[POEMS-syndrome]. / POEMS-sindrom.

POEMS-syndrome (polyneuropathy - P, organomegaly - O, endocrinopathy - E, M-protein - M, skin changes - S) is a paraneoplastic syndrome caused by underlying dyscrasia of plasma cells. The main criteria of the syndrome are polyradiculoneuropathy, clonal proliferation of plasma cells, sclerotic bone lesions, elevated levels of vascular endothelial growth factor and the presence of Castleman disease. Additional signs include organomegaly, endocrinopathy, characteristic skin changes, edema of the optic disc, extravascular volume overload (edema) and thrombocytosis. The diagnosis is often made late, because the syndrome is rare and is often mistaken by specialists for other neurological disorders, most often for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We present two cases of POEMS-syndrome. The description is based on the principle of differential diagnosis with a number of similar neurological disorders. The goal facing the neurologist is to carry out the most complete diagnostic measures for early diagnosis, which further determines timely therapeutic tactics. Hematologists are engaged in specific therapy of POEMS-syndrome. A brief description of possible therapeutic options is presented. On the example of these cases, we demonstrate possible variants of the therapeutic response based on the developed system of risk stratification of patients with POEMS-syndrome.

[Approaches to vaccine prevention in multiple sclerosis]. / Vaktsinoprofilaktika pri rasseyannom skleroze.

The article presents an overview of modern approaches to vaccine prevention in multiple sclerosis (MS). Compared with the general population, patients with MS have been shown to have an increased risk of morbidity, a tendency to have a more severe course, and a greater mortality from vaccine-preventable infections. At the same time, in Russia, until recently, traditionally adhered to a conservative tactic of limiting vaccination in patients with autoimmune diseases, including MS. The use of various disease-modifying therapies (DMT) may also affect the susceptibility to infections and the severity of their course. Screening for latent infections, determination of immune status, collection of history of past infections and development of a vaccination plan based on these data are an important part of the preparation before the appointment of DMT to control the occurrence or reactivation of infections. The use of inactivated, subunit, conjugate, and toxoid-based vaccines are preferable for MS patients. When developing a vaccination plan, avoid live-attenuated vaccines whenever possible. There are no restrictions on vaccination during first line DMT intake. In case of vaccination in MS patients while using immunosuppressants, including drugs for immune reconstitution therapy, an individual risk assessment and timing are required. The available data on the awareness of patients about vaccine prophylaxis are significantly limited and require mass information events.

[Local experience of IL-6 pathway inhibition with satralizumab for patients with neuromyelitis optica spectrum disorder]. / Lokal'nyi opyt primeneniya preparata satralizumab, podavlyayushchego put' IL-6, dlya terapii zabolevanii spektra optikoneiromielita.

Satralizumab is a monoclonal anti-IL6-anibody for patients with neuromyelitis optica or neuromyelitis optica spectrum disorder (NMOSD) seropositive for anti-AQP4-antibody. Satralizumab has been approved in 2021 in the Russian Federation for usage in adults and adolescents from 12 years and older in combination with basic therapy or in monotherapy. The efficacy and safety of satralizumab in comparison with placebo have been demonstrated in two international randomized clinical trials SakuraStar and SakuraSky, phase III. We present clinical experience with satralizumab gained in frames of the Compassionate Use Program that have been initiated in Russia for NMOSD patients. Here, we summarized the results of treatment with satralizumab of 16 patients (14 men and 2 women), aged 13-69 years. Duration of therapy was 9 to 41 week. The first experience of using satralizumab in the Russian Federation in the small group of patients does not yet allow us to draw conclusions about the efficacy due to the short follow-up period. It can be concluded that the safety profile of satralizumab is consistent with the results obtained in international clinical trials. The experience gained in the ongoing program allows us to conclude that satralizumab is a valuable and convenient therapeutical option for seropositive for anti-AQP4-antibodies patients with NMOSD.

[Long-term treatment for multiple sclerosis with interferon beta-1b. Outcomes of an open, retrospective, observational study]. / Dolgosrochnaya terapiya rasseyannogo skleroza interferonom beta-1b. Rezul'taty retrospektivnogo otkrytogo nablyudatel'nogo issledovaniya.

OBJECTIVE: To assess the outcomes of long-term treatment in multiple sclerosis (MS) patients with Infibeta (interferon beta-1b). MATERIAL AND METHODS: The article presents the results a real-world, multicenter, retrospective, observational study of treatment with interferon beta-1b. We enrolled 332 patients with MS who had been receiving Infibeta for at least 8 years. 60.2% of them had a relapsing-remitting MS (RRMS). 73.2% patients received only interferon beta-1b that was initial DMT. RESULTS: During the first year of the treatment, 66% of the patients reported no relapses regardless of the MS type. No relapses in the 8th year of treatment were observed in 86.9% of patients with RRMS and 77.7% with secondary progressive MS (SPMS). The median number of relapses during the whole follow-up period in RRMS patients was 1. The time to first relapse in the subgroup of patients who received interferon beta as the first treatment was longer compared to other treatment (median 4 and 2, respectively, p=0.0017). 42% of patients with RRMS remained progression-free during 8 years of follow-up. The flu-like syndrome was observed in 61.7% for the first year of treatment; in 36.3% it was periodically and was mild in 71.3%. CONCLUSION: The study outcomes confirm a high clinical response to the long-term treatment with Infibeta in patients with RRMS and SPMS and demonstrate that interferon beta-1b is one an optimal option for the initial treatment of patients with moderate disease activity.

