In Russian Federation in 2022, the Expert Council adopted the main definitions and terms for neuromyelitis optica spectrum disorders (NMOSD) and proposed a treatment algorithm for patients with NMOSD with antibodies to aquaporin-4 (AQP4-IgG). The publication is intended to present the results of the work of the Russian Expert Council in September 2024. The experts agreed on clarifications of previously published terminology, new definitions, current issues in the therapy of NMOSD, proposed profiles of patients with NMOSD for ravulizumab and a monitoring plan during treatment with this drug, and agreed on an updated algorithm for prescribing medications that prevent exacerbations in patients with NMOSD with AQP4-IgG aged 18 years and older.

Aim. To describe best practices in using human normal immunoglobulin in patients with immune-mediated neurological disorders according to the data of one clinical center. Materials and methods. From 2016 to 2021, 20 patients with various autoimmune disorders of the peripheral and central nervous system were treated with human normal immunoglobulin at the Neurology Unit No.1 of Pavlov First Saint Petersburg State Medical University. Treatment efficacy was assessed by changes in the neurological examination data according to specialized scales for specific diseases or clinical manifestations (INCAT, QMGS, MoCA, EDSS). Safety of the therapy was assessed considering the instructions to the drug. Results. In the vast majority of patients, treatment allowed to stabilize the course of the disease or was accompanied by pronounced regression. Conclusion. The considered clinical cases of the use of human normal immunoglobulin preparations demonstrate the possibility of their use in the treatment of a number of autoimmune neurological diseases for unregistered indications.

Functional dizziness (FD) is one of the most common causes of chronic dizziness for which there is no effective drug therapy, highlighting the importance of searching for new treatment technologies. Objective: to evaluate the efficacy and safety of Vespireit® (INN buspirone) prolonged-release tablets 15 mg2 (JSC “Valenta Pharm”, Russia) compared with placebo in the treatment of patients with autonomic dysfunction syndrome accompanied by FD. Material and methods . The clinical trial (CT) included a total of 268 patients with autonomic dysfunction syndrome accompanied by FD and a DHI (The Dizziness Handicap Inventory) dizziness scale score of 36 to 52 inclusive, who were randomly divided into 2 groups and treated in a double-blind fashion. 135 patients (Group 1) received Vespireit® prolonged-release tablets 15 mg at a dose of 15 mg (1 tablet) once daily for 28 days. 133 patients (Group 2) received placebo at the same dosage regimen. Treatment was given against a background of vestibular gymnastic exercises. The primary outcome of the clinical trial was assessment of patient response rate (proportion of responders), i.e., a ≥50% reduction in total DHI for dizziness score at Visit 5 (day 28±1) compared with baseline (Visit 1, day 1). Secondary efficacy measures included assessment of: 1) treatment response rates (≥50% reduction in DHI total score compared to Visit 1) at Visits 2, 3, and 4; 2) DHI total score at Visits 2, 3, 4, and 5; 3) changes in DHI total score at Visits 2, 3, 4, and 5 compared to Visit 1; 4) proportion of patients with a 30% or greater reduction in DHI scale dizziness compared with baseline at Visit 2, 3, 4, and 5; 5) time elapsed until total DHI score decreased by ≥50% compared to baseline; 6) time elapsed until total DHI score decreased by ≥30% compared to baseline; 7) changes in Digital Rating Scale (DRS) score from Visit 1 to Visit 2, 3, 4, 5; 8) scores on the DRS at Visits 2, 3, 4, 5; 9) proportion of patients with different response to treatment on the Likert scale at Visits 2, 3, 4, and 5. Additional secondary criteria of efficacy were also assessed: total Hamilton Depression Rating Scale (HDRS) score at Visits 4 and 5; change in total Hamilton scale score at Visits 4 and 5 compared to Visit 1. The safety criterion assessed in the clinical trial was monitoring of adverse events (AEs), clinically significant deviations in vital signs, laboratory parameters, and ECG parameters. Results. The proportion of responders with a ≥50% reduction in DHI total score at Visit 5 (Day 28±1) compared to baseline (Visit 1, Day 1) was 68.7% (n=92) in Group 1, which was 52.9% more than in Group 2 – 15.8% (n=21) (p<0.0001). Evaluation of all secondary (including additional) efficacy criteria also showed a statistically significant benefit of therapy in Group 1 compared to Group 2 (p<0.0001). A total of 61 AEs were recorded in 46 (17.2%) patients: 30 AEs in 21 (15.6%) patients in Group 1 and 31 AEs in 25 (18.8%) patients in Group 2. There was no significant difference between treatment groups in the number of patients with AEs (p=0.5196). In both groups, there were no patients with AEs with severity ≥3, serious AEs (SAEs), SAEs with fatal outcome, or SAEs that led to discontinuation of study therapy. No clinically significant abnormalities were noted during assessment of vital signs, laboratory parameters, or ECG parameters Conclusion. The superiority of Vespireit® prolonged-release tablets (PR) 15 mg therapy over placebo in reducing FD in patients with autonomic dysfunction syndrome was confirmed. The drug demonstrated a favorable safety profile comparable to placebo.

