EXPERT RECOMMENDATIONS 
ORIGINAL INVESTIGATIONS 
Much attention is currently paid to non-dementia cognitive impairment, such as mild cognitive impairment and pre-mild cognitive decline (PMCD), since their timely detection and optimal correction increase the possibility of preventing dementia.
Objective: to analyze the neuropsychological characteristics of patients with PMCD depending on the presence or absence of cardiovascular risk factors (CVRFs): hypertension, cardiac disorders (ischemic heart disease, intracardiac conduction disturbance), and prior stroke and myocardial infarction, as well as diabetes mellitus.
Patients and methods. Examinations were made in 182 patients (132 women, 50 men; mean age, 59.32±5.41 years) with PMCD and CVFRs, 101 patients (77 women, 24 men; mean age, 59.45±7.04 years) with PMCD without CVRFs, and 77 control persons (55 women, 22 men; mean age, 60.55±5.65 years). All underwent general clinical, neurological, and clinical psychological studies using rating scales and tests.
Results and discussion. The patients with PMCD and CVRFs had lower scores on all neuropsychological tests than the control group and on most tests than the patients with PMCD without CVRFs. In addition to some deterioration in memory indicators, the patients with CVRFs performed worse executive function tests. Cluster analysis showed that in the patients with PMCD, the severity of cognitive decline was considerably affected by hypertension, cardiac disorders, and diabetes mellitus; among them, hypertension was of the most significance.
Conclusion. The association of cognitive decline with the burden of CVRFs indicates their important role in the deterioration of cognitive functions in PMCD.
Common peroneal neuropathy (CPN) is the most common tunnel neuropathy in the lower extremities, many issues of diagnosis and treatment of which require further study.
Objective: to analyze the clinical manifestations of CPN, methods of its diagnosis and treatment results.
Patients and methods. Eighty patients (31 women and 49 men) aged 18 to 82 years (mean age, 51 years) with compressive CPN were followed up during 2012–2018. Unilateral CPN and bilateral CPN were found in 76 and 4 patients, respectively. Eighty-four common peroneal nerve decompression operations were performed.
Results and discussion. There was paralytic CPN in 73 (87%) surgical cases, painful CPN in 8 (9.5%), and intermittent CPN in 3 (3.5%). Diagnostic errors (when CPN was regarded as discogenic radiculopathy or lumbar stenosis) were noted in the painful and intermittent forms of the disease. After surgical treatment, complete recovery of peroneal nerve function was observed in 61 (72.6%) of the 84 surgical cases; its partial recovery in 15 (17.9%). Positive results were seen in all cases of painful and intermittent CPN, whereas they were more often observed in paralytic CPN if the operation was performed early (up to 12 months) after the onset of the disease.
Conclusion. Common peroneal nerve decompression is an effective and safe therapeutic method that, in painful and intermittent CPN, leads to complete reversal of symptoms and, in the paralytic form of the disease, it is most effective in the early stages of the disease.
In young patients, the causes of ischemic stroke (IS) are substantially different from those in older patients. Understanding the causes of the disease in patients younger than 45 years is needed to elaborate examination algorithms used in the country’s vascular departments.
Objective: to present the nosological characteristics of IS in patients younger than 45 years according to the hospital register of the regional vascular center.
Patients and methods. The data of the hospital register of the neurological unit for patients with acute cerebral circulatory disorders, who were in the Perm Territorial Vascular Center, City Clinical Hospital Four, in 2014 to 2020, were analyzed. The analysis included 126 patients under the age of 45 years with IS verified by magnetic resonance imaging.
Results and discussion. The pathogenetic subtypes of IS according to the TOAST criteria were large artery atherosclerosis [n=10 (7.9%)], cardioembolism [n=27 (21.4%)], small vessel disease [n=15 (11.9%)], IS of other determined etiology [n=23 (18.3%)], and IS of undetermined etiology [n=51 (40.5%)]. After excluding incomplete examination cases (n=29), the most common causes of IS were cardiac embolism (patent foramen ovale, atrial septal defect, prosthetic valves, acute infective endocarditis, and chronic cardiac aneurysm) (27.8%), large artery disease (atherosclerosis and unspecified arteriopathy) (21.6%), small artery disease (15.5%), as well as cervical and cerebral artery dissection (10.3%). Cryptogenic stroke was observed in 13% of patients. There was a preponderance of cryptogenic IS in the age subgroup of 21–25 years, cardiac embolism (mainly patent foramen ovale) in the subgroup of 26–35 years; the proportions of cardiac embolism, large and small artery diseases, and dissections were comparable in the subgroup of 36–40 years; large and small artery diseases prevailed in the subgroup of 41–44 years.
