[Results of a pilot study of the structure and evaluation of the therapy for chronic sleep disorders in comorbid patients with chronic cerebral ischemia]. / Rezul'taty pilotnogo issledovaniya struktury i otsenki terapii khronicheskikh narushenii sna u komorbidnykh patsientov s khronicheskoi ishemiei golovnogo mozga.

OBJECTIVE: To evaluate the effect of the drug Cortexin on the clinical course and treatment of comorbid insomnia. MATERIAL AND METHODS: The study included 50 patients, average age 50.4±2.26 years, with CHI stage 1-2. with concomitant diseases arterial hypertension, atherosclerosis, diabetes mellitus (study CHRONAS). All patients were examined on the day of treatment, 11-15 days and 30-31 days after the end of therapy. At all visits, complaints, neurological status, and changes in physiological and laboratory parameters were assessed. The condition was assessed using the following scales: mental status assessment (MMSE), quality of life questionnaire (EQ-5D), assessment of general health, Pittsburgh Sleep Quality Index (PSQI), Epworth daytime sleepiness assessment, hospital anxiety and depression (HADS)).: Patients with additional diabetic polyneuropathy were assessed using the Central Sensitization Inventory (CSI). RESULTS: A high percentage of the prevalence of comorbid insomnia in patients was revealed. The structure of sleep disturbances in patients with chronic cerebral ischemia consisted of disturbances in sleep duration, difficulty falling asleep, frequent awakenings at night, and daytime sleepiness. After treatment, there was a regression of the main complaints, the severity of symptoms, including anxiety and depression, decreased, and a significant stabilization of cognitive status was observed. The positive dynamics persisted 1 month after the end of therapy. An additional normalizing effect of the drug on a number of biochemical parameters was revealed. Clinical dynamics were recorded already by the 11-15th day of treatment and persisted for up to 1 month. During observation, no patient had adverse drug interactions with other drugs (hypotensives, antiplatelet agents, statins). CONCLUSIONS: The clinical effectiveness of the drug Cortexin has been proven for all types of sleep disorders. The clinical effectiveness of the drug Cortexin at a dose of 10 mg IM for 10 days has been proven in patients with chronic sleep disorders due to CHI.

[The use of neuropeptides of animal origin in the treatment of neurological diseases]. / Primenenie neiropeptidov zhivotnogo proiskhozhdeniya v terapii nevrologicheskikh zabolevanii.

The issues of effective treatment of neurological diseases remain relevant to this day. Neuropeptide preparations have been used in domestic neurological practice for more than 20 years. The physiological activity of neuropeptides is many times greater than that of non-peptide compounds. Neuropeptides include preparations from the brain of animals and synthetically synthesized analogues. The drugs differ from each other not only in composition, but also in different mechanisms of action, while maintaining the commonality of a pronounced neurotrophic and neuroreparative action. Large peptides and amino acids work on the principle of «replacement therapy¼, minipeptides affect the signaling system of the nuclear erythroid factor and bind to molecular targets, being bioregulators. The specific action of bioregulators is the ability to prolong their action and change the prevailing mechanism by reducing or increasing the required dose when physiologically necessary. They are called SMART-peptides, have high selectivity and efficiency, safety can potentiate the actions of other drugs.

[A complex of B vitamins, choline and inosine in the treatment of chronic pain]. / Primenenie kompleksa vitaminov gruppy B, kholina i inozina pri khronicheskoi boli.

Chronic pain is an independent disease associated with multiple changes in the nervous, endocrine and immune systems. The use of B vitamins is pathogenetically justified. Unlike others, the CompligamB complex contains almost all fractions of B vitamins, inosine and para-aminobenzoic acid, which provides an additional therapeutic effect. The effects of vitamins are summarized, in some cases they are potentiated, while none of them can replace the other, so it is advisable to use vitamin complexes.

[Pathogenetic approaches to the treatment of sleep disorders in comorbid patients]. / Patogeneticheskie podkhody k terapii narushenii sna u komorbidnykh patsientov.

The sharp increase in cardiovascular disease is associated not only with known risk factors, but also with a massive increase in sleep disorders. with insomnia, it triggers a pathogenic vicious circle: insomnia-inflammation-disturbance of the hypothalamic-pituitary-adrenal axis-neurodegeneration-cognitive dysfunction. Currently, a number of pharmacological modulators have been described that can activate the cell survival system. A special role is given to peptide preparations. They have a unique ability to create new conformations with the body's own peptides without causing adverse effects, without entering into antagonistic relationships with other drugs, without affecting systemic hemodynamics. Small peptides, which, while not actually neurotrophins, specifically interact with the corresponding receptors, stimulate the synthesis of releasing active factors in the corresponding regions of the brain. Cortexin, the first Russian peptide with the largest evidence-based experimental and clinical base, can be recommended as a means of pathogenetic therapy for sleep disorders.

