Neurology, Neuropsychiatry, Psychosomatics

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Vol 13, No 4 (2021)
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4-11 304

Antipsychotic-induced parkinsonism (AIP) is one of the prognostically unfavorable complications of psychopharmacotherapy in patients with schizophrenia. Many studies have investigated various drugs that are used to treat this neurological side effect. This review analyzes drugs that are used and may be perspective for the treatment of AIP. We searched for full-text publications in Russian and English in the following databases: E-Library, PubMed, Web of Science, Springer, using keywords and combined word searches over the past decade (2011—2020). The review covers drugs that are promising for the correction of AIP, including anticholinergic drugs; NMDA receptor antagonists; dopamine receptor agonists; selective inhibitors of monoamine oxidase B; catecholamine transferase inhibitors; melatonin preparations; melatonin receptor agonists; benzodiazepines; herbal preparations traditionally used for the prevention and correction of extrapyramidal syndrome of various etiologies. Currently, a small number of medications are used in clinical practice for the treatment of AIP. However, not all of them are registered in the Russian Federation. Along with the differences in the mechanisms of AIP pathogenesis in specific patients, the limited choice of AIP treatments makes it difficult to solve the problem of adverse neurological complications of psychopharmacotherapy in schizophrenia.


12-17 158

Migraine is the first most frequent cause of disability among women of reproductive age globally, and up to 60% of patients note the association of headache attacks with menstruation.

Objective: to determine the features of menstrual cycle and gynecologic pathology in women with menstrual-related migraine (MRM).

Patients and methods. A prospective comparative study included 69 women of reproductive age with a migraine diagnosis who did not receive hormonal contraception. Depending on the association of migraine attacks with menstruation (according to headache diaries), the patients were divided into two groups: the 1st group consisted of 44 patients with MRM; group 2 — 25 patients with non-menstrual migraine (without the association of attacks with menstruation).

Results and discussion. Patients with MRM had heavier menstrual bleeding, longer menstruations (more than six days), abnormal menstrual cycle length and regularity, dysmenorrhea. In addition, the obtained data indicate a comorbid estrogen-associated gynecological pathology (endometriosis, adenomyosis, endometrial polyps, myoma) in MRM.

Conclusion. Presumably, the hypothalamic-pituitary-ovarian axis dysfunction plays the leading role in the MRM. It presents with menstrual cycle abnormalities and increased presence of estrogen-associated gynecological pathology, which should be considered during patient evaluation and suggesting recommendations.

18-24 148

Neuromyelitis optica spectrum disorders (NMOSDs) are a group of central nervous system autoimmune diseases characterized by similar clinical manifestations, optic neuritis, and transverse myelitis being the most frequent among them. In most cases, the pathogenesis of NMOSDs is associated with autoantibodies to aquaporin-4 (AQP4-IgG). However, AQP4-IgG is not detected in at least 10-20% of patients with NMOSDs. In this subgroup and in patients with isolated transverse myelitis or optic neuritis, IgG antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) were detected. Patients seronegative for both AQP4-IgG and MOG-IgG have also been described.

Objective: to evaluate rituximab (RTX) effectiveness in preventing relapses and disability in patients with NMOSDs.

Patients and methods. The study included 27 patients with NMOSDs (9 men and 18 women) aged 20-51 years who received RTX in 2019-2021. The treatment protocol included intravenous infusions of 1000 mg of RTX on the 1st and 15th days, the second and subsequent courses (maintenance therapy) - intravenous infusions of 1000 mg of RTX once every six months. Treatment effectiveness was assessed by the average annualized relapse rate, the median changes of the Expanded Disability Status Scale (EDSS), and based on the magnetic resonance imaging (MRI) changes.

