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.

Frailty is a key geriatric syndrome characterized by an age-associated diminution of the physiological reserve and functions of many body systems leading to increased vulnerability of the elderly people to the eff ects of endo- and exogenous factors. The combination of frailty, cognitive impairment, anxiety and depression is a signifi cant clinical predictor for an unfavorable prognosis.Purpose. Identifi cation and study of the relationship of cognitive impairment, anxiety, depression and frailty assessment indexes in female patients over 60 years old, observed on an outpatient basis.Material and methods. The study included 80 women over 60 years old. All participants were divided into 4 groups: non-frail (10 women), pre-frail (44 women), mildly frail (20 women), more-frail (6 women). A comprehensive clinical examination was carried out: Montreal cognitive assessment (MoCA), Mini-Mental State Examination (MMSE), frontal assessment battery (FAB), phonetic association test, semantic association test, Beck anxiety inventory, geriatric depression scale–15 (GDS-15), questionnaire “Age is no barrier”, Frailty index (FI, Hoover et al., 2013).Results. All women in 4 groups did not signifi cantly diff er in age. There was no statistically signifi cant diff erence in the MMSE, FAB data and mild cognitive impairment (MCI) prevalence among the groups. Lower rates of MoCA scale were associated with higher probability of frailty (odds ratio (OR) = 0.78; 95 confi dence interval (CI) CI: 0.63–0.96, p = 0.016). The cut-off level of 26 and lower according MoCA has sensitivity 69% and specifi city 50% to detect of high frailty risk (according FI). Questionnaire “Age is no barrier” has a sensitivity of 86% and a specifi city of 53% to detect prefrailty (score 1–2) and a sensitivity of 69% and a specifi city of 87% to detect the presence of frailty (score ≥ 3) regarding FI. Combined sensitivity of MoCA (≤ 26 score) and questionnaire “Age is no barrier” (≥ 3 score) of 78%, combined specifi city of 69%. Higher rates of Beck anxiety inventory and GDS-15 were associated with frailty (OR = 1.12; 95 CI: 1.02–1.22, p = 0.0134 and OR = 1.39; 95 CI: 1.05–1.84, p = 0.0201, respectively). A higher index of the Beck anxiety inventory was also associated with mild cognitive impairment according MoCA (OR = 1.12; 95% CI: 1.04–1.2, p = 0.003). Arterial hypertension was signifi cantly more common for women with FS (χ2 = 4.23, p = 0.04).Conclusion. There was no signifi cant association between MMSE, FAB, MCI prevalence and the severity of frailty in senior women due to the insuffi cient study power (< 80%). MoCA cut-off ≤ 26 score is associated with higher burden of frailty. The questionnaire «Age is no barrier» is an acceptable screening method for determining the necessity of additional geriatric examination of independently living women over 60 years old. Higher rates of the Beck anxiety inventory, GDS-15, BMI, lower rates of MoCA scale and arterial hypertension are associated with high rates of FS and may be predictors for the frailty progression.

Multiple sclerosis (MS) is a chronic autoimmune disease of the nervous system of a predominantly progressive nature. In addition to diseasemodifying drug therapy of MS patients require physical rehabilitation, including tele-rehabilitation (TeleRBT). Objective: to evaluate the efficacy of TeleRBT in MS patients as one of the rehabilitation stages during the 2020–2021 coronavirus pandemic. Material and methods. The study involved 36 patients diagnosed with MS who completed a TeleRBT course. The course included 10 lessons of 60 minutes each over 10 days with a two-day break. Various questionnaires and scales were used to assess efficacy, and neurological status was also assessed. Results. In the group of patients who participated in TeleRBT, the level of disability on the EDSS scale did not change; walking function improved: the time to walk 25 feet decreased from 9.77±6.74 to 8.85±5.26 s (p=0.016), tolerance to physical activity increased: 6 minute walking distance without rest increased from 246.02±145.60 to 261.58±118.55 m (p=0.02), the speed of information processing in PASAT test improved from 31.92±18.35 to 43.12±21.39 (p<0.05), the number of correct answers in the SDMT test increased from 40.7±11.75 to 45.16±13.13 (p<0.05). No exacerbations of the disease were recorded during the TeleRBT period. Conclusion. TeleRBT had a positive effect on the cognitive and motor domains of patients with MS. The absence of exacerbations and negative dynamics in neurological status characterizes TeleRBT method as safe.

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.

