Abstract: When examining a patient with lumbosacral pain, it is necessary to rule out the specific cause of the disease. The diagnosis of discogenic lumbosacral radiculopathy (DLSR) is based on clinical examination; magnetic resonance imaging (MRI) is of informative value in excluding other causes of radiculopathy and in evaluating disk herniation. If the signs of cauda equina and spinal cord compression are absent, and no epidural glucocorticoid injection or urgent surgical treatment is scheduled, there is no reason for early (within the first 4 weeks) MRI. It is recommended to inform the patient with DLSR about the possibility of disk herniation regression and natural recovery and about the advisability of maintaining physical activity. Epidural administration of local anesthetics and glucocorticoids and use of non-steroidal anti-inflammatory drugs are advisable to relieve acute pain. Anticonvulsants (pregabalin and gabapentin), muscle relaxants, and B vitamins can be used as additional methods for acute DLSR; psychological therapies (cognitive behavioral therapy), antidepressants, therapeutic exercises (kinesiotherapy), manual therapy, and acupuncture are effective in chronic DLSR. Consultation with a neurosurgeon for possible microdiscectomy is indicated in the presence of cauda equina syndrome (urgently) and in the absence of medical therapy effects within 4–8 weeks. Therapeutic exercises (kinesitherapy) with an educational program for prevention of strenuous physical activity and static and uncomfortable positions for a long time, as well as for teaching how to lift weights properly, etc. are recommended for preventive purposes.

Abstract: 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.

Abstract: 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.

Abstract: Objective: to elucidate the frequency and pathogenesis of myofascial pain syndrome (MFPS) in chronic nonspecific lower back pain (CNLBP) and to optimize the diagnosis and treatment of MFPS in CNLBP. Patients and methods. The investigation covered 121 patients with CNLBP. The patients' mean age was 42.1±10.5 years; the pain duration was 7.9±4.3 months. The possible causes of CNLBP were determined: these were facet joints (FJs); sacroiliac joints (SIJs); skeletal muscles with the development of MFPS; MFPS concurrent with FJs; MFPS concurrent with SIJs. Twenty patients had MFPS only (its mean duration was 5.3±2.2 months; the mean pain intensity scores were 6.5±1.1 on a numerical rating scale). Six patients underwent examinations of open biopsy specimens of the muscle straightening the spinal column; a comparison group consisted of 3 healthy women matched for age and gender. The patients were prescribed therapy with aceclofenac 200 mg/day in combination with tolperisone 450 mg/day and nondrug therapy (cognitive behavioral therapy and kinesio- and ergotherapy). When the treatment was insufficiently effective, ultrasonography of the muscle straightening the spinal column was additionally performed; a local anesthetic was injected into myofascial trigger points (MTPs). Results and discussion. MFPS was a cause of pain syndrome in 63 (52%) patients, while MFPS this was an isolated cause of pain in 20 (16.5%) cases and was concurrent with FJ osteoarthritis in 23 (19%), and with SIJ dysfunction in 20 (16.5%). Muscle ultrasonography in patients with MFPS revealed MTPs, whereas examinations of biopsy specimens of the muscle straightening the spinal column showed no evidence of necrosis, fibrosis, or inflammatory infiltration in the presence of transformation of the myosin phenotype, by increasing the proportion of rapidly fatigued type II muscle fibers. The results of sodium dodecyl sulfate (SDS) gel electrophoresis indicated a decrease in the content of titin and nebulin, the sarcomeric cytoskeletal proteins involved in maintaining muscle contractility. A two-week cycle of therapy with aceclofenac and tolperisone reversed pain syndrome in 5 (25%) of the 20 patients and reduced the intensity of back pain in 15 (75%), but the pain increased during physical exercise and impeded active rehabilitation. The additional administration of anesthetics into MTPs and the continuous intake of aceclofenac and tolperisone in combination with kinesiotherapy could relieve pain syndrome and enhance motor activity. Conclusion. More than half of the patients with CNLBP had MFPS only or concurrent with joint pathology (FS and FJs). The changes found in the back muscle biopsy specimens of patients with CNLBP are potentially reversible and can be reversed during kinesiotherapy.

Abstract: Management of patients with chronic pelvic pain (CPP) is an actual interdisciplinary problem of modern clinical medicine. CPP is chronic or persistent pain lasting more than 6 months, which is located in the structures related to the male or female pelvis and is associated with negative cognitive, behavioral, and emotional consequences, as well as with lower urinary tract, bowel, and pelvic floor symptoms, and reproductive and sexual dysfunction. In accordance with the biopsychosocial model, CPP is the result of a dynamic interaction of biological, psychological and sociocultural factors. When diagnosing CPP, it is most acceptable to phenotype patients according to the UPOINTS classification. To implement the treatment strategy, it is necessary to adhere to a multidisciplinary personalized approach to pain management with active patient participation. Cognitive behavioral therapy (CBT) occupies an important place in the treatment of CPP. There is clinical and neurophysiological evidence of the efficiency of CBT in patients with CPP, a protocol has been developed for the combined use of CBT and physical therapy. CBT is recommended to be included in a comprehensive treatment and rehabilitation program for patients with CPP.