Conclusion. The most common causes of IS in 18–44-year-old patients are cardiac embolism (mainly through the mechanism of paradoxical embolism) and large artery disease, including dissection. The etiology of IS depended on age: cardiac embolism prevailed in the younger age range, whereas large and small artery diseases were dominant in the older age range.
Migraine is often concurrent with endometriosis; however, the mechanisms of comorbidity of these conditions are inadequately studied. Pain is considered as the most significant clinical symptom and maladaptive manifestation of both migraine and endometriosis. Studying the relationship between the clinical manifestations of pain syndrome in patients with endometriosis and migraine is important, since it will contribute to the understanding of the mechanisms of comorbidity of these diseases.
Objective: to analyze the features of pain syndrome in patients with migraine and genital endometriosis to clarify the neurogenic mechanisms of their comorbid relationship.
Patients and methods. A total of 125 patients who had gone to a gynecologist for endometriosis were examined for the presence of migraine. In accordance with the inclusion criteria, 79 patients (mean age, 34.68±7.11 years) with genital endometriosis confirmed by diagnostic laparoscopy participated in the further study. Two age-matched groups were formed: a study group consisted of 38 patients with endometriosis and concomitant migraine; a comparison group included 41 patients with endometriosis without migraine. All the patients underwent clinical neurological examination, questionnaire survey, pelvic ultrasound, assessment of the severity of pelvic pain according to the pelvic pain index, and determination of the level of central sensitization (CS) using the CS Inventory.
Results and discussion. 42% out of the 125 patients who had visited their gynecologist for endometriosis suffered from concomitant migraine, which confirms the comorbidity of these diseases. Chronic pelvic pain (CPP), dysmenorrhea, dyspareunia, and dyschesia were more common in patients with endometriosis and migraine; there were more patients with asymptomatic endometriosis in the comparison group. The patients of the two groups did not differ in the presentation of different forms of endometriosis, which favors the leading role of central mechanisms in the pathogenesis of pain syndrome in comorbidity of these diseases.
In addition, there was a statistically significant increase in the presentation of CPP and dysmenorrhea in patients with chronic migraine compared to those with episodic migraine and to those without migraine. Significantly higher levels of CS according to CSI and pelvic pain index were found in patients with chronic migraine and endometriosis, which suggests that CS plays a key role in the comorbidity of these diseases.
Conclusion. The phenomenon of CS is one of the mechanisms of comorbidity of migraine and endometriosis, contributes to both the worsening of various painful manifestations of endometriosis and the increase in migraine attacks, thereby causing obvious maladaptation in patients. The role of CS in the comorbidity of migraine and endometriosis opens up possibilities for the elaboration of a comprehensive interdisciplinary approach to treating these diseases.
Objective: to study the clinical efficacy and tolerability of naftidrofuryl (Duzofarm®) in patients with chronic cerebral ischemia (CCI).
Patients and methods. A prospective open-label multicenter observational study evaluated the clinical efficiency and tolerability of naftidrofuryl treatment in patients with CCI. To statistically evaluate the efficacy and tolerability of naftidrofuryl, the investigators used data from 200 outpatients with Stages I–II CCI who were included in the program of treatment and received its full cycle. The patients were prescribed naftidrofuryl at a dose of 100 mg (2 tablets) thrice daily. Basic therapy that the patients had received before their inclusion in the observation program was not discontinued. The patients' status was evaluated using a specially designed questionnaire. Four visits were scheduled. All the patients underwent neurological examination. To study the patients' cognitive functions and emotional state, the investigators used the following tests and scales: the Mini-Cog test, the Mini-Mental State Examination (MMSE), the Zung Self-Rating Anxiety Scale, the Asthenia Subjective Assessment Scale, and the Modified Scoring Scale for Subjective Sleep Characteristics. Adverse reactions were recorded to evaluate the tolerability of therapy.