Results and discussion. The annualized relapse rate at baseline and 18 months after the start of treatment was: all patients (n=27) — 0.6±0.3 and 0.07±0.27(p<0.0001); AQP4-IgG+ patients (n=6) — 1.1±0.9 and 0.17±0.41 (p=0.028); MOG-IgG+ patients (n=14) — 0.4±0.3 and 0.07±0.28(p=0.001); AQP4-IgG-, MOG-IgG-patients (n=7) — 0.8±0.4 and 0.0±0.0 (p=0.018). The EDSSscore at baseline and 18months after the start of treatment was: all patients — 4.5 [3.25; 6.0] and 4.0 [3.0; 5.75] (p=0.679); AQP4-IgG+ — 3.5 [2.625; 4.75] and 3.5 [2.5; 4.5] (p=0.869); MOG-IgG+ - 5.5[3.75; 6.5] and 5.5[2.75; 6.25] (p=0.465); AQP4-IgG-, MOG-IgG- - 4.0[3.75; 5.25] and 3.5[3.0; 3.5] (p=0.043). We observed two clinical relapses during the study period: one in an AQP4-IgG+ male and another one in a MOG-IgG+ woman. There was a significant decrease in the annualized relapse rate in all groups. The disability indicator did not increase during the study period, and in AQP4-IgG and MOG-IgG seronegative patients, it slightly but significantly decreased. Brain and spinal cord MRI monitoring during the treatment period revealed new active foci only in two patients with clinical relapses.

Conclusion. RTX treatment in NMOSDs is reasonably efficient and safe, but with the obligatory prior patient evaluation and monitoring of treatment results.

25-29 174

In the past decade, stroke incidence in younger adults increased. Methionine synthase reductase (MTRR) A66G polymorphism is one of the risk factors for ischemic stroke (IS). However, clinical features of IS in MTRR A66G polymorphism are not yet studied.

Objective: to investigate clinical features of IS in MTRR A66G polymorphism.

Patients and methods. One hundred forty-one younger patients with IS, hospitalized in the neurological department of Sverdlovsk Regional Clinical Hospital №1, were included in the study. MTRR A66G polymorphism was detected by the real-time polymerase chain reaction in all participants.

Results and discussion. MTRR A66G polymorphism was present in 83.7% of younger patients with IS. Participants with MTRR A66G polymorphism had a significantly higher prevalence of arterial hypertension (р=0.029). In addition, protein C level was significantly lower in patients with MTRR A66G mutation (р=0.001).

Conclusion. The majority of younger patients with IS have MTRR A66G polymorphism. Therefore, the inclusion of MTRR A66G polymorphism screening in the diagnostic algorithm of stroke in young adults seems necessary.

30-36 270

Objective: to investigate the effect of workplace stress on cognitive functions of younger men and women (25—44 years) in an open population of Novosibirsk.

Patients and methods. The study included a representative sample of Novosibirsk population aged 25—44 years (2013—2016 screening) within the budgetary theme №0541-2014-0004. We screened individuals aged 25—44years: 463 men, mean age 35.94±5.957years, and 546 women, mean age 36.17±5.997 years. Association of workplace stress with cognitive functions were assessed with standardized questions such as: «Has your specialty changed over the past 12 years?», «Do you like your job?» and «How do you rate your work responsibility over the past 12 months?». Cognitive evaluation during screening period included: A.R. Luria 10-words learning task (immediate and delayed recall), Burdon's test, exclusion of concepts «5th extra», animal naming test.

Results and discussion. We observed a decrease in semantic associations number among the respondents who did not change their occupation over the past year and among respondents who assess their work responsibility as «low». Verbal logical reasoning was lower in the respondents who assumed that they «did not like» or «did not like at all» their job and also assessed their work responsibility as «low». Auditory verbal shortterm memory, long-term memory, memorization productivity, and attention were worse in the participants who had either «insignificant» or «average» work responsibility.

Conclusion. Younger adults experiencing workplace stress have a decrease in cognitive functions.

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Objective: to identify the prognostic aspects of the ischemic stroke (IS) focus characteristics according to the data of computed tomography of the brain.

Patients and methods. We examined 80 patients with hemispheric IS up to 1-day old (50 patients for constructing mathematical models of disease outcomes and 30 patients for subsequent testing of the obtained models) aged 30-84 years.

Results and discussion. The analysis of the association between mortality probability and brain midline shift size shown that a brain midline shift of 4.5-5 mm did not increase mortality probability much, which indicates the synergistic stability of this system. System destabilization began after an increase of the brain midline shift for more than 5-5.5 mm. After a mild change in the initial indicator (6-8 mm), mortality probability increased from 25% to 90% and higher. When the brain midline shift was more than 8.5 mm, the system, from the synergistic viewpoint, became stable again but with an unfavorable prognosis. This analysis helps to identify the critical decision-making point when analyzing the IS focus neuroimaging characteristics. Thus, the point for the focus volume is 145 cm3, and for the brain midline shift - 5.0 mm.