An important component of the pathogenesis of neuromyelitis optica spectrum diseases (NMOSD) with antibodies to aquaporin-4 (AQP4-IgG) is a classical pathway of complement system (CS) activation with the implementation of mechanisms of complement-mediated cytotoxicity. Eculizumab is a humanized monoclonal antibody that suppresses the final stage of CS activation and has a high affinity for its C5 component. The most important components in the pathogenesis of NMOSD with AQP4-IgG, the role of CS, the results of clinical trials with the drug eculizumab and its place in the treatment of NMOSD are discussed.

Neuromyelitis optica spectrum disorders (NMOSD) are a group of inflammatory diseases of the central nervous system characterized by episodes of immune-mediated astrocytopathy, inflammatory demyelination and axonal damage, predominantly affecting the optic nerves and spinal cord. Currently, there are several unresolved issues that make it difficult to provide medical care to patients with NMOSD. The objective of this publication is to present the results of the work of the Russian experts panel, held in September 2022. The consensus council of experts adopted the main definitions and terms for NMOSD, proposed a therapeutic algorithm to prevent exacerbations in patients with NMOSD with serum IgG antibodies to aquaporin-4 (AQP4-IgG). The experts formulated profiles of patients with NMOSD to whom eculizumab may be recommended, and proposed a risk management plan during the treatment with this drug. The experts worked out the next steps, which are necessary for the improvement of medical care for these patients: development of unified electronic register of patients with NMOSD in the Russian Federation, development and approval of clinical guidelines.

Satralizumab is a monoclonal anti-IL6-anibody for patients with neuromyelitis optica or neuromyelitis optica spectrum disorder (NMOSD) seropositive for anti-AQP4-antibody. Satralizumab has been approved in 2021 in the Russian Federation for usage in adults and adolescents from 12 years and older in combination with basic therapy or in monotherapy. The efficacy and safety of satralizumab in comparison with placebo have been demonstrated in two international randomized clinical trials SakuraStar and SakuraSky, phase III. We present clinical experience with satralizumab gained in frames of the Compassionate Use Program that have been initiated in Russia for NMOSD patients. Here, we summarized the results of treatment with satralizumab of 16 patients (14 men and 2 women), aged 13-69 years. Duration of therapy was 9 to 41 week. The first experience of using satralizumab in the Russian Federation in the small group of patients does not yet allow us to draw conclusions about the efficacy due to the short follow-up period. It can be concluded that the safety profile of satralizumab is consistent with the results obtained in international clinical trials. The experience gained in the ongoing program allows us to conclude that satralizumab is a valuable and convenient therapeutical option for seropositive for anti-AQP4-antibodies patients with NMOSD.

Irreversible neurological deficit and disability in neuromyelitis optica spectrum disorders (NOSD) are formed as a result of exacerbations, which are often life-threatening. Timely diagnosis and treatment of exacerbations is a key task in the management of this category of patients. A unified structured approach to the diagnosis and treatment of NOSD exacerbations has not been developed. The purpose of this article is to analyze the scientific literature data on this issue in order to optimize the diagnostics and treatment of NOSD exacerbations in everyday clinical practice.

POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes) is a rare paraneoplastic disease associated with plasma cell dyscrasias, the pathogenesis of which is currently not fully understood. The diagnosis of POEMS syndrome is commonly confirmed after an extended period of time from the disease onset, since the syndrome is rare and can be mistaken for other neurological diseases, for instance, chronic inflammatory demyelinating polyneuropathy (CIDP). The article describes a clinical case of the disease in a young male patient with the onset of neurological disorders in the form of the CIDP clinical phenotype, refractory to first-line therapy, and further systemic clinical and laboratory comorbidities of POEMS syndrome. The necessary laboratory and radiological studies were performed to confirm the diagnosis. The diagnosis was established based on the presence of 2 major, 1 additional major and 4 minor criteria of POEMS syndrome in the patient. Then the patient was discharged for further observation of hematologists to initiate basic therapy of POEMS syndrome. Early detection of the POEMS syndrome "red flags" in patients with the CIDP allows for timely treatment initiation, prevention of further disease progression and the development of persistent disabling disorders. KEYWORDS: POEMS-syndrome, chronic inflammatory demyelinating polyneuropathy, paraprotein, monoclonal gammopathy of undetermined significance. FOR CITATION: Korotaeva V.V., Kushnir Ya.B., Kudyasheva O.V. et al. POEMS-syndrome with the disease onset in the form of сhronic dysimmune neuropathy. Russian Medical Inquiry. 2022;6(10):589–595 (in Russ.). DOI: 10.32364/2587-6821-2022-6-10-589-595.

Leukemia-associated myelitis is a rare but underestimated complication. It has a different etiology associated with both, the main disease and its treatment methods. It requires differential diagnosis with funicular myelosis, polyradiculoneuropathy, tumor and hemorrhagic formation, stroke, dysmetabolic manifestations, as well as with the consequences of treatment of the underlying disease using radiation, cytostatic, targeted therapy.It should also be differentiated from paraneoplastic myelopathy and progression of the underlying disease. However,with the help of neuroimaging methods, it can be detected more recently than a detailed clinical picture appears. A case report of myelopathy in a 31 year old patient with acute lymphoblastic leukemia is presented. Treatment of the underlying disease was carried out with the use of chemotherapy, radiation therapy, allogeneic hematopoietic stem cell transplantation and targeted therapy. The nature of the disease,i.e. recurrent course of acute lymphoblastic leukemia, the variety of treatment methods, and the absence of focal changes in neuroimaging in the zone that determines clinical manifestations, made it necessary to consider a wide range of possible etiological factors for the development of myelopathy. Myelopathy was confirmed by MRI 2.5 months after the debut of neurological symptoms, which corresponds to modern concepts and time criteria for visualization in neurooncology. The article presents the criteria for diagnosing myelopathy, a complication of acute lymphoblastic leukemia. It should also be differentiated from However, with the help of neuroimaging methods, it can be detected more recently than a detailed clinical picture appears.

Neuromyelitis optica spectrum disorders (NMOSDs) are autoimmune inflammatory disorders accompanied by central nervous system damage, widespread immunemediated demyelination, and axonal damage, involving mainly the optic nerves, spinal cord, and area postrema. The diagnostic capabilities, administration and routing of patients, and therapeutic approaches to this disease need to be improved. During several expert councils held in 2019–2021 in different regions of the Russian Federation, we discussed multiple issues related to various aspects of medical care for patients with NMOSDs. As a result, the experts developed further steps necessary to improve the medical care to these patients: to write and publish clinical guidelines for the diagnosis and treatment of NMOSDs; to consider the possibility of optimizing the NMOSDs diagnostic program including the aquaporin-4 antibodies (AQP4-IgG) testing; to evaluate the implementation of a set of measures aimed at including the corresponding laboratory investigations into the system of state guarantees (together with the institutions of the Ministry of Health of Russia), if there is clinical and economic feasibility; to include the issues of timely NMOSDs evaluation in educational programs initiated by the scientific medical community, in order to raise awareness of primary care neurologists in relation to the clinical and neuroimaging signs of probable NMOSDs; to assess the possibility of introducing routing schemes for patients with NMOSDs at the regional level; to work out a decision on the collection of NMOSDs epidemiological and clinical data in the Russian Federation.

