involvement of brainstem, limbic and diencephalic structures. We describe a case of anti-Ma2 autoimmune encephalitis with a recurrent course in a patient with two different primary tumors in the anamnesis.

Multiple Sclerosis Is Associated with Immunoglobulin Germline Gene Variation of Transitional B Cells.

The regulatory functions of the B-cell compartment play an important role in the development and suppression of the immune response. Disruption of their anti-inflammatory functions may lead to the acceleration of immunopathological processes, and to autoimmune diseases, in particular. Unfortunately, the exact mechanism underlying the functioning and development of regulatory B cells (Breg) has not yet been fully elucidated. Almost nothing is known about their specificity and the structure of their B-cell receptors (BCRs). In this research, we analyzed the BCR repertoire of the transitional Breg (tBreg) subpopulation with the CD19+CD24highCD38high phenotype in patients with multiple sclerosis (MS), using next-generation sequencing (NGS). We show, for the first time, that the immunoglobulin germline distribution in the tBreg subpopulation is different between MS patients and healthy donors. The registered variation was more significant in patients with a more severe form of the disease, highly active MS (HAMS), compared to those with benign MS (BMS). Our data suggest that during MS development, deviations in the immunoglobulin Breg repertoire occur already at the early stage of B-cell maturation, namely at the stage of tBregs: between immature B cells in the bone marrow and mature peripheral B cells.

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

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

[Myelin oligodendrocyte glycoprotein immunoglobulin G-associated encephalomyelitis]. / Entsefalomielity, assotsiirovannye s antitelami k mielin-oligodendrotsitarnomu glikoproteinu.

The article discusses the role of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) in demyelinating diseases of the central nervous system. Clinical phenotypes of demyelinating syndromes associated with MOG-IgG that are currently included into neuromyelitis optica spectrum disorders (NMOSD) are described. However, it has been shown that encephalomyelitis associated with MOG-IgG (MOG-EM) has certain clinical, radiological, immunological and histopathological features that make it possible to single out these syndromes into a separate nosological form. We provide International recommendations that establish indications for testing MOG-IgG using cell-based assay. We discuss epidemiological issues and classification challenges of the disease. Various approaches to treatment and prevention of relapses of MOG-EM are analyzed.

Differential Diagnostics of Active Progressing Multiple Sclerosis Using a Fluorescent Biomarker with Resonance Energy Transfer.

Previous data showed that myelin-reactive autoantibodies found in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis recognize and hydrolyze various fragments of myelin basic protein (MBP). Moreover, antibody-mediated cleavage of the encephalithogenic fragment MBP81-103 flanked with two fluorescent proteins can serve as a new biomarker of multiple sclerosis. Here we describe creation of the next generation of this biomarker based on antibody-dependent degradation of a new chemically synthesized fluorescent substrate with resonance energy transfer that contains fluorophore Cy5 and quencher QXL680 separated by MBP81-99 protein (Cy5-MBP81-99-QXL680). This substrate is degraded during incubation with purified antibodies and B cells from patients with multiple sclerosis, but not healthy volunteers.

[A case of subtentorial progressive multifocal leucoencephalopathy in a patient treated with natalizumab]. / Sluchai razvitiia progressiruiushchei mul'tifokal'noi leikoéntsefalopatii subtentorial'noi lokalizatsii na fone terapii natalizumabom.

This paper presents a case report of subtentorial progressive multifocal leukoencephalopathy (PML) in a 26-year-old female patient treated with natalizumab. The evolution of clinical features, neuroimaging data and treatment as well as the development of immune reconstitution inflammatory syndrome (IRIS) are described. This case emphasizes the importance to keep accurately the risk management plan during natalizumab treatment. This includes performing MRI scans in order to detect changes typical for PML at the earliest (preclinical) stage in time.

[Neuromyelitis optica and neuromyelitis optica spectrum disorders]. / Optikoneiromielit i zabolevaniia spektra optikoneiromielita.

