Neurology, Neuropsychiatry, Psychosomatics

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Vol 12, No 2 (2020)
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4-11 867
Intracerebral hemorrhage (ICH) is the same etiologically heterogeneous variant of stroke as cerebral infarction. The most common causes of the disease are hypertensive and cerebral amyloid microangiopathy, the use of oral anticoagulants (OACs) and their combination, and arteriovenous malformations, which are of the greatest importance for young patients. The SMASH-U or H-ATOMIC classification of ICH requires a structured diagnostic search that includes an analysis of the clinical presentations of the disease and neuroimaging and angiographic findings. Although brain computed tomography remains a basic diagnostic technique for ICH, most patients need brain magnetic resonance imaging, by mandatorily assessing the ischemic and hemorrhagic markers of cerebral small vessel diseases. This examination is necessary not only to verify the cause of ICH and to select the appropriate method of its treatment, but also to determine the risk of recurrent hemorrhage. The article considers the epidemiology and etiological characteristics of ICH and approaches to its classification. It characterizes the most significant causes of the disease, such as hypertensive and cerebral amyloid angiopathy, vessel structural abnormalities, and the use of OACs. The
diagnosis of ICH and its clinical neuroimaging diagnostic algorithm are presented.

12-16 1262
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.


17-22 492

Phenazepam is a benzodiazepine tranquilizer that is widely used in Russia. The drug is metabolized by cytochrome P450 3A (CYP3A) isozymes. Since their substrates have an affinity for P-glycoprotein, the polymorphic variants in the ABCB1 gene may affect the safety of this drug.

Objective: to analyze associations between the CYP3A5, CYP2C9, CYP2C19, CYP2D6 and ABCB1 gene polymorphisms and the safety of phenazepam treatment for alcohol withdrawal syndrome (AWS).

Patients and methods. The investigation enrolled 102 patients diagnosed with uncomplicated AWS (IDC-10 code F10.30). All the patients were followed up for 6 days within which they took phenazepam. 5-ml venous blood samples were collected from each patient for genotyping. The carriage of  CYP3A4*22, CYP3A5*3, CYP2C19*2, CYP2C19*17, CYP2C9*2, ABCB1 3435C>T, 1236C>T, and  2677G>T/A polymorphic variants was determined by a real-time polymerase chain reaction assay. Therapy safety was evaluated using the UKU Side-Effect Rating Scale on day 6. Statistical analysis was carried out with SPSS Statistics 21.0. Haplotype and combinatorial analyses were performed using SNPStats.

Results and discussion. The greater subjective severity of adverse reactions (ARs) was shown for the homozygotes of ABCB1 1236C>T CC (odds ratio (OR), 2.154; 95% confidence interval (CI), 1.271–3.650; p=0.014) and ABCB1 2677G>T GG (OR, 2.154; 95% CI, 1.271–3.650; p=0.014). On the contrary, a combinatorial analysis revealed the role of ABCB1 3435C>T, 1236C>T, and 2677G>T polymorphic alleles as predictors for the greater subjective severity of ARs. The following statistically significant polymorphic variant combinations were ABCB1 3435-1236–2677 and T-T-T-CYP3A5*3 isozymes (OR=5.03; 95% CI, 1.65–15.34; p=0.0056); T-T-T-CYP2C9*1 (OR=3.61; 95% CI, 1.31–9.92; p=0.015); T-T-T-CYP2C19*1 (OR=2.52; 95% CI, 1.05–6.08; p=0.042). Attention disorders were also established to be associated with the carriage of T-T-T-CYP2D6*1 (OR=2.58; 95 CI, 1.08–6.13; p=0.035).

Conclusion. The carriage of ABCB1 3435-2677-1236 (T-T-T) haplotype is significantly associated with the greater severity of ARs in phenazepam-treated patients with AWS.

23-29 289

An assessment of not only the degree of stenosis, but also the structure of atherosclerotic plaques (ASPs) in the carotid arteries can reveal atheromas that are dangerous for the development of cerebrovascular events in asymptomatic individuals.

Objective: to study the echostructure of ASPs in patients in the acutest period of carotid ischemic stroke (IS) and to analyze predictors for its development according to ultrasonic duplex scanning (DS).