Conclusion. The results of our study about the prognostic value of the IS focus characteristics according to CT data may have additional value for decision-making in the management of patients with a poor prognosis.

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Pharmacodynamic aggravation (PA) is an unpredictable increase in the frequency, the severity of existing seizures, and/or development of new seizure types despite rational (adequate for seizure type and epilepsy form) antiepileptic drug (AED) prescription. Many mechanisms and predictors of its development are still poorly understood.

Objective: to analyze PA of seizures in patients with newly diagnosed focal epilepsy receiving monotherapy with sodium channel blockers with epileptiform activity index (EAI) assessment.

Patients and methods. We enrolled 201 patients with newly diagnosed focal epilepsy aged 16—81 years. In twelve months, patients had five follow-up visits. At each visit, treatment tolerability and efficacy were assessed, taking into account changes in the type, severity, and frequency of seizures. Additionally, at each visit, video-electroencephalographic monitoring was performed with EAI assessment. PA of seizures occurred in patients on oxcarbazepine, carbamazepine, and lacosamide therapy.

Results and discussion. Five patients with PA of seizures had increased total EAI and EAI before sleep at the second follow-up visit after sodium channel blockers prescription. Electroencephalographic correlates of PA occurred earlier than clinical manifestations. In patients with PA, the absolute increase in EAI was minimal in patients receiving oxcarbazepine, and lacosamide therapy was associated with a minimal relative increase in EAI. At the end of the follow-up, total EAI decreased by 54—80% relative to its initial value in all five patients. The difference in the total index during the first and last visits was statistically significant.

Conclusion. Due to the low level of knowledge about PA of seizures, it seems necessary to consider its possibility in all cases of increased frequency, aggravation, or change in the type of seizures after the AED treatment initiation or an increase in its dose. It is also possible to use changes in total EAI and EAI before sleep as an early objective marker of PA in adults with focal epilepsy.

52-59 229

Sialorrhea is a severe medical problem that is difficult to treat, which can lead to serious complications. In almost all cases, chronic sialorrhea is accompanied by a restriction of the child's contacts with peers, socialization difficulties, and a significant decrease in the quality of life. Nowadays, botulinum therapy can be an effective tool that significantly reduces sialorrhea manifestation.

Oblective: to evaluate the effectiveness of Xeomin (incobotulinumtoxinA) in the treatment of sialorrhea in patients with spastic infantile cerebral palsy (ICP).

Patients and methods. We enrolled 24 children with ICP (14 (58.3%) females, and 10 (41.7%) males) with various disease forms: 4 (16.6%) — with spastic hemiparesis, 6 (25.0%) — with spastic diplegia, and 14 (58.3%) — with spastic quadriparesis. IncobotulinumtoxinA injections were performed bilaterally in the parotid and submandibular salivary glands under ultrasound control at a total dose of 40-100 U (min 1.3, max 4.5 U/kg of body weight). IncobotulinumtoxinA. The Drooling Impact (DIS) and the Global Impression of Change Scale (GICS) were used 1, 3 and 6 months after IncobotulinumtoxinA injections to assess treatment effectiveness.

Results and discussion. Botulinum toxin therapy resulted in a significant decrease in saliva discharge from the oral cavity 1 and 3 months after IncobotulinumtoxinA injections, which was demonstrated by a reduction in mean DIS score from 78.6±9.6 (min 62, max 95 points; 95% CI 74.6—82.7) to 48.7±6.7(min 25, max 61 points; 95% CI45.8—51.6) and 52.7±8.5points (min 22, max 65; 95% CI49.1—56.3), respectively, as well as an increase in delta GICSscore up to +1.3+0.8(min 0, max 3points; 95% CI 1.0—1.6) and +1.0+0.7points (min 0, max 3points; 95% CI 0.8—1.3), respectively. Adverse events were observed in 4patients (16.6%), which were classified as mild in 3 patients (did not require special treatment and completely stopped within six days) and moderate in 1 patient (also did not require special treatment and completely stopped within three weeks).

Conclusion. In the majority (79.1%) of patients with ICP, it is possible to achieve high efficiency in reducing sialorrhea and this effect persists for at least 3 months.

60-65 238

Objective: to investigate movement-based therapy (kinesitherapy) effectiveness in the rehabilitation of patients after lumbar microdiscectomy.

