Search

Brief intensive behavioral interventions which promise a one session miracle cure from drug or alcohol dependence are very common in the Russian addiction psychiatry, particularly in its commercial domain. Unlike traditional shamanism these behavioral interventions are presented to the patients as the most recent advances in the main stream addiction medicine and therefore they can be called "scientifically decorated shamanism". The paper includes classification of these methods, reasons for this phenomenon to be so common in the Russian addiction psychiatry (narcology), and also possible approaches to the modernization of the Russian narcology system with evidence based approach to research and clinical practice to be the major one.

Background: Melatonin is known to modulate circadian and seasonal rhythms in metabolism, reproduction, and behavior. However, the effect of exogenous melatonin supplementation on the functioning of the thyroid and adrenal glands in species without a clear seasonality in reproduction is still unclear., Aim: Using a meta-analysis of publications, to investigate the effect of melatonin monotherapy on the concentrations of pituitary thyroid-stimulating hormone, thyroid hormones (TG), pituitary adrenocorticotropic hormone and corticosterone (CS) in rats kept under standard laboratory conditions., Materials and Methods: In our work, using the Review Manager 5.3 program, we conducted a meta-analysis of publications examining the effect of melatonin monotherapy on the functioning of the thyroid gland (22 papers) and adrenal glands (20 papers) in rats kept under standard conditions., Results: According to the results of our meta-analysis, the effects of melatonin on the levels of TG and CS depend on the dose and duration of therapy. A decrease in TG and CS was associated with therapy lasting no more than 4-5 weeks and with high doses of melatonin. An increase in CS and a trend toward increased TG levels were observed with longer therapy. However, a few studies have observed a decrease in TG with very long-term melatonin therapy (≥32 weeks). Among all TGs, total thyroxine (T4) showed maximum sensitivity to exogenous melatonin, which indicates the influence of melatonin on the secretory function of the thyroid gland. In addition, melatonin increased the relative weight of the adrenal glands. There was no convincing evidence that the effects of melatonin were influenced by the route and timing of administration, or the timing of blood sampling., Conclusion: As a result, exogenous melatonin can modulate TG and CS levels, even in species without a clear seasonality in reproductive function.

The main treatment option of prolactin-secreting pituitary adenomas is dopamine agonist therapy, which demonstrates prolactin level normalizing and reducing the size of an adenoma in the majority of cases. However, significant amount of patients - about 20% - poorly responds even to high doses of dopamine agonists that is explained by the resistance to therapy. The occurrence of pharmacodynamic characteristics is one of the causes responsible for the development of resistance to typical therapy. Clinical manifestations of persistent hyperprolactinemia are due to following pathological factors: hormonal hypersecretion and the mass-effect of pituitary adenoma. Prevention of irreversible changes is possible only with timely detection of resistance and determination of the optimal personalized treatment algorithm.We report a clinical case of dopamine-agonist resistant microprolactinoma. Patient's health stabilisation, normal level of prolactin and reduction in size of adenoma were achieved due to administration of combined treatment with tamoxifen and dopamine agonists. Hyperprolactinaemia occurring because of prolactin-secreting pituitary adenoma and associated adverse effects are significant problem, decreasing quality of life and demographics in general. This underlines the importance of figuring out causes and identifying predictors of the therapy resistance.The results of the study, illustrated by a clinical example, are presented in the present paper.

The progressive improvement of the classification using modern analytical methods is an essential tool for the development of precise and personalized approaches to the treatment of pituitary adenomas. In recent years, endocrinologists have witnessed evolutionary changes that have occurred in the histopathological identification of pituitary neoplasms, revealing new possibilities for studying tumorigenesis and predicting biological behavior.The paper considers the historical aspects of the gradual improvement of the classification of pituitary adenomas, as well as the new international 2022 WHO classification, according to which pituitary adenomas are included in the list of neuroendocrine tumors (PitNETs) to reflect the biological aggressiveness of some non-metastatic pituitary adenomas. The characteristics of pituitary adenoma are presented, as well as a list of histological subtypes of aggressive neuroendocrine tumors of the pituitary gland, marked by the main potentials for invasive growth, an increased risk of recurrence and a negative clinical prognosis.The expediency of changing the definition of «pituitary adenoma» to «neuroendocrine tumor» is discussed. It is emphasized that the introduction of a unified clinical, laboratory and morphological protocol into national clinical practice will help provide comparable comparative studies on the prognosis of the disease and the effectiveness of secondary therapy and also contribute to adequate management of potentially aggressive PitNETs.

