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High lipoprotein(a) (LP(a)) level contributes as an independent risk factor to the development of cardiovascular diseases of atherosclerotic origin. The article contains data on the structural features of this particle, the genetic determination of its metabolism and content in blood plasma, and the pathogenic mechanisms of its proatherogenic, proinflammatory and prothrombotic effects. The authors analyzed epidemiological data on the frequency of elevated LP(a) levels in different population groups and its association with the risk of cardiovascular diseases. The data presented concern the indicators of LP(a) as a risk factor for the development of ischemic stroke (including recurrent stroke) and its individual pathogenetic subtypes, as well as the relationship between LP(a) levels and functional outcomes after cerebral accidents. Current recommendations for the treatment of patients with elevated LP(a) levels in the context of primary and secondary prevention of cardiovascular diseases are analyzed.

The paper debates over the classification of spondyloarthritis (SpA). The paper «Diagnosis of spondyloarthritis: Should we need new criteria?» published in the journal «Sovremennaya Revmatologiya=Modern Rheumatology Journal» 2015. No. 1 has given occasion to discussion. Of dispute are the paper’s conclusions: «At present most patients with SpA meet ≥2 classification criteria, which gives the chance to state ≥2 nosological entities in the same patient. This demonstrates the need to elaborate diagnostic criteria that can make a clear distinction between different forms of SpA».The author of this publication touches upon its two interrelated disputable aspects: 1) the specific features of the criteria, which have led to this conclusion and 2) the classification peculiarities, i.e. whether SpA is a single clinical polymorphic disease or a group of a few diseases having a certain common sign.

В первом номере журнала «Современная ревматология» за 2015 г. была опубликована статья И.З. Гайдуковой, А.И. Акуловой, А.В. Апаркиной, А.П. Реброва «Диагностика спондилоартрита: нужны ли нам новые критерии?». В ответ на публикацию статьи в третьем номере журнала вышли комментарии профессора Ш.Ф. Эрдеса.

Depression is one of the most common medical causes of disability and mortality in patients of all ages. Depressive disorders are common in the practice of physicians of a variety of specialties, including psychiatrists, neurologists, and physicians. This paper provides a summary review of the literature on modern ideas about the epidemiology, classification, and clinical picture of depression. Current approaches to the diagnosis and treatment of depressive disorders in neurological and psychiatric practice are discussed. Modern pharmacotherapeutic strategies for the treatment of depression in various patient populations are described in detail. Current clinical practice indicates the high importance of an interdisciplinary approach in the diagnosis and management of patients with depressive symptoms in Russia. The paper suggests organizational and educational strategies that can be recommended to improve the effectiveness of medical care for patients with depressive disorders.

Temporal and parahippocampal glial tumors at early morphological stages of their development may mimic the clinical and neuroimaging picture of limbic encephalitis. Delayed diagnosis of glioblastoma can have a negative impact on the prognosis of the disease, which is why there is a need to find approaches for its earlier detection. The aim of this paper is to analyze possible difficulties and errors in the differential diagnosis of autoimmune encephalitis (AE) and glioblastoma based on literature data and our own clinical observations. Features such as onset of the disease at a young age, subacute development of symptoms, response to immunosuppressive therapy and the MRI imaging of bilateral T2 hyperintense changes in the limbic areas are typical for AE, but do not exclude the diagnosis of a primary tumor of the central nervous system. Therefore, caution should be exercised regarding the likelihood of a primary brain tumor when patients of any age group present with symptoms characteristic of AE, especially if no specific for AE antibodies are detected. To shorten the time to diagnosis, a multidisciplinary approach, critical analysis of clinical data, a shortening of the examination interval and an increase in the frequency of imaging follow-up examinations are required.

The high prevalence of primary affective disorders in patients with epilepsy is beyond doubt. However, patients in this group are often identified as suffering from mood disorders that do not fulfil the criteria for primary mood disorders, such as recurrent depressive disorder and bipolar affective disorder. The aim of this paper is to analyze the classification and clinical picture of affective disorders in patients with epilepsy and differential diagnostic approaches to identify primary affective disorders and secondary affective disorders in epilepsy. A set of diagnostic signs for the differential assessment of affective disorders in patients with epilepsy is presented. Research of affective pathology in patients with epilepsy and the development of strategies for its successful treatment are still needed.

In periodicals, vitamins and vitamin-mineral complexes (VMCs) are “accused” of having allegedly carcinogenic effects. The results of a systematic review of the literature on B vitamins presented in this paper clearly show that vitamins have at least no influence on tumour risk. When analysing experimental and clinical data on this topic, particular attention should be paid to the dosage of vitamins in monotherapy and when used as part of a VMCs.

Impaired cognitive function (CF) is a common manifestation of brain damage as a target organ of arterial hypertension (AH). The presence of hypertension in middle age increases the risk of developing cognitive impairment (CI) and dementia in old age. At the same time, changes in certain indicators characteristic of AH may serve as predictors of CI and dementia in the future. The review presents data on the effects of endothelial dysfunction and increased arterial stiffness on CF. The small number of papers on the effects of hypertension in middle-aged people on the development of CI emphasizes the importance of investigating this topic, as the incidence of CI in young and middle-aged people has increased in recent years.