Анализируются 200 пациентов с положительными тестами на скрытое левшество и исследованием когнитивных функций с применением авторского скринингового теста. Возраст больных — от 30 до 65 лет (в среднем 41,0 ± 5,3 года), из них мужчин — 116 (58,0 %), женщин — 84 (42,0 %). При использовании стандартного исследования неврологического статуса у них были установлены следующие неврологические коморбидные диагнозы: ишемический мозговой инсульт — у 22 больных (11,0 %), дискогенно-венозная люмбосакральная радикуломиелоишемия — у 74 (37,0 %), рассеянный склероз — у 16 (8,0 %), вегетососудистая дистония с гипоталамическими пароксизмами — у 74 (37,0 %), паркинсонизм — у 14 (7,0 %). Исследование тестов на скрытое левшество и состояние когнитивных функций в дополнение к стандартному изучению неврологического статуса значительно расширяет круг диагностических возможностей. Терапевтические и нейрореабилитационные мероприятия должны проводиться с учетом клинических симптомов и признаков всех коморбидных патологий и соблюдением правил хорошей клинической практики.

Анализируются 200 пациентов с положительными тестами на скрытое левшество и исследованием когнитивных функций с применением авторского скринингового теста. Возраст больных — от 30 до 65 лет (в среднем 41,0 ± 5,3 года), из них мужчин — 116 (58,0 %), женщин — 84 (42,0 %). При использовании стандартного исследования неврологического статуса у них были установлены следующие неврологические коморбидные диагнозы: ишемический мозговой инсульт — у 22 больных (11,0 %), дискогенно-венозная люмбосакральная радикуломиелоишемия — у 74 (37,0 %), рассеянный склероз — у 16 (8,0 %), вегетососудистая дистония с гипоталамическими пароксизмами — у 74 (37,0 %), паркинсонизм — у 14 (7,0 %). Исследование тестов на скрытое левшество и состояние когнитивных функций в дополнение к стандартному изучению неврологического статуса значительно расширяет круг диагностических возможностей. Терапевтические и нейрореабилитационные мероприятия должны проводиться с учетом клинических симптомов и признаков всех коморбидных патологий и соблюдением правил хорошей клинической практики.

Siponimod is a selective modulator of sphingosine-1-phosphate (S1P) receptors of types 1 and 5, registered in the Russian Federation for the treatment of patients with secondary progressive multiple sclerosis (SPMS), regardless of the presence or absence of exacerbations. The effectiveness of the drug in comparison with placebo was demonstrated in patients with SPMS in the international clinical trial EXPAND (phase III). This review devotes actual problems in the treatment of patients with SPMS, discusses the pathophysiology of multiple sclerosis progression, describes the peripheral and central mechanisms of siponimod action and its differences from fingolimod. According to analysis of scientific literature experimental, clinical and neuroimaging data are presented, which could explain the reasons for the successful use of siponimod in patients with SPMS, taking into account the pathophysiological mechanisms of the development of progression and the mechanisms of drug action.

Currently, due to the lack of specific etiotropic therapy, rituximab is widely used for the treatment of most autoimmune diseases of the central and peripheral nervous system. Rituximab is a chimeric monoclonal antibody with specificity for CD20, the antigen found on the surface of normal and malignant B-lymphocytes. It is used mainly in hematological practice. It is used off-label for the treatment of neurological diseases. The world literature describes the use of rituximab for the treatment of such pathologies as autoimmune encephalitis, neuromyelitis optica spectrum disorder, multiple sclerosis, primary angiitis of the central nervous system, immune-mediated inflammatory polyneuropathy, myasthenia gravis, refractory to basic immunosuppressive therapy. This article provides an overview of the world literature on the use of rituximab in neurological practice, describes our own experience of its use on the basis of the Department of Neurology № 1 of Pavlov University (Saint Petersburg, Russia).

