The safety of the use of psychotropic drugs, widely used in neurological and psychiatric practice, is an urgent problem in personalized medicine. This narrative review demonstrated the variability in allelic frequencies of low-functioning and non-functional single nucleotide variants in genes encoding key isoenzymes of valproic acid P-oxidation in the liver across different ethnic/racial groups. The sensitivity and specificity of pharmacogenetic testing panels for predicting the rate of metabolism of valproic acid by P-oxidation can be increased by prioritizing the inclusion of the most common risk allele characteristic of a particular population (country).

Introduction . In 2022, new clinical guidelines ‘Epilepsy and status epilepticus in adults and children’ were released, according to which it is recommended for adult patients with epilepsy to include behavioral methods in the form of self-management programs in addition to standard antiepileptic therapy as rehabilitation measures in comprehensive care for patients with epilepsy in order to improve the quality of life, cognitive functions and adherence to treatment. Considering the urgency of this problem and the opportunities offered by new clinical guidelines, there has been interest in a more detailed study of the EpiTapp® technique as an element of a self-management program in addition to standard antiepileptic therapy as a comprehensive care, using the example of a patient with structural focal epilepsy (SFE). Objective . To present a clinical case of using the EpiTapp® application as part of a self-management program in addition to standard antiepileptic therapy as a comprehensive care for an adult patient with SFE. Materials and methods . The study used the author's technique of brush tapping (RF patent No. 2606489 dated 10.01.2017). Patient A. used the EpiTapp® application in addition to the antiepileptic therapy she received, as a part of rehabilitation program for self-management of epileptic seizures, on an outpatient basis. Results . The analysis of the diary of observation of epileptic seizures showed that in 93 % of cases, patient A. managed to stop the incipient motor focal seizure (FS) and prevent its transformation into a bilateral tonic-clonic seizure. Thus, against the background of regular use of the EpiTapp® method, the patient's frequency of FS decreased by 55.8 % by visit 4 compared to visit 2. Patient A. rated the effectiveness and safety of the EpiTapp® application by 95 %. Conclusions . Thus, the use of the EpiTapp® application allowed a woman with difficult-to-treat SFE to gain control over epileptic seizures without changing the regimen and dose of antiepileptic therapy.

An important mechanism for the development of intervertebral disc degeneration (IDD) is an imbalance between anti-inflammatory and pro-inflammatory cytokines. Therapeutic and non-therapeutic approaches for cytokine imbalance correction in IDD either do not give the expected result, or give a short period of time. This explains the relevance of high-tech medical care, which is part of specialized care and includes the use of new resource-intensive methods of treatment with proven effectiveness. The aim of the review is to update knowledge about new high-tech methods based on cytokine imbalance correction in IDD. It demonstrates promise of new approaches to IDD management in patients resistant to previously used therapies, including: cell therapy (stem cell implantation, implantation of autologous cultured cells, and tissue engineering); genetic technologies (gene modifications, microRNA, and molecular inducers of IDD); technologies for influencing the inflammatory cascade in intervertebral discs mediated by abnormal activation of inflammasomes; senolytics; exosomal therapy; and other factors (hypoxia-induced factors; lysyl oxidase; corticostatin; etc.).

Target. To investigate the effect of the EpiTapp® application on alpha rhythm synchronization in patients with genetic generalized epilepsy. Materials and methods. The total sample size was 81 people, including: patients suffering from juvenile myoclonic epilepsy (main group, mean age — 2 7 [23; 38] years) — 30 people; healthy volunteers (control group, mean age — 39 [21; 56] years) — 51 people. Results. The present study showed that wrist tapping using the EpiTapp® application statistically significantly reduced the degree of alpha synchronization in juvenile myoclonic epilepsy. At the same time, a decrease in the synchronization of the alpha rhythm is achieved in 66.7 % of cases. Conclusion. Our results of changes in the bioelectrical activity of the brain after a session of wrist tapping indicate the possibility of using the EpiTapp® application as a non-drug rehabilitation method related to seizure relief programs in patients with juvenile myoclonic epilepsy .

Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy. CTS therapy includes wrist immobilization, kinesiotherapy, non-steroidal anti-inflammatory drugs, carpal tunnel steroid injection, acupuncture, and physical therapy. Carpal tunnel decompression surgery (CTDS) is recommended after failure of conservative therapy. In many cases, neurological disorders continue despite CTDS. The aim of this study was to investigate the efficiency of direct transcutaneous electroneurostimulation (TENS) of the median nerve in the regression of residual neurological symptoms after CTDS. Material and Methods: 60 patients aged 28-62 years with persisting sensory and motor disorders after CTDS were studied; 15 patients received sham stimulation with a duration 30 min.; 15 patients received high-frequency low-amplitude TENS (HF TENS) with a duration 30 min; 15 patients received low-frequency high-amplitude TENS (LF TENS) with a duration 30 min; and 15 patients received a co-administration of HF TENS (with a duration of15 min) and LF TENS (with a duration of 15 min). Results: Our research showed that TENS significantly decreased the pain syndrome, sensory disorders, and motor deficits in the patients after CTDS. Predominantly, negative and positive sensory symptoms and the pain syndrome improved after the HF TENS course. Motor deficits, reduction of fine motor skill performance, electromyography changes, and affective responses to chronic pain syndrome regressed significantly after the LF TENS course. Co-administration of HF TENS and LF TENS was significantly more effective than use of sham stimulation, HF TENS, or LF TENS in patients with residual neurological symptoms after CTDS.

Aim: To present a clinical case of the use of the wrist tapping method in a 30-year-old patient with structural focal epilepsy (SFE). Key points. During 4 visits, we examined patient N., 30 years old, suffering from SFE, which developed against the background of a gunshot wound to the skull, with frequent focal seizures (FS) and bilateral tonic-clonic seizures (BTCS). After 6 months from the start of wrist tapping sessions (4th visit), using the application, the patient noted a 55% increase in quality of life due to the ability to stop AF and prevent the development of BTK. In 87.5% of cases, he was able to stop incipient motor hemifacial FS and prevent its transformation into BTCS. With regular use of the application by the patient, the incidence of FS decreased by 65.4% on the 4th visit compared to that on the 2nd visit. The patient highly rated the effectiveness and safety of the wrist tapping method (97.6%). Conclusion. The use of the application allowed a young man with treatment-resistant post-traumatic SFE, without changing the dosage regimen and dose of the antiepileptic drug, to reduce the frequency of FS by 65.4% from baseline and significantly reduce the number of BTCS, significantly improving the quality of life. Keywords: structural focal epilepsy, wrist tapping.

Intervertebral disc degeneration (IDD) and associated conditions are an important problem in modern medicine. The onset of IDD may be in childhood and adolescence in patients with a genetic predisposition. With age, IDD progresses, leading to spondylosis, spondylarthrosis, herniated disc, spinal canal stenosis. One of the leading mechanisms in the development of IDD and chronic back pain is an imbalance between pro-inflammatory and anti-inflammatory cytokines. However, classical therapeutic strategies for correcting cytokine imbalance in IDD do not give the expected response in more than half of the cases. The purpose of this review is to update knowledge about new and promising therapeutic strategies based on the correction of the molecular mechanisms of cytokine imbalance in patients with IDD. This review demonstrates that knowledge of the molecular mechanisms of the imbalance between pro-inflammatory and anti-inflammatory cytokines may be a new key to finding more effective drugs for the treatment of IDD in the setting of acute and chronic inflammation.

Valproic acid (VPA) and its salts (sodium calcium magnesium and orotic) are psychotropic drugs that are widely used in neurology and psychiatry. The long-term use of VPA increases the risk of developing adverse drug reactions (ADRs), among which metabolic syndrome (MetS) plays a special role. MetS belongs to a cluster of metabolic conditions such as abdominal obesity, high blood pressure, high blood glucose, high serum triglycerides, and low serum high-density lipoprotein. Valproate-induced MetS (VPA-MetS) is a common ADR that needs an updated multidisciplinary approach to its prevention and diagnosis. In this review, we consider the results of studies of blood (serum and plasma) and the urinary biomarkers of VPA-MetS. These metabolic biomarkers may provide the key to the development of a new multidisciplinary personalized strategy for the prevention and diagnosis of VPA-MetS in patients with neurological diseases, psychiatric disorders, and addiction diseases.