—An increase in the prevalence of different cognitive disorders, including Alzheimer’s disease (AD), determines the relevance of the search for methods for the early diagnosis of neurodegenerative diseases. Therefore, various peripheral biomarkers are actively studied for their later measurements by standardized methods available in real clinical practice. Due to the development of the hypothesis about the similarity of biochemical and physiological processes in platelets and neurons, increasing attention is paid to studying the possibility of using different structural and functional platelet parameters as biomarkers for different neurological diseases. This review discusses the main characteristics of platelets in the development of cognitive impairment; the peripheral aspects of amyloidogenesis and tau protein formation, changes in the synthesis and metabolism of active substances, and deregulation of microRNA, as well as the dysfunction of enzymes and proteins, were analyzed, which can be used to develop diagnostic tests for early detection of AD.

Introduction. Tick-borne encephalitis (TBE) is a widespread natural focal viral neuroinfection in Russia and the Sverdlovsk region. The high level of morbidity, leading to disability, and the annual registration of focal forms and lethal cases determine the relevance of the search for early differential diagnostic criteria for acute tickborne encephalitis (TBE). A promising direction in the early diagnosis of TBE is acquired by magnetic resonance imaging (MRI). The aim of the study was to study the features of the MRI picture in patients with focal forms of TBE. Material and methods . The study included 38 patients with focal forms of OKE who were treated in the neurological department of Sverdlonsk regional clinical hospital № 1 since 2009 to 2019. Results. In the acute period of focal forms of TBE, pathological changes of an inflammatory nature during MRI of the CNS were more often detected in the cerebral hemispheres (mainly in the white matter) in 40.4 % and subcortical structures in 36.8 %, in the brainstem in 16.7 %, less often in 6.1 % – in the region of the cerebellum and spinal cord. Bilateral nature and combined lesions of the CNS structures were detected 2 times more often. Discussion A detailed analysis of the localization and nature of MRI changes in the CNS in patients with severe focal forms of the disease, in contrast to single descriptions of the MRI picture of TBE according to the literature, made it possible to identify combined lesions of the frontal and parietal lobes characteristic of TBE in combination with pathological changes in the region of the thalamus and basal ganglia. Conclusion. Identification of typical MRI changes in the CNS in patients with a clinical picture of viral encephalitis in the spring-summer period contributes to the early diagnosis of a severe course of TBE.

В настоящее время в связи с прогрессированием старения населения наблюдается увеличение распространенности когнитивных нарушений различной этиологии. Продолжается активный поиск биомаркеров, которые могут быть использо­ваны в ежедневной клинической практике для ранней диагностики, играющей ключевую роль в разработке новых методов терапии и мониторинга заболеваний, проявляющихся когнитивной дисфункцией. Тромбоциты — безъядерные форменные элементы крови, играющие важную роль в гомеостазе и функционировании эндотелия сосудов, обладают схожим проте­омным составом с нейронами, что позволяет рассматривать их в качестве перспективных кандидатов для моделирования и оценки процессов нейродегенерации. В настоящее время активно исследуются возможности использования структурных и функциональных параметров тромбоцитов для диагностики когнитивных нарушений, в частности, болезни Альцгеймера. В данном обзоре проводится анализ возможного применения основных структурно-функциональных показателей тром­боцитов в качестве биомаркеров когнитивных нарушений. At present, cognitive disorders prevalence of various etiologies increase due to the progressive population aging. An active search continues for biomarkers to be used in daily clinical practice for early diagnosis of diseases manifested by cogni­tive dysfunction, which plays a key role in the development of new treatment and monitoring approaches. Platelets are nuclear-free blood cells with an important role in homeostasis and endothelium functioning. Moreover, platelets have a similar proteomic composition with neurons that allows to estimate them as promising candidates for modeling and evaluating the neurodegener­ative processes. Currently, the possibilities of using the structural and functional platelet parameters for the diagnosis of cognitive disorders, in particular, Alzheimer’s disease, are being actively investigated. This review analyzes the possible use of the main structural and functional platelet parameters as biomarkers of cognitive impairment.