Background:  Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) with upper-normal or elevated blood calcium levels due to primary thyroid gland pathology. PHPT is a rare pathology in children, with a prevalence of 2-5:100,000 children according to the literature. Due to the non-specificity of clinical manifestations at onset (nausea, vomiting, abdominal pain, emotional lability), the disease may remain undiagnosed for a long time., Aim:  To study the features of the course and molecular genetic basis of primary hyperparathyroidism in children., Materials and Methods:  Retrospective observational study of 49 patients diagnosed with primary hyperparathyroidism. All patients underwent a comprehensive laboratory-instrumental and molecular genetic study at the Institute of Pediatric Endocrinology, Endocrinology Research Center of Russia in the period 2014-2022., Results:  The first clinical symptoms of PHPT were noted at the age of 13.8 years [10.6; 1 5.2], among which fatigue, headaches, dyspepsia, lower limb pain, and fractures were the most common. The age of diagnosis was 15.81 years [13.1; 16.8], all children were found to have high levels of PTH, total and ionized calcium, with hypophosphatemia in 93.9% of patients (n=46) and hypercalciuria in 43% (n=21). Five out of 49 patients (10.2%) were found to have ectopy of the thyroid: 3 showed an intrathyroidal location, 2 in the mediastinal region. Molecular genetic study revealed mutations in 32.7% of patients (n=16, CI (21; 47)), mutations in MEN1 being the most frequent (n=11). Pathogenic variants in CDC73 were detected in 3 patients, RET - in 2. Among the operated 39 patients, adenoma of the thyroid was detected in 84.6% of cases (n=33), hyperplasia in 7.7% (n=3), atypical adenoma in 5.1% (n=2), carcinoma in 5.1% of cases (n=2)., Conclusion:  The paper presents the peculiarities of the course and the results of molecular genetic study of pediatric PHPT. This sample is the largest among those published in the Russian Federation.

Breast cancer (BC) is a serious disease and is considered an important health problem worldwide. The prevalence of the disease in women according to Rosstat was 64,951 cases in the Russian Federation in 2020 (21.7% among all types of cancer).  Hormone-dependent estrogen receptor-positive (HR+), human epidermal growth factor receptor type 2 negative (HER2-) metastatic breast cancer (mBC) accounts for 70% of all cases.  About 40% of patients with ER+/HER2- mBC have mutations in the PIK3CA gene, leading to hyperactivation of the alpha isoform (p110α) of phosphatidylinositol 3-kinase (PI3K). Hormonal therapy with or without cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor is considered the standard treatment for patients with ER+/HER2- mBC. However, acquired resistance to this therapy remains a problem. Innovative methods for the treatment of breast cancer are the use of targeted therapeutic agents aimed at direct inhibition of the PI3K pathway in combination with hormone therapy. Alpelisib is a PI3Kα-specific inhibitor. Hyperglycemia is the most common side effect of alpelisib treatment. Currently, there is a consensus on the prevention and correction of hyperglycemia in patients receiving therapy with alpelisib, which recommends that before starting therapy, in  order to diagnose carbohydrate metabolism disorders and assess the risk of developing hyperglycemia, determine in all patients: the level of glycated hemoglobin (HbA1c), glucose fasting plasma (FPG), body mass index (BMI). And also to evaluate such risk factors as the presence of a family history of type 2 diabetes mellitus (DM 2), the presence of gestational diabetes in the patient's history, or the fact of the birth of children weighing more than 4 kilograms.Recently, new combinations of drugs have been actively used to treat disorders of carbohydrate metabolism, such as pioglitazone + metformin. This paper discusses the mechanism of action of PI3K inhibitors, new therapeutic combinations and their undesirable effects, and presents therapeutic experience.

Congenital nephrogenic diabetes insipidus (CNDI, arginine vasopressin resistance) is a rare inherited disorder characterized by insensitivity of the kidney to the antidiuretic effect of vasopressin. NDI is clinically characterized by polyuria with hyposthenuria and nocturia and polydipsia. In the majority of cases, about 90%, nephrogenic diabetes insipidus is an X-linked recessive disorder caused by mutations in the AVP V2 receptor gene (AVPR2). In the remaining cases, about 10%, the disease is autosomal recessive or dominant and, for these patients, mutations in the aquaporin 2 gene (AQP2) have been reported. To date, the nucleotide variants registered in AQP2 were sporadic, there is no data on the presence of «frequent» mutations and the prevalence of the disease both among the global population and among individual ethnic groups. In this paper, we describe 12 cases of arginine vasopressin resistance caused by a new homozygous mutation p.R113C in AQP2 presented among the indigenous population of the Republic of Buryatia.

Disease modifying therapy for adult patients with SMA still raises certain questions regarding its effectiveness, given the long-term chronic process with often significant neurological deficits at the time of initiation of therapy. This paper presents three clinical cases of adult sitter patients with SMA type 2, who began risdiplam therapy 16.5-41 years after the disease onset. All patients have been receiving therapy since 2020, at the time of observation for 2.5-3 years. All patients showed subjective and objective (using specialized scales) improvement during long-term therapy with risdiplam. In addition to an increase in muscle strength, mainly in the proximal and distal parts of the arms, several non-motor effects were also noted (including improved swallowing and breathing), which cannot be recorded using scales. No adverse events were recorded during therapy.

Acute pain syndromes caused by discogenic lumbosacral radiculopathy and lumboischialgia are not uncommon in clinical practice and characterized by a high risk of becoming chronic. The pathogenetic aspects, features of the clinical picture, existing approaches to conservative treatment of these conditions are analyzed in this paper. Data on the efficacy and safety of a fixed combination of diclofenac and orphenadrine (Neodolpasse) use in the treatment of vertebrogenic pain syndromes based on the NEODOLEX study results are presented, and the authors' own clinical observations are given. Possible reasons for the high efficacy of Neodolpasse in patients with discogenic radiculopathies and nonspecific back and neck pain are discussed.