Determination of the Prevalence of Postcovid Syndrome and Assessment of the Effectiveness of the Drug Cortexin in the Treatment of Neurological Disorders in Patients with Postcovid Syndrome. Results of the CORTEX Multicenter Clinical and Epidemiological Observational Program.

Objectives. To study the prevalence and clinical manifestations of postcovid syndrome (PCS) in out-patients and to assess the efficacy of treatment with the drug Cortexin at doses of 10 and 20 mg i.m. for 10 days. Materials and methods. A total of 979 patients with PCS from regions of the Russian Federation, Azerbaijan, Kyrgyzstan, and Kazakhstan were studied; mean age was 54.6 ± 4.5 years; duration of COVID-19 was from one month upwards. Investigations involved three visits. The first was on the day of consultation (assessment of complaints, analysis of scale indicators, prescription of drug Cortexin at a dose of 10 or 20 mg i.m. for 10 days). The second visit (telephone consultation) was on day 10-14. The third visit was on day 30 of out-patient treatment. Assessment of patients' status used an asthenia assessment scale (MFI-20), a brief mental state assessment scale (MMSE), the Schulte test, and the Subjective Treatment Quality Assessment Scale. Results. The proportion of patients with PCS was up to 30% of all neurological admissions. The commonest manifestations were: fatigue, general weakness, decreased memory and concentration of attention, vertigo, sleep impairment, irritability, and aggression; less frequent were breathlessness, pain, increased sweating, anosmia, hyposmia, dysgeusia, paresthesia, hair loss, degradation of vision, tachycardia, allergic reactions, menstrual cycle impairments, erectile dysfunction, panic attacks, suicidal ideation, depression and refusal to eat meat. Conclusions: No associations were found between clinical symptomatology and the severity of COVID-19, the volume of lung tissue affected, or different periods of postcovid syndrome. Cortexin was found to be effective at doses of 10 and 20 mg for correcting the cognitive and asthenic manifestations of PCS. Cortexin was found to have anti-anxiety, antidepressant, and anxiolytic effects, which were more marked at the 20-mg dose.

[Mitochondrial dysfunction]. / Mitokhondrial'naya disfunktsiya.

Hypoergos-energy deficiency, i.e., a mismatch between the body's (tissue, organ, cell) need for energy and the limited amount of macroergs (ATP) that can currently be used to maintain the structural integrity and functional activity of a tissue or organ. The main role in the development of hypoergoses is played by damage to mitochondria, therefore, in recent years, this term has been replaced by mitochondrial dysfunction. Over the past 50 years, drugs have been actively studied and developed that have the ability to influence mitochondrial disorders, both primary and secondary mitochondrial diseases. In this context, Cytochrome C, an original antioxidant/antihypoxant with a dual mechanism of action, deserves attention.

[Possibilities of individual choice of NSAIDs on the example of the oxicam class, taking into account clinical and pharmacological characteristics]. / Vozmozhnosti individual'nogo podkhoda k vyboru nesteroidnogo protivovospalitel'nogo preparata dlya komorbidnogo patsienta s uchetom kliniko-farmakologicheskikh kharakteristik preparata na primere klassa oksikamov.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are traditionally used to relieve pain syndromes. The class of NSAIDs includes oxicams (meloxicam, tenoxicam, lornoxicam) - drugs with pronounced analgesic and anti-inflammatory effects. Oxicams have common properties of the class, but at the same time, due to structural differences from all other NSAIDs, they differ in a number of clinical and pharmacological characteristics, knowledge of which will help to individualize the choice of the drug.

[Prospects of use of research results for drugs with anitihypoxic and antioxidative properties in neuroprotective treatment strategies (Opinion of the Council of Experts dated 26 March 2022)]. / Perspektiva ispol'zovaniya rezul'tatov issledovaniya preparatov s anitigipoksantnymi i antioksidantnymi svoistvami v neiroprotektivnoi strategii lecheniya (Zaklyuchenie soveta ekspertov ot 26 marta 2022 g.).

Cerebrovascular diseases are one of the main causes of death and permanent disability. Effective and timely neuroprotective therapy can reduce the burden of cerebrovascular disease. The possibilities of neuroprotection as a method of prevention and medical rehabilitation of acute and chronic cerebrovascular diseases are addressed.