Introduction. Predicting relapse in acute demyelinating episode (ADE) in children is an urgent problem, since progressive demyelinating diseases are associated with the risk of disability and cognitive impairment.Methods. Descriptive cohort study. The results of long-term follow-up of 75 children after the first episode of demyelination are presented. Based on the clinical and radiological parameters of the first demyelinating event, the prognostic factors for the relapse in children were determined using the logistic regression method.Results. When comparing the clinical and instrumental signs of the first demyelinating event, we identified those that were significantly associated with relapse. These included age ≥ 11 years (p <0.001), brain stem symptoms (p = 0.002), multiple demyelinating lesions on brain magnetic resonance imaging (p = 0.001) periventricular (p = 0.002), subcortical (p = 0.001), brainstem lesions (p = 0.006), well-defined lesions (p = 0.03) and perpendicular to the corpus callosum lesions (p = 0.002), cervical spinal cord lesions (p = 0, 02) and lateralized spinal cord lesions (p = 0.02). Regression analysis showed independent risk factors for relapse in children with demyelinating diseases: age ≥ 11 years (OR = 1.34, 95% CI (1.11: 1.61), p = 0.003), brain stem symptoms (OR = 7.00, 95% CI (0.73: 67.25, p = 0.09), multiple CNS lesions, corresponding to the criteria for dissemination by McDonald (2010) (OR = 8.60, 95% CI (2, 24: 33.07), p = 0.002).Discussion. Existing descriptions of pediatric populations with demyelinating diseases often have short follow-up and focus on outcomes in multiple sclerosis and neuromyelitis optica. The article presents data on previously unexplored risk factors for exacerbation after the first episode of demyelination. Conclusion. The identified predictors of relapse in ADE in children are a simple and generally available tool for predicting the course of demyelinating diseases.

Introduction. Hereditary neurodegenerative diseases are a large genetic deterministic group of nosologies, which is based on the clinic of steadily progressing processes of destruction of neuronal systems. Damage to the nervous system can have various combinations, but the most common are atrophy of the cerebellum, brain stem, spinal cord columns, and also possible damage to the peripheral nervous system. Despite the classical descriptions of the clinical picture of various forms of neurodegenerative pathology and the corresponding genetic markers of the disease, in the practice of a neurologist, there are cases that are difficult to determine the nosological form of the disease.Materials and methods. The article describes a case of combined hereditary pathology associated with laboratory-confirmed mutations in the SLC5A7 genes (associated with the development of type 7A hereditary motor sensory neuropathy) and TGM6 (affecting the development of type 35 spinocerebellar ataxia) and the clinical picture of lower spastic paraplegia.Results. The clinical case presents a combined form of hereditary spastic paraplegia with pseudobulbar syndrome, mild motor-sensory neuropathy of the lower extremities, signs of cerebellar hypotrophy on MRI and moderate impairment of walking and speech function against the background of two mutations previously identified in type 35 spinocerebellar ataxia and hereditary motor-sensory ataxia of type 35 type 7A neuropathy.Discussion. Diagnosis of nosological forms of hereditary pathology, manifested by a combination of lesions of the peripheral and central nervous systems, requires a detailed analysis of the hereditary history, neurological status and genetic examination results from a neurologist.Conclusion. The clinical case demonstrates polymorphism of clinical manifestations of hereditary forms of neurodegenerative pathology and a possible combination of various phenotypic and genotypic variants.

The aim of this study was to search cell structure of induced sputum (IS), activity of tripsin-like proteinase, elastase and their inhibitors: α 1 -proteinase inhibitor, α 2 -macroglobulin and acid-stable inhibitors in the IS and blood serum and of blood neutrophil activity in smokers and healthy nonsmokers. We examined 67 healthy volunteers aged 19 to 42 yrs. The IS cytograms showed that the absolute amount of neutrophils and the percentage of lym phocytes were significantly higher and the percentage of macrophages was lower in smokers. They also had greater tripsin-like proteinase activity in serum and IS. The average cytochemical coefficient and the percentage of neutrophils with myeloperoxidase granules did not differ reliably in smokers and nonsmokers. There were quite strong positive correlations between smoking, neutrophils, lymphocytes, macrophages in IS and the tripsin-like activity in sputum and serum.