Patients and methods. A study group included the results of DS in 668 patients (370 men and 298 women aged  63±11 and 69±9 years, respectively) with IS in the middle cerebral artery bed. Out of 222 patients, 160 (72.1%), 56 (25.2%), 4 (1.8%), and 2 (0.9%) people had atherothrombotic, cardioembolic, hemodynamic, and lacunar subtypes of IS, respectively. A control group consisted of 903 asymptomatic individuals matched to the patients for gender and age.

Results and discussion. In patients with IS, carotid stenoses were characterized by the higher degree of a reduction in the lumen of both the internal carotid arteries (ICA): on the right (r) (53±23%) and left (l) (54±24%) sides, and the common carotid arteries (CCA): on both sides (40±12%) compared to asymptomatic individuals: rICA (40±14%), lICA (39±15%); and both CCAs (32±9%). At the same time, ASPs in the carotid arteries in the acutest period of IS were significantly more frequently homogeneous hypoechoic (21.2%) or heterogeneous with a hypoechoic component (25.6%), and also more frequently had an uneven contour in the rICA (41.3%) and lICA (33.6%), compared to those in asymptomatic individuals (hypoechoicity (7.0 and 5.6%, respectively); the uneven contour was in the rICA (3.2%) and lICA (4.0%). The study indicated that a set of echo signs (the degree of stenosis in the ICA and CCA; the homogeneity and hypoechoicity of ASP in the ICA; the uneven contour of ASP in the carotid arteries) was formed for primary ultrasound carotid stenosis screening carried out using a routine DS
technique. Additional studies that can more accurately identify ASPs that are dangerous for the development of cerebral vascular events are recommended for asymptomatic individuals with ASP and the above signs, which will determine their treatment policy.

Conclusion. Atheromas in the carotid arteries in the acutest period of IS are different from those in asymptomatic individuals by a number of features identified during routine ultrasonic DS. The most valuable individual prognostic sign of the development of carotid IS was the uneven contour of ASP in the carotid arteries.

30-36 286

Quality of life indicators are widely used to determine the efficiency of various medical therapies for cervical myelopathy; however, but these have been insufficiently studied in assessing the results of surgical treatment for this pathology. In addition, the results of surgical treatment for cervical myelopathy are observed to be unsatisfactory in 15–20% of cases, which indicates the need to develop new techniques and to improve existing ones for its correction. Direct electrical stimulation of the spinal cord may become one of the promising areas.

Objective: to comparatively analyze the efficiency of various surgical treatments for cervical myelopathy, by assessing the quality of life indicators in the patients.

Patients and methods. The investigation enrolled 92 patients with cervical myelopathy: 29 (49.2%) patients underwent posterior spinal cord decompression via laminectomy; in 17 of them, that was supplemented with the electrodes placed on the posterior columns of the spinal cord for its postoperative direct electrical stimulation; 63 (50.8%) patients underwent anterior spinal cord decompression, 12 of them had electrodes placed on the anterior horns of the spinal cord.

Results and discussion. After posterior spinal cord decompression with laminectomy, there were increases in physical functioning from 36.7±2.1 to 49.6±3.1 arbitrary units (arb. unit) (p<0.05) and in role physical functioning from 39.4±2.6 to 51.3±2.6 arb. unit (p<0.05) and a decrease in pain sensations from 51.6±2.6 to 30.2±0.8 arb. unit (p<0.05). Electric stimulation of the spinal cord caused increases in physical functioning from 40.3±3.6 to 61.3±2.8 arb. unit (p<0.05) and in role physical functioning from 36.7±1.6 to 69.4±1.6 arb. unit (p<0.05) and a reduction in pain sensations from 49.8±2.4 to 21.0±1.2 arb. unit (p<0.05). The similar trend as also observed in anterior spinal cord decompression concurrent with corporodesis at the cervical level after direct electrical stimulation of the spinal cord. Physical functioning increased from 42.0±3.1 to 57.6±1.4 arb. unit (by 26.4%; p<0.05) and mental health improved (only by 14.3%). After isolated anterior spinal cord decompression with corporodesis, physical functioning was 48.4±0.9 arb. unit by the end of the third month follow-up (p<0.05); following that in combination with electrical stimulation, physical functioning was 57.6±1.4 arb. unit (p<0.05). The posttreatment levels of viability, social functioning, role emotional functioning, and mental health were significantly lower in patients with a disease duration of more than 6 years than in those with that of less than 3 years.

