[Pharmacotherapy approaches to vascular mild cognitive impairment in patients of different age groups]. / Podkhody k farmakoterapii sosudistykh umerennykh kognitivnykh narushenii u patsientov razlichnykh vozrastnykh grupp.

The article discusses the possibilities of pharmacotherapy of moderate vascular cognitive impairment in different age groups. The results of a double-blind randomized clinical trial «MEMO¼ using the antioxidant and antihypoxic drug Mexidol are presented. On the basis of cognitive scales, when using a sequential course of parenteral and oral administration of mexidol, its reliable effectiveness was shown in each of the three analyzed groups: 40-60 years old, 61-75 years old and 76-90 years old. Mexidol showed an optimal safety profile in all age groups.

[Arterial hypertension and cognitive impairment. Neurologist's view]. / Arterial'naya gipertenziya i kognitivnye narusheniya. Vzglyad nevrologa.

The article presents a review of the literature on the relationship of cognitive impairment (CI) with arterial hypertension (AH). The pathogenetic mechanisms AH are characterized by the development of cerebral microangiopathy. Antihypertensive therapy (AHT) should take into account violations of autoregulation of cerebral blood flow in cerebrovascular disease and critical stenoses of large cerebral arteries, especially in fragile patients older than 80 years. The importance of AHT focused on the level of cerebral perfusion blood pressure, the severity of CI and the physical functioning of patients is emphasized. Neurocytoprotective therapy is recommended for correction of CI.

[The glymphatic system in the brain - neurobiology and clinical pathology]. / Glimfaticheskaya sistema mozga ­ neirobiologiya i klinicheskaya patologiya.

Given new information about the neurobiology of the processes of removal of waste products of the brain, consisting of the lymphatic vessels into the dura and the glial-lymphatic (glymphatic) system. The role of astrocytes and water-conducting channels located on them in cell membranes formed by the protein aquaporin-4 is emphasized. The connection between the functioning of the glymphatic system and the slow phase of sleep is discussed. Possible mechanisms for the development of cognitive impairments in violation of the function of the glymphatic system and a delay in the elimination of ß-amyloid are shown. Directions of pathogenetic therapy are given.

[Efficacy of Mexidol in patients with chronic brain ischemia and cognitive impairment of different age groups (results of sub-analysis of the international multicenter, randomized, double-blind, placebo-controlled study of sequential therapy in patients with chronic brain ischemia MEMO)]. / Effektivnost' Meksidola u patsientov raznykh vozrastnykh grupp s khronicheskoi ishemiei golovnogo mozga s kognitivnymi narusheniyami (rezul'taty subanaliza mezhdunarodnogo mnogotsentrovogo randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo issledovaniya MEMO).

OBJECTIVE: To assess the efficacy of sequential therapy with Mexidol and Mexidol FORTE 250 in comparison with placebo in patients of different age groups with chronic brain ischemia. MATERIAL AND METHODS: The study is sub-analysis of data of the international multicenter, randomized, double-blind, placebo-controlled study of sequential therapy in patients with chronic brain ischemia (MEMO), which included 318 patients (25% men) in the age of 40-90 (median 60) years. All subjects were subdivided into 3 age subgroups: 40-60 years (n=163), 61-75 years (n=141) and 76-90 years (n=13). The primary efficacy endpoint was the dynamic of increase of total score by MoCA scale, i.e. the absolute value of difference by MoCA scale at the point of day 75 comparing to values before treatment. As secondary efficacy endpoints results of dynamic by following questionnaires and scales were used: digit symbol substitution test, the Health Survey SF-36, asthenia subjective assessment scale (MFI-20), Vane questionnaire, Beck anxiety scale, Tinetti scale. RESULTS: After 75 days of treatment positive dynamic was revealed in cognitive, emotional and motor impairment in patients of 40-60 and 61-75 age subgroups both in groups of Mexidol and placebo, but in group of Mexidol the changes were more prominent which is proved by significantly higher values of median of absolute difference of total score of studied parameters. CONCLUSION: The results of trial showed that in patients of different age-subgroups with chronic brain ischemia the improvement in cognitive, motor impairment and quality of life, as well as decrease in vegetative impairment, asthenia and anxiety are observed after 75 days of treatment both in Mexidol and placebo group, but in Mexidol group these changes are more prominent. The data obtained confirm the expediency of the use of sequential therapy with Mexidol and Mexidol FORTE 250 in patients of different age subgroups with chronic brain ischemia.