Abstract: Acute pain, especially musculoskeletal and postoperative pain, is widespread pathology associated with quality of life deterioration, temporary disability, a tendency to relapse, and, in some cases, chronicity, so the timely and adequate treatment of this condition is important, including from the point of view of the prevention of serious medical, social, and economic consequences. Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered as first choices in modern guidelines for the treatment of musculoskeletal pain. Centrally acting muscle relaxants and their combinations with NSAIDs are also the basic component of dorsalgia treatment. However, the evidence base is available only for individual muscle relaxants, for orphenadrine in particular. The incorporation of NSAIDs as part of multimodal postoperative analgesia considerably reduces the need for opioids, lowers the risk of developing adverse reactions of the latter, and enhances patient satisfaction with the quality of pain relief. Centrally acting muscle relaxants having analgesic properties, for example tizanidine and orphenadrine, would be appropriate for use as part of multimodal analgesia. The paper discusses the pharmacological properties of a fixed combination of diclofenac and orphenadrine (Neodolpasse ® ), its advantages over monotherapy with individual ingredients, and the results of clinical trials of this combination in spinal pain syndromes and in the postoperative period.

Abstract: Early diagnosis of susceptibility to psychoactive substance (PAS) use and addiction is a pressing problem of addictology. The development of PAS dependence involves a reward system that also plays a key role in the modulation of nociception. The PRDM12 gene associated with congenital insensitivity to pain is involved in neurogenesis and affects the properties of nerve cells. Objective: to comparatively assess pain sensitivity in mental and behavioral disorders caused by the use of PASs in healthy individuals and subjects with their occasional uses according to the genotype of rs10121864 in the PRDM12 gene. Patients and methods. Examinations were made in 103 patients with addiction to PAS (F1x.2), in 114 apparently healthy individuals (a control group) and in 36 subjects who occasionally used PASs (a risk group). The pain sensitivity threshold and pain tolerance were determined by tensoalgometry; a subjective assessment of pain thresholds was made using a visual analogue scale. Genotyping was performed using the PRDM12 rs10121864 polymorphism. Results and discussion. The distribution of the genotypes of PRDM12 rs101218 was statistically significantly different in the comparison groups. Odds ratio (OR) calculation showed that in the subjects who occasionally used PASs, the risk of their dependence was several times greater than that in carriers of the mutant A allele (OR, 2.52; 95% confidence interval (CI), 1.42–4.50) of rs10121864 and its homozygous genotype AA (OR, 6.66; 95% CI, 1.50–29.54) and in those of alternative genotypes. The PRDM12 was also found to be associated with the parameter of subjective assessment of pain sensitivity in PAS-dependent subjects. Thus, this parameter was significantly lower in the carriers of the mutant A allele than in those of the GG genotype. Conclusion. The A allele and AA genotype of PRDM12 rs10121864 were established to be associated with the risk of PAS dependence and with the parameter of subjective perception of the upper pain threshold.

Abstract: Nonspecific back pain (NBP) is one of the most common reasons to see a neurologist or therapist. Acute ( 12 weeks) NBPs are recognized. The diagnosis of NBP is based on anamnestic data, somatic, neurological, and neurologic-and-orthopedic examination findings and on the exclusion of the specific causes of back pain, discogenic radiculopathy, and vertebral canal stenosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants are used in the pharmacotherapy of acute, subacute, and chronic NBP. Tolperisone is widely used as a muscle relaxant in Russia and in the countries of Europe and Asia. Clinical trials have shown the efficacy and good tolerance of tolperisone used alone and in combination with NSAIDs for NBP. The review presents clinical recommendations from different countries on the use of muscle relaxants in the treatment of acute and chronic NBP. It is concluded that a large-scale qualitative randomized trial should be conducted to investigate the efficacy of muscle relaxants, tolperisone in particular, in the treatment of acute, subacute, and chronic NBP.