[Drug synergism as a basis for rational neuroprotection]. / Sinergizm lekarstvennykh preparatov kak osnova ratsional'noi neiroprotektsii.

Optimization of the choice of neuroprotective therapy regimens in patients with CVD, taking into account the synergism of drug interactions, is basic in real clinical practice. Unfortunately, in modern pharmacology there is no unified way to establish the synergistic spectrum of action of drugs, which would allow systematic investigation of the effects of combinations of drugs. By the method of studying the subtle mechanisms of action, combinations of drugs that are as synergistic as possible (summation and potentiation of effects) for various therapies of neurological diseases are proposed. Examples of rational neuroprotection are considered on the preparations Cortexin, citicoline, antioxidants.

[COMPASS study results as a foundation for new treatment approach for neurological patients. Opinion of the expert council of december 18, 2021]. / Znachenie rezul'tatov issledovaniya COMPASS v izmenenii podkhodov k lecheniyu patsientov nevrologicheskogo profilya. Zaklyuchenie soveta ekspertov ot 18 dekabrya 2021 g.

The resolution of the Council of Experts devoted to the discussion of the effectiveness of the use of a combination of rivaroxaban 2.5 mg 2 times a day and acetylsalicylic acid 100 mg per day to prevent recurrent non-coronary ischemic stroke results of the COMPASS study is presented. The advantages of this combination and the safety of its use are considered. Recommendations for the implementation of the results of the study in clinical practice are given.

[Determination of the prevalence of postcovid syndrome and assessment of the effectiveness of the drug Cortexin in the treatment of neurological disorders in patients with postcovid syndrome. Results of the multicenter clinical and epidemiological observational program CORTEX]. / Opredelenie rasprostranennosti postkovidnogo sindroma i otsenka effektivnosti preparata Korteksin v terapii nevrologicheskikh narushenii u patsientov s postkovidnym sindromom. Rezul'taty mnogotsentrovoi nablyudatel'noi programmy KORTEKS.

OBJECTIVE: To study the prevalence of clinical manifestations of postcoid syndrome in patients at an outpatient neurological appointment, to evaluate the effectiveness of therapy regimens using Cortexin at doses of 10 mg and 20 mg IM for 10 days. MATERIALS AND METHODS: 674 neurologists from all regions of the Russian Federation, Azerbaijan, Kyrgyzstan and Kazakhstan took part in the study. A total of 979 COVID-19 patients were recruited. The average age is 54.6±0.45 years. The duration of the transferred SARS-CoV-2 days and from 1 month or more 12. 3 visits were carried out: 1 on the day of treatment (assessment of complaints, analysis of scale indicators, prescription of the drug Cortexin in doses of 10-20 mg/m for 10 days). 2 (telephone survey) visit for 10-14 days, 3 visit - for 30 days at the reception. The condition was assessed using the Asthenia Assessment Scale (MFI-20), the Brief Mental Status Assessment Scale (MMSE questionnaire), the Schulte test, and the Subjective Treatment Quality Assessment Scale. RESULTS: The daily proportion of patients with complaints after a previous coronavirus infection was 30% in the total structure of neurological admission. The most common complaints: fatigue, general weakness, decreased memory and concentration, dizziness, sleep disturbance, irritability, aggression, shortness of breath, pain syndromes, excessive sweating, anosmia, hyposmia, perverted taste of paresthesia, hair loss, blurred vision, unstable blood pressure, tachycardia, allergic reactions, menstrual irregularities, erectile dysfunction, apathy, panic attacks, suicidal thoughts, depression, refusal to eat meat. CONCLUSION: There was no significant correlation of clinical symptoms with the severity of COVID-19, the percentage of lung tissue damage, and different periods of postcovid syndrome. The clinical efficacy of the drug Cortexin in dosages of 10 and 20 mg for the correction of cognitive and asthenic disorders has been proven. Revealed anti-anxiety, antidepressant and anxiolytic activity of Cortexin is more pronounced when using a dosage of 20 mg.

Drug Synergism as the Basis of Rational Neuroprotection.

Optimization of the choice of neuroprotective therapy regimens in patients with cerebrovascular diseases (CVD), taking into account the synergism of drug interactions, is a basic approach in clinical practice. Unfortunately, modern pharmacology has no unified way of establishing synergistic spectra of drug actions, which would allow systematic investigation of the effects of combinations of drugs. An approach based on studying detailed mechanisms of action suggested combinations of drugs with the greatest possible synergism (by summation and potentiation of effects) for various directions in the treatment of neurological diseases. Examples of rational neuroprotection are considered, using Cortexin, citicoline, and antioxidants.

