[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.

[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.

[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.

[Efficacy and safety of divozilimab during 24-week treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-2]. / Effektivnost' i bezopasnost' 24 nedel' primeneniya divozilimaba sredi patsientov s rasseyannym sklerozom v ramkakh randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo klinicheskogo issledovaniya BCD-132-2.

OBJECTIVE: To find the optimal therapeutic dose of the anti-B cell mAb divozilimab (DIV) based on the efficacy and safety data of intravenous administration at a dose of 125 mg or 500 mg in patients with relapsing remitting multiple sclerosis (RRMS) compared to placebo (PBO) and teriflunomide (TRF). To study the efficacy and safety of DIV within 24 weeks of treatment. MATERIAL AND METHODS: A multicenter, randomized, double-blind and double-masked, placebo-controlled phase 2 clinical trial (CT) BCD-132-2 involved 271 adult patients with RRMS from 25 centres In Russia. Patients were randomly assigned (2:2:2:1) into 4 groups: TRF, DIV 125 mg, DIV 500 mg and PBO. After screening patients entered to the main period, which consisted of one cycle of therapy for 24 weeks. The primary endpoint was the total number of gadolinium-enhancing T1 lesions (Gd+) observed on brain MRI scans after 24 weeks (per scan - involves estimating the mean value of the score from all the MRI assessments performed for each participant in the study). RESULTS: 263 patients completed 24 weeks of treatment. Most of the patients in the DIV groups had no lesions on T1-weighted MRI after 24 weeks of treatment (94.44% on 125 mg and 93.06% on 500 mg). In the TRF and PBO groups the values were significantly lower: 68.06% and 56.36% respectively (both p<0.05). The proportions of relapse-free patients in the DIV groups were 93.06% and 97.22% (125 mg and 500 mg, respectively). As expected, DIV reduced the CD19+ B-cells. However, the repopulation rate of CD19+ B-cells in the 125 mg group was more pronounced (mainly due to the recovering pool of CD27-naive B-cells) compared to the 500 mg group. DIV showed a favorable safety profile at both doses. CONCLUSION: Thus, the assessment of 24 weeks treatment demonstrated that DIV is a highly effective, safe and convenient option for the treatment of RRMS patients, both naive and previously treated with disease modifying therapy. A dose of 500 mg is recommended for further efficacy and safety evaluation during phase 3 CT.

[Long-term Efficacy and Safety of Sampeginterferon-ß1a in the Treatment of Relapsing Remitting Multiple Sclerosis: a Randomized, Double-Blind Clinical Trial 104-Week Results]. / Dolgosrochnye dannye po effektivnosti i bezopasnosti preparata sampeginterferon-ß1a u patsientov s remittiruyushchim rasseyannym sklerozom: rezul'taty 104-nedel'nogo randomizirovannogo dvoinogo slepogo klinicheskogo issledovaniya.

OBJECTIVE: To assess the efficacy and safety of sampeginterferon-ß1a (samPEG-IFN-ß1a) 180 µg and 240 µg administered once every 2 weeks compared to placebo and low dose interferon beta-1a (LIB) 30 µg administered once weekly. MATERIAL AND METHODS: Patients with relapsing-remitting multiple sclerosis aged 18-60 years, with Expanded Disability Status Scale score ≤5.5 were randomized at a ratio of 2:2:2:1 to the following groups: samPEG-IFN-ß1a 180 µg, samPEG-IFN-ß1a 240 µg, LIB, placebo. After 20 weeks, the placebo group completed the study. After week 52, the final analysis was performed, which included the primary endpoint analysis, the LIB group patients completed their participation in the study. The patients in samPEG-IFN-ß1a groups continued to receive therapy with samPEG-IFN-ß1a 240 µg until week 100 inclusive. The results of the final analysis after 52 weeks have been previously published. The current article presents a long-term efficacy and safety of samPEG-IFN-ß1a after 104 weeks of the trial. RESULTS: The annualized relapse rate over the second year was 0.16 in the samPEG-IFN-ß1a 180 µg group and 0.09 in the samPEG-IFN-ß1a 240 µg group. By week 104, the proportion of relapse-free patients was 77.0% (87/113) and 83.3% (95/114) in the samPEG-IFN-ß1a 180 µg and 240 µg groups, respectively. There were no negative dynamics of MRI markers, neurological deficit parameters and cognitive functions by scales and tests. The safety profile of samPEG-IFN-ß1a was consistent with the known safety profile of IFN-ß therapy. CONCLUSION: Treatment with samPEG-IFN-ß1a is an effective and safe first-line therapy for relapsing-remitting multiple sclerosis patients.