Kabuki syndrome is a rare hereditary disease characterized by distinctive facial features, skeletal abnormalities, mental retardation, developmental delay, and anomalies in multiple organ systems development.Congenital hyperinsulinism is a rare manifestation of his Kabuki syndrome. However, early diagnosis is crucial to prevent neurological complications of hypoglycemia.There are 2 types of Kabuki Syndrome depending on severity of symptoms. Kabuki syndrome Type 1 is associated with heterozygous mutations in gene KMT2D. Kabuki syndrome Type 2 is inherited in an X-linked manner. It's associated with heterozygous mutations in gene KDM6A and characterized by more severe course of the disease.This paper presents 2 cases of children with congenital hyperinsulinism as the feature of Kabuki syndrome Type 1 and Type 2.

This paper reports two cases of Guillain-Barre syndrome associated with coronavirus infection COVID-19. The clinical symptoms and neurological status of patients, the data of the additional examination and the features of the prescribed therapy are described in detail. The issue of the tropicity of the SARS-CoV-2 virus to human nervous tissue and its possible ways of affecting the peripheral nervous system is discussed.

Visual object agnosia (VOA) is a loss of the ability to recognize visible objects in patients with the intact primary visual functions and in the absence of dementia. The apperceptive and associative variants of VOA are marked out. The apperceptive VOA is thought to be due to «pre-semantic» impairment of visual information processing. The associative VOA is caused by the loss of access to knowledge about the objects, and its semantic subtype is due to the disintegration of this knowledge itself. It is important to diagnose VOA and its variants in time to provide individualized approaches to medical rehabilitation of patients. Case reports of apperceptive and associative VOA in acute ischemic stroke are presented in this paper. These case reports indicate the possibility of the development of apperceptive and associative VOA in unilateral acute ischemic brain lesion. The variants of VOA can be recognized only by a detailed neuropsychological examination.

The prevalence of cervical dizziness, still not recognized by the entire medical community, not only does not become less frequent, but even increases today. This phenomenon is facilitated by the widespread computerization of our lives and, in particular, the strain on the neck when working with portable electronic equipment. Despite the fact that criteria that reliably confirming the association of dizziness with cervical pathology have not yet been defined, experimental and clinical evidence of such an association continues to accumulate. This review presents data from studies of the last few years on cervical pathology as a causative factor in some types of dizziness and vertigo. To date, the following variants of cervical vertigo are distinguished: Barre-Lieu syndrome, rotational vertebral artery syndrome, proprioceptive cervical vertigo, migraine-associated cervical vertigo. The paper considers the features of all four cervical vertigo types, as well as methods for diagnosing and the first randomized trials on the treatment of dizziness associated with the pathology of neck structures. The results of own observations of similar cases (diagnosis and treatment) are described; as well as principles of differential diagnosis of some conditions manifested by headache and dizziness in patients with various types of disorders of cervico-cranial region. The similarities of clinical presentation and pathogenetic mechanisms characteristic of skull base and neck anomalies, Meniere's syndrome and cervical vertigo are discussed. In conclusion, an assumption was made about the common origin of a whole group of the diseases associated with the cranio-cervical region.

The article is dedicated to the 350 th anniversary of the death of the Dutch anatomist, physiologist, yatrochemist and the greatest physician of the XVII century, Franciscus Sylvius (Franz de le Boe) (1614-1672). His contribution to the study of the structure of the nervous system is characterized, as well as the main scientific discoveries and achievements in building a rational system of medical science and practice. It is stated that eponym «aquaeductus Sylvii» was coined by Lorenz Heister in 1717 in his paper «De admiranda cerebelli structura».

This review addresses current issues in post-COVID syndrome with a focus on neurocognitive impairment. The results of studies on complications in patients of different ages and health statuses recovered from mild to severe COVID-19 are discussed. Current data on the pathogenetic mechanisms of the development of various post-COVID disorders are presented, including a detailed discussion of central nervous system damage. The paper summarizes data on the relationship between neurocognitive disorders and accelerated cell aging, chronic nonspecific inflammation, and reduced neuroplasticity in the central nervous system. The main pathogenetic ways to prevent COVID-related complications, including neuronal tissue damage and the prospects for managing such patients are discussed. The choice of pathogenetic therapy in patients with neurocognitive impairment in the post-COVID period is assessed. The main benefits of choline alfoscerate therapy for neurocognitive impairment in patients with post-COVID syndrome are discussed.

Constipation is one of the most common non-motor symptoms of Parkinson's disease. The pathogenetic mechanisms of constipation, diagnostic criteria, approaches to investigations and treatment are discussed in the paper.

This paper describes two cases of congenital bilateral perisylvian syndrome (CBPS), a rare disorder of late neuronal migration, which is characterized by language delay, intellectual disorders, epilepsy and bilateral perisylvian polymicrogyria. Pseudobulbar paralysis and orofacial muscles dyspraxia causing drooling and feeding difficulties are common for patients with CBPS. Communicational problems lead to low self-esteem and social maladaptation. Literature data regarding correlation between polymicrogyria topography and speech disorders and articulation impairment severity are presented. The results demonstrate the association of diffuse spreading of bilateral polymicrogyria and more severe speech disorders comparing to mild speech disorders in patients with more local polymicrogyria. Known etiology factors of this syndrome are bilateral cerebral hypoperfusion, brain damage while neuronal migration period, postmigrational vascular insults and gene mutations. Syndrome can be inherited in autosome dominant and X-linked manner. Speech apraxia with normal impressive speech, refractory epileptic seizures and status dysraphicus must be red flags for a physician regarding this syndrome. Overnight video-EEG monitoring and brain MRI confirm a thesis that this syndrome is underdiagnosed in everyday clinical practice.

