[A case of COVID-associated encephalopathy in a patient with multiple sclerosis]. / Klinicheskii sluchai COVID-assotsiirovannoi entsefalopatii u patsienta s rasseyannym sklerozom.

A case of acute encephalopathy manifested with impaired consciousness, hemichorrhea, speech and cognitive impairment in a female patient with COVID-19 and multiple sclerosis is presented. In the literature, there are isolated reports of such a combination of diseases, and therefore difficulties arise in carrying out differential diagnosis and prescribing therapy. Given the limited knowledge about the long-term consequences of COVID-19, systematic analysis of such cases and follow-up of such patients is necessary.

[A clinical case of multiple sclerosis with an episode of schizophrenia-like syndrome]. / Rasseyannyi skleroz s epizodom shizofrenopodobnogo sindroma.

The article presents a clinical observation of a schizophrenia-like disorder in a patient with multiple sclerosis (MS). The patient had highly active MS with a relapsing course, the diagnosis was made based on the McDonald 2017 criteria. During the course of a demyelinating disease of the nervous system, the patient developed an episode of psychotic disorders with symptoms of mutism, hallucinations, delusions and impaired thinking, which was quickly stopped in stationary conditions. This case is of particular interest to neurologists and psychiatrists, since psychotic disorders occur in MS patients and cause difficulties in diagnosis and treatment.

[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.

[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.

[Efficacy and safety of sampeginterferon ß-1a in the treatment of relapsing remitting multiple sclerosis: results of 52 weeks of therapy in a randomized, double-blind clinical trial]. / Effektivnost' i bezopasnost' sampeginterferona ß-1a dlya lecheniya remittiruyushchego rasseyannogo skleroza: rezul'taty 52-nedel'nogo randomizirovannogo dvoinogo slepogo klinicheskogo issledovaniya.

OBJECTIVE: To evaluate the efficacy and safety of samPEG-IFN-ß1a 180 µg and 240 µg administered once every 2 weeks for the treatment of relapsing remitting multiple sclerosis (RRMS) compared to placebo and low dose interferon beta-1a (LIB) 30 µg administered once weekly. The primary endpoint after 52 weeks of therapy was the time to first relapse, the hypotheses of non-inferiority and superiority to LIB were tested. MATERIAL AND METHODS: This international, multicenter, double blind, comparative, placebo-controlled clinical study enrolled 399 patients with the diagnosis of RRMS, randomized in 4 groups: samPEG-IFN-ß1a180 µg (n=114), samPEG-IFN-ß1a 240 µg (n=114), LIB (n=114) and placebo (n=57). Placebo group patients participated in the study for 20 weeks. After 52 weeks of therapy and 4 weeks of follow-up, LIB group patients completed their participation in the study, patients from PEG-IFN-ß1a groups continued to receive therapy until week 100 inclusive. The article presents the results of an analysis conducted after the end of 52 weeks of a double-blind, comparative, randomized, placebo-controlled clinical trial. RESULTS: Final analysis of the efficacy and safety was performed after 52 weeks of study. Main statistical hypothesis testing proved that both doses of samPEG-IFN-ß1a were equally effective when compared to LIB by the primary endpoint - «Time to first relapse¼. Due to detection of statistically significant differences in the primary endpoint between the study drug and the reference drug, indicating a greater efficacy of the study drug, an additional testing was carried out and the hypothesis of superiority of samPEG-IFN-ß1a at a dose of 240 µg over the reference LIB was proved. Evaluation of the dynamics of certain key parameters of magnetic resonance imaging (MRI) of the brain and clinical outcomes demonstrated a positive effect of samPEG-IFN-ß1a therapy in the form of decreased activity of the demyelinating process in the brain and reduce the number of relapses. The proportion of patients without new T2 lesions after 52 weeks was 87.6% and 90.4% in 180 µg and 240 µg samPEG-IFN-ß1a groups, versus 72.6% in the LIB group (p=0.0199 and p=0.0033). No progression of multiple sclerosis was shown based on EDSS scale evaluation. During the study, the most common adverse reactions were flu-like symptoms and injection site reactions. CONCLUSION: The new drug samPEG-IFN-ß1a is an effective and safe agent for relapsing remitting multiple sclerosis treatment, while having an advantage over other low-dose interferons in the form of reduced frequency of intramuscular injections.

[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.

[The role of glutamate in the pathogenesis of multiple sclerosis]. / Rol' glutamata v patogeneze rasseiannogo skleroza.

The results of recent studies indicate that the hyperactivation of the glutamatergic system plays an important role in the pathophysiology of multiple sclerosis (MS). In addition to the well-known direct toxic effect of the excessive extracellular level of the glutamate neurotransmitter on neurons, additional mechanisms of glutamate-induced cell damage have been described in the literature, including effects on oligodendrocytes, astrocytes, endothelial cells and immune cells. The study of these toxic effects will reveal the possible link between various pathological hallmarks of MS, such as axonal damage, oligodendrocyte death, demyelination, neurodegeneration, autoimmune reactions and dysfunction of blood-brain barrier. Understanding the mechanisms underlying the glutamate toxicity will contribute to the development of new therapeutic approaches for the diagnosis and treatment of patients with MS. This review focuses on the mechanisms that lead to an increase in the concentration of neurotransmitter glutamate and excitotoxicity in the context of the pathogenesis of this disease. Also the authors present the data on existing and currently developed medicines and therapeutic approaches to regulate the activity of the glutamatergic system.