An elite athlete’s status is associated with a multifactorial phenotype depending on many environmental and genetic factors. Of course, the peculiarities of the structure and function of skeletal muscles are among the most important characteristics in the context of athletic performance. Purpose: To study the associations of SNV rs1815739 (C577T or R577X) allelic variants and genotypes of the ACTN3 gene with qualification and competitive distance in Caucasian athletes of the Southern Urals. Methods: A total of 126 people of European origin who lived in the Southern Urals region took part in this study. The first group included 76 cyclical sports athletes (speed skating, running disciplines in track-and-field): SD (short distances) subgroup—40 sprinters (mean 22.1 ± 2.4 y.o.); LD (long distances) subgroup—36 stayer athletes (mean 22.6 ± 2.7 y.o.). The control group consisted of 50 healthy nonathletes (mean 21.4 ± 2.7 y.o.). We used the Step One Real-Time PCR System (Applied Biosystems, USA) device for real-time polymerase chain reaction. Results: The frequency of the major allele R was significantly higher in the SD subgroup compared to the control subgroup (80% vs. 64%; p-value = 0.04). However, we did not find any significant differences in the frequency of the R allele between the athletes of the SD subgroup and the LD subgroup (80% vs. 59.7%, respectively; p-value > 0.05). The frequency of the X allele was lower in the SD subgroup compared to the LD subgroup (20% vs. 40.3%; p-value = 0.03). The frequency of homozygous genotype RR was higher in the SD subgroup compared to the control group (60.0% vs. 34%; p-value = 0.04). The R allele was associated with competitive distance in the SD group athletes compared to those of the control group (OR = 2.45 (95% CI: 1.02–5.87)). The X allele was associated with competitive distance in the LD subgroup compared to the SD subgroup (OR = 2.7 (95% CI: 1.09–6.68)). Conclusions: Multiplicative and additive inheritance models demonstrated that high athletic performance for sprinters was associated with the homozygous dominant genotype 577RR in cyclical sports athletes of Caucasian origin in the Southern Urals.

Chiari 1 Malformation (CM1) is classically defined as a caudal displacement of the cerebellar tonsils through the foramen magnum into the spinal cord. Modern imaging techniques and experimental studies disclose a different etiology for the development of CM1, but the main etiology factor is a structural defect in the skull as a deformity or partial reduction, which push down the lower part of the brain and cause the cerebellum to compress into the spinal canal. CM1 is classified as a rare disease. CM1 can present with a wide variety of symptoms, also non-specific, with consequent controversies on diagnosis and surgical decision-making, particularly in asymptomatic or minimally symptomatic. Other disorders, such as syringomyelia (Syr), hydrocephalus, and craniocervical instability can be associated at the time of the diagnosis or appear secondarily. Therefore, CM1-related Syr is defined as a single or multiple fluid-filled cavities within the spinal cord and/or the bulb. A rare CM1-related disorder is syndrome of lateral amyotrophic sclerosis (ALS mimic syndrome). We present a unique clinical case of ALS mimic syndrome in a young man with CM1 and a huge singular syringomyelic cyst with a length from segment C2 to Th12. At the same time, the clinical picture showed upper hypotonic-atrophic paraparesis in the absence of motor disorders in the lower extremities. Interestingly, this patient did not have a disorder of superficial and deep types of sensitivity. This made it difficult to diagnose CM1. For a long time, the patient's symptoms were regarded as a manifestation of ALS, as an independent neurological disease, and not as a related disorder of CM1. Surgical treatment for CM1 was not effective, but it allowed to stabilize the course of CM1-related ALS mimic syndrome over the next two years.