Abstract: Addictive behavioral disorders are multifactorial diseases with clinical, neurophysiological, and genetic heterogeneity, a high comorbidity with other disorders, and a low curability. The etiopathogenetic mechanisms of non-chemical forms of addictive behavior have not been sufficiently studied, which makes it difficult to search for effective therapeutic procedures. Objective : to study the psychological and genetic components of a non-chemical addictive disorder as the phenomenon of codependency. Patients and methods . The investigation enrolled 256 women who were divided into three comparison groups: 1) those with the phenomenon of codependency, 2) phenotypically healthy women; 3) a population sample. Psychometric testing was carried out using the «Hand Test» by E. Wagner (adapted by A.I. Gerasimov and S.N. Enikolopov) and the clinical and genealogical characteristics of women with the phenomenon of codependency were studied. Results and discussion. There was a statistically significant predominance of the level of aggressiveness as autoaggression in the structure of the personality profile of women with the phenomenon of codependency (t=2.924–3.015; p=0.004–0.005). The clinical and genealogical characteristics of persons with addictive behavioral disorder as the phenomenon of codependency suggest that there is a statistically significantly high frequency of secondary alcoholism among first-degree and second-degree relatives or both and first-degree male relatives (p<0.001). Conclusion . The phenomenon of codependency as a non-chemical addiction includes psychological and genetic components. Women with codependency had autoaggressive destructive behavior patterns and a family history of alcoholism. The identified psychogenic characteristics can be considered as a risk for an addictive disease and somatoform disorders.

Abstract: Biological ageing is a process that changes living systems over time, causing impairments in their structure and function. Studying the individual biomarkers of ageing is regarded as the most plausible current theory of age-related inflammatory processes (inflammageing). According to this theory, slightly pronounced chronic aseptic inflammation develops during ageing, which is the basis for the pathogenesis of age-related syndromes and diseases. A key role in implementing different cellular interactions and in regulating the type of an inflammatory response is assigned to the cytokine status (nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and IL-6) in an elderly patient with age-related diseases, such as osteoarthritis (OA) and diabetes mellitus (DM), developed in the altered background. Anti-inflammatory drugs include chondroitin sulfate (CS) that, in addition to directly affecting the severity of pain syndrome in OA, also has a modulating effect on the level of systemic inflammation. Pharmaceutical CS plays an important role in tissue remodeling, cell proliferation, migration, and differentiation, apoptosis, activation and deactivation of chemokines and cytokines, by increasing the synthesis of hyaluronic acid and proteoglycans, by suppressing the synthesis of prostaglandin E 2 (PGE 2 ), IL-1, and IL-6 and the expression of cytokines and NF-κB. CS belongs to anti-aging drugs.

Abstract: Studies of the biomarkers of atrial cardiopathy seem to be promising for identifying patients with cryptogenic stroke (CS), in which an intensive search for atrial fibrillation is indicated. Nevertheless, the diagnostic value of these markers and their threshold values require clarification. Objective : to present the characteristics of echocardiographic markers for atrial cardiopathy and the serum concentration of N-terminal pro-Btype natriuretic peptide (NT-proBNP) in embolic CS versus cardioembolic stroke (CES) and non-cardioembolic stroke (non-CES) to determine the threshold values of parameters with the highest sensitivity and specificity in differentiating CES and non-CES. Patients and methods . A total of 259 patients with ischemic stroke were examined. The standard examination additionally involved calculation of the parameters that reflected left atrial LA) function (LAF): LA emptying fraction (LAEF), and LA functional index (LAFI). The serum NT-proBNP concentration was also determined in 75 patients. Results and discussion . The patients with CES versus those with CS and non-CES were characterized by a considerable increase in LA diameter (4.3 [3.5; 4.5] cm vs 3.7 [3.4; 4.0] cm vs 3.7 [3.4; 3.9] cm; p=0.005 and p=0.009, respectively), LAVI (35.7 [30.5; 39.9] ml/m 2 vs 28.5 [25.6; 34.6] ml/m 2 vs 27.1 [24.5; 31.2] ml/m 2 ; p< 0.001) and NT-proBNP level (559 [409; 1144] pg/ml vs 164 [65; 308] pg/ml vs 191 [63; 446] pg/ml; p=0.002 and p=0.019, respectively), as well as by a lower LAEF value [50.3 [48.5; 51.1]% vs 54.7 [51.6; 56.6]% vs 54.9 [52.5; 56.8]%; p< 0.001). The only parameter that showed significant differences between all the three groups (CES, CS, and nonCES) was LAFI (0.24 [0.2; 0.32] units vs 0.37 [0.3; 0.47] units vs 0.40 [0.34; 0.47] units; p<0.00 1), while maintaining the differences in the values for the two groups (CS and non-CES) (p=0.004). The following threshold values of biomarkers were obtained for CES and nonCES; these were a LA diameter of 41.5 mm (p< 0.001), a LAVI of 36.3 ml/m 2 (p< 0.001), a LAEF of 51.8% (p< 0.001), a LAFI of 0.28 units (p< 0.001), and an NT-proBNP of 316 pg/ml (p< 0.001). Analysis of the ROC curves and the area under the curve (AUC) revealed that the most informative criteria for sensitivity and specificity were LAEF (79 and 88%, AUC 0.89), NT-proBNP (67 and 91%, AUC 0.89) and LAFI (93 and 72%, AUC 0.81). Conclusion . The CS group and non-CES one are comparable in the echocardiographic manifestations of atrial cardiopathy and in serum NTproBNP values. LAEF and NT-proBNP concentrations are promising biomarkers to classify CS patients into potential arterio- and cardioembolic types.