In the past decade, stroke incidence in younger adults increased. Methionine synthase reductase (MTRR) A66G polymorphism is one of the risk factors for ischemic stroke (IS). However, clinical features of IS in MTRR A66G polymorphism are not yet studied.Objective: to investigate clinical features of IS in MTRR A66G polymorphism.Patients and methods. One hundred forty-one younger patients with IS, hospitalized in the neurological department of Sverdlovsk Regional Clinical Hospital №1, were included in the study. MTRR A66G polymorphism was detected by the real-time polymerase chain reaction in all participants.Results and discussion. MTRR A66G polymorphism was present in 83.7% of younger patients with IS. Participants with MTRR A66G polymorphism had a significantly higher prevalence of arterial hypertension (р=0.029). In addition, protein C level was significantly lower in patients with MTRR A66G mutation (р=0.001).Conclusion. The majority of younger patients with IS have MTRR A66G polymorphism. Therefore, the inclusion of MTRR A66G polymorphism screening in the diagnostic algorithm of stroke in young adults seems necessary.

Diagnosis of Alzheimer's disease (AD) is based on clinical examination of patient's cognitive state. In 2018, the A/T/N system was developed, which expanded a spectrum of biomarkers recommended for AD diagnostics. However, the high price and low availability of the suggested methods, including lumbar puncture or positron-emission tomography, limit their use in daily clinical practice. An active search for other diagnostic tools led to studies on biomarkers in peripheral tissues, such as the blood and saliva. Development of ultrasensitive methods allowed detection of minimal alterations of concentrations of various substances, proteins, or metabolites, which can be used for AD diagnosis at the preclinical stage. Saliva is one of the most important biological fluids and potential candidates for study of various biomarkers. However, the absence of a single protocol for collection and conservation as well as the effects of multiple confounding factors make the development of diagnostic panels difficult. In this review, we consider and analyze the main difficulties in saliva research and the results of studies on the possibility of using beta-amyloid, tau-protein, acetylcholinesterase, lactoferrin, and metabolome as the markers of the early stages of AD.

Number of young people with ischemic stroke increases at the present. One of independent risk factors of stroke is hyperhomocysteinemia, wich can be caused by genetic disorders. Objective: to analyze frequency of gene polymorphism of methylentetrahydrofolate reductase C 677T and level of homocysteine among patients with stroke and people without one. Materials and methods. Data of 141 young patients with ischemic stroke, including 30 people with atherothrombotic stroke, 35 with cardioembolic, 36 with lacunar and 40 ones with cryptogenic stroke were analyzed. The control group included 40 young patients without stroke. Results. The frequency of polymorphism MTHFR C 677T (OR = 6,7; 95 % CI: 1,20–37,45: р = 0,027), allel T (OR = 2,29; 95 % CI: 1,10–4,74; р = 0,028) and the level of homocysteine are higher among stroke patients.

Fibromyalgia (FM) is a condition characterized by generalized pain syndrome and by the presence of fatigue, cognitive impairment, affective and multiple somatic symptoms. Pain syndrome can have national, ethnic, gender, and age characteristics.Objective: to evaluate the features of the course of FM in a large industrial center of the Russian Federation and to present its phenotypic options.Patients and methods. The investigation enrolled 92 FM patients (8 men, 84 women) aged 18 to 86 years (mean age, 50.5 years). The diagnosis was established according to the 2016 ACR criteria. Account was taken of data on disease duration, occupation, sport training loads, previous therapy, pain intensity, and somatic symptoms according to the 2010 ACR diagnostic criteria and on general health assessment in the patients. All the patients completed the hospital anxiety and depression scale (HADS).Results and discussion. The most significant somatic symptoms in the clinical picture of FM were shown to be muscle pain and muscle weakness, the manifestations of irritable bowel syndrome and fatigue; moreover, the prevalence of many symptoms in people over 60 years of age was lower than that in younger patients. Female gender was an additional risk factor for increases in pain and cognitive impairment. The presence of concomitant depression verified by HADS was associated with a substantial deterioration of the clinical manifestations of FM. At the same time, professional activities and sports were found to be protective factors against a number of symptoms of FM. It was hypothesized that there were several FM phenotypes (anxious, anxiety-depressive, egocentric, and vascular ones).Conclusion. The authors have demonstrated the features of the course of FM in a large industrial center of the Russian Federation and identified various disease phenotypes, which can be useful for determining the treatment policy for patients.

