[Modern pathogenetic treatment of rare demyelinating diseases]. / Sovremennoe patogeneticheskoe lechenie redkikh demieliniziruyushchikh zabolevanii.

Rare demyelinating diseases are a group of diseases whose pathogenesis is based on the process of demyelination. This group of diseases includes acute multiple encephalomyelitis (ADEM), opticoneuromyelitis spectrum diseases (NMOSD) and anti-myelin-oligodendrocyte glycoprotein-associated diseases (MOG-antibodies-associated diseases - MOGAD). Recently, new biological drugs for pathogenetic therapy have been developed, which have shown their effectiveness and good tolerability in comparison with therapy with first- and second-line drugs. Aim of the study - analysis of modern possibilities of pathogenetic treatment of patients with ADEM, seronegative and seropositive patients with NMOSD. The analysis was carried out on the basis of English-language publications in PubMed published over the past five years. This review summarizes current ideas about the possibilities of pathogenetic treatment of rare diseases. The advantages of using ravulizumab over other representatives of a new biological therapy associated with the use of monoclonal antibodies are shown. The analyzed data allow us to conclude that there is a significant development of pathogenetic treatment options for ZSONM. However, the effectiveness of new therapeutic biological drugs is still limited due to the lack of a large amount of clinical data to confirm, which creates the need to continue analyzing the experience of their use.

[The diagnostic effectiveness of criteria for neuromyelitis optica spectrum disorders in the Russian clinical practice]. / Diagnosticheskaya effektivnost' kriteriev zabolevanii spektra optikoneiromielita v rossiiskoi klinicheskoi praktike.

OBJECTIVE: To compare the diagnostic criteria of 2006 (DC 2006) and 2015 (DC 2015) in the Russian population of patients with suspected neuromyelitis optica spectrum disorders (NMOSD), with the calculation of their sensitivity, specificity, accuracy and predictive value. MATERIAL AND METHODS: We reviewed medical records of suspected NMOSD patients who were therefore examined for the presence of serum autoantibodies targeting the aquaporin-4 water channel protein (AQP4-IgG) in 6 specialized Russian (Nizhny Novgorod and Moscow) medical centers. One hundred patients (78 female), aged 17 to 74 years (mean 38.1±13.3 years), were included. The follow-up period ranged from 4 to 108 months (mean 59.7±31.6 months). RESULTS: During the follow-up the diagnosis of NMOSD was confirmed in 32 people, and 68 patients had diagnoses different from NMOSD. At the disease onset, 68.8% of patients were seropositive for AQP4-IgG. The mean time for confirming NMOSD diagnosis was 15.2±14.2 months. At the disease onset, 36% of patients fulfilled the DC 2015, the diagnosis was subsequently confirmed in 77.8% out of them. 26% of the patients fulfilled the DC 2006, the diagnosis was subsequently confirmed in 84.6% out of them. The sensitivity of DC 2006/DC 2015 was 69%/88%, specificity 94%/88%, accuracy 86%/88%, negative predictive value 85%/94%, positive predictive value 86%/78%. CONCLUSION: The specificity, sensitivity and accuracy of modern diagnostic criteria for NMOSD In Russian patients is comparable to those obtained in foreign studies. DC 2015 helps to diagnose NMOSD earlier than DC 2006, but they have a lower specificity.

[The central vein sign in the differential diagnosis of multiple sclerosis]. / Simptom tsentral'noi veny v differentsial'noi diagnostike rasseyannogo skleroza.