Currently, more than 15 molecules are already approved for the treatment of multiple sclerosis, and sometimes physicians encounter problems selecting a drug for therapy when considering patients with the initial equivalent characteristics. When selecting a drug, it is important to consider not only the efficacy and safety of the drug, but also the possibility of further therapy after discontinuation of the initially selected drug. This paper discusses the results of clinical trials on the efficacy and safety of ofatumumab and its potential advantages over other anti-CD20 agents.

Dynamic monitoring of the patient's condition is a fundamental element of the modern strategy for the treatment of rheumatoid arthritis (RA), which aims to achieve remission or low inflammatory activity of the disease. A simple and informative indicator that can be used to assess treatment outcomes from a patient's perspective is the Patient Acceptable State Status (PASS).Objective: to determine the severity of patient-reported outcomes (PROs) and their relationship to the PASS indicator in patients with RA in reallife clinical practice.Material and methods. A one-time survey of 945 patients with RA was conducted in paper and electronic form from January to June 2023. The survey included the determination of PROs (pain, fatigue, anxiety, depression, activities of daily living, global assessment of health – GAH, – global assessment of disease activity – GADA) and PASS. The majority of patients were women – 87.8%, mean age – 46.3±13.2 years, median disease duration – 6 [3; 14] years. 80.4% of patients received synthetic disease modifying antirheumatic drugs, 23.9% – biologic disease modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi), 36.5% – glucocorticoids (GC), 82.8% – nonsteroidal anti-inflammatory drugs (NSAIDs).Results and discussion. According to the survey, the severity of joint pain (according to a numerical rating scale, NRS 0–10) was on average 5.3±2.6, fatigue – 6.2±2.6, GAH – 5.4±2.4, GADA – 5.4±2.7, median anxiety – 5 [3; 8], depression – 5 [2; 7], limitation of daily activity – 5 [3; 7]. Satisfaction with their health condition (PASS+) reported 54.8% of patients, dissatisfaction (PASS-) was associated with the presence of moderate/severe pain (NRS ≥4; odds ratio, OR 2.665; 95% confidence interval, CI 2.072–3.429; p ˂ 0.001), fatigue (OR 2.497; 95% CI 1.818–3.430; p ˂ 0.001), anxiety (OR 1.683; 95% CI 1.395–2.029; p ˂ 0.001). PASS- was statistically significant more common in patients taking NSAIDs and GCs and significantly less common in patients receiving bDMARDs and JAKi.Conclusion. PASS is associated with the main PROs (pain, fatigue, anxiety and depression) and can be used as one of the indicators for evaluating the effectiveness of RA treatment.

Multiple sclerosis (MS) is a chronic autoimmune disease that limits the ability to work and lead an active lifestyle, mostly in young adults. Physical activity, along with drug therapy, is an essential part of the life of a person with MS. In the last decades, rehabilitation of MS patients has made great progress. However, the problem of compliance is still relevant. Virtual reality (VR) based rehabilitation can not only improve the quality of the training process but also increase patient compliance.Objective: to study the literature data on the effectiveness of the techniques of VR in reducing the severity of symptoms of MS and improving the quality of life.Materials and methods. A thorough literature search of the MEDLINE (Pubmed), eLibrary, and Google Schcolar databases was performed. Papers that met two criteria were included in the study: study population – patients with MS; presence of at least one comparison group (standard therapy or no therapy).Results. Based on the results of the analysis, 44 articles were selected. The efficacy of VR in reducing symptoms of MS such as fatigue, balance disturbances, risk factors for falls, mobility, apraxia, impaired hand function was described, as well as the impact on overall quality of life and its components.Conclusions. The VR rehabilitation can have its own place in the general system of physical rehabilitation and also become an effective tool to increase motivation and quality of life at all stages of rehabilitation.

Optic neuritis (ON) can often occur at the onset of a demyelinating autoimmune CNS disease or as one of its clinical manifestations. The introduction of novel laboratory techniques, technical advances in magnetic resonance imaging (MRI), electrophysiologic studies, and ocular imaging have significantly expanded the spectrum of autoimmune optic neuropathies. Identification of different forms of ON based on clinical and instrumental data can lead to early diagnosis of the underlying neurologic disorder. According to current guidelines, one can distinguish between typical ON, which are mainly associated with multiple sclerosis (MS), and atypical ON, which are the main clinical manifestation of neuromyelitis optica spectrum disorders (NMOSD) and diseases associated with myelin oligodendrocyte glycoprotein antibodies (MOGAD). In this paper, we present four clinical cases of atypical ON at the onset of NMOSD and MOGAD and illustrate the high diagnostic value of a multidisciplinary approach.

The paper is devoted to frontotemporal dementia (FTD), one of the most common forms of frontotemporal degeneration. The main symptoms of the disease include disinhibition, lack of empathy, obsessive-compulsive symptoms, apathy, cognitive impairment, appetite changes, and progressive changes in social behavior. In parallel, there are personality changes that are characterized by lower levels of self-awareness and by progressive psychological and social maladaptation of patients in society.The paper describes a clinical case of FTD in a female patient with marked behavioral changes and personality disorder. A 52-year-old woman was admitted to the alcoholism treatment department for alcohol intoxication and symptoms of mental confusion. According to her relatives, drinking too much alcohol every day, she was found to become rude, indifferent to others and her own duties, sharply limited the range of her activities and communication, and showed a decline in memory for current events. Psychopathological examination determined a distinct motivational-volitional decrease, the patient’s inability to mobilize mental activity, non-critical thinking, and indifference. X-ray diagnosis revealed the changes characteristic of frontotemporal neurodegeneration (atrophy of the frontal and temporal lobes prevails). The described case confirms that alcohol abuse can mask organic disorders that develop in systemic cerebral atrophy.