[Dance therapy in the rehabilitation of neurological diseases]. / Tantseval'no-dvigatel'naya terapiya v reabilitatsii nevrologicheskikh zabolevanii.

A literature review of clinical trials on the effectiveness of the use of dance movement therapy in patients with neurological diseases is presented. A systematic review and meta-analysis of the effectiveness of dance movement therapy on non-motor manifestations of Parkinson's disease is presented. Dance movement therapy was found to have a significant positive effect on cognitive impairment, but no effect on depression, fatigue, and apathy. The effectiveness of dance movement therapy in post-stroke rehabilitation is shown. The data of a systematic review are presented, which found that dance movement therapy is effective not only in the rehabilitation of Parkinson's disease and stroke, but also in the rehabilitation of patients with multiple sclerosis, Huntington's disease and the consequences of spinal cord injury.

[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.

[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.

Vaccination and Multiple Sclerosis - Current Situation.

Active immunization of patients with autoimmune diseases is a current challenge. Vaccination of patients with multiple sclerosis (MS) has been shown not to be associated with increased risk of exacerbation. A personalized approach to immunization of this group of patients is required, taking account of ongoing therapy and the nature of the course of illness. MS is not an absolute contraindication for vaccination against the new coronavirus infection. Vaccination can be with any of the currently authorized immunoformulations.

[Vaccination and multiple sclerosis at the present stage]. / Vaktsinatsiya i rasseyannyi skleroz na sovremennom etape.

Immunization of the patients with autoimmune diseases is rising a lot of concerns. It was previously demonstrated that vaccination in MS patients was not associated with an increased risk of exacerbations. A personalized approach is needed to define the immunization schedule. A decision should be made based on the course of the disease and the treatment used. Multiple sclerosis is not an absolute contraindication to vaccination. Any authorized vaccine can be used in MS patients.

[Possibilities of art therapy and color therapy in the rehabilitation of multiple sclerosis]. / Vozmozhnosti art-terapii i tsvetoterapii v reabilitatsii pri rasseyannom skleroze.

THE PURPOSE OF THE STUDY: To study the effectiveness of non-drug methods of prevention and rehabilitation of patients with various variants of multiple sclerosis (MS) in outpatient settings. MATERIAL AND METHODS: In a group of 35 patients with limited mobility with various variants of the course of MS, continuous art therapy was performed (art lectures, work with various art materials - markers, pastels, etc.). The average duration of the training cycle in the group was 6 months. Classes were held on an outpatient basis, and if it was impossible to attend classes - remotely. RESULTS: Positive results were obtained in double psychological testing. 68% of patients had decreased levels of depression and anxiety on the HADS scale, 34% of patients refused to take antidepressants. However, positive psychotherapeutic dynamics against the background of art therapy is not a reason to cancel the main basic treatment. CONCLUSION: Art therapy-art therapy and, as its division, color therapy (diagnosis of the condition and treatment of color) is a synthesis of medicine, art and psychology. In MS patients, the following color combinations are recommended when working with art materials:stimulating (red, orange, coral, yellow); soothing (green, blue, blue, purple). Negative colors are excluded - black, gray, dirty shades with a mixture of black or gray.

[Preliminary results of rehabilitation intervention for the correction of cognitive impairment in patients with multiple sclerosis]. / Predvaritel'nye rezul'taty reabilitatsionnoi interventsii dlya korrektsii kognitivnykh narushenii u bol'nykh rasseyannym sklerozom.