OBJECTIVE: To carry out a clinical and radiological assessment of the central vein sign (CVS) as a diagnostic marker for multiple sclerosis (MS) and other demyelinating and non-demyelinating diseases with focal brain damage, using clinical and laboratory examination data, as well as MRI. MATERIAL AND METHODS: The results of clinical and neuroradiological examination of 107 patients diagnosed with MS or with other diseases accompanied by focal brain damage according to MRI data were analyzed. RESULTS: CVS is a sensitive but low-specific diagnostic marker of MS. According to our data, the sensitivity and specificity of 40 and 50% of the threshold of perivenular lesions in the diagnosis of MS are the same and amount to 100% and 39.4%, respectively. Neither the type of MS course, nor the severity of the course, nor the intake of DMT (disease modifying treatment), affect the proportion of foci with CVS. The spread of the proportion of foci with CVS in patients with MS was 60-100%. The proportion of foci with CVS is below 40 and 50% of the threshold in patients with demyelinating and non-demyelinating diseases (NMOSD, migraine, systemic lupus erythematosus, Susak disease, CLIPPERS), which allows for differential diagnosis with MS. The proportion of foci with CVS comparable to MS in patients with acute disseminated encephalomyelitis, small vessel disease, as well as in patients with radiologically isolated syndrome does not allow using this symptom in the differential diagnosis of these conditions. CONCLUSION: The use of CVS as a diagnostic marker of MS is possible only in combination with the already existing diagnostic criteria of MS.

[Mistakes in the diagnosis of neuromyelitis optic spectrum diseases lead to wrong therapy and deterioration of patients' condition]. / Oshibki v diagnostike zabolevanii spektra optikoneiromielita privodyat k nepravil'noi terapii i ukhudsheniyu sostoyaniya patsientov.

Neuromyelitis optic spectrum diseases (NMOSD) are a group of rare neuroimmunological diseases involving mainly the optic nerves and spinal cord, to a lesser extent the brain, and causing severe exacerbations that lead to persistent disability of patients. For many years, opticoneuromyelitis was considered a prognostically unfavorable variant of the course of multiple sclerosis (MS), however, in 2004, specific autoantibodies to aquaporin-4 were found in such patients, which made it possible to isolate NMOSD into a separate group of demyelinating diseases other than MS. Due to similar clinical signs and the predominantly remitting course of diseases, it is often difficult to make a correct diagnosis and, accordingly, prescribe effective therapy, which often leads to incorrectly selected therapy with incorrect diagnosis. In some cases, this leads to a worsening of the course of NMOSD. We present a case of late diagnosis of NMOSD that confirms the development of exacerbation in the patient 2 months after the first course of therapy with alemtuzumab prescribed as a highly effective therapy for highly active remitting MS. Timely diagnosis of NMOSD makes it possible to exclude such cases.

[Optimal patient profile for ofatumumab treatment: analysis of Russian data from the Phase 3 study]. / Optimal'nyi profil' patsienta dlya lecheniya ofatumumabom: analiz rossiiskikh dannykh iz issledovaniya 3-i fazy.

The article provides an analysis of the features of the action of ofatumumab in subgroups of patients with multiple sclerosis (MS) who participated in phase 3 ASCLEPIOS I and II studies both in the general subgroup of 1882 patients and among 352 patients from the Russian Federation who participated in these studies. The results of the influence of age, gender, body weight of patients, as well as the basic level of disability on the EDSS scale, the presence of active foci on MRI and previously received therapy with drugs that alter the course of MS (PITRS) are presented. In a total group of 1.882 patients, a more positive effect of ofatumumab compared with teriflunomide was noted on the average annual incidence of exacerbations in men, younger people and with a mild baseline disability level - with a baseline EDSS level less than or equal to 3. In a subgroup of 352 patients from Russia, the same trends were noted, but dependencies were also revealed from the number of previously taken PITRS: a more significant difference was noted in patients with the lowest number of PITRS in the anamnesis. This feature was also confirmed by analyzing the secondary endpoints of the study: the number of active foci on MRI and the confirmed progression of disability according to the EDSS scale. Analysis in clinical subgroups makes it possible to clarify the profile of patients in whom the greatest clinical effect can be expected when using this new drug for the treatment of MS.

[Questionnaires for arm function assessment in patients with multiple sclerosis]. / Oprosniki dlya otsenki funktsii ruki u patsientov s rasseyannym sklerozom.