Patients and methods. We enrolled 90 patients (33 men and 57 women, mean age — 59.78±12.0 years) after lumbar microdiscectomy due to the ineffectiveness of conservative management of discogenic lumbosacral radiculopathy. One-half of the participants (45 patients: 15 men and 30 women, mean age — 60.24±12.0 years) underwent kinesitherapy under the supervision of a physician; in other 45 patients (18 men and 27 women, mean age — 59.33±11.0 years), kinesitherapy was not included in the radiculopathy treatment protocol. We assessed pain intensity with visual analogue scale (VAS) and disability using the Roland-Morris scale (RMS) before surgery, ten days after the surgery, and 1, 3, and 6 months after surgery.

Results and discussion. We observed a significant decrease in pain intensity - up to 4 points on the VAS, and an improvement in activities of daily living up to 10 points on the RMS 10 days after microdiscectomy. After six months, there was a decrease in pain intensity according to the VAS to 2 points in the kinesitherapy group and to 3 points in the group without kinesitherapy (p=0.088), as well as an improvement in activities of daily living according to RMS up to 5 points in the kinesitherapy group and up to 8 points in the group without kinesitherapy (p=0.003). Reoperations were required in two of 45 patients in the group without kinesitherapy (4.4%) and in one of 45 patients (2.2%) in the kinesitherapy group (p≥0.05).

Conclusion. Kinesitherapy can improve functional recovery in patients after lumbar microdiscectomy.

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Recently, maximum attention has been drawn to the earliest forms of cognitive deficit - pre-mild cognitive decline (PMCD), which includes subjective (SjCD) and subtle cognitive decline (SCD), being the most promising in cognitive decline prevention.

Objective: to assess the influence of genetic and comorbid emotional-affective factors on PMCD in middle-aged patients.

Patients and methods. The study included 50 middle-aged people (60.76±9.5 years) with cognitive complaints. All patients underwent a cardiovascular assessment, including: biochemistry blood test (lipid profile, urea, glucose, vitamin В12, folic acid, homocysteine, thyroid hormones), duplex scan of the extracranial arteries, blood assay for АРОЕ4 determination, neuropsychological assessment with quantitative neuropsychological methods, emotional-affective background evaluation. In addition, magnetic resonance imaging (MRI) with morphometry of the hippocampus was performed in 20 patients.

Results and discussion. Arterial hypertension, diabetes mellitus, and changes in laboratory parameters are significantly were more frequent in patients with SCD than patients with SjCD. The neuropsychological assessment showed maximum differences between SjCD and SCD groups in tests that evaluated reaction time (verbal fluency test, trail making test, part A, digit symbol substitution test, and Munsterberg test). Analysis of neuroimaging parameters revealed a smaller volume of the right hippocampus in APOE4 carriers. patients without depression performed significantly better on memory tasks, when depression was included in the analysis. In addition, patients with depression showed a significantly more pronounced degree of cortical atrophy on MRI.

Conclusion. Patients with SCD have lower scores in neuropsychological tests than patients with SjCD. In addition, we observed a high significance of cardiovascular and emotional-affective risk factors in the PMCD development, emphasizing the importance of their evaluation and treatment in the management of patients with PMCD.

75-80 272

Objective: to analyze the psychopathological structure, risk factors and tretment of depressive disorders in women in the postpartum period.

Patients and methods. A prospective cohort study included 150 women in the postpartum period (0-3 days after birth), aged 18 to 41 years, with follow-up every two weeks for six months. The evaluation included clinical interviews, Montgomery-Asberg Depression Rating Scale, and the 17-item Hamilton Anxiety Rating Scale.

Results and discussion. 11.3% of women developed depression within six weeks after childbirth. Among them, 94.2% presented with mild depression, and 5.8% - moderate. Risk factors associated with postpartum depression included: periods of low mood and anxiety before and during the current pregnancy, traumatic situations during pregnancy, unwanted pregnancy, pathology of pregnancy and childbirth, cesarean section, perinatal status, lack of breastfeeding. All women with postpartum depression were treated with rational-emotive and cognitive-behavioral therapy. A short course of pharmacotherapy was prescribed to 17.6% of them to correct insomnia and anxiety symptoms. Psychotherapy was highly efficient in the treatment of postpartum affective disorders.

Conclusion. The postpartum depression prevalence was 11.3%. The severity of postpartum depression was predominantly mild, and the symptoms regressed during treatment within five months in all women.

81-87 168

Patient needs, drug intake patterns, and adherence to therapy are significant challenges in the management of migraine patients.