Results and discussion. Naftidrofuryl therapy significantly improved health and reversed complaints in the patients. By the end of the treatment cycle, there was a significant improvement on all scales, which suggested a decrease in the severity of cognitive impairment and asthenic and mild anxiety disorders. When performing the Mini-Cog test, the proportion of patients who were able to remember and recall three words without errors increased from 43 to 86%, and when doing the clock drawing test, the proportion increased by 65%. Cognitive functions on the MMSE were observed to statistically significantly improve by 1.2 scores. According to the Zung Anxiety Self-Rating Scale, the number of patients with anxiety disorders decreased by 24%, those with insomnia significantly declined by 31% compared with the baseline level.
Conclusion. The findings showed the high efficiency and appropriateness of naftidrofuryl administration to patients with Stages I–II CCI and hypertension.
In our country, alpha-lipoic acid is widely used as a pathogenetic therapy for diabetic polyneuropathy (DPN).
Objective: to compare the efficiency and safety of using oral and injectable α-lipoic acid for DPN.
Patients and methods. The investigation enrolled 47 patients with a verified diagnosis of DPN, who were divided into two groups. Group 1 included 23 patients (10 men and 13 women; mean age, 62.9±7.5 years), Group 2 consisted of 24 patients (9 men and 15 women, mean age, 65.5±7.9 years). All the patients used Berlithione: Group 1 received its intravenous doses of 600 mg for 14 days, then oral ones of 600 mg for other 16 days; Group 2 took oral doses of 600 mg for 30 days. The therapy results were assessed using the digital rating scale (DRS), the Douleur Neuropathique 4 (DN4) neuropathic pain rating scale, and the neurological soft signs (NSS), and electroneuromyography (ENMG) data.
Results and discussion. Berlithione was found to have a good tolerability. No adverse reactions were detected in any case; and there was no need to discontinue this drug. On day 21 of therapy, there were statistically significant differences in the indicators of pain intensity on DRS in Group 1 patients (p<0.05), some of them (n=8) had positive clinical changes as a reduction in the severity of hypesthesia. Both groups showed a tendency to improve ENMG parameters as a certain increase in excitation propagation velocity and M-response amplitude; however, these changes did not reach a statistical significance level. At the same time, in 6 out of the 8 patients in Group 1 with positive clinical changes, the described ENMG changes correlated with a reduction in the severity of hypesthesia. There were no significant changes on the NSS scale after 3 weeks of therapy. On day 30 of treatment, both groups were recorded to have statistically significant changes in pain intensity measures versus the baseline values, but no significant inter-group differences.
Conclusion. Thus, Berlithione demonstrated its efficacy in both patient groups, but its positive effect occurred 1 week earlier in the step therapy group. It is noted that it is expedient to use this drug long (>1 month) for DPN.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a peripheral neuropathy, predominantly motor neuropathy, with a progressive or relapse-remitting course. Fatigue is a condition characterized by a physical or mental feeling of lack of energy or lack of motivation for action, which is often present in patients with CIDP.
Objective: to assess the severity of asthenia in CIDP patients.
Patients and methods. Examinations were made in 34 inpatients treated for documented CIDP that met the international European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria. A study group included patients with CIDP, whereas a comparison group consisted of volunteers without psychiatric illness, who were compensated for somatic diseases.
Results and discussion. In the patients with CIDP, the level of fatigue was found to be much higher than normal. Approximately half of the CIDP patients had obvious asthenia. However, the level of fatigue did not correlate with the severity of the course of CIDP.
Conclusion. The findings suggest that fatigue is important in patients with CIDP that should be taken into account in the treatment of these patients.
COVID-19 worsens the course of cerebrovascular diseases (CVD), including chronic cerebral ischaemia (CCI). The Actovegin drug, which has long been widely used in CCI treatment, has an antioxidant and endothelium protective effect. It makes sense to study the effect of Actovegin therapy on the clinical manifestations of CCI in patients with a recent experience of COVID-19.
Objective: to evaluate Actovegin efficacy in the treatment of CCI in patients with a recent experience of COVID-19.
Patients and methods. The study included 440 patients (234 female; 206 male) with a recent experience of COVID-19, suffering from CCI, their average age being 67.8 years (from 54 to 85 years). All patients were broken down into two groups of 220 people (the patients in Group 1 were administrated Actovegin, the ones in Group 2 – were not). All patients were followed up for 90 days; their condition was assessed by the severity of clinical manifestations of CCI, using special scales and questionnaires.