Arm dysfunction is one of the disabling manifestations of multiple sclerosis (MS), especially in later stages of the disease. Assessment of the functioning of the upper limbs is necessary to objectify the course of MS, determine the effectiveness of therapy, and individualize rehabilitation measures. The tools that assess the upper extremity dysfunction include tests and questionnaires. Questionnaires (patient-reported outcome measures) represent the special importance, since the opinions and preferences of patients themselves help to implement a patient-centered approach to treatment. The article presents a brief description of three multidimensional MS-specific and four unidimensional MS-nonspecific questionnaires that used in assessment of upper limb function in MS patients. The disease-specific unidimensional Arm Function in Multiple Sclerosis Questionnaire (AMSQ), specifically designed to assess the arm use in patients with MS, is discussed in more detail. The use of AMSQ in the Russian population is possible only after the procedure of cultural adaptation and validation of the Russian version.

[A role of cerebrovascular diseases in the progression of multiple sclerosis]. / Rol' tserebrovaskulyarnykh zabolevanii v progressirovanii rasseyannogo skleroza.

OBJECTIVE: To identify the association between cerebrovascular diseases (CVD) and multiple sclerosis (MS) among patients over 50 years old in two independent populations of Moscow and Tyumen. MATERIAL AND METHODS: The study included 94 patients with MS in combination with CVD (main group) and 90 age-and sex-matched patients with MS without a vascular history (comparison group). An analysis of parameters such as disease duration, EDSS at different time points, disease progression index, duration of first remission in each population separately and in both populations together was carried out. RESULTS: The presence of CVD in patients with MS was associated with the presence of other diseases that are associated with an increased risk of developing cerebrovascular pathology. In the main group, there was a statistically significant decrease in the duration of the first remission and an increase in the disease progression index. In addition, other diseases and syndromes were identified in the main group that, in combination with CVD in patients with MS, could lead to a worsening of the course of MS. These included arterial hypertension, diabetes mellitus, obesity, dyslipidemia, chronic venous insufficiency, and regular use of proton pump inhibitors. CONCLUSION: Comorbid vascular pathology can affect the severity of MS from the very beginning of the disease. It can lead to a shorter duration of the first remission and a higher disease progression index, increasing the degree of disability. The combination of autoimmune-inflammatory, demyelinating, and vascular processes can worsen the prognosis for MS.

[Long-term efficacy and safety of divozilimab during 2-year treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-4/MIRANTIBUS]. / Effektivnost' i bezopasnost' dvukhletnei terapii divozilimabom u patsientov s rasseyannym sklerozom v ramkakh randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo klinicheskogo issledovaniya BCD-132-4/MIRANTIBUS.

