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.

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.

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<0.05), the number of correct answers in the SDMT test increased from 40.7±11.75 to 45.16±13.13 (p<0.05). No exacerbations of the disease were recorded during the TeleRBT period.

Conclusion. TeleRBT had a positive effect on the cognitive and motor domains of patients with MS. The absence of exacerbations and negative dynamics in neurological status characterizes TeleRBT method as safe.

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.

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 (p<0.05; |log2FC| >1) 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.

Neuromyelitis optica spectrum disorders (NMOSD) are a group of chronic autoimmune diseases of the central nervous system with a relapsing course. Unfortunately, the symptoms of exacerbation cannot always be completely stopped, and in addition to motor disorders, chronic pain and depression can worsen the patient's condition. Currently, one of the factors that significantly affects the quality of life of patients in this group is chronic, debilitating pain.

Objective: to determine the prevalence of the pain syndrome in the population of NMOSD patients in Moscow region, to investigate its clinical characteristics and its impact on quality of life.

Material and methods. The study included 33 patients with NMOSD (6 men and 27 women) aged 22 to 64 years. The following criteria were used to assess the neurological condition, presence and severity of the pain syndrome: Expanded Disability Status Scale (EDSS), Diagnostic Neuropathic Pain Questionnaire (DN4), Pain Detect Questionnaire (PDQ), McGill Pain Questionnaire (MPQ), SF-36 Quality of Life Questionnaire, Beck Depression Inventory and MRI data.

Results. Among the patients analysed, the pain syndrome occurred in 19 patients (57.6%): 4 patients with NMOSD without antibodies against aquaporin-4 (AQP4-) and 15 with antibodies against AQP4 (AQP4+). In this group, neuropathic pain was observed in 14 patients (11 – AQP4+ and three – AQP4-), pain due to spasticity in 6 patients (5 – AQP4+ and 1 – AQP4-), painful tonic spasms in 2 patients with AQP4+ and neuropathic itching – in 1 patient with AQP4-. According to the questionnaires of the seropositive patients, the median DN4 was 3 [2; 3] (here and below the data are given in Me format [25th; 75th percentile]), PDQ – 6 [5; 12], on the MPQ scale: pain rank index – 11 [9; 15], index of the number of selected symptoms – 3 [3; 4], pain intensity – 2 [1; 3]. The results for the physical and psychological health domains of the SF36 questionnaire were 35.9 [6.5; 36] and 50.5 [5; 51.5] respectively. Among AQP4+ patients, 7 out of 15 patients were diagnosed with depression; in the AQPpatients, only one man was diagnosed with depression. There was a statistically significant correlation between the age of the patients and pain level: neuropathic pain according to DN4 was more pronounced in younger patients (p=0.009), and neuropathic pain was significantly more severe in patients with an early onset of the disease (p=0.04).

Conclusion. There is currently no clear approach for the treatment of pain in NMOSD. In the present small study, different causes of pain were identified, depending on the location and severity of the lesion, the age of the patient and the duration of the disease. The most important factor in the prevention and treatment of pain syndrome in NMOSD is probably adequate immunotherapy of the disease.

Multiple sclerosis (MS) is an autoimmune-inflammatory and neurodegenerative disease of the central nervous system. The article analyses the ability of cladribine, which due to its selective lymphotoxic effect on activated cells and central effect on immunomodulation in brain tissue underwent successful clinical trials in 2010, when it was (temporarily) approved in Russia.

Objective: to analyse the effect of cladribine tablets in daily practice on the course of MS over 3–4 year observational period after immune reconstitution therapy (IRT) in several neurological clinics from different regions of Russia.

Material and methods. We collected data on 235 patients from 12 neurological clinics and regional MS centres who were followed for an average of 3.4 years after starting cladribine treatment.

Results. An independent analysis of cases in which cladribine tablets were prescribed showed that the reason for prescribing cladribine was highly active MS (HARS) in 159 (67.7%) patients, rapidly progressive MS (RPMS) in 20 (8.5%), active relapsing-remitting MS – in 50 (21.3%) and secondary progressive MS with exacerbations – in 6 (2.5%). Only 12 (5.1%) of these patients had not previously received disease-modifying therapies (DMTs), i.e. in these cases the drug was the first DMT prescribed. Among patients who had received a second-line DMTs before switching to cladribine, 22 had previously received natalizumab, 5 had received ocrelizumab and only 1 had received fingolimod. Remaining patients (n=195) were switched from first-line DMTs. In all cases, a decrease in the frequency of exacerbations was observed during and after completion of the IRT course. Exacerbations between the first and second course of cladribine were observed in 36 patients (15.3% of all treated patients), including in almost half of the cases those who were switched from natalizumab (17 exacerbations or 47.2% of all exacerbations, that developed between the first and second course of therapy) and in three cases – from ocrelizumab (8.3 % of exacerbations that developed between the first and second course of therapy, or 60 % of all those switched from ocrelizumab to cladribine). After completion of full cladribine treatment during the four-year observation period, exacerbations occurred in 14 patients (6% of all patients included in the analysis), six of which occurred after switching from natalizumab.

Conclusion. The results are generally consistent with the results of recently published meta-analyses and reviews, but the high likelihood of exacerbations in patients switched from second-line therapies such as natalizumab and ocrelizumab is noteworthy. Both drugs are prescribed for aggressive types of MS with exacerbations (highly active and rapidly progressive) who had a high frequency of exacerbations and an increase in Expanded Disability Status Scale (EDSS) scores prior to being prescribed these drugs. The switch from natalizumab is usually due to an increased risk of developing progressive multifocal encephalopathy with a high titre of antibodies against the JC-virus and the duration of natal izumab use of more than 2 years. It is likely that the resumption of MS activity after discontinuation of natalizumab is quite pronounced, and replacement with treatment with cladribine in tablet form is not able to completely prevent this. In this respect, such a switch does not appear to be optimal, in contrast to cases where first-line drugs are switched to cladribine.