Objective: to analyze the roles of undifferentiated connective tissue dysplasia (UCTD) in the development of cartilage and ligamentous apparatus diseases.Material and methods. This paper presents the results of analyzing the literature on fundamental and clinical studies of relationships between chondroitin sulfate (CS) and connective tissue (CT) disease. A total of 922 publications on the relationship between CT dysplasia and CS and 2249 publications on CS receptor molecules were analyzed. These arrays of publications were analyzed using topological and metric approaches to data analysis.Results and discussion. The genetic predisposition to UCTD is substantially aggravated by inadequate nutrition that leads to deficiency of certain micronutrients that support CT reconstructive processes. The paper presents the results of a systematic analysis of prospects for the use of drugs based on standardized CS substances in patients with UCTD. CS is a material for CT reconstruction. CS increases the activity of growth factors and reduces CT inflammatory destruction (inhibition of the secretion of histamine, pro-inflammatory chemokines, Toll-like receptors, and the NF-κB cascade through exposure to the CD44 receptor).Conclusion. The pharmacological effects of CS indicate the importance of using standardized CS forms in the treatment of patients with UCTD.

The paper presents generalized data on psychopathological symptoms that cause food refusal in mentally ill patients. It systematizes information about methods for preventing and supplying nutrient deficiencies in mentally ill patients who refuse to eat. The paper describes clinical cases of probe feeding in psychiatric inpatients when they refuse eat or cannot take food. It provides evidence for the rationality of describing food refusal in mentally ill people and the methods for symptomatic correction of this condition in the current fundamental guidelines on psychiatry.

Chronic pain (CP) is still one of the urgent problems of modern medicine. The paper provides a review of the main pharmacotherapeutic approaches from the standpoint of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) guidelines. When preparing this material, the authors have analyzed the publications available in the resources: PubMed, EMBASE, Cochrane, and еLIBRARY. The paper presents the main pathogenetic mechanisms of pain syndrome development in osteoarthritis (OA), including synovial inflammation and associated immune disorders. It considers the types of development of pain syndrome and the main prognostic outcomes according the mechanism of pain, providing a rationale for the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or chondroprotectors (CPs). In accordance with the ESCEO guidelines, it is noted that when starting OA therapy, CPs should be considered as the first step (in their long-term prescription and pharmaceutical quality), then NSAIDs should be added (topically), then (if ineffective) orally, by excluding patients with hip OA. It is known that the intramuscular administration of CPs (chondroitin sulfate (CS) in particular) can increase their bioavailability. The use of glucosamine sulfate (GS) is recommended for patients over 60 years of age. According to the recommendations of the 2019 ESCEO experts, CS and GS should be used as a disease-modifying OA drug from the first step and at all subsequent stages.

The paper presents the current etiopathogenetic classification of chronic cerebrovascular diseases (CVD) and discusses the role of hypertension, cerebral amyloid angiopathy, and genetically determined syndromes in the development of this pathological condition. It gives recommendations for the neuroradiological diagnosis of chronic CVD in accordance with the international standards. The paper discusses the clinical manifestations of chronic CVD, primarily vascular cognitive impairment. It discusses international guidelines for the examination and treatment of patients with chronic CVD, as well as the rules for stroke prevention in this patient cohort. The possibilities of pathogenetically based therapy in decreasing the severity of vascular cognitive impairment in the presence of chronic CVD are also highlighted.

The paper reviews clinical trials evaluating the efficacy of N-methyl-D-aspartate (NMDA) receptor antagonists used to treat various neurological diseases: neurodegenerative dementias, vascular cognitive disorders, including post-stroke cognitive impairment. It discusses the possibility of treating cognitive disorders with NMDA receptor antagonists in Parkinson's disease, traumatic brain injury, and some other diseases, as well as the potential possibilities of using drugs of this pharmacotherapeutic group in childhood. The paper describes a clinical case illustrating the use of akatinol memantine in a child with a delay in speech and mental development in the presence of fetal alcohol syndrome. The possibilities of using akatinol memantine in the treatment of childhood cognitive impairments are sure to be of particular interest; however, in view of the small amount of data, this aspect requires further clinical trials.

The paper deals with the actual problem of managing patients with drug-induced headache (DIH) in patients with primary headaches. It describes a clinical case of extremely severe DIH in a patient with chronic tension headache (TH). The paper analyzes the typical and atypical manifestations of DIH and discusses the role of prolonged stress in the development of TH. Special attention is paid to the problems with therapy and compliance during a long-term follow-up of the patient. Based on the clinical features of pain syndrome in the described patient, the authors suggest for the first time that the use of extremely high number of daily doses of combined narcotic analgesics for many years can result in recurrent DIH statuses. The paper discusses whether it is expedient to introduce the concept “DIH severity” and whether an additional clinical parameter “the number of doses of painkillers per month” can be of informative value, which has not been proposed yet in the literature. All the issues given in the paper are conjectural and are raised by the authors for further investigation of the DIH problem.