OBJECTIVE: To evaluate the efficacy and safety of the anti-CD20 monoclonal antibody divozilimab (DIV) used as an intravenous infusion at a dose of 500 mg every 24 weeks during 100 weeks for the treatment of patients with multiple sclerosis (MS), including relapsing-remitting multiple sclerosis (RRMS) and secondary progressive MS (SPMS) with relapses. MATERIAL AND METHODS: The multicenter, randomized, double-blind and double-masked phase III clinical trial (CT) BCD-132-4/MIRANTIBUS (NCT05385744) included 338 adult patients with MS distributed in a 1:1 ratio into two groups: DIV 500 mg and teriflunomide (TRF) 14 mg. After screening, subjects were included in the main CT period, which consisted of two cycles of therapy over 48 weeks, then entered an additional period from weeks 49 to 100, which included three cycles of therapy. The efficacy was assessed based on the results of brain MRI and registration of data on relapses. RESULTS: 308 subjects completed 5 therapy cycles according to the study protocol. An analysis of the effectiveness of DIV therapy over 2 years showed a persistent suppression of MRI and clinical activity of the disease in comparison with TRF, which was confirmed by all the studied MRI indicators (including CUA; total number of gadolinium-enhancing (GdE) lesions on T1-weighted scans ; number of new or enlarged lesions on T2-weighted scans; lesions volume change on T2-weighted scans; change in the volume of hypointense lesions on T1-weighted scans). The use of DIV was associated with a statistically significant decrease in ARR compared to TRF (p=0.0001). The ARR in the DIV group was 0.057, in the TRF group - 0.164 with 95% confidential interval for the frequency ratio [0.202; 0.593]. The incidence of GdE lesions on T1-weighted scans in the DIV group was significantly lower than in the TRF group. The average number of such lesions was 0.0±0.08 and 1.0±4.46 in the DIV and TRF groups, respectively (p<0.0001). Progression of EDSS was detected in 18 (10.7%) and 36 (21.3%) patients in the DIV and TRF groups, respectively (p=0.0075). The proportion of patients with relapses was 11.2% (n=19) in the DIV group and 23.1% (n=39) in the TRF group (p=0.0039). In the subpopulation of patients with SPMS, no cases of increase in EDSS were detected, and not a single case of exacerbation was recorded over 2 years of using DIV. Also, DIV has shown a favorable safety profile. Among the adverse reactions (AR), infusion reactions and laboratory abnormalities, such as a decrease in the number of leukocytes, neutrophils, and lymphocytes, were most often recorded. Identified AR were expected, had mild to moderate severity, and resolved without any negative consequences. CONCLUSION: The results of the BCD-132-4/MIRANTIBUS CT indicate a high sustained efficacy and safety of long-term use of DIV in comparison with TRF during 2 years of therapy.

[The effectiveness of tele-rehabilitation for patients with multiple sclerosis during the COVID-19 pandemic in 2020-2021 was evaluated in this study]. / Effektivnost' telereabilitatsii patsientov s rasseyannym sklerozom v usloviyakh pandemii koronavirusnoi infektsii v 2020­2021 gg.

OBJECTIVE: To evaluate the effectiveness of telerehabilitation (TELEREBT) of patients with multiple sclerosis (MS) in the context of the coronavirus pandemic 2020-2021. MATERIAL AND METHODS: The study included 37 patients with MS who underwent a course of teleRBT. The course included 10 classes of 60 minutes for 10 days with a two-day break. Various questionnaires and scales were used to assess the effectiveness, as well as an assessment of the neurological status. RESULTS: 19 patients refused to participate in the program. The level of disability on the EDSS scale decreased from 4.86±1.19 at the initial level to 4.73±1.12 after the course of teleRBT, while no statistically significant changes were found. CONCLUSION: TeleRPT in patients can be an effective way to correct existing disorders. Further research is required to establish the effectiveness of teleRBT.

[Clinical features and modern diagnostic criteria of the disease associated with myelin oligodendrocyte glycoprotein antibody disease]. / Klinicheskie osobennosti i sovremennye diagnosticheskie kriterii zabolevaniya, assotsiirovannogo s antitelami k glikoproteinu oligodendrotsitarnogo mielina.

Demyelinating disease of the central nervous system associated with antibodies to myelin oligodendrocyte glycoprotein (MOGAD) has been proposed to be distinguished from neuromyelitis optica spectrum disorders (NMOSD) into a separate nosological form. The basis for the recognition of nosological independence was the presence of clinical features of this disease and the detection of a specific biomarker in the blood serum of patients - IgG class antibodies to MOG. The article summarizes the current data on the clinical and radiological phenotypes of MOGAD in children and adults and the features of the course of the disease. The requirements for the laboratory diagnosis of the disease and diagnostic criteria for MOGAD proposed by an international group of experts in 2023 are given.

[Multiple sclerosis and melanoma]. / Rasseyannyi skleroz i melanoma.