[The result of prospective randomized study CITADEL - the efficacy and safety of drug cytoflavin in postcovid rehabilitation]. / Effektivnost' i bezopasnost' Tsitoflavina pri reabilitatsii bol'nykh s postkovidnym sindromom: rezul'taty prospektivnogo randomizirovannogo issledovaniya TsITADEL''.

OBJECTIVE: To investigate the structure of postcovid syndrome, age and gender characteristics of its course, and to assess the effect of Cytoflavin on the clinical course of neurological disorders in patients who have undergone COVID-19. MATERIAL AND METHODS: The study included 100 patients, the average age was 40.4±11.7 years, there were statistically more men than women. The duration of the transferred SARS-CoV-2 days is from 30 to 90 days from the date of recovery). By random sampling, the patients were divided into two groups, the main group, received Cytoflavin tablets, a course of 25 days, 2 tablets 2 times a day. Comparison group - other drugs (vitamins, nootropic drugs). All patients were examined on the day of treatment and 25-30 days after the end of therapy. The status was assessed using Asthenia Assessment Scale (MFI-20), Brief Mental Status Assessment Scale (MMSE), Quality-of-Life Questionnaire (EQ-5D), General Health Assessment Scale, and Pittsburgh Sleep Quality Index (PSQI). The analysis of laboratory parameters was carried out retrospectively. RESULTS AND CONCLUSION: Postcovid syndrome was more common in men, among comorbid conditions arterial hypertension and atherosclerosis prevailed, neurocognitive and autonomic disorders predominated. Appointment of Cytoflavin made it possible to achieve a pronounced anti-asthenic effect with the correction of cognitive impairments, which was reflected in a significantly more significant positive dynamics of indicators of all scales. An additional effect of Cytoflavin was revealed - a decrease in the severity of thrombocytopenia. During the observation period, no patient had any serious adverse events or side effects associated with taking the drug. Prescription of the drug does not require age-related dose adjustment and is well combined with basic therapy for concomitant pathology.

Direct and Indirect Neurological Signs of COVID-19.

Objective. To systematize the neurological manifestations of COVID-19. Materials and methods. A systematic computerized analysis of all currently available publications on the neurological manifestations of COVID-19 was undertaken (2374 reports in PubMed) by topological data analysis. Results. A set of interactions between infection with SARS-CoV-2, metabolic impairments affecting neurotransmitters (acetylcholine, dopamine, serotonin, and GABA), enkephalins, and neurotrophins, micronutrients, chronic and acute inflammation, encephalopathy, cerebral ischemia, and neurodegeneration (including demyelination) was described. The most typical neurological manifestations of COVID-19 were anosmia/ageusia due to ischemia, neurodegeneration, and/or systematic increases in proinflammatory cytokine levels. COVID-19 provoked ischemic stroke, Guillain-Barré syndrome, polyneuropathy, encephalitis, meningitis, and parkinsonism. Coronavirus infection increased the severity of multiple sclerosis and myopathies. The possible roles of the human virome in the pathophysiology of COVID-19 are considered. A clinical case of a patient with neurological complications of COVID-19 is described. Conclusions. In the long-term perspective, COVID-19 promotes increases in neurodegenerative changes, which requires special neurological rehabilitation programs. Use of cholinergic drugs and antihypoxic agents compatible with COVID-19 therapy is advised.

[Asthenic disorders as a manifestation of chronic fatigue syndrome]. / Astenicheskie rasstroistva kak proyavlenie sindroma khronicheskoi ustalosti.

The article explains the changes in terminology and diagnostic criteria for asthenic disorders as manifestations of chronic fatigue syndrome CFS (myalgic encephalomyelitis). Chronic fatigue syndrome is defined as neuroimmune endocrine dysfunction with a purely clinical diagnosis. Probably, viral infections can play a leading role in the pathogenesis. Published diagnostic criteria reveal possible correlations between chronic fatigue syndrome and COVID-19 disease. A promising strategy for the therapy and rehabilitation of patients is the use of smart peptides, a representative of which is the drug cortexin.

[Prospects for pharmacological adaptation of neurovascular unit in conditions of neurotropic viral infection]. / Perspektivy farmakologicheskogo konditsionirovaniya neirovaskulyarnoi edinitsy v usloviyakh neirotropnoi virusnoi infektsii.