The paper provides a review of the data available in the literature on the relationship of pain to the risk of OA progression. Network analyses and numerous studies, including those conducted at the V.A. Nasonova Research Institute of Rheumatology, have confirmed that pain syndrome is one of the significant predictors of knee OA progression. The major class of medications for OA pain includes nonsteroidal anti-inflammatory drugs. The paper gives data on the efficacy of meloxicam in OA patients, which is widely used in both Russia and other countries of the world. Meloxicam is characterized by a good safety profile in the gastrointestinal tract, cardiovascular and renal systems. It is the drug of choice in patients with musculoskeletal diseases, in particular OA. Good results in severe pain syndrome have been shown by a step-by-step regimen of meloxicam when the injection formulation of the drug is used in the first days of treatment, and then, to consolidate what has been gained from therapy, its oral dosage form is administered in terms of concomitant diseases.

The paper deals with an update on biologically active additives (BAAs) and emphasizes their role in normalizing and/or improving the functional status of organs and systems, including the gastrointestinal tract microflora, in reducing the risk of diseases, etc. It gives data on the consumption and turnover of BAAs, definitions and classifications of this group of substances, the basic documents governing the control of their production and promotion in different countries and in Russia. Undenatured type II collagen (UC-II® ) that is made from the chicken sternal cartilage and is a component of Sustaflex is considered as an example of the BAA that is compliant with good medical practice regulations. The therapeutic properties of UC-II® have been confirmed in clinical trials. The paper describes the mechanism of action of the BAA, evidence for its efficacy and safety, and the possibility of its administration for the prevention and combination treatment of knee osteoarthritis (OA) and its use as an alternative treatment for OA.

The paper describes three clinical cases of ischemic stroke (IS) in the presence of patent foramen ovale (PFO) in young women. The first patient has experienced two episodes of focal neurological deficit related to physical exercise. A cerebellar stroke focus was visualized by brain magnetic resonance imaging (MRI). During emotional stress, the second patient having migraine with aura developed transient weakness in the right extremities, and a stroke focus was verified in the left parietal lobe. The third patient suddenly had facial asymmetry and left arm numbness after awakening in the morning. The patient underwent intravenous thrombolysis; control brain MRI revealed a right parietal lobe stroke. Standard examinations of all the patients established no cause of IS. Transcranial Doppler with a bubble test and subsequent transesophageal echocardiography revealed PFO that was regarded as clinically significant. Endovascular occlusion was successfully accomplished in all the patients. The paper discusses the problems of secondary prevention of PFO-related stroke and proposes an algorithm for the diagnosis and treatment of this disease.

The paper reviews Russian and foreign literature on atypical depression (AtD). It sets forth the historical aspects of identifying AtD among other depressive disorders: the authors have traced the path from depression with individual atypical manifestations to a syndrome with a clearly defined pattern and inclusion criteria in the international DSM-4 and DSM-5 classifications. The paper gives epidemiological indicators and shows their diversity due to various approaches to the determination and clinical assessment of AtD. It analyzes the results of studying AtD in the presence of various affective disorders, such as recurrent depressive disorder, bipolar affective disorder, and psychogenic depression, and notes their heterogeneity in both symptoms and genesis. The authors present approaches to treating AtD and the results of investigating drug (antidepressant) and non-drug (cognitive-behavioral psychotherapy, increased physical activity therapy) treatments.

The paper considers the aspects of clinical manifestations, diagnosis, and therapeutic approaches in alcoholic polyneuropathy (PNP). It gives the data available in the literature on the prevalence of this disease in different countries and on the frequency of alcohol drinking in men and women. The author describes main risk factors for alcoholic PNP, such as malnutrition, thiamine deficiency, direct alcohol toxicity, and a familial history of alcoholism. She characterizes the most important pathogenetic mechanisms in the development of PNP. Particular attention is paid to the clinical presentations and diagnosis of main types of PNP, such as toxic alcoholic (due to directly toxic effects of alcohol metabolites) and alcohol-related thiamine-deficient ones. The paper presents the management tactics in patients with various types of alcoholic PNP, which include combination treatment and ensure the impact (alcohol refusal; balanced nutrition with the addition of various medications) on the etiological factor of the disease. Taking into account the available evidence base, it is necessary to prescribe B-group vitamins to these patients. Alpha-lipoic acid preparations that have an effect on the peripheral and central nervous systems occupy a separate place in the treatment.

The paper systematizes the history of studying the neurochemical activity of mianserin and mirtazapine. The concept of the development of the antidepressant effect of these drugs, by stimulating the release of norepinephrine into the synaptic cleft, is shown to have gained unanimously acceptance. The data on manifestation of their thymoleptic effect due to stimulation of the release of serotonin into the synaptic cleft have been disputed. Other neurochemical theories of the development of the antidepressant activity of mianserin and mirtazapine have been unproven or rejected. The history of identifying the position of mianserin and mirtazapine in the classification of antidepressants has been generalized. The paper shows the ambiguity of approaches to this issue. As turned out, the legality of using the term «noradrenalinergic and specific serotonergic antidepressant» has been criticized. Analysis of historical facts has identified that it is rational to assign mianserin and mirtazapine to one neurochemical group and its designation by the term «norepinephrine and (presumably) serotonin release stimulators – α2-adrenergic receptor and serotonin 5-HT2 receptor blockers».