Results and discussion. After 90 days of follow-up, the frequency of complaints of cognitive impairment, sleep disorder, dizziness, fatigue, emotional disorders, and headache in Group 1 was significantly lower than in Group 2 (p<0.05). According to Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), Multidimensional Fatigue Inventory (MFI-20), and Spiegel Sleep Questionnaire (SSQ), the average indicators improved significantly more in Group 1 than in Group 2 (p<0.05). The absence of quality of life impairment and their minimal severity were observed in Group 1 in 77.9%; in Group 2 – in 33.7% (p<0.001). Statistically significant differences between the groups of patients were also observed in relation to emotional state recovery according to the Wakefield Questionnaire and the Spielberger State Trait Anxiety inventory.
Conclusion. The observational study demonstrated the efficacy of Actovegin in the treatment of main clinical manifestations of CCI in patients with recent COVID-19 experience.
CLINICAL OBSERVATIONS 
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.
Currently, in various world regions, the prevalence of depressive and anxiety disorders due to the impact of coronavirus infection is repeatedly increased compared to that in previous years. Among the predictors of their development during the pandemic, there are COVID-19 symptoms, a history of mental disorders, as well as restrictive measures, and financial losses.
The paper describes three clinical cases of depressive disorders during the COVID-19 pandemic, with the depiction of the anamnesis, somatic and mental status, the patholopsychogical qualification of the condition, and the justification of a therapy regimen. The multifactorial stressor effect of the COVID-19 pandemic has provoked an exacerbation of depression in a male patient with a history of affective disorder; the development of a nosogenic depressive reaction of demoralization in a female patient with coronavirus pneumonia; the worsening of somatization dysthymia in a female patient of involutional age. The timely recognition of depression and its treatment with currently available antidepressants have contributed to the achievement of high-quality remission, the increase of stress resistance, and the improvement of quality of life in the patients.
REVIEWS 
In recent years, some progress has been achieved in elaborating the algorithms and standards for the treatment of many conditions accompanied by vertigo. The current possibilities of treating vestibular vertigo consist of a gradually expanding arsenal of symptomatic and pathogenetic drugs. Among the drugs used for the symptomatic treatment of vestibular vertigo, there are vestibular suppressants (antihistamines, benzodiazepines, and calcium antagonists) and antiemetics (dopamine antagonists and serotonin 5-HT3 receptor antagonists). The paper discusses the possibilities of using betahistine and vitamin D as pathogenetic agents for recurrent benign paroxysmal positional vertigo; diuretics, betahistine (including the new prolonged release formulation Betaserc® Long), glucocorticoids, and gentamicin for Meniere's disease; triptans, beta-blockers, tricyclic antidepressants, and anticonvulsants for vestibular migraine; glucocorticoids, antiviral agents, and drugs that accelerate vestibular compensation for acute unilateral peripheral vestibulopathy (vestibular neuritis and Ramsey Hunt syndrome).
The emergence of new drugs, as well as the design of new dosage forms that enhance patient adherence to the prescribed treatment, can improve quality of life in patients suffering from diseases that have recently led to long-term disability or even incapacitation.
CONSENSUS OF EXPERT MEETING 
EXPERIMENTAL STUDIES 
Objective: to carry out a systematic computer-assisted analysis of scientific literature on on the relationships between the effects of vitamin and nociception (including the impact of vitamin D deficiency on the development of pain syndrome.
Material and methods. For the query “(pain OR nociception) AND (vitamin D OR cholecalciferol OR VITD OR CALCITRIOL OR HYDROXYVITAMIN OR DIHYDROXYVITAMIN OR ALPHACALCIDOL)", 2318 references, including 77 references on alpha-calcidol, were found in the biomedical publications database PubMed. The computer-assisted analysis of this array of publications was carried out using the current big data analysis methods developed within the topological and metric approaches to recognition/classification problems.
Result and discussion. A systematic computer-assisted text analysis of 2318 studies on the relationships between nociception and vitamin D showed that the analgesic effects of the vitamin are by anti-inflammatory action and the regulation of serotonergic, dopaminergic, and opioidergic neurotransmission. The lower blood levels of the major vitamin D metabolite 25 (OH)D is a risk factor for decreased pain threshold in myalgia, fibromyalgia, arthralgia, dorsalgia, and a number of neuralgias.
Conclusion. In patients with impaired renal conversion of active vitamin D metabolites (especially in the elderly), the efficacy of cholecalciferol-based drugs is reduced, which makes it necessary to use the active forms of vitamin D.
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.
ISSN 2310-1342 (Online)