Objective: This paper presents an analysis of polymorphic gene loci, the products of which are directly involved in the molecular mechanisms of regulation of neurophysiological processes., Material and Methods: The sample of subjects consisted of 128 unrelated males and females living in the European part of Russia. The study assessed the frequency of occurrence of 11 single-nucleotide substitutions located in genes encoding serotonin receptors, ciliary neurotrophic factor, uncoupling protein 2, methylenetetrahydrofolate reductase, methionine synthase, methionine synthase reductase, dipeptidyl carboxypeptidase 1, gamma-coactivator of the receptor activated by the proliferator peroxisome and neurotrophic factor of the brain. Genotyping of the samples was carried out by PCR with fluorescence detection and analysis of the polymorphism of the lengths of restriction fragments., Results: The distribution of polymorphism genotypes corresponded to the Hardy-Weinberg equilibrium with the exception of rs1801133 MTHFR (χ 2 =5.3088, p =0.0212) in which a decrease in heterozygosity was observed. These studies of minor allele distribution have no statistically significant deviations from the European population, but there are deviations from the Asian, African, and Latin American populations., Conclusion: Statistically significant correlations of allele frequencies in the study group with populations from other regions and the studies conducted in them are the basis for the inclusion of selected single-nucleotide polymorphisms in the list of a limited set of molecular genetic markers, which makes it possible to supplement the system of mental health monitoring and improve the professional training of people in extreme professions.

Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder characterised by lack of pubertal development and infertility, due to deficient production, secretion or action of gonadotropin-releasing hormone (GnRH). Clinically, there are variants of CHH with hypo-/anosmia (Kalman syndrome) and normosmic hypogonadotropic hypogonadism. Given a  growing list of gene mutations accounting for CHH, the application of next generation sequencing (NGS) comprises an excellent molecular diagnostic approach because it enables the simultaneous evaluation of many genes. Biallelic mutations in GNRHR gene lead to the development of hypogonadotropic hypogonadism with normosmia. In this paper, we describe 16 patients with proven GnRH resistance and estimate the frequency of pathogenic variants in the GNRHR gene in the Russian population.

Acute and chronic thyroid diseases are the most frequently detected disorders being second only to diabetes mellitus.The World Health Organization points out that thyroid diseases' incidence tends to grow every year. The present paper consists of clinical practice guidelines that consider etiology, clinical course, diagnostics and treatment of acute and chronic inflammatory thyroid diseases (except those of autoimmune type).The clinical practice guidelines provide an important working tool for clinicians including specialty physicians and medical experts. Containing structured and concise information on the specific nosology, diagnostic methods and treatment tips these guidelines allow medical specialists to quickly resolve difficulties and choose the most efficient and personalized treatment (following strict principles of evidence-based medicine at the same time).The clinical practice guidelines were drawn up by highly-skilled professional team of specialty physicians approved by the Expert Council of Russian Federation's Health Department. These guidelines contain the most complete and up-to-date information required to diagnose acute and chronic thyroiditis, provide patient care and treatment.The working group publishes the present paper in the professional journal dealing with endocrinology topics to improve healthcare quality and refine treatment of acute and chronic thyroiditis (autoimmune thyroiditis excluded). It is advisable to acquaint as many endocrinology and general (family) medicine specialists as possible with the full text of these clinical guidelines.

Background: Primary hyperparathyroidism (PGPT) is an increase in the secretory activity of the parathyroid glands (OSH), due to their tumor or hyperplastic changes. Due to the lack of an effective alternative to the treatment of PGPT, the surgical method is still the only correct tactical solution for the management of patients with an established diagnosis of PGPT. The paper presents the long-term results and assessment of the quality of life of patients who underwent surgical treatment from standard and small access. The results obtained showed the promise of a sparing approach to the treatment of PGPT caused by LV adenoma., Aim: To study the effectiveness of surgical treatment of patients with PGPT based on the assessment of the quality of life of patients who underwent parathyroidectomy from standard and small access., Materials and Methods: A retrospective study of the quality of life of patients with PGPT after surgical treatment was conducted using the SF-36 questionnaire and the linear analog scale (LAS). Statistical data processing is performed in the R programming language using the FMSB package. The quantitative parameters were presented as median (Median) and interquartile range (25th (1st Qu) - lower quartile and 75th (3rd Qu ) - upper quartile). As a nonparametric statistical criterion, the Mann-Whitney U-test was used, on the basis of which the p-value was calculated. The calculated data of the research results are presented in graphical form - in the form of bar charts, spider plot and barplot., Results: This study involved 264 patients. The patients were divided into 2 groups: GR1 - patients operated from the Kocher access with mandatory revision of all 4 OSH, GR2 - patients who received surgical treatment from the small access with the removal of the altered OSH, without revision of the remaining OSH. When analyzing the quality of life of patients before surgery, there were no statistically significant differences in the groups in terms of PF (Physical Functioning) and VT (Vitality). Small-access parathyroidectomy (patients with GR 2) significantly improved the quality of life in the GH (General Health) and VT (Vitality) domains. The analysis of LAS before surgery between the groups showed no statistically significant differences, while after surgical treatment, the indicators on the linear analog scale differ in the direction of improvement in GR2., Conclusion: The results obtained in the course of the study showed the promise of a gentle approach to the treatment of PGPT caused by LV adenoma, which is reflected in higher quality of life indicators.