[Neurological disorders in the postcovid period]. / Nevrologicheskie narusheniya v postkovidnom periode.

The consequences of COVID-19 include a wide range of neurological, emotional and cognitive impairments. The pathogenesis of postcovid disorders is complex and has not been fully studied. The article discusses the pathogenesis and clinical manifestations of neuropostocoid. A hypothesis is formulated about the possible role of circumventricular organs in its formation. The main directions of treatment of patients with postcovid disorders are proposed.

[Results of an international multicenter, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of sequential therapy with Mexidol and Mexidol FORTE 250 in patients with chronic brain ischemia (MEMO)]. / Rezul'taty mezhdunarodnogo mnogotsentrovogo randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo issledovaniya otsenki effektivnosti i bezopasnosti posledovatel'noi terapii patsientov s khronicheskoi ishemiei mozga preparatami Meksidol i Meksidol FORTE 250 (issledovanie MEMO).

OBJECTIVE: To assess the efficacy and safety of sequential therapy with Mexidol solution for intravenous and intramuscular administration, 50 mg/ml and Mexidol FORTE 250 film-coated tablets, 250 mg in patients with chronic brain ischemia (CBI). MATERIAL AND METHODS: An international multicenter, randomized, double-blind, placebo-controlled trial, conducted in 15 clinical centers located in Russian Federation and Republic of Uzbekistan, included 318 patients with CBI aged 40 to 90 years. The patients were randomized into 2 groups, the patients of the 1-st group received Mexidol intravenously 500 mg once daily for 14 days, followed by Mexidol FORTE 250 - 250 mg 3 times a day orally for 60 days; patients of the 2-nd group received a placebo in a similar mode. The primary endpoint was the mean value of difference by MoCA scale at the point of completing the therapy comparing to initial value. RESULTS: According to the results of the assessment of the primary endpoint, statistically significant changes in the MoCA scores at the stage of completion of study were revealed when comparing the dynamics between the 1-st and 2-nd groups (p<0.000001). The lower limit of the 95% confidence interval for the difference in the average of the main efficacy endpoint between the 1-st and 2-nd groups was 1.51, which allows to state a higher efficacy of the use of Mexidol. According to the estimates of secondary endpoints, a statistically significant advantage over placebo at the last visit achieved while evaluation by the following scales and tests: digit symbol substitution test, MFI-20 asthenia assessment scale, Beck anxiety scale, Vane questionnaire, Tinetti scale, SF-36 questionnaire (mental component of health), CGI scale. The comparable nature of the safety profile of Mexidol and Placebo was established. CONCLUSION: The validity and expediency of the use of Mexidol and Mexidol FORTE 250 in the treatment of patients with CBI has been demonstrated.

[Multimodal therapeutic strategies in the treatment of cerebrovascular disease]. / Mul'timodal'nye terapevticheskie strategii v lechenii tserebrovaskulyarnoi bolezni.

The review presents the scientific substantiation of the relationship between age-related cerebrovascular changes and dysregulation of cerebral perfusion, blood-brain barrier (BBB) function and neurovascular units. The ischemic cascade in cerebrovascular disease (CVD) is considered, the main links of which are glutamate excitoxicosis, oxidative stress and neuroinflammation. Endothelial dysfunction and increased BBB permeability play an important role in the development of neuroinflammation. The use of multifunctional drugs aimed at various pathological targets of acute and chronic cerebral ischemia for the purpose of neuroprotection has been substantiated. These drugs include the peptide Cortexin (cattle cerebral cortex polypeptides). Experimental data on the study of its molecular partners in the brain are presented. The clinical efficacy of Cortexin as a neuroprotective drug in CVD has been established in many studies.