Multiple sclerosis (MS) is a chronic autoimmune progressive demyelinating disease of the central nervous system, mainly in young people. The clinical picture of MS has a variety of neurological symptoms, which manifests itself during periods of exacerbation or progression and stabilizes at the moments of remission. The widespread introduction of new drugs with immunosuppressive and immunomodulatory mechanisms of action has led to the development of special risk management plans for monitoring patients during therapy and preventing adverse events and new comorbid conditions. This article presents a review of the literature and a case report on the combination of MS and melanoma in patients. Melanoma can rarely develop in patients treated with DMD, so it is necessary to introduce such a specialist in dermatology and venereology into a multidisciplinary team.

[The development of multiple sclerosis over the age of 50]. / Razvitie rasseyannogo skleroza u lits starshe 50 let.

Multiple sclerosis (MS) is a common neurological disease among young people of working age, which tends to increase the number of cases registered in the world and in the Russian Federation. However, with improved diagnostics and the emergence of new drugs that change the course of MS (disease-modifying therapy), people's life expectancy increases and the percentage of patients in the older age group increases as well. In this article, we consider the possibility of developing MS among people over 50 years of age, features of the course, diagnosis and treatment.

[Assessment of the efficacy and safety of alemtuzumab in patients with highly active relapsing-remitting multiple sclerosis in Russian population]. / Otsenka effektivnosti i bezopasnosti alemtuzumaba u patsientov s vysokoaktivnym techeniem rasseyannogo skleroza v rossiiskoi populyatsii.

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.

[Combination of post-infectious optic neuritis and Guillain-Barré syndrome]. / Sochetanie postinfektsionnogo nevrita zritel'nykh nervov i sindroma Giiena­Barre.

The coexistence of optic neuritis and Guillain-Barré syndrome is a rare combination of neurological diseases. The trigger of an autoimmune inflammatory process is often a respiratory mycoplasma infection. Ignorance of such combination can lead to diagnostic and therapy mistakes. This article describes the case of a rare combination of overlapping optic neuritis and Guillain-Barré syndrome, associated with Mycoplasma pneumoniae and provides the short literature review. Further studies are required to identify common pathogenetic mechanisms of combined inflammatory lesions of the optic nerves and peripheral nervous system.

[DNA Methylation Profile of CD14+ Monocytes Changes in Primary Progressive Multiple Sclerosis].

Multiple sclerosis (MS) is a chronic autoimmune inflammatory and neurodegenerative disease of the central nervous system, which is characterized by significant clinical heterogeneity. Primary progressive MS (PPMS) develops in 10-15% of patients. Unlike the most common relapsing-remitting form of MS, PPMS involves steady progress of neurodegeneration and, as a consequence, a persistent gradual increase in neurological symptoms. The peculiarities of epigenetic regulation of gene expression may be one of the reasons for the differences in the pathogenesis of the two MS forms. DNA methylation is one of the key epigenetic mechanisms, which remains almost unexplored in different cell populations of PPMS patients. The goal of this work was to identify differential methylation profiles of the CpG sites in the CD14+ monocyte DNA, which characterize PPMS. A genome-wide analysis of DNA methylation in PPMS patients and healthy individuals has identified 169 differentially methylated positions (DMPs), 90.5% of which were hypermethylated in PPMS patients. More than half of all DMPs are located in/near known genes and within CpG islands and their neighboring regions, which indicates their high functional significance. We have found six differentially methylated regions (DMRs) in the OR2L13, CAT, LCLAT1, HOXA5, RNF39, and CRTAC1 genes involved in inflammation and neurodegeneration, which indicates active epigenetic regulation of their expression.

[New neuroimaging methods in assessing the activity of neuroinflammation in multiple sclerosis]. / Novye metody neirovizualizatsii otsenki aktivnosti neirovospaleniya pri rasseyannom skleroze.