Conclusion. Posterior and anterior spinal cord decompression with laminectomy for cervical myelopathy increases the indicators of physical functioning and role physical functioning and reduces pain sensations. The additional use of electrical stimulation of the spinal cord allows one to increase role physical functioning.

37-41 5975

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.

42-47 739

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.

48-56 2246

Selective serotonin reuptake inhibitors (SSRI)-induced apathy syndrome occurs in 5–20% of patients taking these drugs.

Objective: to investigate the possibility and advantages of switching patients with SSRI-induced apathy to treatment with a SSRI and norepinephrine reuptake inhibitor.

Patients and methods. The investigation enrolled 105 depressive patients without psychotic symptoms, who were observed to develop symptoms of SSRI-induced apathy during SSRI antidepressant monotherapy for at least 6 months. The patients were randomized to groups: 1) 35 patients were switched to milnacipran (Ixel 50–100 mg/day) with simultaneous antidepressant replacement; 2) 35 patients were prescribed milnacipran with a 2-week gradual discontinuation of the previous SSRI; 3) 35 patients were switched to combined therapy with milnacipran 50–100 mg/day and sulpiride (Eglonyl 50 mg/day). The latter was prescribed to test the hypothesis for the benefits of combined correction of SSRI-induced apathy syndrome. The duration of the investigation was 3 months. Changes in the condition of the patients were assessed during their visits before and 1, 2, 4, 8, and 12 weeks after changing therapy. The efficiency of antidepressant therapy was studied using the 21-item Hamilton Depression Rating Scale (HDRS-21) and the Clinical Global Impression (CGI) rating scale; the changes in the severity of asthenic manifestations were examined according to a subjective asthenia assessment (Multidimensional Fatigue Inventory (MFI-20)). The UKU side effect rating scale was used to verify side effects.

Results and discussion. A significant (p<0.05) pronounced thymoleptic effect of various treatment regimens (simultaneous and gradual replacement with monnacipran monotherapy, as well as a milnacipran-sulpiride combination) was confirmed at week 4 of treatment. There was a reduction in SSRI-induced apathy syndrome when switching to treatment with milnacipran or milnacipran-sulpiride in 71.4–80% of patients. Different therapy replacement regimens showed varying changes in the reduction of heterogeneous asthenoapathic symptoms. A favorable safety profile was established for both monotherapy with milnacipran and its combination with sulpiride.

Conclusion. The antidepressant milnacipran (up to 100 mg/day) exhibits a high efficacy and a good tolerance in case of SSRI-induced apathy syndrome, as well as by a pronounced thymoleptic effect, including when combined with the antipsychotic sulpiride (50 mg/day).

57-63 2438

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.


64-71 643

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-κB 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. 


72-78 752
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.

79-85 349
The paper describes a female patient with neurocutaneous melanosis (NCM) concurrent with Dandy–Walker malformation and a spinal arachnoid cyst, who has been treated in the A.Ya. Kozhevnikov Clinic of Nervous System Diseases. Over the course of one year, the patient had progressive neurological symptoms as central lower paraparesis and coordination disorders; her medical treatment was ineffective. Neuroimaging revealed Dandy–Walker malformation and a spinal arachnoid cyst. Surgical intervention (fenestration of the upper and lower poles of the arachnoid cyst at the CVI-VII and TIX-X level) was performed. After one month, reoperation (commissure resection in the arachnoid cyst cavity at the TV-VI level; implantation of a cystoperitoneal shunt) was made because of the absence of a clinical result. Reversal of neurological disorders was noted postoperatively.
The described clinical case is unique, since NCM is an extremely rare abnormality, especially when concurrent with  Dandy–Walker malformation and an arachnoid cyst. In addition, it is of interest that the manifestation of neurological symptoms and verification of the diagnosis occurred just in adulthood, although NCM is most commonly diagnosed in children.
The present case shows that an operation aimed at improving cerebrospinal fluid dynamics in patients with arachnoid cysts and Dandy–Walker complex in the presence of NCM can lead to a significant reversal of neurological symptoms and improvement in the quality of life despite gross brain structural changes detected by magnetic resonance imaging.