[Oxidative stress in focal symptomatic and cryptogenic epilepsy in young patients]. / Okislitel'nyi stress pri fokal'noi simptomaticheskoi i kriptogennoi epilepsii v molodom vozraste.

OBJECTIVE: To study oxidative stress in young patients with focal symptomatic and cryptogenic epilepsy and after the new-onset epileptic seizures. MATERIAL AND METHODS: Patients, aged from 19 to 44 years, were distributed into three groups, 30 patients in each: patients after a few (first) epileptic seizures, patients in the clinical remission that has lasted at least one year, and patients with treatment-resistant epileptic seizures. The control group included 20 healthy people. Parameters of the pro-oxidant status (TBA-reactive products) and the antioxidant defense (total superoxide-scavenging activity, catalase, total antioxidant activity, and reduced thiols (SH groups)) were measured in the blood plasma. RESULTS: No significant differences in the concentrations of TBA-reactive products were identified in patients with epilepsy compared with healthy controls while concentrations of reduced SH groups, total superoxide-scavenging activity, catalase activity and the total antioxidant activity were significantly decreased in patients. In addition, some of the parameters displayed significant differences between different groups of patients. CONCLUSION: In patients with epilepsy, the changes in the free-radical processes are seen already after the first seizures and persist in the treatment-resistant epilepsy and in clinical remission. Since the parameters of the activity of the antioxidant defense are significantly different in different groups of patients, one can assume that different elements of the oxidative stress are present after the first epileptic seizures and in different courses of the disease.

[Review of clinical guidelines for the treatment and prevention of ischemic stroke]. / Obzor klinicheskikh rekomendatsii lecheniia i profilaktiki ishemicheskogo insul'ta.

One of the leading causes of death, disability and severe maladaptation of patients is ischemic stroke, which accounts for about 80% of all types of acute cerebrovascular accidents. At the same time, approximately 2/3 of the patients show residual effects of cerebral circulation disorders of varying severity. Currently, the problem of ischemic stroke attracts great attention and international and domestic recommendations developed for the prevention, treatment and rehabilitation of stroke patients are one of the aspects of work in this area. The article provides an overview of the latest clinical guidelines for the early management of patients with acute ischemic stroke of the American Heart Association and the American Stroke Association, as well as features of stroke therapy and prevention in Russia, Europe and USA.

[Pharmacoeconomic analysis of the neuroprotective medicines in the treatment of ischemic stroke]. / Farmakoékonomicheskii analiz neiroprotektorov, primeniaemykh v terapii ishemicheskogo insul'ta.

AIM: To perform a pharmacoeconomic analysis of the most frequently prescribed neuroprotective medicines for treating patients with mild ischemic stroke in the acute and early rehabilitation periods in the Russian Federation. MATERIAL AND METHODS: Three medical technologies were compared: ethylmethylhydroxypyridine succinate (mexidol), inosine + nicotinamide + riboflavin + succinic acid (cytoflavin) and a deproteinized hemoderivate of the blood of calves (actovegin). Cost minimization analysis, budget impact analysis and sensitivity analysis were performed based on the indirect comparison results. RESULTS: Efficacy analysis shows that mentioned above medicines have the same efficacy: mean difference mexidol is 0,2 (CI min 0,25; max 0,65), cytoflavin - 0,61 (CI min 0,23; max 0,99), actovegin 0,2 (CI min 0,18; max 0,22). The cost minimization analysis for the Russian Federation shows that mexidol therapy is associated with the lowest costs, while savings are observed both in the evaluation of total costs and separate components: intravenous ampoules and tablet forms. The savings in comparison with cytoflavin and actovegin are 231 RUB and 12,872 RUB, respectively. These savings will be enough to treat five patients with ischemic stroke (IS) with mexidol. Moreover, oral mexidol therapy is cheaper than the same dosage forms of cytoflavin and actovegin by 481 RUB and 3,164 RUB, respectively. This is an advantage for the treatment of population at the outpatient stage. Budget impact analysis has shown that the budget for the medicines for treating IS at the current distribution between treatment regimens, is estimated at 1.99 BN RUB. The increase in the proportion of patients receiving mexidol by 10% reduces total costs to 1.75 BN RUB, which is 240 M RUB less than current costs. With these savings 85 thousand patients with IS could be treated. The sensitivity analysis reveals that the result of the cost minimization analysis and the budget impact analysis remain stable when both the amount of the population and the cost of 1 mg of mexidol vary from -10% to + 10%. CONCLUSIONS: Mexidol has the same efficacy as alternatives. However mexidol is superior to cytoflavin and actovegin in terms of cost minimization analysis. The savings from one course of alternatives will cover costs of treatment of five patients with IS using mexidol. The increase in the proportion of patients receiving mexidol is associated with savings, which allows us to consider mexidol therapy of mild IS as budget-saving in the Russian Federation.