One of the leading symptoms in patients with multiple sclerosis (MS) is cognitive impairment. It often affects aspects of cognition such as learning ability, memory, processing speed, and attention. It has been proven that patients often complain of difficulties in multitasking and choosing the right words. These problems are often underestimated. Various studies show that regular physical activity, mainly aerobic exercise, can potentially improve cognitive function. Positive effects on concentration, memory, and multitasking were described. In March 2019, the Tyumen regional center of MS, together with the clinical Institute of the brain (Yekaterinburg), launched a clinical study of methods for rehabilitation of cognitive disorders in patients with MS. There was a statistically significant improvement in MOCA-test scores, according to SDMT and PASSAT data in the main group of MS patients. Despite a significant improvement in cognitive function, the self-assessment of mental function according to the MSQOL54-MN test in this group of patients did not change. Our preliminary results suggest that a comprehensive and well-controlled training program can improve cognitive abilities in MS patients even after a short course of treatment.

The Novel Coronavirus Infection (COVID-19) and Nervous System Involvement: Mechanisms of Neurological Disorders, Clinical Manifestations, and the Organization of Neurological Care.

The new coronavirus SARS-CoV-2 and the disease it causes COVID-19 involves not only respiratory system damage, but can also lead to disorders of the central and peripheral nervous system, as well as the muscular system. This article presents published data and our own observations on the course of neurological disorders in COVID-19 patients. There is a relationship between the severity of COVID-19 and the severity and frequency of neurological manifestations. Severe neurological disorders are mostly seen in severe cases of COVID-19 and include acute cerebrovascular accidents (aCVA), acute necrotizing encephalopathy, and Guillain-Barré syndrome. Factors potentially complicating the course of COVID-19 and increasing the development of neurological complications include arterial hypertension, diabetes mellitus, and chronic cardiac and respiratory system diseases. Questions of the possible effects of human coronaviruses on the course of chronic progressive neurological diseases are addressed using multiple sclerosis (MS) as an example. We discuss the management of patients with aCVA and MS depending on the risk of developing coronavirus infection.

[The use of music therapy in the treatment of adverse effects in patients with multiple sclerosis treated with alemtuzumab]. / Primenenie muzykal'noi terapii dlya korrektsii nezhelatel'nykh yavlenii pri terapii alemtuzumabom u bol'nykh rasseyannym sklerozom.

Alemtuzumab (Lemtrada) is a recombinant humanized IgG1 kappa monoclonal antibody against cell surface glycoprotein CD 52. It is authorized in more than 65 countries worldwide including the Russian Federation. This is one of the most effective drugs for the treatment of the aggressive form of multiple sclerosis. Its safety profile includes different infusion reactions. Current publication demonstrates our experience of using music therapy during alemtuzumab infusion and its role in the adverse reactions management.

[Novel coronavirus infection (COVID-19) and nervous system involvement: pathogenesis, clinical manifestations, organization of neurological care]. / Novaya koronavirusnaya infektsiya (COVID-19) i porazhenie nervnoi sistemy: mekhanizmy nevrologicheskikh rasstroistv, klinicheskie proyavleniya, organizatsiya nevrologicheskoi pomoshchi.

Novel coronavirus SARS-CoV-2 and COVID-19, besides affecting the respiratory system, may lead to central and peripheral nervous system disorders and also cause muscular symptoms. The authors review the literature and own clinical case with respect to nervous system involvement in COVID-19 patients. There is a correlation between the severity of COVID-19 and the severity and frequency of neurologic complications. Severe neurologic symptoms are primarily observed in patients with severe COVID-19. Neurologic-associated symptoms may include stroke, acute necrotizing encephalopathy, and Guillen-Barre syndrome. Diseases that potentially aggravate COVID-19 and increase the risk of neurologic complications include arterial hypertension, diabetes, chronic diseases of the heart and respiratory system. The probable impact of human coronaviruses on chronic and progressive diseases of the nervous system with particular respect to multiple sclerosis is reviewed. A triage plan for stroke and MS patients during the COVID-19 pandemic, depending on the risk of coronavirus infection, is presented.

[New directions of immunocorrection in multiple sclerosis]. / Novye napravleniia immunokorrektsii pri rasseiannom skleroze.

