[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.

[Spinal motor segment labeling with a mixture of n-butyl-2-cyanoacrylate and iohexol in determining the level of thoracic spine surgery]. / Opyt markirovaniya pozvonochno-dvigatel'nogo segmenta smes'yu kleya na osnove n-butil-2-tsianoakrilata s iogeksolom pri opredelenii urovnya operativnogo vmeshatel'stva na grudnom otdele pozvonochnika.

Erroneous determining the level of spine surgery is an urgent problem in modern vertebrology. Incidence of this complication is up to 1 per 3110 patients, among patients undergoing thoracic spine surgery - 1 per 25 patients. Despite widespread use of spine surgery, there is still no standard rational method for prevention of erroneous determining the level of intervention. OBJECTIVE: To develop a safe minimally invasive low-traumatic and cost-effective method for preoperative marking the level of thoracic spine surgery. MATERIAL AND METHODS: A mixture of biodegradable adhesive based on cyanoacrylate and water-soluble iodine-containing X-ray contrast agent was used for preoperative marking in 8 patients scheduled for thoracic spine and spinal cord surgery. This mixture was injected into paravertebral tissues at the level of further intervention. RESULTS: Preoperative marking ensured a fixed and clearly visible landmark during intraoperative fluoroscopy in 7 patients. In 1 patient, mixture spread in paravertebral soft tissues that did not allow us to obtain appropriate landmark during intraoperative radiography. CONCLUSION: The described method makes it possible to create an immobile X-ray-positive «mark¼ in paravertebral soft tissues, which can be used to control the level of intervention at all surgical stages.

[Registry-based comparison of multiple sclerosis epidemiology trend data in 1999 and 2019: the case of Yaroslavl]. / Dinamika osnovnykh epidemiologicheskikh pokazatelei rasseyannogo skleroza po rezul'tatam sravneniya registrov patsientov 1999 i 2019 gg. v Yaroslavle.

OBJECTIVE: To compare the epidemiological indicators of multiple sclerosis (MS) in Yaroslavl when comparing the 1999 and 2019 registers to study the pathomorphism of the disease in this territory. MATERIAL AND METHODS: During the work, the data of the 1999 and 2019 registers were used, including the age of the debut, the date of diagnosis, the form of the disease, clinical characteristics, the treatment received and its duration. In 1999, 257 patients living in the city of Yaroslavl (155 women and 102 men) were included in the MS registry with a reliable diagnosis of MS according to Poser's criteria with confirmation according to neuroimaging data. In 2019, 479 people living in the territory of Yaroslavl (342 women and 137 men) were included in the register with a diagnosis of MS based on the criteria of MacDonald 2005, 2010, 2017. As of 01.01.19, 970 patients (530 women and 440 men) were included in the patient register of the Yaroslavl region. RESULTS AND CONCLUSION: Clinical and epidemiological review of Yaroslavl MS Registry data in 1999 and 2019 showed significant changes in disease pattern. The prevalence rate increased from 42.6 to 78.5 cases per 100,000 people. The morbidity rate rose from 1.58 to 3.28 cases per 100,000 people. The reasons for the increase are improvement in the diagnostic quality, new diagnostic criteria and the true growth of prevalence and morbidity. The use of disease modifying drugs (DMDs) has extended «the time to EDSS 3,0¼ by 4 years, «the time to EDSS 6,0¼ by 5-8 years.

[Acute back pain: minimizing the risks of therapy as the basis for effective treatment]. / Ostrye boli v spine: minimizatsiia riskov terapii kak osnova éffektivnogo lecheniia.

Dorsopathies are one of the most common pathologies in the practice of a neurologist and therapist. Lower back pain as a leader in years lived with disability. Clinical differential diagnosis using red flags can significantly reduce the proportion of patients with unreasonable examinations. Stratifying patients for the risk of chronic pain and delayed recovery also reduces the risks of prolonged NSAID therapy. Identification of risk groups for cardiovascular and gastrointestinal complications and differentiated prescription of drugs helps to reduce the risks of therapy.

[The pegylated form of interferon beta in the treatment of multiple sclerosis]. / Pegilirovannaia forma interferona beta v terapii rasseiannogo skleroza.

Interferons-beta (IFN-ß) along with glatiramer acetate is one of the most commonly used disease modifying treatment (DMT) of multiple sclerosis (MS) associated with effectiveness and acceptable safety profile. At the same time, therapy with IFN-ß has a number of limitations associated with a high frequency of injections and production of neutralizing antibodies. The development of the pegylated form of IFN-ß (PEG-IFN-ß) is aimed at resolving these issues. This article reviewed the mechanism of action, efficacy, safety and tolerability of PEG-IFN-ß in the treatment of MS.

