[A panel of serum biomarkers, including damage, apoptosis and neurotrophic markers, for the assessment of prognosis of the course of ischemic stroke]. / Primenenie syvorotochnykh biomarkerov povrezhdeniya, apoptoza i neirotrofichnosti v otsenke prognoza ishemicheskogo insul'ta.

OBJECTIVE: Identification of the relationship between clinical and neuroimaging data and the content of serum biomarkers (damage marker - neuron-specific enolase (NSE), apoptosis - p53 protein and neuroplasticity - brain-derived neurotrophic factor (BDNF)) in acute, early and late recovery periods of ischemic stroke. MATERIAL AND METHODS: Eighty patients in the acute, early and late recovery periods of ischemic stroke, aged from 49 to 75 years, were examined. The comparison group included 20 patients with chronic cerebral ischemia, comparable to the study group. A clinical assessment was carried out on the following scales: The National Institutes of Health Stroke Scale (NIHSS), the European Stroke Scale (ESS), the modified Rankin scale, the Bartel Index and SS-QOL. In the acute, early and late recovery periods of ischemic stroke, the dynamics of biomarker levels (NSE, p53 protein, BDNF) in blood serum and brain MRI in T1, T2, FLAIR, DWI modes were quantified. RESULTS: In patients with a favorable course in the acute period of stroke, low values of the NSE level and a trend towards increased levels of serum BDNF by the 10th day of the disease were noted. For the first time, it was found that high NSE and stable BDNF levels or a tendency to their decrease were observed in the acute period in patients with an unfavorable course of ischemic stroke. In the early recovery period of ischemic stroke, a strong correlation was established between the degree of independence and disability of patients, and the levels of serum NSE and BDNF. A significant inverse correlation was proved between the severity of neurological deficit, assessed on the ESS, in the late recovery period of ischemic stroke (12 months) and the level of BDNF in blood serum (r=-0.464). CONCLUSION: The selected complex of biochemical methods allowed us to assess the severity of damage, the activity of apoptotic and compensatory neurotrophic capabilities of brain tissue in ischemic stroke, as well as their relationship with clinical and neuroimaging data. We have shown the prognostic significance of the selected markers, which will allow, with an integrated approach, more accurate prediction of the further course and outcome of stroke.

[Hypoxia and oxidative stress in cerebral circulation insufficiency - effective ways of correction]. / Gipoksiya i oksidantnyi stress pri nedostatochnosti mozgovogo krovoobrashcheniya i effektivnye puti ikh korrektsii.

Cerebrovascular diseases (CVDs) are one of the urgent problems of clinical neurology and the second most common cause of dementia. Vascular factors leading to the development of hypoxia, oxidative stress, mitochondrial, endothelial dysfunction and, ultimately, to the development of apoptosis with the formation of degenerative brain changes are considered among the main risk factors for the development of CVD. The most important mechanisms of the development of TFR are hypoxia and oxidative stress, which indicate the need for the use of drugs with antihypoxant and antioxidant activity. Such drugs include Mexidol (ethylmethylhydroxypyridine succinate). Mexidol directly affects the pathogenetic factors of the formation of ischemic-hypoxic brain damage, has a high clinical efficacy in the treatment of various forms of cerebral circulatory insufficiency.

[The cerebral microangiopathy]. / Tserebral'naya mikroangiopatiya.

The review article highlights the main points of the development of cerebral microangiopathy - «small vessel diseases¼. Cerebral microangiopathy or small vessel disease. Cerebral microangiopathy is one of the leading causes of the development of acute and/or chronic cerebral circulatory disorders and cognitive disorders up to severe dementia. The article analyzes the relationship of pathoanatomic, neuroimaging and clinical manifestations of the course of cerebral microangiopathy.

[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.

[The efficacy of antioxidant treatment with mexidol forte in 250 patients with chronic cerebral venous insufficiency]. / Klinicheskaya effektivnost' antioksidantnoi terapii Meksidolom FORTE 250 patsientov s khronicheskoi tserebral'noi venoznoi nedostatochnost'yu.