Abstract: Patent foramen ovale (PFO) is an important cause of embolic cryptogenic stroke (ECS) in young patients. The main mechanism in this case is paradoxical embolism (PE), the basis for which is a right-to-left (R-L) shunt. Objective: to comparatively characterize patients who have undergone ECS, with and without an R-L shunt, as evidenced by transcranial Doppler with the bubble test (TCD-BT). Patients and methods . In 40 patients with acute ECS, an R-L shunt was sought using TCD-BT, followed by transesophageal echocardiography (TEE). The left atrial volume index (LAVI) was additionally calculated. Brain damage was analyzed by probabilistic mapping of foci according to magnetic resonance imaging. Results and discussion. The mean age of the examined patients was 51.5 (39.5–60.0) years; of them there were 22 women and 18 men. An RL shunt was detected in 24 (60.0%) of patients with cryptogenic embolism that was mainly grades 2 and 3 (41.0 and 35.0%). TEE could visualize PFO (1.0 to 5.5 mm in size) in 16 (40%) patients and atrial septal aneurysm in 3 (7.5%). PFO was not found in 5 patients with positive results of TCD-BT, which may suggest that there is either a pulmonary shunt or a false-negative TEE. The patients with an R-L shunt versus those without an R-L-shunt showed lower LAVIs (23.9 and 26.5 mL/m2) (p=0.016). This fact may additionally confirm the causative role of PFO in the development of stroke, whereas higher LAVIs in the non R-L shunt subgroup should alert to the presence of atrial cardiopathy and initiate an appropriate diagnostic search for latent atrial fibrillation. According to the presence or absence of an R-L shunt, the groups did not significantly differ in gender, age, and clinical characteristics of the stroke. In patients with PFO, a lesion focus was most commonly localized in the middle cerebral artery bed (35.3%), cerebellum (23.5%), and posterior cerebral artery (17.6%). Five (29.0%) patients were ascertained to have several foci of acute stroke. There was a trend towards the larger size of cerebral infarction foci and their specific localization in the vertebrobasilar bed in PE, which determined the high (35.3%) incidence of ataxia with the onset of the disease. Conclusion. PE causes ECS in 60.0% of cases. The distinctive feature of patients with an R-L shunt is lower LAVIs and a trend towards the larger size of cerebral infarction foci and their specific localization in the vertebrobasilar bed.

Abstract: The chondroprotectors glucosamine sulfate (GS) and chondroitin sulfate (CS) show a complex anti-inflammatory effect and therefore may be used in the therapy of many diseases concurrent with osteoarthritis. Objective: to carry out a systematic analysis of the relationship between the molecular pathophysiology of tenosynovitis and the potential mechanisms of pathogenic action of CS/GS in this disease. Material and methods. The texts of 15 097 publications were systemized using the current methods for topographic big data analysis, which had been developed as part of topological and metric approaches to recognition/classification problems. Results and discussion. The investigators created a map showing the molecular pathophysiology of tendosynovitis and including 15 molecular mechanisms and 27 comorbidities and identified mechanisms, through which GS/CS could prevent the development of tenosynovitis, such as inhibition of the effects of proinflammatory cytokines (IL-1, IL-8, γ -interferon, and TNF- α ), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein, NLRP3 inflammasome, NF- κ B and JAK/STAT signaling pathways, and O-glucosamination of proteome proteins. To date, no randomized clinical or cohort (non-interventional) studies of the effects of CS/GS have been conducted in patients with tendosynovitis and comorbidities. However, preclinical studies of GS and CS in the treatment of tendinopathies showed that the drugs had analgesic properties, alleviated chronic inflammation and edema, and improved the maturation of collagen bundles and therefore the mechanical properties of connective tissue in the tendons and ligaments. Conclusion. The experimental and clinical studies indicate that pharmaceutical-grade GS/CS preparations of high standardization are promising in treating tenosynovitis.