The article discusses the prospects for pharmacological conditioning as a method for adaptation of neurovascular unit in conditions of neurotropic viral infection. A step-by-step mechanism for development of preconditioning and postconditioning is presented with a detailed description of it's main stages (trigger, signal and effector). The role of neuroinflammation as the leading mechanism of damage and the possibility of influencing the brain neurotrophic factor are considered. It is shown that different medications including neurotrophic drugs (cerebrolysin) can serve as inducers of conditioning. Usage of neurotrophic drugs in different doses for preconditioning and postconditioning is pathogenetically justified.

SARS-CoV-2 (COVID-19) as a Predictor of Neuroinflammation and Neurodegeneration: Potential Treatment Strategies.

The SARS-CoV-2 (COVID-19) pandemic has attracted attention to the challenge of neuroinflammation as an unavoidable component of viral infections. Acute neuroinflammatory responses include activation of resident tissue macrophages in the CNS followed by release of a variety of cytokines and chemokines associated with activation of oxidative stress and delayed neuron damage. This makes the search for treatments with indirect anti-inflammatory properties relevant. From this point of view, attention is focused on further study of the treatment of patients with COVID-19 with dipyridamole (Curantil) which, having antiviral and anti-inflammatory effects, can inhibit acute inflammatory activity and progression of fibrosis, is a drug with potential, especially among patients with early increases in the D-dimer concentration and severe signs of microangiopathy.

[Locomotive syndrome: from paradigms to clinical reality].

Locomotive syndrome is an unsatisfactory condition of patients over 60 years of age who need or may require outside help in the near future due to functional deterioration of the musculoskeletal system, including pathology of bone tissue, joints, muscles and nervous tissue. In real clinical practice, one often has to deal with the following manifestations of locomotive syndrome: osteoarthritis, sarcopenia, balance disorders, chronic musculoskeletal pain. Today, there is a clear understanding that drug therapy should be long-term, include comprehensive support for muscle tissue, balance training, and mandatory cognitive-behavioral therapy. Maximum safety of long-term drug therapy can be ensured by the use of vital micronutrients, which include highly purified forms of chondroitin sulfate and glucosamine sulfate, which have a wide range of anti-inflammatory and regenerative effects.

[Direct and indirect neurological manifestations of COVID-19]. / O pryamykh i kosvennykh nevrologicheskikh proyavleniyakh COVID-19.

OBJECTIVE: To systemize the neurological manifestations of COVID-19. MATERIALS AND METHODS: A systematic computer analysis of all currently available publications on the neurological manifestations of COVID-19 (2374 publications in PUBMED) using algorithms of topological data analysis was performed. RESULTS: A complex of interactions between SARS-CoV-2 infection, metabolic disorders of neurotransmitters (acetylcholine, dopamine, serotonin and GABA), enkephalins and neurotrophins, micronutrients, chronic and acute inflammation, encephalopathy, cerebral ischemia and neurodegeneration, including demyelination, was described. The most common neurological manifestation of COVID-19 is anosmia/ageusia arising as a result of ischemia, neurodegeneration, and/or systemic elevation of proinflammatory cytokine levels. COVID-19 provokes ischemic stroke, Guillain-Barré syndrome, polyneuropathy, encephalitis, meningitis and parkinsonism. Coronavirus infection significantly aggravates the course of multiple sclerosis and myopathies. Possible roles of the human virome in the neuropathophysiology of COVID-19 are considered. A case of clinical management of a patient with neurological complications of COVID-19 is described. CONCLUSION: In the long term, COVID-19 stimulates neurodegenerative changes, which require specific programs of neurological rehabilitation. It is advisable to use choline drugs and antihypoxants that are compatible with COVID-19 therapy.

[SARS-CoV-2 (COVID-19) as a predictor of neuroinflammation and neurodegeneration: potential therapy strategies]. / SARS-CoV-2 (COVID-19) kak prediktor neirovospaleniya i neirodegeneratsii: potentsial'nye strategii terapii.

The pandemic caused by the SARS-CoV-2 virus (COVID-19) made it necessary to evaluate in more detail the processes of neuroinflammation as an integral component of the pathogenesis of viral infection. The acute neuroinflammatory response includes the activation of resident tissue macrophages in the CNS and the subsequent release of various cytokines and chemokines, which probably activates oxidative stress, causing long-term neuronal damage. This makes urgent the search for drugs with indirect anti-inflammatory effects with proven effectiveness. From this point of view, it is worth further studying the treatment of patients with COVID-19 with dipyridamole, which, with its antiviral activity and anti-inflammatory effect, inhibiting acute inflammation and progressive fibrosis, is the drug of choice, especially for patients with early signs of elevated D-dimer concentrations and pronounced clinical symptoms of microangiopathy.