Objective: Neuroprotective and nootropic drugs often exhibit complementary, «synergistic» effects, the consideration of which is important for choosing the most effective and safe drug combinations., Material and Methods: Chemoinformatic analysis of vinpocetine, piracetam and cinnarizine on neuron cultures, on model organisms (mice, rats) based on modern data mining and machine learning methods., Results: The paper presents the results of the chemoreactom analysis of vinpocetine, piracetam, and cinnarizine. Estimates of various biological activities of molecules on neuronal cultures, on model organisms (mice, rats) and estimates of modulation of the activity of target proteins in rats and humans were obtained. The data obtained made it possible to quantify the value of the synergism score for the combination «vinpocetine + piracetam» (54 points) compared with the combination «piracetam + cinnarizine» (25 points)., Conclusions: The combination of «vinpocetine + piracetam» in the fixed combination (Vinpotropil) is thus more preferable for combined use than for the combination of «piracetam + cinnarizine».

The paper addresses associations between sleep disorders and emotional and behavioral disturbances in children. These associations are considered in a view of commonly found co-occurrences of sleep problems, signs of anxiety and depression, oppositional-defiant behavior, and increased aggressiveness. The authors put forward a conception of reciprocal influences of these disturbances and provide information on potential physiological mechanisms responsible for associations between sleep problems and emotional and behavioral disturbances in children. Attention is drawn to hypothalamus-hypophysis-adrenal axis activation, serotonergic and aminergic systems imbalance, impaired melatonin and orexins production. Possibility of an existing pattern encompassing sleep problems, emotional and behavioral disturbances is discussed. Practical recommendations aimed at timely identification and treatment of the mentioned disorders are suggested.

Chronic migraine (CM), a condition where patients experience over 15 days of headache per month, was identified as a separate disease in the International Classification of Headache Disorders 3-beta version. Onabotulinumtoxin type A was approved for the treatment of CM in 2010 after the completion of the extensive PREEMPT (Phase III Research Evaluating Migraine Prophylaxis Therapy) clinical program. The efficacy of onabotulinumtoxin type A was demonstrated in numerous studies in CM and medication-overuse headache. The paper focuses on the PREEMPT injection paradigm and provides guidance for successful and safe treatment of CM.

The neurological symptoms of COVID-19 in children (in Dyurtyuli area, Republic of Bashkortostan) are analyzed and brief review of the literature is undertaken in the paper. 137 children underwent swab test for COVID-19. The disease was diagnosed in 9 of them. Only respiratory symptoms were observed in 3 children, a combination of respiratory with anosmia or/and headache - in 3, asymptomatic form - in another 3. A case of a 7-years old girl suffering from COVID-19 with respiratory symptoms as well as anosmia and headache is presented. According to the review of the literature, COVID - 19 in children is usually milder than in adults, but in some cases may lead to neurological consequences. Multisystem inflammatory syndrome may lead to the development symptoms of encephalopathy (altered mental status, headache) and stroke. Autoimmune complications such as Gillian-Barre syndrome develop simultaneously or after resolving of the infectious process. The development of viral meningoencephalitis in COVID-19 is questionable.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants (MR) are successfully used to relieve pain, both in monotherapy and in combinations. The use of fixed drug combinations not only greatly facilitates daily clinical practice and increases patient adherence, but due to the potentiation of pharmacological effects, it allows to achieve better treatment results. This paper presents 3 clinical cases of successful inpatient use of a fixed combination of diclofenac 75 mg and orphenadrine 30 mg in the form of an infusion solution (NEODOLPASSE) for relief of acute back musculoskeletal pain syndrome.

This paper explores the potential of recent research on metacognition to offer new avenues to assess and address the phenomenon of fragmentation in schizophrenia, which was described by E.Bleuler as «splitting». The concepts of metacognition characterize and quantify alterations or decrements in the processes by which fragments or pieces of information are integrated into a coherent sense of self and others. A method for assessing metacognition is presented along with research examining the presence and importance of metacognitive deficits in schizophrenia. Greater levels of metacognitive deficits have been detected in different phases of schizophrenia and linked to poorer psychosocial outcomes. These data were obtained both in foreign and preliminary Russian studies. The authors suggest that treatments, which successfully target metacognitive capacity, may uniquely promote wellness and recovery in schizophrenia.

The paper summarizes the literature and author's data on the development of early (preclinical) diagnosis of Parkinson's disease (PD). Implementation of this diagnosis will promote the use of preventive therapy and change investments in diagnosis and treatment of patients. The paper declares that at present the only approach to early diagnosis of PD is positron-emission tomography of the nigrostriatal dopaminergic system, but it cannot be used for preventive examination due to its high cost. The authors consider that a less specific, but more promising approach to the development of early diagnosis of PD is the search for markers in body fluids, mainly in the blood, in patients at the prodromal stage of PD. Indeed, a number of markers as changes in the level of metabolites of monoamines, sphingolipids, urates, and indicators of oxidative stress were found in patients selected for the risk group of the prodromal stage of PD, according to characteristic premotor symptoms. In addition, it is assumed that the search for blood markers at an earlier - pre-prodromal stage is possible only in animal models of PD at the early preclinical stage. This approach can also be used to verify blood markers identified in patients at the clinical stage of PD. It is also evident that the complex socio-economic factors influencing the incidence of PD is different in developed versus developing countries. The societal and medical costs of Parkinson's are huge and efforts to improve early preclinical diagnosis of PD will lead to considerable economical and societal benefits. For instance this will allow efficient selection of patients for preclinical diagnostic tests. To assess the effectiveness of this strategy considering the uncertainty of socio-economic issues, a modification of the «cost-utility» analysis is proposed. For the first time, a Markov model of PD including preclinical diagnostic tests and possible neuroprotective therapy was developed and studied. Analytical outcomes of this process suggest that the idea of developing a new multimodal strategy is promising from a socio-economic point of view.

Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by autoimmune inflammation, demyelination, and neurodegeneration. MS is a complex disease that develops under the influence of environmental factors in genetically predisposed individuals. Currently, more than 200 genetic loci associated with MS have been identified by various methods. Some of them are located in the mitochondrial DNA. This paper collects data on mtDNA variants associated with MS in the Russian ethnic group, and shows the possibility of using this information to construct and refine models for predicting the development of MS.

Objective: Systematization of the array of publications on cytidyldiphosphocholine (CDP-choline)., Material and Methods: Systematic computer analysis of all currently available publications on CDP-choline (1750 publications in PUBMED) using the topological theory of big data analysis., Results: CDP-choline is essential for acetylcholine biosynthesis, phospholipid metabolism, and DNA methylation. The article describes the effects of CDP-choline on acetylcholinergic and other types of neurotransmission, anti-inflammatory, neuroprotective and neurotrophic effects of CDP-choline. Also, the paper presents the effects of the molecule on lipid metabolism and gene expression within the post-genomic paradigm (in particular, an increase in the expression of nicotinic and muscarinic acetylcholine receptors). The results of fundamental and clinical studies of CDP-choline in the treatment of cognitive impairments associated with cerebral ischemia and neurodegeneration are presented., Conclusion: The pharmacological effects of CDP-choline are mediated through multiple molecular mechanisms that contribute to the nootropic action of this molecule.

This paper reviews the literature on functional neurological disorders (Dissociative (conversion disorders - F44). The authors present a change in views on the etiology and the main mechanisms of the pathogenesis of this pathology during the period of its study. The modern ideas about the types of cerebral dysfunction characteristic of functional neurological disorders are considered. The description of the most characteristic mental and somatic symptoms observed in dissociative disorders and the features of their clinical manifestations are given. The current approaches to the therapy of functional neurological disorders are considered.

Objective: To test hypothesis that music embedded with binaural beats can boost activity of parasympathetic part of autonomic nervous system (PPANS) with the development of nap., Material and Methods: The power of high-frequency component of heart rate variability spectrum computed on successive 2-minute intervals during 20-minute nap was a comparison criterion. The criterion was compared during nap accompanied by music with embedded binaural beats (stimulus condition) and nap in silence (control condition)., Results and Conclusion: Statistical comparison revealed the increase of PPANS activity during nap in stimulus condition vs. control condition. It is consistent with conclusions of other papers about positive effect of sound stimuli embedded with binaural beats on PPANS.

Approximately 30% insomnia patients have associated somatic, neurological and psychiatric conditions. Clinician has to define causality of these conditions to determine a treatment plan. Secondary insomnia can result from the symptoms of a primary condition or form an impairment of central nervous system due to neurological disorder. Some associated conditions are characterized by high coincidence with insomnia, similar triggers and crossing genotype, neurophysiological and functional findings. This association with insomnia is observed in anxiety disorders, depression, chronic pain syndromes. The paper presents a concept of comorbid insomnia disorder which proposes the existence of a common neural structure which when affected causes the symptoms of both insomnia and comorbid disorder. Comorbid disorders can also be interconnected due to the overlap of the responsible nerve centers. Positive effect of specific pharmacological, psychotherapeutical and behavioral treatment on both conditions evidences this concept.

This paper discusses modern approaches to the diagnosis and management of patients with piriformis syndrome. Epidemiological data on the prevalence of this syndrome in neurological practice are presented. The anatomical features of this region, leading to the formation of piriformis syndrome, are described in detail. The authors provide diagnostic criteria based on neurological examination and manual muscle testing and discuss the differential diagnosis of piriformis syndrome. New possibilities of treating this syndrome using a fixed combination of diclofenac and orphenadrine registered in the Russian Federation as a drug for intravenous infusion neodolpasse are discussed in detail. The authors cite materials from their own work, a clinical case of managing a patient with piriformis syndrome using neodolpasse is analyzed.

For a long time it was believed that respiratory disorders (RD) in Parkinson's disease (PD) are rare. However, the situation has changed dramatically over the past 10 years. Thus, special studies have revealed RD in almost half of patients with PD. The paper presents: a literature review, classification of RD in PD, various mechanisms of their development and general approaches to their treatment. Classification of RD in PD is presented.