Objective: to identify drug treatment needs, drug use patterns and adherence factors in migraine patients.

Patients and methods. An online survey was conducted among Internet users through social networks (Instagram, Facebook, Vkontakte) from 01/22/2020 to 02/22/2020. The selection of respondents was based on an anamnesis of headaches and passing the ID Migraine screener. One thousand five hundred ninety-eight individuals (93.8% women and 6.2% men) aged 18—39years participated in the survey.

Results and discussion. Among 1598 participants, 1490 experienced any headache, 937 respondents noted migraine symptoms, and 542 (58.4%) had a migraine diagnosis. 899 (96%) of responders used medications to relieve headaches, and in 59% of them drugs were self-prescribed. 125 (13%) patients received prophylactic therapy for migraine, of which only 47 (37.6%) complied with the prescribed treatment. We found a significant (p=0.019) association between the degree of adherence to therapy and the number of days with migraine.

Conclusion. The study revealed a low referral rate in patients with headaches. In addition, more than half self-prescribed the drug for headache relief, and only a third of patients complied with the prescribed prophylactic treatment.

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Post-COVID syndrome can develop in all patients who have had COVID-19, regardless of the disease severity. Clinical manifestations postCOVID syndrome vary greatly, but the most common symptoms include fatigue, anxiety and depression disorders (ADDs), and cognitive impairment (CI).

Objective: to evaluate the efficacy and safety of Cholytilin (choline alfoscerate) and the combined drug MexiB 6 in patients with post-COVID syndrome and fatigue, ADDs, and CI.

Patients and methods. The study included 100 patients aged 22 to 71 years who have had COVID-19 5.4 months ago. Inclusion criterion: cognitive complaints, fatigue, and emotional disturbances. The evaluation included neurological exam, Montreal Cognitive Assessment Scale (MoCA), Frontal Assessment Battery (FAB), 10-words list task, Multidimensional Fatigue Inventory (MFI-20), Hospital Anxiety and Depression Scale (HADS). Study participants were divided into two groups. Patients who had ADDs (anxiety/depression level according to HADS ≥8 points; n=50) were prescribed with MexiB 6 (1 tablet three times per day). Patients with CI (mean MoCA score ≤25 points; n=50) were prescribed with Cholytilin (2 capsules (800 mg) in the morning and 1 capsule (400 mg) at lunchtime). The follow-up period was 60 days.

Results and discussion. According to MoCA scores, a decrease in cognition was observed in 58% of participants, while 28% did not notice CI earlier. ADD fere present in 51%, and fatigue — in 100% of patients. We observed a significant reduction in fatigue severity (from 62.42±7.18 to 52.32±16.36 points; p<0.05) in patients prescribed with MexiB 6. The majority of patients noted a significant increase in physical activity, decreased fatigue, improvement of attention and physical well-being, and increased workplace efficiency. We also found a significant decrease in ADDs severity: ADDs either regressed completely (in 42% of participants) or became subclinical (in 48%; р<0.001). CI severity also reduced according to mean МоСА (from 26.60±1.31 to 27.28±1.39 points; p<0.05) and FAB (from 16.98±1.06 to 17.20±0.90 points; p<0.05) scores. In a subgroup of patients with mild CI treated with Cholytilin mean МоСА (from 23.50±0.99 to 26.36±1.34; р<0.001) and FAB (from 16.02±0.91 to 16.96±0.99; р<0.001) scores significantly increased. Complete regression of CI was observed in 74% of participants (р<0.001). We also found a decrease in ADDs (р<0.001) and fatigue (mean MFI-20 scores decreased from 42.28±10.73 to 35.60±8.10; р<0.001) severity in all study participants.

Conclusion. Patients who have had COVID-19, regardless of the disease severity, have a high prevalence of fatigue, ADDs and CI, and MexiB 6 and Cholytilin have a potential in their treatment.


94-102 277

The review discusses the role of neuroprotective therapy in the acute period of ischemic stroke in the era of active introduction of reperfusion treatment methods. The main mechanisms of brain damage during ischemia/reperfusion and the leading neuroprotective strategies studied in clinical trials are considered. Neuroprotective approaches aimed at suppressing excitotoxicity, oxidative stress, and neuroinflammation are presented. Current data on the safety and efficacy of uric acid, edaravone, fingolimod, natalizumab, interleukin 1 receptors antagonists, cerebrolysin, and other drugs have been analyzed. Non-drug methods of neuroprotection are characterized, including remote ischemic conditioning, therapeutic hypothermia, and neurostimulation. According to the author's position, the safest and most effective neuroprotective agent in acute ischemic stroke is cerebrolysin.