OBJECTIVES:To evaluate efficacy, safety, and tolerability of the treatment with teberif/interferon β-1a, to analyze safety, tolerability and dynamics of key efficacy variables after switching from referent drug rebif to biosimilar teberif in patients with remitting multiple sclerosis (RMS).MATERIAL AND METHODS:During the main period of the international multicenter randomized study patients were randomized to receive treatment with teberif for 52 weeks, or rebif for 52 weeks, or placebo for 16 weeks to evaluate efficacy and safety of treatment. After the main study period, patients were group-independently switched to take open-label teberif treatment during the next 48 weeks.RESULTS AND CONCLUSION:The analysis of multiple evaluation parameters of the efficiency during the 1st study period (blinded) and the 2nd study period (open-label) has shown that teberif and rebif demonstrate equivalent efficacy and stable 2-year efficacy of teberif was proven. There were no significant differences between teberif and rebif for all safety, and tolerability parameters. Switching from rebif to teberif didn't influence treatment efficacy. The 2-year study results confirmed a biosimilar teberif's benign tolerability and expected safety profile to other interferons β-1a in patients with RMS.

Objectives. To analyze the involvement of immune response genes in the pathogenesis of primary progressive multiple sclerosis (PPMS). Materials and methods. A representative cohort of 111 ethnically Russian patients with PPMS took part in a multicenter study. The involvement of immune system genes in the pathogenesis of PPMS was analyzed by investigating the associations of variants of cytokines genes and genes involved in antigen processing and presentation by antigen-presenting cells with the disease. Results and conclusions. Carriership of the IL4 genotype (rs2243250)*C/C and CLEC16A (rs6498169)*G/G was found to have a positive association with the development of PPMS in Russian patients. The association described in studies of other populations, HLA-DRB1*15 with a high risk of developing this form of MS, was confirmed.

Objectives. To demonstrate equivalence of the efficacies of the drugs Teberif (BCD-033, interferon β-1a) and Rebif (interferon β-1a) in patients with remitting multiple sclerosis (RMS). Materials and methods. A multicenter, double-blind, placebo-controlled, comparative, randomized phase III trial included 163 patients with diagnoses of MS. Patients were randomized to the Teberif, Rebif, and placebo groups at a ratio of 1:1:1. Results and conclusions. Analysis of efficacy after 52 weeks of the trial demonstrated equivalence between the study drug Teberif and the original formulation Rebif in patients with RMS. Evaluation of primary endpoint results – CUA (combined unique active lesions, i.e., the total number of MRI T1 plaques and new T2 plaques or cases of increases in T2 plaques without double counting) – demonstrated that there were no significant differences (0.727 ± 1.042 and 0.652 ± 1.059, p = 0.7354, Student’s t test) between the Teberif and Rebif groups. There were no statistically significant between-group differences in other MRI indicators or measures associated with exacerbations. The safety profile and tolerance of Teberif were satisfactory and comparable with the safety and tolerance profile of Rebif. These data provide evidence of therapeutic equivalence of these drugs, which may provide grounds for the use of the interferon β-1a bioanalog in patients with RMS.

AIM:The Neurogenic Bladder Symptom Score (NBSS) is widely used now for the bladder symptoms assessment in neurogenic low urinary tract dysfunction. It is suitable for all patients, regardless of a bladder management method. NBSS contains 24 questions, which focus on incontinence, storage and voiding symptoms, urinary complicationsand life quality.With the permission of the authors (Dr.Welk et al.), NBSS had been translated into Russian according to the cultural and lingual adaptation algorithm. OBJECTIVES:Validate the Russian version of NBSS for multiple sclerosis patients. DESIGN, SETTING, AND PARTICIPANTS:The study included 80respondents: group A - 40 multiple sclerosis (MS) patients with neurogenic bladder, group B - 40 multiple sclerosis (MS) patients without bladder dysfunction, group C - healthy controls. All participants filled out the NBSS two times with an interval of two weeks. They also completed other measurement tools (IPSS,OAB Awareness Tool, WHOQOL BREF).Data were used to determine the internal consistency (Cronbachs alfa), external validity (Pearson correlation), and test-re-test reliability with interclass correlation coefficient. RESULTS:The mean of the NBSS total in the group A was 22.56+/-12.6, which significantly (p<0.001) exceeded score in comparable groups B (6.42+/-2.3) and C (5.31+/-1.9). The Cronbachs alfa of the total and the in continence, storage/voiding, and consequences domains was 0.939, 0,965, 0,801 and 0.712 respectively, which confirms the high internal consistency of the Russian version of the NBSS. External validity was verified by the relevant correlations with other questionnaires. Test-retest reliability was excellent. The interclass correlation coefficients were >0.85 (p<0.001) for all subdomains and the overall score. CONCLUSION:The Russian version of the NBSS demonstrated good validity and reliability and may be recommended for use in clinical practice.