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<0.001). The sensitivity of the integrated laboratory and radiological model was 96.3 %, the specificity – 96.2 %.

Conclusion. A comprehensive laboratory and radiological model based on the simultaneous analysis of FKC and CVS has high sensitivity and specificity parameters for the diagnosis of MS. This paves the way for the further inclusion of these two markers in the criteria for the diagnosis of the disease.

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<0.001) and a decrease in the levels of IL1β, IL17F, IL22, IL25 and TNFα were found in patients with MS compared to controls. In patients with CNB, the levels of IL6, IL22, TNFα and sCD40L were significantly lower than in donors (p<0.05 and p<0.001), and the levels of IL10, IL17A, IL23, IL31, IL33 did not differ from the control. The concentrations of IL1β, IL4, IL17F, IL21, IL25 and IFNγ in patients with CNB were below the detection limit for these analytes. In patients with MS, the concentrations of IL6, IL10, IL17A, IL31, IL33, TNFα and sCD40L were significantly higher than in CNB. In contrast, IL23 levels were higher in CNB than in MS (p<0.01). High levels (M+3σ in the control group) of IL33 occurred significantly more frequently in MS than in CNB (52.8 and 0.0% of cases; p<0.001). In MS, overproduction of IL17A (2.8%), IL17F (5.6%), IL21 (5.6%) and IL31 (13.8%) was found. In CNB, an isolated increase in IL31 concentration was found in 4 (19.4%) patients. In MS with and without PHVI reactivation, the concentrations of IL6, IL10, IL17A, IL31, IL33, TNFα and sCD40L were significantly higher than in CNB; the greatest differences to CNB were found in the group of MS patients with PHVI reactivation. In CNB, IL23 levels were significantly higher than in MS with or without manifestations of PHVI.

Conclusion. There are significant differences in the production of proand anti-inflammatory cytokines in patients with MS and CNB, which are due to different etiological factors and characteristics of the immune response. In MS, against the background of an increase in IL10 levels, a concomitant increase in blood serum levels of IL6, IL17A, IL31, IL33, TNFα and sCD40L is characteristic, whereas in CND, with a low concentration of IL10 and most of the above proinflammatory cytokines, high levels of IL23 and an isolated increase in IL31 levels are seen. The differences identified can have practical application in the differential diagnosis between these diseases.

In recent decades, the prevalence of demyelinating diseases in paediatric patients has increased rapidly. In this context, there is an increasing need for the study of this pathology in children to enable timely diagnosis and early prescription of highly effective pathogenetic treatment. Neuromyelitis optica spectrum disorders (NMOSD) are a group of severe demyelinating disorders that are united by a single pathogenetic mechanism and primarily affection of the optic nerves and spinal cord. The review presents the main clinical and epidemiological features of NMOSD in the paediatric population. The issues of pathogenesis, which is based on the formation of antibodies against aquaporin-4, and possible therapeutic targets are discussed in detail. The diagnostic criteria and the underlying clinical manifestations as well as their characteristics in childhood are analysed. We present a differential diagnostic framework of the most common diseases, which have to be distinguished from NMOSD in children. Particular attention is paid to the pathogenetic treatment of exacerbations and targeted therapy to prevent exacerbations, which has relatively recently proven its efficacy and been approved for use in paediatric patients.

Neuromyelitis optica spectrum disorders (NMOSD) is a general term for immune-mediated diseases of the central nervous system whose phenotype includes affection of the optic nerve, brainstem encephalitis and myelitis. NMOSD is most commonly associated with class G antibodies against aquaporin-4 (aquaporin-4 immunoglobulin G, AQP4-IgG), less commonly with class G antibodies against the glycoprotein of myelin oligodendrocytes. There are also seronegative variants of NMOSD.

The article describes our own experience in treating two boys with resistant NMOSD with AQP4-IgG positivity with high-dose immunosuppressive therapy (HIST) followed by haematopoietic stem cell transplantation (HSCT). In the first clinical observation, a case of resistant NMOSD in a 13-year-old boy is presented. Over the course of 6 months, the child’s neurological deficit progressed to 9.5 points on the Expanded Disability Status Scale (EDSS). After mobilization of peripheral stem cells (PSC), HIST was performed, followed by autologous HSCT (autoHSCT). During the 18-month follow-up, no NMOSD activity and the decrease in EDSS to 7.0 points were maintained. In the second clinical observation, the experience with the treatment of a child with resistant high-activity NMOSD is presented. A 10-year-old boy had two exacerbations within four months against the background of two lines of immunosuppressive therapy. PSCs were collected before auto-HSCT, but due to a further exacerbation and lack of clinical response to the mobilization dose of cyclophosphamide, it was decided to perform an allogeneic HSCT from a haploidentical donor. The follow-up period was 9 months. The EDSS score decreased from 6.5 to 3.5. AQP4-IgG was not detected in the blood of either patient. Both patients received satralizumab as part of consolidation therapy. No significant complications were observed after transplantation.

Thus, HIST followed by HSCT can be considered a promising method for the treatment of resistant forms of NMOSD. The choice of HSCT type may depend on the severity of the patient’s somatic and neurological condition as well as the clinical response to immunosuppressive therapy.

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.

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.