103-108 178

Cervical dystonia (CD) is a form of focal muscular dystonia. The pathophysiology of CD includes central and peripheral sensorimotor mechanisms that lead to a pathological posture, imbalance, gait disturbances, and pain. Current CD treatment guidelines include botulinum toxin (BT) injections as first-line therapy. It has been established that a combination of BT injections and rehabilitation programs can reduce the disease severity, disability, and pain, improve the quality of life, and increase the duration and intensity of the BT. Even though different opinions exist on rehabilitation standards in patients with CD, several strategies are distinguished for its different types. Currently, complex kinesiotherapy for CD is being introduced, proposed by the French specialist J.P. Bleton and based on sensorimotor retraining. Other rehabilitation methods include biofeedback, transcutaneous electrical neurostimulation, and proprioceptive rehabilitation. Each of these methods has its own pathophysiological rationale in CD.

109-115 247

The prevalence of vitamin В12 deficiency is about 3—16% in the general population, while in older people, it ranges from 10 to 20%. An increase in the proportion of people on reduced-calorie diets, the widespread use of drugs that can result in vitamin В12 deficiency, an increase in life expectancy, on the one hand, a variety of clinical manifestations and the lack of precise algorithms for laboratory diagnostics, on the other hand, suggest that the number of patients with vitamin В12 deficiency is significantly higher. Vitamin В12 can be absorbed by passive diffusion, regardless of intrinsic factor and other underlying causes of the deficiency. The presence of an additional route of absorption brings in new expectations for the oral administration of cyanocobalamin in therapeutic doses. Comparative clinical trials of the use of cyanocobalamin have shown that the oral route of administration is as effective as the parenteral. Considering the need for long-term, and in some cases — life-long, use of the drug, there is a need to develop dosage regimens for oral administration comparable in effectiveness to parenteral administration. The use of functional vitamin В12 deficiency biomarkers, such as vitamin В12 levels, cholotranscobalamin, methylmalonic acid, homocysteine, made it possible to establish that a daily dose of 1000 mkg is the most effective, which at the initial stage is as efficient as intramuscular administration. In some circumstances, maintenance therapy (intramuscularly at a dose of 1 mg/month) was more effective; thus, a differentiated approach scheme to determining the maintenance oral dose was proposed, depending on the result obtained at the initial stage of therapy. Comparative studies covering the entire spectrum from the recommended dietary allowance to the dose commonly used for cobalamin injections have shown that an oral daily dose of 1000 mcg of cyanocobalamin normalizes serum vitamin В12 levels and causes an 80—90% decrease in plasma methylmalonic acid concentration from the assumed maximum value. The oral route of administration provides a higher patient treatment adherence.


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Hereditary neuropathy with liability to pressure palsies (HNPP) is a rare hereditary disorder characterized by recurrent episodes of nerve compression. The first attack usually occurs in the second or third decade of life. In the majority of cases, HNPP is associated with a mutation at chromosome 17 p11.2-12 comprising the gene encoding peripheral myelin protein 22 (PMP22). Here we present a case report of a 43-year-old male with HNPP confirmed by DNA testing. The patient complained of recurrent episodes of bilateral foot extensor muscles weakness and/or hyperesthesia on the outer surface of the hands and forearms, which started after a prolonged posture maintaining and without evident precipitating factors. We also describe typical clinical, electrophysiological, and nerve ultrasound characteristics of the disease.


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Toll-like receptors (TLRs) act as receptors for bacterial lipopolysaccharides (LPS) and participate in innate immunity. Excessive TLRs activity leads to chronic inflammation and the development of several comorbid pathologies, including osteoarthritis (OA). Computer analysis of 52,312 publications devoted to TLRs was made to systematically describe the mechanisms of biological action of TLRs and their influence on the OA pathophysiology. In addition, we identified the mechanisms by which slow-acting drugs based on standardized forms of chondroitin sulfate (CS), which have symptom-modifying and structural-modifying effects, can decrease TLRs activity and be used in the treatment of OA. Our conclusions are supported by the results of TLRs chemoreactom analysis, as well as by clinical and experimental data.


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