Antipsychotic (AP)-induced adverse drug reactions (ADRs) are a current problem of biological and clinical psychiatry. Despite the development of new generations of APs, the problem of AP-induced ADRs has not been solved and continues to be actively studied. One of the important mechanisms for the development of AP-induced ADRs is a genetically-determined impairment of AP efflux across the blood-brain barrier (BBB). We present a narrative review of publications in databases (PubMed, Springer, Scopus, Web of Science E-Library) and online resources: The Human Protein Atlas; GeneCards: The Human Gene Database; US National Library of Medicine; SNPedia; OMIM Online Mendelian Inheritance in Man; The PharmGKB. The role of 15 transport proteins involved in the efflux of drugs and other xenobiotics across cell membranes (P-gp, TAP1, TAP2, MDR3, BSEP, MRP1, MRP2, MRP3, MRP4, MRP5, MRP6, MRP7, MRP8, MRP9, BCRP) was analyzed. The important role of three transporter proteins (P-gp, BCRP, MRP1) in the efflux of APs through the BBB was shown, as well as the association of the functional activity and expression of these transport proteins with low-functional and non-functional single nucleotide variants (SNVs)/polymorphisms of the ABCB1, ABCG2, ABCC1 genes, encoding these transport proteins, respectively, in patients with schizophrenia spectrum disorders (SSDs). The authors propose a new pharmacogenetic panel "Transporter protein (PT)-Antipsychotic (AP) Pharmacogenetic test (PGx)" (PTAP-PGx), which allows the evaluation of the cumulative contribution of the studied genetic biomarkers of the impairment of AP efflux through the BBB. The authors also propose a riskometer for PTAP-PGx and a decision-making algorithm for psychiatrists. Conclusions: Understanding the role of the transportation of impaired APs across the BBB and the use of genetic biomarkers for its disruption may make it possible to reduce the frequency and severity of AP-induced ADRs, since this risk can be partially modified by the personalized selection of APs and their dosing rates, taking into account the genetic predisposition of the patient with SSD.

Patients with drug-resistant epilepsy (DRE) due to an arteriovenous malformation (AVM) located in a functionally significant area of the brain experience a significant decrease in quality of life and require additional non-drug rehabilitation methods aimed at controlling epileptic symptoms. Aim. To present a clinical observation of the use of the Epi-Tapp (R) application in a 29-year-old patient with an AVM. Materials and methods. We used the author's wrist tapping method EpiTapp (R) (RF patent No. 2606489 dated January 10, 2017). Results. Using the EpiTapp (R) application allowed a 29-year-old man with an AVM to reduce the severity and duration of focal seizures in 85% of cases and prevent secondary bilateral transformation of incipient bilateral tonic-clonic seizures in more than 50% of cases. Conclusions. This clinical case demonstrates the possibility of effectively using the EpiTapp (R) application in a patient with drug-resistant epilepsy as an element of a rehabilitation program aimed at controlling epileptic seizures.

Background. One of the main goals of rehabilitation programs is to improve the quality of life (QoL) of patients with various chronic diseases, including epilepsy. However, the issues of rehabilitation of adult patients with drug-resistant epilepsy remain not fully resolved. Objective: to evaluate an impact of the author-proposed EpiTapp ® method on QoL of patients with drug-resistant structural focal epilepsy (SFE). Material and methods. The study involved 60 patients with drug-resistant SFE: main group – 30 patients (median age 33.5 years) with drug-resistant SFE who along with antiepileptic therapy regularly used the wrist tapping EpiTapp ® method as an element of emergency self-help upon appearance of the first signs of arising epileptic seizure; control group – 30 patients (median age 39.5 years) with drug-resistant SFE who used no EpiTapp ® method, but continued to receive previously selected antiepileptic therapy. QoL was assessed by the questionnaire approach using author-translated Quality of Life in Epilepsy Inventory (QOLIE-31). Results. While comparing QoL of two patient groups over a 6-month follow-up period, a significant (p<0.05) positive parameter dynamics was demonstrated only in main group but not in control group. Conclusion. The author-based EpiTapp ® technique improves QoL of patients with drug-resistant SFE and can be used as an additional method of rehabilitation.