Abstract: Migraine is a common chronic neurological disease. Many neurogenic, vascular, autonomic, and other mechanisms at different levels of the central and peripheral nervous systems are assumed to be implicated in the pathophysiology of headache and other manifestations of migraine. Advances in understanding the neurobiology of migraine have made it possible to clarify the main patterns of neurogenic-vascular relationships that explain the leading clinical manifestations of migraine, as well as to identify some biological markers that have triggered the creation of new targeted therapies for the disease. This review is dedicated to the latest advances in studying the pathophysiology of migraine and to new pharmacological approaches to its treatment.

Abstract: On March 11, 2020, the WHO announced the COVID-19 outbreak a pandemic The disease was established to be caused by a new singlestranded RNA virus (ss-RNA, 29903 bp) that belongs to a group of coronaviruses (CoV) Objective : to assess the results of a pilot analysis of the efficiency of using Angiovit in the combination treatment of acute COVID-19 with pneumonia or acute respiratory viral infection Patients and methods The study enrolled 50 patients with acute COVID-19 In all the patients, the diagnosis of coronavirus infection was confirmed by polymerase chain reaction Angiovit was used in 25 patients (13 (52%) women) (mean age, 394 years) with moderate infection who had been admitted on an average of disease day 3 (a study group) A comparison group consisted of 25 patients whose gender, age, and clinical features of COVID-19 did not differ at the time of admission; they were prescribed only mainstay therapy Results and discussion Adding Angiovit to the mainstay therapy contributed to an average reduction in the fever period from 588 to 412 days (p<005) and to the earlier hospital discharge of patients with an improvement (on day 13 versus on day 168 days in the comparison group; p<005); Normalization of CRP, D-dimer, and homocysteine levels occurred considerably and faster Conclusion The pilot study has shown that the use of Angiovit in the combination therapy of COVID-19 reduces the clinical and laboratory manifestations of inflammation and hypercoagulation, which may also be associated with the action of folic acid

Abstract: The main target for COVID-19 is the lung with the development of acute respiratory failure. But the virus also displays tropism to the central nervous, muscle, and immune systems. The paper gives the data available in the literature on nervous system damage and the characteristics of clinical and magnetic resonance imaging manifestations of brain damage in COVID-19. Among the neurological symptoms of COVID-19, there may be stroke, encephalitis, and neuropathy. An account is given of the features of multiple sclerosis patient management during the COVID-19 pandemic depending on the risk of developing coronavirus infection.

Abstract: Back pain significantly affects quality of life in patients. Therapy for acute and chronic nonspecific back pain (NBS) includes non-drug and drug treatments. The non-drug treatment includes educational conversations with a patient, recommendations to maintain an active lifestyle, therapeutic exercises, behavioral and cognitive-behavioral therapy, and mindfulness. Manual therapy and injections of anesthetics into the area of tender joints may be prescribed. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for drug treatment of acute and chronic NBS. Antidepressants may be prescribed for chronic pain and depression symptoms. B vitamins (thiamine, pyridoxine, and cyanocobalamin) can be considered as adjuvant analgesics in NBS. The results of animal experimental studies have shown that B vitamins at high doses have analgesic and anti-inflammatory effects. Clinical studies, a systematic review, and a meta-analysis published in 2020 demonstrated the safety and advantages of combination therapy with NSAIDs and B vitamins over NSAID monotherapy in the treatment of acute NBS and exacerbations of chronic NBS. The addition of B vitamins to NSAIDs can reduce the duration of treatment by 2 times. By reducing the duration of pharmacotherapy, the risk of adverse reactions to NSAIDs decreases and the patient returns to daily activities more quickly. It is advisable to conduct further, larger studies of combined pharmacotherapy for NBS.

Abstract: 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.

Abstract: Diabetes mellitus (DM) and chronic alcoholism (CA) are diseases that damage many organs and systems of the body and, in particular, lead to peripheral neuropathies. The pathogenesis of peripheral neuropathies caused by diabetes mellitus (DM) and CA is complex and diverse. Different types of peripheral neuropathies develop according to the leading pathogenetic mechanism. The most common type of peripheral neuropathy in DM is diabetic distal symmetric polyneuropathy (DSPN) and that in CA is alcoholic polyneuropathy (APN). The principles of diagnosis and treatment of DSPN and APN are considered. Treatment of DSPN and APN is complex, which is aimed at treating the underlying disease and includes non-drug and drug treatments. The mainstay of DSPN treatment is achievement of the optimal blood glucose level, maintenance of a healthy lifestyle (diet, daily activity), and correction of cardiovascular comorbidities (if any) with symptomatic pharmacotherapy for neuropathic pain (if any) with antidepressants or anticonvulsants. Antioxidants, such as B group vitamins (B 1 , B 6 and B 12 ) and alpha-lipoic acid (ALA), are widely used to treat DSPN in clinical practice. APN treatment involves cessation of alcohol consumption, physical and mental rehabilitation, and intake of B group vitamins (B 1 , B 2 , B 6 and B 12 ). The use of ALA in DSPN and APN is discussed.