[The new pegylated interferon beta-1a (sampeginterferon beta-1a, BCD-054) in the treatment of remitting multiple sclerosis]. / Novyi pegilirovannyi interferon beta-1a (sampéginterferon beta-1a, BCD-054) v terapii remittiruiushchego rasseiannogo skleroza.

AIM: To evaluate the efficacy and safety of BCD 054 180 µg and 240 µg administered once every 2 weeks for the treatment of remitting multiple sclerosis compared to placebo and low dose interferon beta-1a (LIB) 30 µg administered once weekly. Results of a 20 week blinded interim analysis from a double blind, comparative, randomised, placebo-controlled clinical study are included. MATERIAL AND METHODS: This multinational, multicentre, double blind, comparative, placebo-controlled study enrolled 399 patients with the diagnosis of remitting multiple sclerosis: 114 patients in the sampeginterferon beta 1a and LIB groups each and 57 patients in the placebo group. To ensure the objectivity of data, the study protocol includes a blinded interim analysis to demonstrate the superiority of BCD 054 over placebo based on the number of combined unique active lesions (CUA) on MRI scans after 20 weeks of treatment. RESULTS AND CONCLUSION: An integrated analysis of the efficacy, safety, pharmacokinetics, and pharmacodynamics was performed after 20 weeks of study. Mean CUA per scan was lower in the active treatment groups compared to placebo: 0,986±2,046, 0,619±1,055, 0,665±1,165, 1,673±2,376 (groups 1, 2, 3 and placebo group, respectively). The data for CUA per scan demonstrated the superiority of both BCD 054 180 µg and 240 µg over placebo. Patients receiving active treatment had fewer new and/or enlarging lesions after 20 weeks of treatment. The proportion of patients without new T2-weighted lesions was 74,3%, 86,7%, and 78,1% in groups 1, 2, and 3 compared to 64,9% in the placebo group. Manifestations of flu-like syndrome that is expected for interferon treatment were observed with the same incidence in all the active treatment groups. Its severity, duration or the need for symptomatic treatment did not appear to depend on the type of interferon used.

[The efficacy and safety of siponimod in the Russian population of patients with secondary progressive multiple sclerosis]. / Éffektivnost' i bezopasnost' siponimoda u patsientov s vtorichno-progressiruiushchim rasseiannym sklerozom v rossiiskoi populiatsii.

AIM: To study the efficacy and safety of siponimod in patients with secondary progressive multiple sclerosis (SPMS) in the Russian population of the EXPAND study. MATERIAL AND METHODS: Ninety-four patients with SPMS from Russia were included in the analysis. Sixty-three patients received siponimod and 31 patients received placebo. The primary endpoint of the study was time to 3-month confirmed disability progression (3m-CDP) events, other clinical and radiological endpoints were also evaluated. RESULTS: The siponimod group showed a 54% reduction in the risk of 3m-CDP compared with the placebo group (p=0.0334). Secondary endpoints also showed the advantage of the drug over placebo. In the siponimod group, mild adverse events associated with impaired liver function, as well as arterial hypertension, were more common. No patient left the study due to an adverse event. CONCLUSION: The use of siponimod in patients with SPMS in the Russian population reduced the risk of disability progression. Siponimod showed a favorable safety profile.

[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 .

[Provision of alemtuzumab safety is one of the main components of pharmacovigilance]. / Obespechenie bezopasnosti terapii alemtuzumabom - odna iz glavnykh sostavliaiushchikh farmakonadzora.

Modern multiple sclerosis therapy with disease-modifying drugs is characterized by the risks of dangerous infectious complications. In the last 5 years, there have been several reports of severe, sometimes lethal, listeriosis infection in patients treated with alemtuzumab. This article presents a clinical case of lethal listeriosis meningoencephalitis, which developed within 7 days after the completion of the first cycle of alemtuzumab therapy. In January 2018, a meeting of the expert Council was held, at which the clinical recommendations published in 2017 were revised and updated.

[A case-report of Balo concentric sclerosis transformed into definite multiple sclerosis]. / Klinicheskii sluchai kontsentricheskogo skleroza Balo, transformirovavshegosia v dostovernyi rasseiannyi skleroz.

The authors present the results of an 8-year retrospective-prospective follow-up of a patient with Balo concentric sclerosis. The disease meets the diagnostic criteria of remitting-relapsing multiple sclerosis.

[Clinical and molecular genetic analysis of a case of familial multiple sclerosis in the Republic of Bashkortostan]. / Klinicheskii i molekuliarno-geneticheskii analiz sluchaia semeinogo rasseiannogo skleroza v Respublike Bashkortostan.

AIM: To investigate clinical manifestations of multiple sclerosis (MS) and the genetic makeup of six affected members of one family. MATERIAL AND METHODS: Six members of the family of Russian ethnic origin were examined. Pedigree analysis and genotyping of polymorphic markers of candidate genes for multiple sclerosis were performed. RESULTS AND CONCLUSION: The accumulation of alleles that were associated with autoimmune diseases according to the results of genome-wide association studies (rs1109670*C, rs3129934*T, rs9523762*G, rs1570538*T) was found in the family. The results confirm the contribution of several genetic variants to familial forms of MS.

[Primary progressive multiple sclerosis: current issues of timely diagnosis]. / Pervichno-progressiruiushchii rasseiannyi skleroz: sovremennoe sostoianie problemy svoevremennoi postanovki diagnoza.

This article presents a review of international data on primary progressive multiple sclerosis (PPMS) and an analysis of factors influencing timely diagnosis of PPMS in a number of regions of the Russian Federation.