[Steps to personalized therapy of multiple sclerosis: predicting safety of treatment using mathematical modeling]. / Shagi k personifitsirovannoi terapii rasseiannogo skleroza: prognozirovanie bezopasnosti terapii s ispol'zovaniem matematicheskogo modelirovaniia.

AIM: To construct a mathematical model capable of predicting the drug safety of a patient receiving multiple sclerosis disease modifying drugs (DMD), on a model of flu-like syndrome (FLS). MATERIAL AND METHODS: The study included 457 patients with multiple sclerosis (MS), aged from 18 to 68 years, mean 38.79 years, the mean duration of disease 122.58 months. All patients received first-line injections drug (interferon-beta). The sample included data from a three-year prospective dynamic observation with a frequency of observation of 1 every 6 months, with only the data of those examinations for which the presence or absence of FLS was known for the next 6 months (1203 cases). At the first step, the frequency of factors in the compared groups using the W Wald-Wolkovitz test, then the prognostic coefficients (PC) and the Kulbak informativity coefficient (CI) were calculated for each factor gradation. To determine the predictive ability of signs, the Spearman's R criterion was used. At the second step, a model of a two-layer neural network was constructed based on the data obtained. RESULTS: A simple static model and algorithm were developed to assess the risks of the onset and persistence of FLS during the next 6 months of interferon beta therapy. An attempt was also made to create an active model using neural network technology. Both models showed good sensitivity and specificity - 81.2% and 80.6% for the neural network, and 73.4 and 71.6% for the static model. CONCLUSION: Using of these algorithms allows to significantly increase the possibility of predicting the occurrence of AE at the time of drug prescribing. From the mathematical point of view, for the first time the mechanism and possibilities of using a neural network in conditions of incomplete initial information were determined.

[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.

[An effect of disease-modifying drugs on the development of children born to mothers with multiple sclerosis]. / Vliianie na razvitie rebenka terapii preparatami, izmeniaiushchimi techenie rasseiannogo skleroza, u materei s rasseiannym sklerozom.

AIM: To evaluate an effect of mother's treatment with disease-modifying drugs (DMD) on the mental and physical development of the child in the first year of life. MATERIAL AND METHODS: Thirty pregnancies resulted in birth of live babies in patients with multiple sclerosis (MS) were studied. The diagnosis of MS was made to the mother before conception of the child. Seven mothers did not receive DMD at the moment of conception (controls), 13 mother were treated with interferon-beta (IFN) and 10 with glatiramer acetate. A structure interview, examination of the child with the assessment of common anthropometric indices, the WHO scale for achievement of six milestones, medical history and statistical analysis were used. RESULTS AND CONCLUSION: The data on the negative effect of MS on the growth and development of the fetus and the positive impact of treatment of the mother with DMD in the early stages of pregnancy on anthropometric indices and development of the child in the first year of life were confirmed. It has been concluded that DMD positively influence the disease course of the female patient and potentially improve the prognosis for her future offspring.

[The results of an open prospective study of ß-interferon biosimilars (an Yaroslavl' cohort)]. / Rezul'taty otkrytogo prospektivnogo issledovaniya bioanalogov ß-interferonov.

OBJECTIVE: to study safety and efficacy of the biosimilars of disease-modifying drugs (DMDs) in the prospective nonrandomized open long-term study of patients with multiple sclerosis in the Yaroslavl oblast (an Yaroslavl' cohort). MATERIAL AND METHODS: The study included 203 patients treated with DMD biosimilarsduring 30 months according to the instruction for using. The efficacy was assessed by the relapse frequencychanges in EDSS scores, changes of lesions on MRI T2-weighted images (T2-WI). The safety was assessed by the determination of the percentage of patients with side-effects due to the treatment. Results at baseline and month 30 visit were compared. RESULTS: There was a significant decrease in the frequency of relapses in patients treated with biosimilars compared to baseline (cinnovex by 0.03, genfaxon by 0.29, ronbetal/interferon by 0.13, infibeta by 0.36). For all biosimilars, with the exception of infibeta,EDSS scores significantly increased (cinnovex +0.31, genfaxon +0.38, ronbetal/interferon +0.66, infibeta +0.26). MRI results revealed an increase in the number of lesions in patients treated with cinnovex (+16.6%), genfaxon (+14.4%) and ronbetal (+10.6%) and a decrease of lesions on T2-WI in patients treated with infibeta (-14.5%). The most marked generalized reasponses were in the cinnovex group (flu-like syndrome - 66% of the patients), local reactions were most marked in the genfaxon group (82%). CONCLUSION: The differences between some biosimilars and original DMDs in the safety profile and efficacy suggest that attention should be drawn to the thorough study of drug effects in clinical trilas and postmarketing studiesincluding registers of patients treated with DMDs managed independently from pharmaceutical companies.