A.R. Luria is one of the most prestigious scientists in neuroscience, neuropsychology in particular. His contribution to aphasiology and neurolinguistics is well known. However, today some researchers believe that A.R. Luria's main ideas have lost their relevance and have little influence on contemporary discussions. The paper presents the views of A.R. Luria on the brain organization of speech and aphasia. Although he developed his concept of the relationship between cognitive processes and brain work several decades ago, scientific and technological achievements in our days largely confirm many of his ideas and hypotheses. A.R. Luria's basic views of the brain and language are considered in this article in the light of modern neuroscience. Two main monographs and some works of A.R. Luria, which are dedicated to the brain organization of speech and to the classification of aphasia, are analyzed. In particular, comparisons are made between his initial assumptions about aphasia and their theoretical rationale in the book «Traumatic Aphasia» (1947) and his more complex interpretation of the cerebral organization of speech, which is presented in his work «Basic Problems of Neurolinguistics» (1975). The paper discusses differences between these two books and also linguistic issues, which received much attention in his later publication. It considers the concepts of functional systems, systemic and dynamic organization of speech, proposed by A.R. Luria. It is shown that his interpretation of the cerebral organization of speech as a specific contribution of various brain regions to the speech system continues to be widely used, and his significant contribution to neurolinguistics is widely recognized.Many ideas of A.R. Luria have been integrated into contemporary aphasiology, while some questions of his proposed classification of aphasia remain debatable.

The paper considers the epidemiology and general etiological characteristics of cryptogenic stroke (CS). It discusses the concept of embolic stroke with an unknown source of embolism. It also characterizes the most significant causes of CS, such as paroxysmal atrial fibrillation, atrial cardiopathy, aortic atheroma, non-stenotic cerebral atherosclerotic plaques, and malignant neoplasms. The paper describes approaches to the diagnosis and secondary prevention of CS and proposes etiological and neuroimaging diagnostic algorithms for CI. Clinical cases are also presented.

The paper presents experience with antithrombotic therapy in a critically ill patient with acute coronary syndrome and transient ischemic attack. It characterizes problems in triple antithrombotic therapy in a very ill patient with comorbidity. The paper demonstrates an incremental approach to choosing therapy according to the clinical picture of disease, an assessment of risk factors for ischemic and hemorrhagic complications over time, which is very important in the routine practice of a physician. It also shows how, based on existing recommendations, the optimal anticoagulant is chosen as part of triple and double antithrombotic therapy in terms of its potential risks and possible complications.

The paper describes a clinical case of the rare status epilepticus syndrome FIRES (febrile infection responsive encephalopathy) + NORSE (new-onset refractory status epilepticus). The difficulty of diagnosing this condition is due to the fact that it occurs extremely rarely and the laboratory and instrumental findings are nonspecific. The disease is characterized by acute onset, fever, and subsequent development of status epilepticus, cognitive impairment, and pharmacotherapy-resistant epilepsy. The paper describes a 19-year-old male patient who was observed to have a favorable course of FIRES + NORSE syndrome without pharmacotherapy-resistant epilepsy, motor deficiency, and with the preservation of self-care skills.

The problem of alcohol abuse and its social and medical consequences has remained relevant for many years. Damage to the nervous system is one of the most common manifestations of alcoholic disease. The effect of ethanol and its metabolites results in damage to all parts of the nervous system and skeletal muscles. The paper provides a brief overview of Russian and foreign literature on the neurological manifestations of chronic alcohol intoxication. It considers modern ideas about the pathogenesis of alcoholic neuropathy (APN). It also discusses differences in the clinical presentation, course, and developmental mechanisms of the main (chronic toxic and acute/subacute) forms of APN associated with thiamine deficiency. The paper notes difficulties in diagnosing peripheral nerve damage, especially in the early stages of the disease and describes modern methods for objectifying damage to thin nerve fibers in chronic APN. It presents approaches to treating alcohol-induced damage to the peripheral nervous system, by taking into account the leading mechanisms of pathogenesis. Special attention is paid to B-complex vitamins and alpha-lipoic acid preparations frequently used in this disease, to the mechanisms of their therapeutic action, and to the evaluation of their efficacy in APN.

Nonsuicidal self-injuries (autotomy, self-inflicted destruction, self-mutilation) is a variant of autoaggression in a patient without the intent to take his/her own life. Patients with the consequences of self-injuries receive help from physicians of various specialties, who often cannot determine their motivation for autoaggressive actions, since it is associated with mental disorders. The paper presents data on phenomenology, some classifications and motivation of nonsuicidal self-injuries. Various mental disorders are noted to be the most common cause of autoaggressive behavior. The paper describes a clinical case of a female patient who has mutilated her face for a long time, hiding the cause of her autoaggressive action. A detailed clinical and psychopathological analysis of her medical history and mental status allowed for classifying hypochondriacal delirium within schizophrenia as a cause of self-mutilating actions. The motivation for this behavior was to fight against a pseudotumor, for which the patient suffered pain and prolonged suppurative processes on the skin of the face, without visiting physicians.