OBJECTIVE: To study the efficacy and safety of complex treatment with 2-ethyl-3-hydroxy-6-methylpyridine (mexidol forte 250) and venotonic drugs L-lysine aescinat and diosmin/hesperidin in patients with chronic cerebral venous insufficiency (CCVI). MATERIAL AND METHODS: One hundred and twenty CCVI patients with clinical and ultrasonic signs of cerebral venous discirculation were studied. Patients were stratified into group 1 (n=40) treated perorally with mexidol forte 250 and diosmin/hesperidin during 74 days in combination with two courses of L-lysine aescinat intravenously on the 1st and 30th days from baseline, group 2 (n=40) treated with mexidol forte 250 and diosmin/hesperidin during 74 days, group 3 (n=40) treated perorally with diosmin/hesperidin during 74 days. RESULTS AND CONCLUSION: The efficacy and safety of the complex treatment of CCVI patients with venotonic drugs with the inclusion of mexidol forte 250 at a dose of 750 mg/day for 74 days is shown. The study demonstrates a significant positive effect of mexidol forte 250 on the dynamics of complaints and indicators of the neurological and psychoemotional status of patients. Monotherapy with the venotonic drug diosmin/hesperidin shows its insufficient efficacy.

[Efficacy and safety of the drug mexidol FORTE 250 as part of sequential therapy in patients with chronic ischemia of the brain]. / Éffektivnost' i bezopasnost' preparata Meksidol FORTE 250 v ramkakh posledovatel'noi terapii u patsientov s khronicheskoi ishemiei mozga.

AIM: To study the efficacy and safety of mexidol dripped intravenously (500 mg once a day) in the form of infusions for 14 days, followed by oral administration of mexidol FORTE 250 at a dose of 250 mg (1 tablet) 3 times a day for 60 days, in treatment of chronic brain ischemia in patients with hypertension and atherosclerosis. MATERIAL AND METHODS: The open observation program included 60 patients with an established diagnosis of chronic brain ischemia confirmed by neuroimaging methods. RESULTS AND CONCLUSION: The results of the study show the high efficacy and safety of sequential therapy (injections followed by tablets of mexidol FORTE 250). The treatment improves emotional and cognitive status, decreases motor disorders and severity of subjective manifestations. High adherence of patients to the therapy is shown.

[Alpha-lipoic acid in the treatment of diabetic polyneuropathy]. / Al'fa-lipoevaia kislota v lechenii diabeticheskoi polineiropatii.

The issues of classification, pathogenesis, pathomorphology and treatment of diabetic polyneuropathy (DPN) are addressed. Pathogenetic mechanisms of the action of alpha-lipoic acid in treatment of DPN are justified. The authors present the results of randomized placebo-controlled trials of alpha-lipoic acid that revealed the high clinical efficacy and absence of side-effects even during the long-term treatment.

[Pathogenetic aspects of the development of acute focal cerebral ischemia]. / Patogeneticheskie aspekty formirovaniia ostroi fokal'noi ishemii golovnogo mozga.

Current concepts on the main mechanisms of brain damage in ischemic stroke are considered. Chemical regulation of physiological and pathological processes of maintaining cellular pool is supported by a multistep system that included compounds of different structure and complexity. A complex assessment and comparison of the processes taking place during the development of acute local cerebral ischemia (necrosis, apoptosis, autoimmune inflammatory reaction, neuroplasticity) can help in the objectification and prognosis of individual characteristics of the course and outcome of ischemic stroke. Understanding of the cascade of events that occur during the acute ischemic damage is critical for determining current and future diagnostic and therapeutic approaches.

[Cerebral venous thrombosis]. / Tserebral'nye venoznye trombozy.

There is ample evidence that arterial and venous links of the vascular bed are interrelated, with the venous part, as the highly organized reflexogenic zone, responsible for the development of complex reactions providing the stability of the cerebral blood flow. There is few publications devoted to the venous pathology of the brain however the prevalence of cerebral venous thrombosis (CVT) is relatively high. The annual prevalence of CVT is 4-7 per 1 million of population. Timely recognition and early diagnosis of CVT are most important for successful treatment of patients. It can lead to effective therapy, decrease the consequences of this disease and the fatal outcomes. The review and systematization of the literature on the epidemiology, etiology, risk factors, clinical presentations, diagnosis and treatment of CVT are presented.

[Treatment of chronic cerebral venous insufficiency: a study on an effect of L-lysine aescinat]. / Lechenie khronicheskoi tserebral'noi venoznoi nedostatochnosti: izuchenie vliyaniya L-lizina estsinata.