Abstract: Hypertension is a widespread disease related to modifiable vascular risk factors for stroke and chronic cerebrovascular diseases. The pathogenetic basis of brain damage in hypertension is cerebral microangiopathy that leads to vascular cognitive impairment (CI), instability, and falls. Microcirculatory changes in the presence of hypertension at the initial stages of cerebrovascular disease occur without visible clinical manifestations of brain damage. Pathogenetically justified treatment used at an early stage of the disease makes it possible to achieve good results in the prevention of vascular brain damage. An important aspect of selecting effective therapy is the competent diagnosis of the causes of dizziness and instability, which can be caused not only by brain damage, but also by peripheral vestibular system diseases. Early diagnosis of vascular CI, selection of adequate therapy, and prevention of their further progression are of great importance. The studies performed have shown the high efficacy of vinpocetine (Cavinton®) that has a multifactorial mechanism of action in the treatment and prevention of CI, dizziness, and instability caused by cerebrovascular disease.

Abstract: Objective: to evaluate the clinical efficacy and tolerability of the Russian drug tolperisone (calmyrex) versus tizanidine and baclofen in the therapy of acute nonspecific musculoskeletal pain (NSMSP) in the elderly. Patients and methods. Examinations were made in 135 elderly (60–75-year-old) patients with acute NSMSP. To relieve pain syndrome, all the patients were prescribed nimesulide suspension 100 mg twice a day after meals. The patients were randomized using an envelope method to three groups, each of which took a muscle relaxant as tablets for 15 days: Group 1 received the Russian drug tolperisone (calmyrex) 150 mg thrice a day; Group 2 used tizanidine 2 mg thrice a day; Group 3 had baclofen 10 mg twice a day. Pain syndrome was rated on a visual analogue scale (VAS). To measure orthostatic blood pressure, to check the coordinator system, and to record adverse events (AEs) were mandatory. Results and discussion. At 15 days, treatment substantially reversed pain syndrome according to VAS scores in all the groups: from 68 to 14 in Group 1, from 64 to 17 in Group 2, and from 62 to 18 in Group 3 (without significant differences between the groups). AEs were more common in Groups 2 and 3 patients who received tizanidine or baclofen. Orthostatic hypotension was reported in 3 patients taking baclofen. The high safety and good tolerability of a combination of a non-steroidal anti-inflammatory drug (NSAID) and a muscle relaxant were noted in the calmyrex group. Although muscle relaxants ensure clinically significant short-term pain relief in acute nonspecific back pain, it is necessary to take into account that elderly patient can develop AEs when taking the drugs, which is associated with delayed metabolic reactions, reduced hepatic blood flow and glomerular filtration rate, and a larger number of diseases and used medications. Conclusion. Therapy with NSAIDs and centrally acting muscle relaxants for acute NSMSP in elderly people calls for special precautions due to the fact that there may be AEs that are less likely to occur with calmyrex than with tizanidine and baclofen.

Abstract: Objective : to retrospectively assess the Russian experience with perampanel (PER) in everyday clinical practice as an adjunctive medication for the treatment of patients aged 12 years or older with focal epilepsy (FE) Patients and methods A multicenter retrospective study was conducted, during which the physicians filled out standard questionnaires assessing the characteristics of the disease and the therapy performed The maximum follow-up period was 12 months Each patient was included in the study only once for the duration of the study A total of 164 cases of pharmacoresistant FE were analyzed The patients' mean age was 377 years; the male to female ratio was 1:1 The disease duration over 10 years was in 687% of patients; structural epilepsy was present in 682% (temporal and frontal lesions in 534 and 391%, respectively) Results and discussion Most (266%) patients were prescribed PER after three previous lines of therapy; before PEP administration, there was a maximum of 2 (509%) and 3 (296%) drugs, respectively, in the combination The initial frequency of all seizure types reached 9 [3; 34] per month; that of focal-onset bilateral tonic-clonic seizures was 3 [2; 6] per month Combined therapy including PER could lead to the disappearance of seizures in 227% of cases; the responders (by all seizure types) were 528%, whereas the remission rate of bilateral tonic-clonic seizures was 608% of patients, the responder rate was 27,8% At 12 months of follow-up, the therapy retention rate reached 807% (95% confidence interval, 723—891) Adverse events (AEs) were noted in 313% of patients; the most frequent AEs were drowsiness (104%), aggression (98%), irritability (67%); other AEs were observed in individual cases The average dose of PER was 8 mg Conclusion PER was effective in patients with resistant PEs at a maximum follow-up of 12 months in routine clinical practice Remission of all seizure types was achieved in 227% of cases, the decrease in the number of seizures >50% was seen in 528% of cases; the therapy retention rate was 807% The drug had a therapeutic effect in all types of focal seizures and was most effective in focal-onset bilateral tonic-clonic seizures Along with its good clinical effect, PER demonstrated a predictable safety profile

Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the main class of analgesics for the relief of acute nonspecific back pain (NSBP) and for the control of chronic one (CNSBP). The choice of a NSAID is determined by the efficacy, ease of use, and safety profile of a particular drug. Etoricoxib is one of the most successful representatives of NSAIDs, which is advisable to be used in CNSBP. Double-blind, controlled studies of patients with CNSBP have indicated that etoricoxib at a dose of 60 mg/day is significantly superior to placebo and that at a dose of 150 mg/day is not inferior to diclofenac. The important advantages of etoricoxib are its good tolerance and a relatively low risk of gastrointestinal complications. The frequency of cardiovascular and renal complications with etoricoxib is not higher than those with the most popular nonselective NSAIDs. In 2020, etoricoxib was included in the number of official indications approved by the Ministry of Health of Russia for the treatment of chronic lower back pain.

Abstract: Patent foramen ovale (PFO) is detectable in more than 25% of the adult population and is generally clinically insignificant. However, it can be a cause of paradoxical embolism in some cases. Randomized trials indicate that endovascular PFO closure in patients with a history of cryptogenic stroke is an effective method for the secondary prevention of catastrophic brain damage. Objective : to study the safety and efficiency of endovascular PFO closure in young patients with a history of cryptogenic stroke. Patients and methods . Sixty-two patients, including (22 males and 40 females) women, underwent percutaneous PFO closure in May 2018 to March 2020. The patients' mean age was 37.4±7.6 years. The inclusion criteria were a prior cryptogenic ischemic stroke lasting less than 12 months and PFO with a high risk for paradoxical embolism (PFO concurrent with atrial septal aneurysm or hypermobility; PFO, ≥2 mm size; the presence of the Chiari network and/or the Eustachian valve). Results and discussion . The technical success of the operation was achieved in all cases. In 50 (80.6%) patients, the right chamber of the heart was completely isolated from the left one in the first 3 months. During the first year, the atria were also completely isolated in 10 (16.1%) patients. A left-to-right shunt persisted in 2 (3.2%) patents 12 months later. Two patients were found to have main procedural complications: one had perioperative atrial fibrillation and the other had pseudoaneurysm formation at the puncture site. Conclusion . Endovascular PFO closure is a safe and effective operation for the secondary prevention of recurrent ischemic stroke. In our study, blood shunting through the PFO was stopped in 96.6% of patients at less than 6 months after surgery, which suggests that there is a rapid and effective reduction in the risk of paradoxical embolism.

Abstract: The current diagnosis of multiple sclerosis (MS) is based on confirmation of the disseminated pathological process in space and time in accordance with the McDonald criteria. Despite this, the search continues for specific markers of the disease, including those detected using neuroimaging techniques that have high sensitivity and specificity in the diagnosis of MS. The paper considers the central vein sign, a new promising diagnostic one of MS. This sign refers to a parenchymal vein visualized in the focus of demyelination, by using special magnetic resonance imaging (MRI) modes. Studies show that the central vein sign has high sensitivity and specificity in the diagnosis of MS, allowing it to be differentiated from other demyelinating, vascular, and systemic diseases that have an MRI pattern similar to that of MS. According to various authors, a threshold of 40–50% perivenular lesions allows MS and MS-like diseases to be differentiated with high accuracy.

Abstract: Objective: to comparatively study several nonsteroidal anti-inflammatory drugs (NSAIDs) (their analgesic effect; dynamics of quality of life; side effects, such as NSAID-gastropathy and gastric dyspepsia) in acute pain in the neck and back (dorsalgia). Patients and methods. The investigators followed up 120 patients (4 groups, each having 30 people) with acute dorsalgia who took different oral NSAIDs for 7 days: long-acting ketoprofen, aceclofenac, naproxen, and dexketoprofen (Flamadex). To evaluate their possible side effects, dyspepsia symptoms were monitored and blood pressure (BP) was measured daily; gastroscopy was repeated after completion of a treatment cycle. The Nottingham Quality of Life Questionnaire and the Visual Analogue Scale (VAS) for pain were used. Results and discussion. A gradual and substantial reduction in pain measured according to VAS was noted in all the NSAID-treated groups. The intensity of pain syndrome decreased faster in the dexketoprofen group; the analgesic effect of naproxen and long-acting aceclofenac was significantly less (p=0.012 and 0.002, respectively). This patient group showed a tendency to maximum improvement according to the Nottingham Quality of Life Questionnaire and VAS. Elevated BP was observed in all the groups, but statistically significantly more frequently in the naproxen group (p=0.05). Gastric dyspepsia was also registered in all the groups, but a tendency to its lower frequency was seen in the dexketoprofen group. Conclusion. Dexketoprofen showed fewer side effects and a more pronounced analgesic effect than ketoprofen, aceclofenac, and naproxen in acute dorsalgia.