The review presents current data on the use of positron emission tomography and single-photon emission computed tomography in multiple sclerosis (MS) to assess the activity of the pathological process, including neuroinflammation, demyelination, activation of microglia, neurodegeneration and local blood flow disorders. These methodologies are a new approach for studying the mechanisms of action and evaluating the clinical effect of disease modifying therapy of MS, especially those capable of penetrating into brain tissue. Among them, the most attention is attracted by cladribine tablets acting on the mechanism of immune reconstitution therapy, most likely with the modulation of immune reactions directly in the brain tissue.

[Efficacy and safety of antiCD20 monoclonal antibody divozilimab during 48-week treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-4/MIRANTIBUS]. / Effektivnost' i bezopasnost' 48 nedel'nogo primeneniya monoklonal'nogo antitela protiv CD20 divozilimaba u patsientov s rasseyannym sklerozom: rezul'taty randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo klinicheskogo issledovaniya BCD-132-4/MIRANTIBUS.

OBJECTIVE: To evaluate the efficacy and safety of the anti-CD20 monoclonal antibody divozilimab (DIV) used as an intravenous infusion at a dose of 500 mg for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS) in comparison with the teriflunomide (TRF). The study of the efficacy and safety of the use of the drug DIV was carried out for 48 weeks of therapy. MATERIAL AND METHODS: The multicenter, randomized, double-blind and double-masked phase III clinical trial (CT) BCD-132-4/MIRANTIBUS included 338 adult patients with RRMS distributed in a 1:1 ratio into two groups: DIV 500 mg and TRF 14 mg. After screening, subjects were included in the main CT period, which consisted of two cycles of therapy over 48 weeks. The primary end point was «Mean annualized relapse rate 48 weeks after the last patient is randomized in the study¼. RESULTS: 321 subjects completed 48 weeks of therapy according to the study protocol. The analysis of the of efficacy data for the primary endpoint successively proved the hypothesis of superiority of the test drug DIV at a dose of 500 mg over the reference drug TRF. A rapid suppression of acute disease activity according to the brain MRI and clinical manifestations of the disease was shown after the first infusion of DIV in patients with RRMS. Thus, after 48 weeks of therapy in patients treated with DIV, there were no T1 gadolinium-enhancing lesions, while in the TRF group such lesions were observed in 20.7% (35/169) of subjects. Evaluation of the CUA per scan showed that the mean values for the estimated period were statistically significantly lower in the DIV drug group compared to the TRF group: the ratio of the adjusted per scan rates (DIV/TRF) was 0.125 [95% CI: 0.089; 0.177]. Over the 48 weeks of therapy, the proportion of subjects with relapses was 9.5% (n=16/169) in the DIV group and 19.5% (33/169) in the TRF group (p=0.0086). DIV has shown a favorable safety profile. Among the adverse reactions (AR), infusion reactions and deviations of laboratory data, such as a decrease in the number of leukocytes, neutrophils, and lymphocytes, were most often recorded. Identified AR were expected, had mild to moderate severity, and resolved without any negative consequences. CONCLUSION: The results of the clinical study indicate the high efficacy and safety of DIV in comparison with TRF.

[A comparison of DNA methylation profiles of blood mononuclear cells in patients with multiple sclerosis in remission and relapse]. / Sravnenie profilei metilirovaniya DNK mononuklearnykh kletok krovi bol'nykh rasseyannym sklerozom v stadiyakh remissii i obostreniya.