Cervical artery dissection (CeAD) due to arterial wall weakness (dysplasia) is one of the most common causes of ischemic stroke (IS) at a young age. A rare and little known cause of CeAD is Turner's syndrome (TS)-is an inherited disease caused by completely or partially missing X chromosome. In this paper, we describe 2 female patients, aged 27 and 33 years, with genetically confirmed TS (karyotype 45X0) and internal carotid artery dissection(ICAD).TS frequency among our 304 patients with CeAD was 0.07%. Both patients had short stature, received hormone replacement therapy from the age of 14 and had arterial hypertension. In addition, the first patient suffered from hypothyroidism, osteoporosis and survived a nephrectomy for hydronephrosis. ICAD in first patient manifested by IS. MRI of the neck arteries, MRA and CTA revealed intramural hematoma, hemodynamically significant stenosis, which regressed in 4 months. In the second patient, dissection was manifested by local symptoms (Horner's syndrome, cervicocephalic pain on the dissection side). MRA and CTA revealed a precranial dissected aneurysm of the left ICA (on the side of local symptoms), fusiform expansion of the right ICA, and pathological tortuosity of both ICA. The paper discusses the cause of vasculopathy in TS. It is assumed that connective tissue damage is associated with a deficiency of biglycan - extracellular matrix protein, which interacts with collagen and elastin to strengthen the arterial wall. Biglycan gene is linked to X-chromosome which is completely or partlially missing in TS resulting in a biglycan deficiency. The role of sex hormone deficiency as a cause of arterial wall weakness is unlikely.

Pain is influenced by multiple emotional and cognitive factors. This paper provides an overview of the most important emotional and cognitive factors affecting pain, which has been confirmed in experimental and clinical studies. Emotional factors that increase pain perception include anxiety, depression, and other negative emotions. Positive emotions lead to a decrease in pain. Cognitive factors such as attention, expectation anxiety, and pain assessment can both increase and decrease pain sensations, depending on their specific focus. It becomes clear that pain is not just a reflection of nociceptive irritation, but also a feeling formed by psychological factors that can be individual in each case.

Depression is one of the leading causes of decreased quality of life and social functioning of patients. In the context of preventive medicine, the prevention of depression becomes a priority. To achieve the goals of prevention, it is necessary to identify specific population risk groups - individuals with a high genetic risk of depression. The paper describes the project aimed at developing a genetic test system based on polygenic risk scores (PRS) for depression, considering the multi-ethnicity and multicultural diversity of the Russian population. As a result of the study, data on the genetic architecture of depression (GWAS) and PRS for depression will be obtained for the first time. The emergence of a genetic test system developed in the study of the Russian population and in the conditions of a constant decrease in the cost of genetic research will allow an effective transition to preventive medicine in the area of mental health.

The paper provides an overview of the current state of the problem of antithrombotic therapy in angioneurology. Given the importance and prevalence of cerebral atherosclerosis as one of the leading etiological factors of acute and chronic cerebrovascular disorders (CCD), the paper focuses mainly on antiplatelet therapy. The most recent recommendations for the use of acetylsalicylic acid and clopidogrel, the main antiplatelet drugs, are highlighted. The clinical failure of primary or secondary prevention of cerebrovascular diseases, one of the reasons for which is resistance to the therapy, is considered separately. The authors discuss the causes of aspirin resistance and ways to overcome it, one of which may be a switch to another drug. The well-known medication dipyridamole is proposed as a possible alternative and/or addition to the treatment regimen. The most modern ideas about the mechanisms of its action are described, the pleiotropy of its effects is emphasized. The results of own studies on assessment of the effectiveness and safety of dipyridamole (curantil) in patients with various forms of CCD are presented. The results of the CCD pilot project to study the antiplatelet profile of dipyridamole in patients with such a cause of ischemic NMC as Ph-negative myeloproliferative diseases are discussed separately. It is noted that when prescribing both dipyridamole and acetylsalicylic acid preparations, comparable platelet aggregation levels are determined. In conclusion, the need to follow the paradigm of personalized therapy is emphasized, in which individually selected therapy is prescribed (including) taking into account resistance to a particular drug.

In this paper, the authors review experimental data on the ability to perceive the passage of time during wakefulness and sleep. The evolutionary significance of the sense of time and its role in cognitive functions is discussed. Recent findings on neural mechanisms underlying perception and estimation of time as well as temporal order judgments are described. Similarities and differences of the awareness of time in wakefulness, REM, and NREM sleep are analyzed.

Introduction: This paper is an adapted translation of recommendations on telestroke provided by the European Stroke Organization. Lack of stroke specialists determines that many European rural areas remain underserved. Use of telemedicine in stroke care has shown to be safe, increase use of evidence-based therapy and enable coverage of large areas of low population density. An aim of the study is to summarise the following recommendations of the Telestroke Committee of the European Stroke Organization on the setup of telestroke networks in Europe: Hospitals participating in telestroke networks should be chosen according to criteria that include population density, transportation distance, geographic specifics and in-hospital infrastructure and professional resources. Three hospital categories are identified to be part of a hub-and-spoke network: (1) the Telemedicine Stroke Centre (an European Stroke Organization stroke centre or equivalent with specific infrastructure and setup for network and telemedicine support), (2) the telemedicine-assisted stroke Unit (equivalent to an European Stroke Organization stroke unit but without 24 h onsite stroke expertise) and (3) the telemedicine-assisted stroke ready hospital (only covering hyperacute treatment in the emergency department and transferring all patients for further treatment).

The coronovirus COVID-19 pandemic is a very strong challenge for the public health system and the general population. Despite the existing experience in eliminating epidemics and their consequences in the world, including experience in maintaining mental health, the new coronavirus infection entails new problems that need to be addressed as soon as possible. Important is the need to mobilize psychological and psychiatric service. The article is a review of literature published mainly in 2019-2020. The databases used were PubMed, Elsevierscience and Google Scholar. The paper presents relevant data on risk factors for mental disorders during a pandemic, the range of psychological reactions and symptoms of mental disorders in the population, the characteristics of the management of patients with mental disorders, and the role of the psychological and psychiatric unit during this period. The consolidation of efforts and the quickest possible start of solving mental health problems will help to avoid significant consequences in the future.