Multiple sclerosis is a central nervous system disease with autoimmune and neurodegenerative mechanisms of development. This disease can lead to severe disability and neurological defects. Although its etiology and pathogenesis remain unclear, research data show that multiple sclerosis is a multifactorial disease, the development of which depends on environmental factors, as well as a genetic predisposition. The impact of these factors lead to the death of neural cells, accompanied by demyelination of nerves and neuronal dysfunction. Therapy of multiple sclerosis is based on the use of anti-inflammatory and immunomodulating substances, however, there are certain disadvantages associated with the constant use of these drugs and a possible change in dosage over time. This review discusses the pathogenesis of multiple sclerosis and the role of various subpopulations of immune cells in the development of diseases, as well as existing approaches to therapy. It is noted that immunoreconstitution therapy has advantages over immunomodulation and immunosuppression maintenance therapy for some patients. Thus, short courses of therapy provide more adequate treatment for patients and lower risks of adverse events associated with chronic immunosuppression. The review also discusses the data of clinical studies on the immunoreconstitution therapy drugs, such as alemtuzumab, ocrelizumab and cladribine. It is noted that nowadays the exact mechanisms underlying this type of therapy remain unclear. In this regard, further studies are needed to explain the therapeutic effects. It is assumed that patients with a high risk of multiple sclerosis progression are the optimal group of patients for the early use of selective immunoreconstitution therapy. Thus, immunoreconstitution therapy may be the treatment of choice for many patients with highle active multiple sclerosis.

[Updated recommendations of the Council of Experts on the use and safety of alemtuzumab (Lemtrada)]. / Obnovlennye rekomendatsii soveta ekspertov po primeneniyu i obespecheniyu bezopasnosti terapii preparatom alemtuzumab (Lemtrada).

Alemtuzumab (Lemtrada) is a recombinant humanized IgG1 kappa monoclonal antibody to the surface cell glycoprotein, a CD52 differentiation cluster. The drug is approved for use in more than 65 countries, including the Russian Federation. The drug is one of the most effective methods of treating patients with aggressive multiple sclerosis, but the risk management plan should be followed. The safety profile of the drug includes infusion-associated reactions, thyroid dysfunction, immune cytopenia, acute cardiovascular events, infections, and other autoimmune diseases. This publication provides updated practical recommendations for the use of the drug and ensuring the safety of patients treated with alemtuzumab.

[Clinical cases of multiple sclerosis in children with cerebral palsy]. / Klinicheskie sluchai rasseiannogo skleroza u detei s detskim tserebral'nym paralichom.

The careful differential diagnosis is very important in pediatric cases of multiple sclerosis (MS). It has special difficulties, if MS started in patients with residual neurological pathology. Two cases of development of MS in children with cerebral palsy (CP) are presented. The clinical features and diagnostic difficulties in such comorbid situations are discussed .

[Primary-progressive multiple sclerosis in Russia: a medical-sociological study involving patients and neurologists]. / Pervichno-progressiruiushchii rasseiannyi skleroz v Rossii: mediko-sotsiologicheskoe issledovanie s uchastiem patsientov i nevrologov.

The main results of a medical-sociological study aimed at the evaluation of the level of satisfaction with treatment in patients with primary progressive multiple sclerosis (PPMS) are presented. The survey was conducted in 19 regions of the Russian Federation and involved 437 patients with confirmed diagnosis of PPMS and 80 neurologists specialized in multiple sclerosis. The research was carried out by the All-Russian Public Organization of Disabled People with Multiple Sclerosis with the participation of the Russian Committee for Treatment and Research in Multiple Sclerosis. This is the first medical-sociological study in the Russian Federation involving patients with PPMS and neurologists. The study revealed typical medical and social problems patients with PPMS faced. A significant decrease in quality-of-life of PPMS patients was shown.

[The risk of ischemic stroke in patients with multiple sclerosis]. / Risk razvitiia ishemicheskogo insul'ta u bol'nykh rasseiannym sklerozom.

A brief literature review on risk factors of ischemic stroke in patients with multiple sclerosis (MS) is presented. A case of ischemic stroke in a MS patient was demonstrated, and risk factors were identified.