[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.

[Susac syndrome, review and clinical case]. / Sindrom Susaka, obzor i opisanie klinicheskogo sluchaia.

Susac syndrome (SS) is an extremely rare neurological disorder characterized by symptoms of a clinical triad: encephalopathy, retinopathy and hearing loss. These problems arise from the microangiopathy of blood vessels that supply blood to the brain, the retina and the cochlea. SS is more common in young women. The authors present a literature review on the diagnosis and treatment of SS and the clinical observation of patients with classic signs of the disease triad.

[Polymorphic variants of the immune response genes as risk factors for primary progressive multiple sclerosis]. / Polimorfnye varianty genov immunnogo otveta kak faktory riska razvitiia pervichno-progressiruiushchego rasseiannogo skleroza.

AIM: To analyze the involvement of immune response genes in the pathogenesis of primary progressive multiple sclerosis (PPMS). MATERIAL AND METHODS: This multicenter study included 111 patients with PPMS from the Russian ethnic group. The association of PPMS with genes of immune system was analyzed by the study of polymorphic variants of genes of cytokines and genes of antigen-presenting cells. RESULTS AND CONCLUSION: The genotypes of IL-4 (rs2243250)*C/C and CLEC16A (rs6498169)*G/G were associated with PPMS in Russians. The association between the HLA-DRB1*15 and PPMS found out in other populations was confirmed in Russians.

[A retrospective analysis of the effect of pregnancy on the course of multiple sclerosis]. / Retrospektivnyi analiz vliianiia beremennosti na techenie rasseiannogo skleroza.

AIM: For a long time it was believed that pregnancy worsens the clinical course of multiple sclerosis. In several European countries, there have been several studies that have demonstrated remission of autoimmune aggression during pregnancy. We studied the effect of pregnancy on the course of multiple sclerosi. MATERIAL AND METHODS: A retrospective analysis of disease course of 279 patients was performed for the first time in three major Russian centers (Moscow, Novosibirsk, Tyumen). RESULTS AND CONCLUSION: There was a remission of autoimmune aggression during pregnancy. The use of DMT before pregnancy was a predictor of a more favorable course of the disease after delivery. An earlier beginning of DMT after delivery led to a significant risk reduction of relapses.

[The first results of a combined all-Russian study on clinical genetics of multiple sclerosis].

Multiple sclerosis is a classic multifactorial disease in which etiology interaction of external factors and structural features of a large number of genes plays an important role. Identifying risk factors for multiple sclerosis and creating an integrated model of pathogenesis are urgent tasks of neurology. Revealing true risk factors is possible only in studies with sufficient statistical power, so with a large amount of samples. We conducted the association study of CD40 gene's polymorphisms and multiple sclerosis among residents of the Russian Federation. The results demonstrated the need to combine data from different researchers in clinical studies to increase the power of the study.

[The effect of genetic factors on the phenotypic expression of multiple sclerosis].

A total of 326 patients with multiple sclerosis (MS) according to the McDonald criteria (2005) were recruited to the study. Single nucleotide polymorphisms in the CD40 gene (rs6074022, rs1883832, rs1535045 and rs11086998) and the KIF1B gene (rs10492972 and rs3135388) were genotyped using TaqMan technology. We found a significant association of rs1883832 (risk allele T, OR=1.74, 95% CI 1.34-2.32, p=2.96·10-7) and rs3135388 (risk allele T, OR=3.23, 95% CI 2.43-4.29, p=3.8·10-17) with the risk of MS in the Novosibirsk region population. The study demonstrated a significant effect of genetic factors on phenotypic expression of MS: an C allele of rs6074022 polymorphism (CD40) was associated with a higher rate of MS progression, and the TT genotype of rs1535045 was associated with a slower progression of MS and early MS onset. A more benign course and a higher frequency of an T allele of rs3135388 (44% vs 33%, p=0.003) was found in familial cases compared to sporadic cases. The further specific research is needed for understanding the genetic basis of susceptibility to MS.

[Association between polymorphisms of cytokine genes and the rate of multiple sclerosis progression].

A genetic predisposition due to the polygenic system responsible for the formation of immune response plays a key role in the development of multiple sclerosis. We genotyped the following polymorphisms: TNFα (rs1800629), TNFRSF1A (rs4149584), CD40 (rs6074022 and rs11086998) using TaqMan technology. The significant genotype effect on the disability index on EDSS and rate of MS progression was found. The association between GA and AA TNFα genotypes and higher average annual frequency of exacerbations was revealed. Genotypes CC (rs6074022) and GG (rs11086998) were associated with the higher disability level. Genotype CC (rs11086998) was associated with the higher rate of MS progression. The results may be used as potential predictors of high rate of MS progression and allow to tailor treatment on early stages of the disease.