The paper is devoted to the safe use of hormonal contraception in women with migraine, an urgent interdisciplinary problem daily faced by gynecologists, neurologists, and specialists in headache diagnosis and treatment. It gives information on the prevalence of migraine, the risk of ischemic stroke and other cardiovascular disorders in women with different types of migraine, including those receiving contraception and hormone replacement therapy. The paper presents the main provisions of the new interdisciplinary consensus «Hormonal contraceptives and the risk of ischemic stroke in women who have migraine», which are recommended to be taken into account by specialists of any profile when prescribing hormonal therapy to women with migraine in order to avoid cardiovascular events.

The paper reviews of the data available in the literature on the clinical efficacy and safety of tofacitinib (TOFA) in the treatment of psoriatic arthritis (PsA). It considers the mechanism of action of TOFA, which is mainly in the selective inhibition of signal transmission due to its effect on the activity of JAK3 and/or JAK1, the enzymes that ensure the function of turning on and turning off the signals transmitted by cytokines. TOFA is noted to directly or indirectly act on a wide range of a number of molecules that play an important role in the pathogenesis of PsA.The paper analyzes the current data on the clinical efficacy of TOFA in treating PsA, which have been obtained in the 12-month OPAL Broaden study including patients with PsA and an inadequate response to synthetic disease-modifying anti-rheumatic drugs and in the 6-month OPAL Beyond study enrolling those with PsA and an inadequate response to tumor necrosis factor-α (TNF-α) inhibitors. It is noted that the results of these studies confirmed the efficacy of the drug in treating PsA not only according to the data of objective (medical) monitoring, but also to the subjective characteristics of pain, to the global assessment of disease activity, fatigue, as well as the mental and physical components of the SF-36 quality of life questionnaire.It is concluded that the current findings allow JAK inhibitors to be recommended as a new pathogenetically sound approach to treating PsA and suggest that TOFA has benefits in managing patients unresponsive to therapy with TNF-α inhibitors.

For the first time, the paper presents in detail the prevalence of osteoarthritis (OA) and considers the predictors of disease development and progression. The clinical classification of OA and its place in the ICD-10 are described. The clinical presentation of the disease is characterized in detail according to the localization of the process. It is noted that there is a change in the understanding of OA as a classic model of nociceptive pain. The paper depicts clinical, laboratory, and instrumental methods for diagnosing the disease, as well as classification and diagnostic criteria; much attention is paid to the current principles of OA therapy according to the Russian clinical recommendations and the guidelines of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the European League Against Rheumatism (EULAR).

The COVID-19 pandemic is a global health emergency. The relevance of this problem in immunoinflammatory rheumatic diseases is due to the increased risk of infection with SARS-CoV-2 and its severe course. The paper describes the clinical features and morphological changes in organs in a patient with rheumatoid arthritis and secondary amyloidosis of the heart and kidneys, who died from an infection caused by SARS-CoV-2.

It is well known that a complex of nervous and hormonal signals during stress stimulates adrenal glands to secrete adrenaline, norepinephrine and cortisol. Much less attention has been paid to the roles of intermediate signaling proteins mediating the effects of “stress hormones”, neurotransmitters, and other signaling molecules. This paper presents the results of a systematization of studies of glycogen synthase kinases GSK-3α and GSK-3β, whose excessive activity aggravates the course of chronic stress, has a negative effect on neuronal survival and adaptation processes. Lithium ions are a natural inhibitor of the excessive activity of both GSK-3, which partly determines the normothymic and antidepressant effects of lithium drugs. Taking lithium salts based on organic anions is the safest and most effective way to replenish lithium deficiency in the body. The prospects for the use of lithium ascorbate to increase the body's adaptive reserves are considered.

Gout is associated with the high frequency of comorbidities, among which there are cardiovascular disease and kidney diseases. In this case, cardiovascular mortality rates are in the first place among the causes of death in patients with gout and exceed the death rates in the population. This may be associated with the main signs of gout, such as a high serum uric acid (UA) level and its related chronic inflammation. Drug correction of hyperuricemia is the mainstay of gout therapy and it is supposed to be able to neutralize the negative effect of UA on the risk of its associated adverse events. Xanthine oxidase inhibitors (allopurinol and febuxostat) are first-line urate-lowering agents. Their effect on UA levels, comorbidities, long-term outcomes (including overall and cardiovascular mortality, development and progression of chronic kidney disease), and occurrence of adverse reactions is studied in large-scale studies, the results of which may affect the strategy of such therapy.The paper discusses the advantages and disadvantages of the CARES (Gout and Cardiovascular Morbidities) study that has compared the cardiovascular safety of allopurinol and febuxostat. The findings suggest that there is no substantial difference in the frequency of cardiovascular events with febuxostat and allopurinol, but at the same time these demonstrate a high risk for cardiovascular and overall mortality in the febuxostat group. Analysis of this paper cannot conclude that there is a greater cardiovascular risk with therapy with febuxostat; however, it shows that when compared with allopurinol, this risk may be higher. A more detailed study of this issue is required after obtaining the results of already started and planned investigations comparing the effects of allopurinol and febuxostat on the risk of adverse cardiovascular events in patients with asymptomatic hyperuricemia.