The review is devoted to up-to-date data on epidemiology, aspects of the pathogenesis of neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD). The authors consider a role of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) in the syndromes phenotypically similar to NMO and NMOSD. Special attention is drawn to the methods of MOG-IgG antibodies detection and indications for testing. The approaches and management for treatment and prevention of NMO relapses, risks of complications during pregnancy and immediately after delivery, as well as methods for their prevention and treatment, are described.

[Area postrema lesion as a cause of intractable nausea, vomiting and hiccups in neuromyelitis optica spectrum disorders]. / Porazhenie area postrema kak prichina neukrotimoi ikoty, toshnoty i rvoty pri zabolevaniiakh optikomielitnogo spektra (nabliudenie iz praktiki).

Neuromyelitis optica (Devic's disease) is a chronic autoimmune disease associated with the production of anti-bodies to aquaporin-4 (AQP4). Area postrema lesions is the third, after optic neuritis and myelitis, syndrome of opticomyelitis-related disorders. Clinical symptoms of this disorder include intractable nausea, vomiting and hiccups. In many cases, area postrema syndrome manifests as the first clinical symptom of a neuromyelitis optica spectrum disorder that hampers the diagnosis. The authors present a case report of a female patient with area postrema lesions developed several months before the first disabling attack of myelitis.

[Comparative, placebo-controlled clinical study of efficacy and safety of glatiramer acetate 20 mg in patients with relapsing-remitting multiple sclerosis: results of the first year of the study]. / Sravnitel'noe platsebo-kontroliruemoe klinicheskoe issledovanie effektivnosti i bezopasnosti preparatov glatiramera atsetata 20 mg u patsientov s remittiruyushchim rasseyannym sklerozom: rezul'taty pervogo goda nablyudeniya.

The article presents the results of international multicenter randomized double-blind, active and placebo-controlled, comparative phase 3 trial. The goal of the study was to demonstrate non-inferiority of BCD-063 (glatiramer acetate, manufactured by JSC «BIOCAD¼, Russia) to copaxone-Teva (Teva Pharmaceutical Enterprise Co., Ltd., Israel) in patients with relapsing-remitting multiple sclerosis. METHODS: 158 patients with relapsing-remitting multiple sclerosis were randomly assigned into 3 groups: BCD-063, copaxone-Teva and placebo, at a ratio of 2:2:1, respectively. RESULTS AND CONCLUSION: Efficacy analysis after 48 weeks of therapy demonstrated no differences between BCD-063 group and copaxone-Teva group in both MRI parameters and frequency of relapses. The mean (SD) of number of MRI-confirmed relapses per patient per year (the primary endpoint) in BCD-063 group was 0.098361 (0.351422), in copaxone-Teva group - 0.098361 (0, 351 422) and in placebo group - 0.178571 (0.390021). There were also no differences between the groups for all other efficacy parameters (EDSS and MSFC). Both investigational BCD-063 and copaxone-Teva demonstrated a favorable safety profile. The data obtained from the present study confirm the therapeutic equivalence of BCD-063 (CJSC BIOCAD, Russia) and copaxone-Teva, that is important for further implementation of glatiramer acetate generic in the clinical practice of multiple sclerosis therapy.

[Neuromyelitis optica and aquaporin-associated syndromes]. / Optikomielit i akvaporin-assotsiirovannye sindromy.

Identification of aquaporin-4 antibodies in neuromyelitis optica (NMO) is highly important to provide early diagnosis for starting pathogenetic treatment, and for differential diagnosis in neuromyelitis optica spectrum disorders (NMO-SD). In this paper, we review current pathogenetic and clinical aspects of NMO and NMO NMO-SD. We present our data on the identification of aquaporin-4 antibodies in CNS disorders. Aquaporin-4 antibodies were detected in 86.36% of patients with neuromyelitis optica, in 12.5% of patients with partial syndromes and in 100% of patients with systemic lupus erythematosus with longitudinally extensive transverse myelitis or optic neuritis. There was the correlation between the extent of lesion in the spinal cord and positive aquaporin-4 antibodies.