86-91 633
Creutzfeldt–Jakob disease (CJD) is a rare neurodegenerative disease caused by the accumulation of the pathological isoform of prion protein. The classic clinical presentation of CJD is characterized by rapidly progressive dementia, ataxia, myoclonus, and akinetic mutism at the terminal stage of the disease. Of the instrumental techniques, brain magnetic resonance imaging plays a leading role in clinical practice. The authors followed up 4 patients with probable CJD in the Republic of Sakha (Yakutia) in 2014 to 2019. All the patients had approximately the same age (50–60 years) at disease onset and onset with non-specific cerebral symptoms. However, the subsequent development of rapidly progressive dementia and other characteristic features might suggest CJD. The patients were found to have characteristic neuroimaging signs as hyperintensity of the caudate nuclei and pulvinars in the fluid-attenuated inversion recovery (FLAIR) and diffusion weighted imaging (DWI) modes to form the typical signal of hockey sticks, as well as hyperintensity of the gray matter in the DWI mode (the symptom of the «Venus necklace»). In 3 patients, the disease ended fatally within a year of its onset. The fourth patient with a disease duration of 6 months is being supervised at home. The authors reason that the diagnosis of CJD is now insufficient due to the similarity of its clinical symptoms at the onset with other disorders, including cerebrovascular and neurodegenerative diseases.


92-97 342
Management of patients with cognitive impairment is one of the most relevant and important problems of neurology. It is especially important to identify cognitive impairment at the early (pre-dementia) stages, when appropriate medical measures are implemented, the progression of cognitive decline can be slowed down or stopped. Near-moderate  cognitive decline (NMCD) at elderly and senile ages may be a predictor for the development of clinically significant cognitive impairment up to dementia. In most Western works, NMCD is associated with subjective cognitive decline, but it would be more legitimate to distinguish a form (a stage) of mild cognitive decline among NMCDs. It is assumed that NMCD is not necessarily a precursor to more severe cognitive impairment – the former can be a manifestation of age-related changes, emotional-affective disorders, and neurological and somatic diseases, although their presence substantially increases the risk of moderate and severe cognitive impairment. The review provides current ideas about the initial forms of cognitive decline, as well as neuroimaging data in these patients. It considers the influence of emotional-affective and cardiovascular factors on the development of cognitive deficit.

98-103 1401
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.

104-108 2675
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».

109-113 346
Since 2008, a group of international experts has been studying the population risk of serious complications of NSAIDs (the Safety Of nonSteroidal anti-inflammatory drugs (SOS) project) as part of the Seventh Framework Program of the European Union for Research and Technological Development (2007–2013). Four large-scale studies assessing the individual risk of gastrointestinal bleeding, heart failure (HF), ischemic stroke (IS), and myocardial infarction (MI) while taking various NSAIDs have been published over the past time. Meta-analysis of 28 population studies has shown that the risk of bleeding is minimal for aceclofenac: the relative risk is 1.43 (95% confidence interval (CI), 0.65–3.15). Analysis of national databases in the Netherlands, Italy, Germany, and the UK has indicated that aceclofenac does not increase the risk of hospitalization for heart failure (odds ratio (OR), 1.03; 95% CI, 0.91–1.15) and MI (OR, 1.04; 95% CI, 0.90–1.19). The risk of IS from the use of aceclofenac is slightly increased (OR, 1.17; 95% CI, 0.98–1.39), but is not statistically significant. Thus, according to the Pan-European SOS program, aceclofenac is characterized by a very low risk of gastrointestinal and cardiovascular events.

114-118 410
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.

119-124 633
Vascular cognitive impairment (VCI) is the main manifestation of dyscirculatory encephalopathy (DEP). According to the severity of cognitive impairment, Stage I DEP corresponds to mild (subjective) cognitive impairment; stage II DEP to moderate cognitive impairment; stage III DEP to severe cognitive impairment or vascular dementia. VCI is diagnosed on the basis of cognitive impairment, the clinical and neuroimaging findings confirming the presence of cerebrovascular disease, and the neuropsychological study results indicating a cognitive defect.
Citicoline is one of the most widely used nootropic drugs for cerebrovascular pathology. The treatment of VCI involves the prevention of stroke and progressive chronic cerebrovascular disease (CCVD) and the use of drugs improving cognitive functions.
Citicoline is one of the most widely used nootropic drugs for cerebrovascular disease. This drug was synthesized in Japan to treat stroke, then it became widely used in different countries in patients with CCVD and VCI. The data of clinical trials and a Cochrane systematic review prove the efficacy and safety of citicoline in the elderly and senile patients.

125-130 1491
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.

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