Abstract: Neck pain is a widespread disease that significantly impairs quality of life in patients. General approaches to managing patients with acute neck pain are generally consistent with the recommendations for the treatment of acute back pain: its pharmacotherapy includes nonsteroidal antiinflammatory drugs (NSAIDs) and muscle relaxants. Objective of the observational program: to compare the efficiency of treatment for nonspecific acute neck pain with tolperisone 150 mg/day, followed by dose escalation up to 450 mg/day, versus meloxicam 15 mg/day for 14 days. Patients and methods. The observational program covered 37 patients aged 18–65 years who were diagnosed with acute nonspecific neck pain; of them 19 patients made up Group 1 and 18 formed Group 2. Group 1 was prescribed tolperisone (Calmirex) as tablets: 150 mg/day on day 1, 300 mg/day on day 2, and 450 mg/day on day 3 until the end of therapy. On day 1 of the investigation, Group 2 received meloxicam 15 mg/day in two divided doses (7.5 mg in the morning and evening). At baseline and on days 7 and 14 days of therapy, the investigators assessed the dynamics of pain using a visual analogue scale (VAS), as well as its intensity at rest and during movement; neck disability index (NDI) and recorded adverse events. Results and discussion . The two groups showed a significant decrease in pain intensity on both 7 and 14 days of therapy. The rate of effect onset was significantly faster in the meloxicam group. On day 14 of treatment, both patient groups showed a considerably better functional state in terms of activity limitations due to neck pain (NDI); patients' perceptions of therapy were rated as good and excellent in most cases. On 14 days of therapy, the degree of pain reduction in the meloxicam group was higher, but the differences with that in the tolperisone group did not reach statistical significance, which can indicate the comparable efficacy of the drugs. Conclusion. The data of this observational program are consistent with the recommendations for the treatment of nonspecific acute neck pain, which indicate NSAIDs and muscle relaxants as drugs for the treatment of this disease.

Abstract: Children and adolescents are more likely than adults to experience adverse side effects when taking antipsychotics. Pharmacogenetic testing allows one to more accurately choose the initial dose of a drug. The genes of pharmacokinetic factors have been shown to be of high prognostic value for the safety of antipsychotics in adults. Patients and methods . The study enrolled 36 adolescents (58.3% male) (mean age, 14.83±1.84 years). All the patients took an antipsychotic. The follow-up lasted 28 days. On 14 and 28 days of treatment, its efficiency and safety were evaluated using the Children's Global Assessment Scale (CGAS), the Positive and Negative Syndrome Scale (PANSS), the Udvalg for Kliniske Undersњgelser Side Effects Rating Scale (UKU-SERS), the Simpson-Angus Scale (SAS), and the Barnes Akathisia Rating Scale (BARS). The patients were genotyped for CYP3A4*22, CYP3A5*3, CYP2D6*4, *9, *10, ABCB1 1236C>T, 2677G>T/A, 3435C>T, DRD2 rs1800497, DRD4 rs1800955, and HTR2A rs6313. Results and discussion . The decrease in the mean score of the PANSS subscale “Productive symptoms” was more pronounced in carriers of the DRD2 rs1800497 polymorphic variant (-6.5 [-10.25; -3.75] vs -3 [-6.5; -2 ] on 14 day (p=0.028) and (-11 [-13; -9.5] vs -5 [-9; -3.5] on 28 day (p=0.001) compared to baseline. The carriage of ABCB1 3435CT+TT was associated with worse tolerance to pharmacotherapy on 14 day (the total score of the UKU-SERS M, 8 [3; 11.75] vs M, 2 [1; 6]; p=0.034). The carriers of DRD2 rs1800497 reported a greater severity of antipsychotic-induced neurological disorders (UKU-SERS subscale score M, 1 [0; 2.25] vs M 0 [0; 1]; p=0.029). Conclusion . The polymorphic variants DRD2 rs1800497 and ABCB1 3435C>T were established to be significantly associated with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode.

Abstract: 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.