Wound healing is a complex, multi-step process. This process begins immediately after skin damage. The outcome of wound healing depends on the quality of each stage of this process: a normal or pathological scar. Violation of wound healing entails a decrease in the function of scar tissue as well as aesthetic dissatisfaction with the patient. This problem is especially important in aesthetic surgery. Patients who have come for beauty feel frustration, obtaining pathological scars. We have been dealing with the problem of wound healing after plastic surgery for about 10 years. Our approach includes the assessment of the risk of pathological wound healing and the treatment of high-risk patients. The risk assessment includes historical data on wound healing, signs of connective tissue dysfunction (especially patients with connective tissue dysplasia), and genetic polymorphisms of genes responsible for the structure of the components of the extracellular matrix of the skin. In the future, patients with a high risk of pathological scarring can be prescribed treatment after surgery. This article presents a clinical case in which we demonstrate our approach.

The objective of our review was to analyze studies of prevalence sleep disorders among medical workers during COVID-19 pandemic. Material and Methods — Overall, during the analyzed period, studying domestic and foreign databases, we identified 94 publications on the development of sleep disorders among medical personnel working during COVID–19 pandemic in 2000-2021. However, only 88 of these publications complied with the objective of the review. We included 75 full-text publications in this review. Results — Physicians and nurses during COVID-19 pandemic do not have the opportunity to take therapy aimed at combating the symptoms of sleep disorders, due to the need to maintain sufficient attention and the risk of developing excessive drowsiness while on duty in a COVID -19 hospital. The latter can have a negative impact on their professional activities. Thus, this problem certainly requires professional psychotherapeutic correction. Unfortunately, not all medical institutions have such specialists. Conclusion — Based on the literature review, we found out that health care workers have a high risk of developing sleep disorders. This can include violations of the circadian rhythm, a decrease in the quality and duration of night sleep, daytime hypersomnia caused by shift work in a hospital. An additional factor affecting the frequency and severity of sleep disorders in healthcare workers (physicians and nurses) is chronic stress, the importance of which has increased during the COVID-19 pandemic. Currently, the above problem has not been completely solved and requires research in this area and the development of new programs to help medical personnel.

Sleep is one of the most important and vital physiological processes in the human body. In addition to the length of daylight hours, the nature of work activity, bad habits (smoking, alcohol abuse, excessive consumption of caffeine-containing drinks, psychostimulants), the factors that violate the duration and quality of sleep include the nature and style of nutrition, as well as eating habits that affect daily intake vital nutrients (vitamins, essential amino acids, polyunsaturated fatty acids, etc.). Tryptophan is one of the essential amino acids associated with sleep disturbance. Given the high clinical significance of sleep disorders in the development of neurological diseases and mental disorders, the interest of researchers in the study of modifiable and non-modifiable risk factors for sleep disorders is growing. Objective: to analyze and systematize the results of fundamental and clinical studies of recent years on the role of tryptophan in the development of sleep disorders and anxiety-depressive disorders in adults. Materials and methods. This thematic review included available full-text publications obtained as a result of a literary search in the domestic (E-Library) and foreign databases (PubMed, Scopus, Oxford University Press, Springer, Web of Science Core Collection). Results. The role of tryptophan as a key link in the synthesis of melatonin and serotonin in the occurrence of sleep disorders and anxiety-depressive disorders is significant and can be used for further study. Conclusion. Based on the review of the literature, it can be concluded that one of the important mechanisms of sleep disturbance and the occurrence of anxiety and depressive disorders is insufficient intake of tryptophan in the body. This pattern is a consequence of the consumption of food with a low content of this essential amino acid. Considering the consequences that tryptophan depletion can lead to in the human body, competent nutritional support is a necessary measure.