Regulatory T cells (Tregs) is a CD4+ lymphocyte subpopulation that maintains autotolerance by suppressing the activity of autoreactive lymphocytes. There is a hypothesis that functional defects or a smaller number of Tregs underlie the pathogenesis of a number of autoimmune diseases. The paper considers the main features of the phenotype of Tregs. It discusses the number of Tregs in both peripheral blood and affected organs in systemic lupus erythematosus, as well as the time course of changes in the level and functional abilities of different subpopulations of Tregs during immunosuppressive therapy. In addition, the paper presents various approaches to using Treg lymphocytes in the therapy of autoimmune diseases.

Osteoarthritis (OA) belongs to diseases with high comorbidity and is most frequently concurrent with hypertension and other cardiovascular diseases (coronary heart disease, atherosclerosis), obesity, and diabetes mellitus. The paper deals with the use of delayed-release symptomatic medications in the treatment of patients with OA and comorbidity. It reviews clinical trials of the efficacy and safety of diacerein in OA patients and its effect on comorbidity. The paper discusses the possibility of using diacerein as an alternative to traditional nonsteroidal anti-inflammatory drugs in patients with contraindications to the latter.

The paper is devoted to the most common variant of cerebral small-vessel disease Р sporadic cerebral non-amyloid microangiopathy (SCNAMA) in the context of acute and chronic cerebral circulatory disorders. It highlights the topical issues of neuropathology and pathogenesis of the disease. The paper presents the current neuroimaging markers of SCNAMA with a detailed discussion of lacunar infarcts, cerebral microinfarctions, and microbleeds. It considers the clinical manifestations of the chronic form of the disease, including cognitive impairment. The problem in the differential diagnosis of SCNAMA and cerebral amyloid angiopathy is highlighted. The current possibilities of minimizing risks and improving the efficiency of treatment in this category of patients are discussed.

Despite progress in the development of treatments and prevention for the new coronavirus infection COVID-19, there is still insufficient data on the impact of the global pandemic on people's mental health, in particular on the nature of mental disorders resulting from both the impact of SARS-CoV-2 on the central nervous system, and the impact of stress factors associated with the pandemic on the mental state, which indicates the relevance of the problem and the need for further research. The article presents data on mental disorders that occur for the first time in life under the influence of restrictive measures, quarantine and other factors caused by the epidemic in the general population. The specificity of the influence of these factors on persons diagnosed with mental illness is also shown. The papers that present the results of studies of mental disorders in patients in the acute period of infection and after recovery are analyzed. The possible consequences of COVID-19 for the mental health of people are considered.

Epileptic seizures require differential diagnosis with other paroxysmal conditions, including metabolic seizures. A variety of electrolyte changes can result in central nervous system dysfunction, including that as convulsive seizures. The paper describes electrolyte disorders leading to seizures, as well as their clinical features. It separately presents the syndromes accompanied by hypocalcemia, in which there may be convulsive paroxysms. The paper describes three clinical cases of hypocalcemic seizures. It gives recommendations for the diagnosis and management of patients with suspected metabolic seizures.

The paper systematizes data on the pharmacokinetics, molecular and cellular mechanisms of action of chondroprotectors (CPs), by using chondroitin sulfate (CS) and glucosamine (GA) as an example. It presents current ideas about the mechanisms of their absorption and penetration into the joint tissues during oral administration, the effect of CS on the cytoplasmic membrane of chondrocytes in osteoarthritis (OA). The paper also describes the plastic and regulatory functions of GA at the intracellular level after its penetration into the cells by glucose carriers. The combination of benefits from targeted and metabolic therapy determines the efficacy of combined CPs, the active principle of which is CS and GA.

The clinical picture of the symptomatic phase of antineutrophil cytoplasmic antibody-associated systemic vasculitis (ANCA-SV) can vary widely and be accompanied by joint damage, which complicates the early diagnosis of the disease. The paper presents a case of ANCA-SV with acute kidney injury, the manifestations of the symptomatic phase of which were confined to joint damage, myalgia, and Raynaud's syndrome, which led to delayed diagnosis at the stage of renal failure requiring hemodialysis (HD). Urgent adequate induction therapy could preserve kidney function, despite 10-day anuria and 5-week HD.The paper discusses the need for a systematic detailed examination of patients with the onset of a joint inflammatory lesion, especially in those with its systemic manifestations, and the inclusion of serum ANCA tests in the standards of diagnosis in early arthritis.

Charles Bonnet syndrome (CBS) includes the visual hallucinations in patients with decreased/lost vision in both eyes or hemianopsia, which are unassociated with cognitive dysfunction or confusion. The paper describes a clinical case of a 77-year-old woman who had daily complex mobile visual hallucinations occurring mainly in the early dawning with open eyes and in clear consciousness. The patient was referred to the vascular center with lacunar stroke detected by magnetic resonance imaging, which was asymptomatic and could not cause hallucinations. The latter appeared for the first time a year before stroke in the presence of a dramatic bilateral visual decrease caused by proliferative diabetic retinopathy. The hallucinations were regarded as a manifestation of the CBS. Adequate therapy led to their disappearance. The paper provides a review of current publications on the prevalence, causes, clinical presentations, and treatment of CBS.