Objective: To develop an electronic registry of patients with MS in the Russian Federation and to analyze the collected epidemiological and clinical data., Materials and Methods: Patients aged 18 and older with definite multiple sclerosis were included in the study. We designed a specialized electronic individual registration form (registry) to gather information about study participants. This paper presents data collected in the project between September 25, 2017 and March 25, 2020., Results: We collected information on 2728 patients. This paper presents the results of data analysis from the registry of MS patients, including demographic, clinical and epidemiological characteristics, the type and timing of treatment received. Based on the data obtained, certain issues with primary diagnosis of multiple sclerosis and delayed initiation of disease-modifying therapy can be highlighted, which contribute to the transition of the disease to a secondary progressive course and disability increase.

Aim: Magnetic resonance spectroscopy (MRS) allows studying the content of many metabolites in neural tissue in vivo. There are numerous studies devoted to the MRS data analysis in Alzheimer's disease (AD), but their results are contradictory. Thus, it is rational to compare the data obtained with MRS and positron emission tomography (PET) with fluorodeoxyglucose (FDG), which allows evaluating the brain functional state. In this paper, the authors compared MRS data in AD and mild cognitive impairment (MCI) with the cerebral glucose metabolism changes according to FDG PET., Material and Methods: Multivoxel proton MRS of the supraventricular area was performed in patients with AD (n=16) and MCI (n=14). The following metabolites ratios were evaluated: NAA/Cr, Cho/Cr, NAA/Cho (NAA - N-acetylaspartate, Cr - creatine, Cho - choline). All patients underwent neurological examination, assessment of cognitive status and PET with FDG., Results: A decrease in NAA/Cr and Cho/Cr ratios in the supraventricular white matter and medial cortex in both hemispheres was observed in AD patients. In the MCI group, NAA/Cr ratio were decreased only in left white matter adjusting to the parietal cortex. Positive correlations of NAA/Cr and Cho/Cr ratios with cognitive status, as well as the cerebral glucose metabolism rate according to the PET data in frontal, parietal, temporal and cingulate cortex were revealed., Conclusion: The decrease in the NAA/Cr ratio in the supraventricular white matter and the medial cortex in AD and the correlation of this index with the results of cognitive tests and cerebral glucose metabolism suggest that it can be of diagnostic significance, reflecting the severity of cognitive impairment. In this case, the NAA/Cr ratio should be evaluated taking into account the changes in concentrations of both metabolites (NAA and Cr) in dementia.

This paper presents a case report of subtentorial progressive multifocal leukoencephalopathy (PML) in a 26-year-old female patient treated with natalizumab. The evolution of clinical features, neuroimaging data and treatment as well as the development of immune reconstitution inflammatory syndrome (IRIS) are described. This case emphasizes the importance to keep accurately the risk management plan during natalizumab treatment. This includes performing MRI scans in order to detect changes typical for PML at the earliest (preclinical) stage in time.

The paper considers the phenomenon of «mental atony» in children with developmental delay, intellectual disability and autism. The condition of mental atony is a congenital or early acquired even decrease in mental tone, manifested by the reduced ability to concentrate attention, a decline of the targeted activity, difficulties in contacting, weakening of unconditioned reflexes, lack of instinctive manifestations, «mobilization» of mental functions by persistent verbal and tactile stimulation. The article provides the history of the «mental atony» theory, as well as clinical features, epidemiology, etiology, pathogenesis and nosological specificity of the condition. Moreover, the criteria for the differential diagnosis between the atonic form of intellectual disability and autism are discussed in detail. Based on the analysis of literature and the results of own clinical observations, the authors conclude that a thorough differential analysis between childhood autism and atonic form of intellectual disability in children is necessary, otherwise, there is a risk of overdiagnosis of autistic disorders. The authors also point to the role of the brain lesion, particularly in the area of reticular formation, in the occurrence of phenomena of mental atony.

This paper presents a case report of a patient with neurotic depression. The features of personal predisposition and clinical characteristics of the disease are considered. The authors note the advantages of an integrated approach to the treatment of neurotic depression with antidepressants and psychotherapy (cognitive behavioral therapy).

The paper presents the literature data concerning the results and surgical approaches to the treatment of tandem occlusion in the ICA system. The authors describe two clinical cases of endovascular treatment of tandem ipsilateral occlusion of ICA and middle cerebral artery (MCA). In both cases, the cause of two-level occlusion was complicated by thrombosis atherosclerotic plaque in ICA in the extracranial part with distal thromboembolism in SMA. The antegrade endovascular approach was used in both patients, when ICA was stented at the first stage, and at the second stage aspiration thrombectomy from SMA was performed. The period from the onset of symptoms to revascularization of the ICA system was 285±63 minutes. There were no fatal outcomes, patients were discharged with different neurological deficits: scores of the first patient were as following: 2 points on the NIHSS, 1 point on a Rankin scale, 13 points (initial 12 points on NIHSS) on the Rivermead mobility index and of the second patient: 14 points on the NIHSS, 5 points on a Rankin scale, 0 points (of the original 17 points on the NIHSS) on the Rivermead mobility index.