[Oxidative stress in epilepsy]. / Okislitel'nyi stress pri épilepsii.

This article contains an analysis of clinical and experimental studies in which oxidative stress is considered as a possible mechanism in the pathogenesis of epilepsy. Oxidative stress occurs as a result of brain damage after epileptic seizures and may later cause epileptogenesis. Patients with epilepsy showed a high level of lipid peroxidation markers, while the activity of antioxidant defense system was low. The level of oxidative stress was shown to be significantly higher in epileptics with associated mental disorders and in patients with refractory epilepsy. Further study of oxidative stress in epilepsy may play the key role in the treatment of this disease.

[Dose-dependent effects of cortexin in chronic cerebral ischemia (results of a multicenter randomized controlled study)]. / Dozozavisimoe deistvie korteksina pri khronicheskoi ishemii mozga (rezul'taty mnogotsentrovogo randomizirovannogo kontroliruemogo issledovaniia).

AIM: To study an effect of cortexin on neurological symptoms and oxidative stress as part of the ischemic cascade in chronic cerebral ischemia (CCI), I-II stages. MATERIAL AND METHODS: The multicenter randomized controlled study included 189 patients with CCI, 42 (22.2%) men and 147 (77.8%) women, mean age 64.3±0.5 years. Patients were randomized into three groups. Group 1 received intramuscular injection of 20 mg of cortexin, group 2 received 10 mg of cortexin; group 3 received basic treatment only. The duration of treatment was 10 days, the treatment course was repeated after 6 months. The patients were examined at baseline and during treatment (in total 5 times). Along with clinical and neurological examinations, some scales and tests ('Fedin Outpatient scale of chronic brain ischemia', MFI-20, Spiegel sleep scale, the Zung self-rating depression scale, Spielberger's inventory, the clock-drawing test, the 5-word test) were used. The severity of oxidation stress was assessed by the content of reduced SH-groups and total superoxide dismutase activity. RESULTS AND CONCLUSION: A dose-dependent effect of cortexin on the severity of neurological disorders, asthenia, sleep disturbance was shown. Antidepressant and anxiolytic effects were insignificant and were determined after repeated courses of the drug. The laboratory data confirmed the antioxidant effect regardless of the dose of cortexin. The safety and good tolerability of the drug were shown.

[The efficacy of cortexin and memantinol (memantine) in the treatment of cognitive impairment in patients with chronic cerebral ischemia]. / Éffektivnost' korteksina i memantinola (memantina) v lechenii kognitivnykh narushenii u bol'nykh s khronicheskoi ishemiei mozga.