The widespread use of parenteral chondroprotectors is a feature of Russian medical practice. There are many drugs of this series in a Russian physician's arsenal, including chondroitin sulfate (CS), glucosamine sulfate (GS), glycosaminoglycan-peptide complex, and bioactive concentrate from small sea fish for intramuscular injections. The paper analyzes Russian trials of the efficacy and safety of two injectable formulations of CS and GS (ICS and IGS). ICS was tested in 17 articles containing a total of 1639 patients with osteoarthritis (OA), non-specific back pain (NBP), or shoulder fractures and pain after stroke. Standard therapy (NSAIDs + physiotherapy) served as a control in the majority of the paper. In these trials, the reductions in visual analog scale (VAS) and WOMAC pain in OA treated with ICS averaged 58.2±22.3% and those were 26.1±14.7% in the control groups; the reductions in VAS NBP reached an average of 87.1±16.8 and 62.2±21.7%, respectively. ICS also showed a good effect in shoulder fractures and pain after a stroke. The number of local adverse reactions after injections was insignificant (4.4%); they did not threaten the health of patients and they caused ICS to be discontinued only in 3 cases. IGS was investigated in two trials (n=154), which confirmed its efficacy (total pain relief >50%) and relative safety. Thus, the data of Russian trials suggest that ICS and IGS have good therapeutic potential and favorable tolerance.

The paper presents an analytical literature review of the use of rituximab (RTM) in patients with systemic lupus erythematosus (SLE). It considers current views on the mechanisms of action of RTM, its efficacy in different organ damages in patients with SLE, particularly in those with lupus nephritis and central nervous system involvement. There is evidence suggesting that it is expedient to use RTM in patients with high activity of SLE, especially when the latter is refractory to standard therapy with glucocorticoids and cytostatics. Attention is paid to the steroidsparing effect of RTM and to the reduction of the risk of irreversible organ damages associated with high-dose prednisone. The paper discusses the possibility of using a RTM biosimilar (Acellbia) and prospects of RTM therapy for early SLE.

The paper presents an overview of studies assessing health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE). It describes the HRQoL concept and prerequisites for its creation. The classification of questionnaires used in patients with SLE is considered in relation to the study objectives. The main key triad (fatigue, pain, and depression), which causes a reduction in HRQoL in SLE patients, is derived on the basis of many studies. The paper provides brief comparative characteristics of eight specific HRQoL questionnaires in SLE patients: Symptom checklist (SSC), SLEQol, LupusQol, L-QoL, LupusPRO, and Lupus Impact Tracker (LIT), LUP-QoL, and SMILEY. Special attention is paid to HRQoL assessment in patients receiving different treatment options: glucocorticoids, cytostatic and anti-B-cell therapy.

The paper gives the data available in the literature on the relatively rare disease hypertrophic osteoarthropathy (HOA). This syndrome includes symptoms, such as clubbed fingers (hypertrophy of the distal phalanges), periostosis (subperiosteal new bone formation along the distal diaphysis of the long bones with further progression in the proximal direction) and arthritis, as well as skin changes (pachydermia) that are not an obligate sign. There is information concerning the pathogenesis, clinical, laboratory, and instrumental manifestations of this disease. The paper describes a clinical case of primary HOA in a teenager who has been misdiagnosed with juvenile idiopathic arthritis (JIA). It shows the necessity of including HOA in the spectrum of differential diagnosis in children with articular involvement since HOA may resemble JIA in its clinical manifestations. Patients with primary HOA who have been misdiagnosed with JIA have a long ineffective experience with immunosuppressive and sometimes even glucocorticoid therapies. The specific features that can distinguish the full form of primary HOA from chronic arthritis is the absence of inflammatory changes in the synovial fluid, the presence of clubbed fingers, pachydermia and the lack of morning stiffness.

Slow-acting symptomatic drugs (SYSADOA) occupy one of the leading positions in the complex treatment of osteoarthritis (OA). These drugs have a symptomatic and structure-modifying effect, while they are well tolerated and rarely cause serious adverse reactions (AEs). This review examines the evidence base for the use of one of the most popular SYSADOAs, avocado-soybean unsaponifiable compounds (ASACs, Piascledine 300).Objective: to provide the most complete analysis of clinical trials of ASACs in OA.Patients and methods. We performed a search in English-language (PubMed) and Russian-language (eLIBRARY.ru) electronic libraries for publications on clinical studies of the efficacy and safety of ASACs in OA. Among the English-language publications were selected: 3 randomized controlled trials (RCTs) of ASACs and their symptomatic effect (n=587), 2 RCTs of the structure-modifying effect of ASACs (n=562), 1 RCT comparing the effect of ASACs and chondroitin sulfate (n=364), and 1 observational study of ASACs in real practice (n=4185). Among the Russian- language publications, 1 observational study of ASACs in real practice (n=6448) and 5 papers containing data from open clinical trials of ASACs (n=356) were found.Results and discussion. According to the results of the presented studies, ASACs have proven efficacy in reducing the intensity of pain and dysfunction in knee OA. There are data confirming the structure-modifying effect of ASACs in OA of the hip joint (HJ). This drug is well tolerated: in RCTs, the incidence of AEs during ASACs and placebo usage was comparable. In observational studies (n=10 634), there were no serious AEs associated with the use of ASACs.Conclusion. There is a robust evidence base for the expediency of the active use of ASACs in knee OA. Given the similarity of the pathogenesis of OA of different localizations, the data of individual successful studies and a favorable safety profile, the use of ASACs can also be considered as a component of the complex treatment of OA of the hip joint, hand joints and spine.