OBJECTIVE: To study the whole-genome DNA methylation profiles of peripheral blood mononuclear blood cells (PBMCs) of patients with relapsing-remitting multiple sclerosis (RRMS) in remission and relapse in order to assess the contribution of this epigenetic mechanism of gene expression regulation to the activity of the pathological process. MATERIAL AND METHODS: Eight patients with RRMS in remission and 6 patients in relapse were included in the study. Methylation levels of DNA CpG sites in PBMCs were analyzed using Infinium HumanMethylation450 BeadChip DNA microarrays. RESULTS: Seven differentially methylated positions (DMPs) were identified, of which 3 were hypermethylated (cg02981003, cg18486102, cg19533582) and 4 were hypomethylated (cg16814680, cg1964802, cg18584440, cg08291996) during RRMS relapse. Five DMPs are located in protein-coding genes (GPR123, FAIM2, BTNL2, ZNF8, ASAP2), one in microRNA gene (MIR548N), and one in an intergenic region. For all identified DMPs, we observed a change in DNA methylation levels of more than 20% (range 20.2-57.5%). Hierarchical clustering of DNA samples on the heatmap shows their clear aggregation into separate clusters corresponding to RRMS patients in the stages of relapse and remission. CONCLUSION: For the first time it was shown that during relapse and remission of RRMS there are differences in the DNA methylation profile that allow discrimination between these clinical stages. These data indicate the involvement of the epigenetic mechanism of DNA methylation in the activation of the pathological process in RRMS.

[The influence of fluoxetine on neuroimmune interaction in multiple sclerosis]. / Vliyanie fluoksetina na neiroimmunnoe vzaimodeistvie pri rasseyannom skleroze.

OBJECTIVE: To study the effect of fluoxetine on Th17- and Th1-immune response, which plays an important role in the pathogenesis of multiple sclerosis (MS). MATERIAL AND METHODS: Ten patients with relapsing-remitting MS and ten healthy subjects were examined. The functions of Th17- and Th1-immune responses were assessed by the production of cytokines interleukin-17 (IL-17) and interferon-gamma (IFN-γ) by CD4+ T cells stimulated with macrophages or microbeads coated with anti-CD3 and anti-CD28-antibodies. To assess the effect of fluoxetine on the macrophages-induced Th17- and Th1-immune response, macrophages were pre-incubated in the presence of fluoxetine and co-cultured with autologous CD4+ T-cells. In the case of stimulation of CD4+ T-cells with anti-CD3/CD28-microbeads, fluoxetine was added directly to the T-helper cells before adding of microbeads. In addition, we evaluated the effect of fluoxetine on the production of the factors of differentiation of Th17-cells cytokines IL-6 and IL-1ß by macrophages. The levels of cytokines in the cell culture supernatants were measured by ELISA. RESULTS: The production of IL-17 and IFN-γ by CD4+ T-cells stimulated with macrophages or anti-CD3/CD28-microbeads was comparable between the groups. Fluoxetine suppressed the production of IL-17 and IFN-γ by anti-CD/CD28-stimulated CD4+ T-cells in both groups. Fluoxetine also suppressed the production of IL-6 and IL-1ß by macrophages as well as their ability to induce IL-17 and IFN-γ production by CD4+ T-cells in both groups. CONCLUSIONS: Fluoxetine may have an anti-inflammatory effect in MS that could be mediated by suppression of Th17- and Th1-cells or macrophage-induced Th17- and Th1-immune response.

[Knee range of motion as a marker of the effectiveness of medical intervention in multiple sclerosis]. / Diapazon dvizheniya v kolennom sustave kak marker effektivnosti meditsinskogo vmeshatel'stva pri rasseyannom skleroze.

OBJECTIVE: To measure the knee range of motion (ROM) in the sagittal plane by video analysis in patients with multiple sclerosis (MS) after a course of medical rehabilitation and determine the minimal clinically important differences (MCID). MATERIAL AND METHODS: We examined 45 patients (37 women, 8 men) with relapsing-remitting (n=38) and secondary-progressive MS before and after a course of medical rehabilitation. Gait parameters were recorded on video analysis system Physiomed Smart («Physiomed¼, Germany, the Davis protocol). RESULTS: The course of complex medical rehabilitation contributes to an increase knee ROM in MS patients in a wide range of disability (EDSS <6.5 points). MCID is estimated as 7.14° in mild (EDSS ≤4.0) and as 7.67° in moderate (EDSS=4.5-5.5) gait impairment. CONCLUSION: The results will assist clinicians and researchers in interpreting the significance of observed kinematic changes in the knee joint in MS patients after medical intervention.