AIM: To study the dynamics of cognitive impairment in patients with chronic cerebral ischemia (CCI) treated with cortexin and memantinol (memantine). MATERIAL AND METHODS: The authors present the results of the multicenter observational program 'KORMEN' that studied the efficacy of cortexin and memantinol in the treatment of cognitive impairment in patients with CCI. The study included 495 patients, 204 (41.2%) men and 291 (58.8%) women. Patients were stratified into two groups: cortexin group (n=388 (78.4%)) and cortexin + memantinol group. RESULTS AND CONCLUSION: A significant positive effect of treatment based on the scores on 4 cognitive scales was shown in both groups of patients. The addition of memantinol significantly improved cognitive functions in patients with severe cognitive impairment (р<0.05). The safety profile of the drugs was confirmed.

[Modern approaches to neuroprotective treatment of ischemic stroke]. / Sovremennye podkhody k neiroprotektivnoi terapii ishemicheskogo insul'ta.

The authors present the results of domestic clinical trials on the efficacy and safety of mexidol in patients with cerebrovascular disorders including ischemic stroke (IS). The use of mexidol is associated with complete and rapid regression of the focal neurological deficit. Mexidol is well tolerated with no significant side-effects. The drug is recommended for enteral and parenteral administration in patients with IS.

[Liposomal form of lipoic acid: preparation and determination of antiplatelet and antioxidant activity]. / Liposomal'naia forma lipoevoi kisloty: poluchenie i opredelenie antiagregatsionnoi i antioksidantnoi aktivnosti.

Optimal conditions for obtaining phosphatidylholine (PC) liposomes with lipoic acid (LA) are chosen that lead to the formation of nanoparticles with a size of 175¸284 nm with efficiency (extent) of inclusion of LA in liposomes equal 85% and characterized by a slow release of substance from the nanoparticles. The effect of "empty" liposomes and liposomal form of LA on platelet aggregation induced by arachidonic acid (AA) is established. It is found that liposomes with LА inhibit platelet aggregation, caused by AА, to 80%. In addition, it is shown that "empty" liposomes slightly (to 30%) suppress platelet aggregation, caused by AА. The amount of TBA-sensitive products in samples of platelet-rich plasma (PRP) incubated with liposomal LA is determined. It is shown that LA in the composition of liposomes retains its antioxidant properties, and the amount of products of lipid peroxidation in platelet-rich plasma decreases in a dose-dependent manner when arachidonic acid is used as an inductor of platelet aggregation. It is assumed that the antiplatelet action of the liposomal form of LА is induced by inhibition of the initiation of lipid peroxidation products caused by exogenous inducer AА. It is supposed that, after additional research, the liposomal form of LA can be considered as a new drug in complex treatment of cerebral ischemia.

[The use of L-lysine aescinat in the treatment of microcirculatory disturbances in patients young and middle age with violation of the intracranial venous outflow]. / L-lizina estsinat v lechenii mikrotsirkulyatornykh rasstroistv pri narushenii intrakranial'nogo venoznogo ottoka u patsientov s sindromom vegetativnoi distonii.

AIM: To study the efficacy of L-lysine aescinat in the treatment of vascular and microvascular disorders in patients with cerebral venous dystonia. MATERIAL AND METHODS: Sixty-eight patients, 25 male and 43 female, aged from 25 to 56 years, with disturbances of venous cerebral blood circulation and venous outflow difficulties were examined. The examination included the assessment of cerebral hemodynamics using the algorithm of complex ultrasound examinations and functional status of the microcirculation by the laser Doppler flowmetry (LDF) at baseline and 10 days after treatment with L-lysine aescinat. RESULTS AND CONCLUSION: L-lysine aescinat improves intracranial venous outflow, significantly improves the functioning of microcirculation, while not affecting the normal type of microcirculation or changing it in the direction of improvement of hemodynamic parameters, has a modulating effect on the autonomic response, and can be recommended in the complex treatment of young and middle aged patients with disturbances of cerebral venous blood circulation with the predominance of vagotonia as well as hypersympathicotonia.

[The efficacy of pharmacological preconditioning in carotid endarterectomy].