[A place of first-line drugs in treatment of multiple sclerosis]. / Mesto preparatov pervoi linii v lechenii rasseiannogo skleroza.

A rapidly changing set of drugs for treatment of multiple sclerosis (MS) leads to the necessity of searching for predictors of their efficacy. Understanding of pathogenetic processes in MS and mechanisms of action of different drugs play an important role in the search for markers of potential responders. The author analyses the presently accumulated information on the original drug copaxone (glatiramer acetate) including current concepts on the mechanism of action, long-term safety and efficacy. Data on the frequency and significance of adverse effects during treatment with glatiramer acetate as well as on the influence of the drug on pregnancy, postpartum course of MS and development of the infant who received glatiramer acetate prenatally compared to other disease-modifying drugs are presented.

[Current strategy of treatment of cognitive impairment: potential points of application of drugs used for treatment of cognitive functions].

The article reviews the literature on the diagnosis and treatment of cognitive impairment in the aspect of activity of main functional systems involved in functioning of the higher mental functions, cortical/subcortical interactions, afferent activating pattern of the reticular system and the cerebral blood flow system. The role of the latter is considered in frames of the concept of the neurovascular unit. Main points of application of drugs used for treatment of cognitive functions, including those which exert an effect on the capillary blood flow, are defined.

[Unified assessment of adverse events of multiple sclerosis disease modifying drugs]. / Unifikatsiia otsenki pobochnykh éffektov terapii preparatami, izmeniaiushchimi techenie rasseiannogo skleroza.

One of the important components of effective treatment оf multiple sclerosis is adherence to therapy and long-term patient compliance, as well as timely detection and correction of adverse events. Using disease modifying drugs (DMD) in general medical practice is very different from that in clinical trials, in particular, there is no uniform approach to identify the adverse events of therapy. The authors developed a form of the Adverse events of DMD questionnaire, and checked its reliability and validity.

[Differential diagnosis of late-stage neuroborreliosis with affection of the central nervous system].

Chronic neuroborreliosis is an actual problem in neurology due to its under-investigation in Russia, variety of clinical forms, and the absence of well established diagnostic criteria. We present clinical and laboratory differential diagnostic criteria of chronic borrelial encephalomyelitis in comparison with multiple sclerosis. Distinguishing characteristics of Lyme encephalopathy versus vascular encephalopathy are considered. Problems and possibilities of immunological methods for identification of B. burgdorferi are discussed. The results of the antibiotic treatment of different clinical forms of neuroborreliosis with affection of the central nervous system are described.

[Side-effects of the treatment with disease modifying drugs in patients with multiple sclerosis: an analysis of register data in the Yaroslavl region].

Authors have followed up 230 patients with multiple sclerosis treated with disease modifying drugs (DMD) using the data of the Multiple sclerosis register of the Yaroslavl oblast during 2009-2011. Original drugs and their generics registered in Russia are used. Patients received interferon-beta 1a for intramuscular introduction (avonex - 3.0%), interferon-beta 1a for hypodermic injection (rebif - 19.2%, genfakson - 8.5%), interferon-beta 1b (betaferon - 16.5%, extavia - 18.2%, ronbetal - 18.0%), glatimer acetate (copaxone - 16.7%). Adverse effects were recorded and subjective tolerability of the drug by the patient was assessed. Statistically significant differences in the safety profile between some bioanalogues and original DMD were identified. This finding suggests that effects of different DMD should be studied in depth in clinical and post marketing trials.

[Multiple sclerosis or recurrent disseminated encephalomyelitis?].

Two cases of acute demyelinization with recurrent course are described. The problem of differentiation between acute disseminated encephalomyelitis and multiple sclerosis is discussed. Clinical presentations with the prevalence of memory and praxis impairment and large MRI lesions in the subcortical white matter support the diagnosis of acute disseminated encephalomyelitis.