BACKGROUND:Transcutaneous electrical nerve stimulation (TENS) is presently one of the main methods of treatment for neuropathic pain in type II diabetes mellitus. The discussion about which TENS frequency is more effective in the treatment of neuropathic pain has been ongoing for many years. Despite this, the response of different aspects of neuropathic pain to various TENS modalities has not been sufficiently studied.AIM:To analyze changes in characteristics of neuropathic pain depending on the frequency of TENS.MATERIALS AND METHODS:Seventy-five Russian diabetic patients with painful distal axonal neuropathy were enrolled in the study. Patients were assigned to three groups: in the HF TENS group, 25 patients received standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin) + high-frequency TENS (HF); in the LF TENS group, 25 patients received standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin) + low-frequency TENS (LF); in the control group, 25 patients underwent just standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin). Pain intensity was calculated before and after treatment with visual analogue scale (VAS), McGill pain questionnaire (MPQ), Douleur Neuropathique 4 Questions (DN4) and Pain Drawing.RESULTS:TENS increased the therapeutic effect of standard drug therapy, in the treatment of neuropathic pain, by 65.9% and prolonged its efficacy by 31% for up to 6 months after treatment. HF TENS had a more pronounced analgesic effect than LF TENS based on VAS (34.7%), sensory (57.6%) MPQ dimensions and DN4 (21%). Affective MPQ dimension with the use of LF TENS was lower than HF TENS by 34.7% immediately after treatment, by 47.3% after 2 months and by 34.8% after 6 months of the follow-up period.CONCLUSION:There are significant differences between HF and LF TENS based on pain assessment using various pain scales. This reflects the distinctive effects of different TENS modalities on different aspects of neuropathic pain.

Background: Patients with schizophrenia have an increased risk of depressive disorders compared to the general population. The comorbidity between schizophrenia and depression suggests a potential coincidence of the pathophysiology and/or genetic predictors of these mental disorders. The aim of this study was to review the potential genetic predictors of schizophrenia and depression comorbidity. Materials and Methods: We carried out research and analysis of publications in the databases PubMed, Springer, Wiley Online Library, Taylor & Francis Online, Science Direct, and eLIBRARY.RU using keywords and their combinations. The search depth was the last 10 years (2010–2020). Full-text original articles, reviews, meta-analyses, and clinical observations were analyzed. A total of 459 articles were found, of which 45 articles corresponding to the purpose of this study were analyzed in this topic review. Results: Overlap in the symptoms and genetic predictors between these disorders suggests that a common etiological mechanism may underlie the presentation of comorbid depression in schizophrenia. The molecular mechanisms linking schizophrenia and depression are polygenic. The most studied candidate genes are GRIN1, GPM6A, SEPTIN4, TPH1, TPH2, CACNA1C, CACNB2, and BCL9. Conclusion: Planning and conducting genome-wide and associative genetic studies of the comorbid conditions under consideration in psychiatry is important for the development of biological and clinical predictors and a personalized therapy strategy for schizophrenia. However, it should be recognized that the problems of predictive and personalized psychiatry in the diagnosis and treatment of schizophrenia and comorbid disorders are far from being resolved.

Background. Non-pharmacological methods of palliative therapy for structural focal epilepsy (SFE) have been extensively investigated. Development of self-care methods based on behavioral psychotherapy and reference bioadaptation is a promising and economically justified approach.Objective: to present a clinical case of administering EpiTapp application based on the author-proposed wrist tapping method for palliative care in adult SFE.Material and methods. The author-proposed method of wrist tapping (RF patent No. 2606489 of 01.10.2017) for a smartphone Android OS application was used. Wrist tapping was performed during the period of aura and/or focal seizures (FS) in patients with SFE. Patients used the smartphone application as an element of emergency palliative therapy for SFE outpatient settings.Results. Patient L., 33 years old, suffering from SFE with frequent FS and bilateral seizures (BS), received duotherapy in the preoperative period. The woman used the EpiTapp application regularly that allowed to reduce FS rate by 65%, as well as prevent BS development without altering the antiepileptic therapy regimen.Сonclusion. The experience of using the EpiTapp application based on the author-proposed method of wrist tapping has demonstrated that it holds promise for SFE palliative therapy. The proposed technique requires additional research to confirm its effectiveness.

Currently, a search for a solution to the problem of drug-resistant epilepsy is being actively pursued. Along with personalized (including targeted) drug methods, personalized nondrug methods of treating drug-resistant epilepsy are being actively developed. Our previous studies have shown that the developed author's technique with an individual selection of the wrist tapping (WT) leads to an increase in the activity of the frontotemporal cortex, mainly of the right hemisphere, involved in emotional control, and a decrease in the fear of recurrence of focal epileptic seizures (FS) or transformation of FS into bilateral tonic-clonic seizures (BTCS). In addition, WT leads to a decrease in intrahemispheric coherence in the frontotemporal regions of the left hemisphere, which is a biomarker for reducing the risk of generalized epileptic activity.