OBJECTIVE: To assess the efficacy of pharmacological preconditioning with actovegin in carotid endarterectomy. MATERIAL AND METHODS: The study was based on the results of surgical treatment of 80 patients with hemodynamically significant uni- and bilateral lesions of carotid arteries. Half of the patients was operated immediately and others after pharmacological preconditioning with actovegin in dose of 1200 mg/daily during 1,5 months. RESULTS: Pharmacological preconditioning with actovegin increased the cerebral perfusion determined with one-photon emission computed tomography that improved significantly results of the surgery. There were significant changes in patient's state 7 days and 6 months after surgery. The improvement was correlated with the less number of asymptotic post-surgery ischemic strokes in different brain areas. CONCLUSION: A positive role of pharmacological preconditioning with actovegin in surgical treatment of carotid artery stenosis has been demonstrated.

[The effect of cholesterol on the electrokinetic properties of erythrocyte membranes in chronic cerebral ischemia]. / Vliianie kholesterina na élektrokineticheskie svoĭstva membran éritrotsitov pri khronicheskoĭ ishemii golovnogo mozga.

AIM: To determine the effects of total plasma cholesterol on the electrokinetic properties of erythrocyte membranes of healthy volunteers and patients with chronic cerebral ischemia (CCI). MATERIAL AND METHODS: Authors studied the erythrocytes from venous blood of 95 patients with CCI and 54 healthy people (controls). To perform an electrophoretic cell analysis of erythrocytes, we used the shorthand method of computer microelectrophoresis. RESULTS AND CONCLUSION: Plasma cholesterol level increased with the age. In the control group, there were the increase in percentage of fixed red blood cells, decrease in the amplitude of oscillations and electrophoretic mobility of red blood cells. In CCI patients, a significant increase in the share of fixed red blood cells, decrease in the amplitude of oscillations and electrophoretic mobility were observed compared to the controls. An increase in percentage of fixed red blood cells as well as in the qualitative heterogeneity of red blood cells in the amplitude of the oscillations was identified both in patients and controls, regardless of sex and age, with higher levels of total cholesterol.

[Pharmacological preconditioning in carotid endarterectomy].

The study was aimed at examining efficacy of preoperative preparation (pharmacological preconditioning) for carotid endarterectomy in patients with chronic cerebrovascular insufficiency. For this purpose, we analysed the outcomes of surgical treatment in a total of 80 patients presenting with haemodynamically significant unilateral and bilateral lesions of carotid arteries. Of these, 40 patients were operated on immediately and a further 40 patients underwent surgery after pharmacological preconditioning with Actovegin taken at a daily dose of 1,200 mg for 1.5 months. It was demonstrated that preoperative preparation prior to surgery increases cerebral perfusion which is determined by means of single-photon emission computed tomography, thus substantially improving the outcomes of surgical treatment. Statistically significant differences in cognitive function of these groups of patients were revealed 7 days and 6 months after the operation. Improvement of cognitive functions was associated with fewer symptom-free postoperative cerebral ischaemic foci in various regions of the brain. A conclusion was made on a positive role of pharmacological preconditioning with Actovegin in surgical management of cerebrovascular insufficiency, first of all in relation to more complete restoration of cognitive functions.

[Treatment of asthenic syndrome in patients with chronic brain ischemia: results of the non-interventional observational program TRIUMPH].

OBJECTIVE: To assess the severity of asthenic syndrome (AS) in chronic brain ischemia (CBI) in primary health care settings. MATERIAL AND METHODS: The study included 1170 patients with brain ischemia, aged 45-65 years, treated with phenotropil in dose 100 mg during 2 and 3 months. Clinical examination and MFI-20 subscales were administered. RESULTS AND СONCLUSION: The high incidence of asthenic syndrome was observed across all MFI-20 subscales. The decrease in asthenic syndrome severity was significant already in the end of the first month of treatment with phenotropil. Such dynamics maintained to the end of the second and third month of treatment. More than 2-fold decrease in the severity of asthenia symptoms was achieved in all subgroups 3 months after treatment. More rapid and apparent decrease in asthenic syndrome was observed in younger patients.