The purpose — to systematize the modern concepts of diagnosis and treatment for myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disorder. Material and methods. A search for modern publications was carried out using electronic scientific databases PubMed, Science Direct Open Access, Free Medical Journals. Keywords such as MOG-IgG-associated disorder, MOG-encephalomyelitis, MОG-antibody-associated disease were used for search of literature. Modern publications on the nomenclature, pathogenesis, diagnosis and treatment of MOG-IgG-associated disorder as well as scientific works devoted to the history of the study of this problem published in the period from 1987 to 2020 were selected and analyzed. Results. The diagnosis of MOG-IgG-associated disease is based on a combination of clinical, neuroimaging and laboratory assessments with exclusion of alternative conditions. There are many challenges in pathogenesis and nomenclature. Diagnostic criteria were published in 2018. Presence of certain indications is advisable for conducting a blood serum test for MOG-IgG according to the international recommendations. The key diagnostic test proposed is antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) detected in serum with cell-based assays (indirect fluorescence test or fluorescence-activating cell sorting) with strictly employing conformationally intact full-length human MOG as target antigen. There are no generally accepted standards of therapy.The approaches to therapy recommended by various expert working groups are based on the protocols for the management of patients with AQP4-IgG-positive forms of neuromyelitisoptica spectrum disorder. Conclusion. MOG-IgG-associated disorder is a recently proposed group of inflammatory demyelinating syndromes which are different from other demyelinating diseases. Currently it is advisable to use the diagnostic criteria published in 2018. Current knowledge allowed formulating recommendations for laboratory diagnostics which have limited availability in everyday practice. Treatment issues need to be systematized after achieving eхpert consensus.

The comorbidity of neuromyelitis optica spectrum disorder (NMOSD) and systemic lupus erythematosus (SLE) is a poorly studied problem. The issues of the pathogenetic relationship between these diseases, timely diagnosis of their co-existence in one patient, disease course and therapeutic approaches are the most relevant. The authors summarize current views on the state of the problem and analyze three clinical cases of NMOSD and SLE comorbidity including the diagnostic issues and therapeutic approaches.

Myelopathy occurs in 1% of patients with sarcoidosis and is usually caused by the underlying disease. Comorbidity as its possible cause should be excluded, especially in a case of atypical neurosarcoidosis.Objective: to analyze the features of myelopathy in patients with systemic sarcoidosisPatients and methods. Twelve patients (7 women and 5 men) aged 41.5 [32.5; 45.3] years with systemic sarcoidosis and myelopathy were examined. The clinical and radiographic features of spinal cord (SC) injury and the nature of changes in laboratory parameters were analyzed.Results and discussion. The cause of myelopathy was sarcoidosis (neurosarcoidosis (NS)) in 7 (58%) patients (Group 1) and multiple sclerosis in 4 (33%) (Group 2). One more patient developed myopathy due to extradural lipomatosis (this case is described in the clinical observation section). In Group 1, myelopathy was the first manifestation of sarcoidosis in 4 (57%) of the 7 patients. Six (86%) patients were observed to have incomplete regression of symptoms; 5 (71%) showed a progressive course. Magnetic resonance imaging (MRI) revealed the signs of a lesion in the thoracic SC in 4 (57%) patients with NS, as well as damage to three or more of its segments in 5 (71%) and a radiological pattern of sarcoidosis-induced SC lesion in 6 (86%). MRI findings showed that all the 4 (100%) patients in Group 2 had cervical SC injury, no patterns typical of NS, as well as the signs of meningeal contrast agent accumulation. None of them displayed pleocytosis and low glucose levels in the cerebrospinal fluid. Extradural lipomatosis-induced myelopathy was compressive with positive changes after discontinuation of glucocorticoids.Conclusion. It is necessary to take into account the possibility of comorbidity as a cause of myelopathy in patients with sarcoidosis and the likelihood of SC lesion as a complication of therapy for the underlying disease.