AIM: To study an effect of L-lysine aescinat on the dynamics of complaints, severity of neurological syndromes and parameters of cerebral blood flow estimated by transcranial doppler and duplex scanning in patients with chronic cerebral venous insufficiency (CCVI). MATERIAL AND METHODS: Eighty patients with ultrasound-confirmed CCVI were examined. The basic group included 40 patients who received two treatment courses (intravenous drop-by-drop/stream introductions of L-lysine aescinat in the dose of 5ml during 7 days in 2nd and 30th days of examination). The comparison group consisted of 40 patients. RESULTS AND CONCLUSION: Treatment with L-lysine aescinat led to the significant decrease in complaints and improved the scores on the scales used in the study. There was an improvement in the cerebral hemodynamics (an increase of hemodynamic reserve and normalization of the linear blood flow velocity in deep veins) in the patients with CCVI. The safe profile of L-lysine aescinat used in recommended doses was confirmed.

[Antithrombotic treatment as primary and secondary prevention of stroke]. / Antitromboticheskaia terapiia kak pervichnaia i vtorichnaia profilaktika insul'ta.

The use of antithrombotic drugs (ATD) is necessary in the treatment and prevention of thrombosis. The correction of risk factors of ischemic stroke (IS) and transitory ischemic attacks (TIA) is important as well. The drugs inhibiting the activation and aggregation of thrombocytes allow to decrease the number of myocardial infarctions by 35%, stroke by 25% and mortality from cardiovascular causes by 15%. Currently, the clinical efficacy of acetylsalicylic acid (ASA), thienopyridines (ticlopidine, clopidogrel), dipyridamole or the combination of dipyridamole and ASA as well as glycoprotein antagonists IIb-IIIa for intravenous introduction have been confirmed. A review of experimental and clinical studies confirming the efficacy of dipyridamole in the treatment of acute stage of stroke and primary and secondary prevention of II is presented.

[An experience of using divasa in the treatment of cerebrovascular insufficiency].

AIM: To evaluate the clinical efficacy and safety of divasa in the treatment of patients with cerebrovascular insufficiency. MATERIAL AND METHODS: The main group included 40 patients (mean age 56.2±5.7 years) with asthenic/autonomic and vestibular/ataxic disorders developed during chronic cerebrovascular disease. The severity of symptoms was measured with the Visual Analogue scale (VAS). Neuropsychological and psychoemotional status was assessed with MMSE, MFI-20, HAM-A, a subjective sleep questionnaire, a scheme for detection of signs of autonomic disorders. Quality of life questionnaire (SF-36) and CGI scale were used as well. The plasma levels of fibrinogen and the von Willebrand factor were determined in all patients. The control group included 40 patients with chronic cerebrovascular insufficiency matched for age, sex and severity of neurological symptoms to the main group. RESULTS: The scores of asthenic symptoms, anxiety, sleep disorders and autonomic disorders were decreased significantly that led to the improvement of quality of life of patients. A significant decrease and normalization of the plasma levels of fibrinogen and the von Willebrand factor were identified in the patients of the main group. The drug was well-tolerated, side-effects (allergic reactions) were noted only in 5%. CONCLUSION: The positive effect of divasa on patient's condition was demonstrated. The drug may be recommended for the use in complex treatment of these patients.

[The results of the study of the efficacy and safety of mexidol in patients with chronic cerebral ischemia].

OBJECTIVE: To analyze the efficacy and safety of mexidol and their effect on the dynamics of neurological signs of the disease, emotional status and quality of life in patients with chronic cerebral ischemia (CCI). MATERIAL AND METHODS: We studied 45 patients with CCI who received mexidol in dose 500 mg a day during 14 days by introvenal introduction with the following peroral administration in doses 500 mg twice a day during 60 days. A comparison group included 30 patients with CCI matched for age, risk factors and severity of neurological symptoms, who did not receive mexidol. Patients of both groups received standard treatment that included medications needed for the complete correction of the risk factors. Cognitive function (MMSE), movement activity and quality of life (SF-36) were assessed. RESULTS: To the end of the study (74th day), a decrease in the severity of movement disorders, normalization of SF-36 scores and improvement of mean values of screening-assessment of cognitive function were identified in patients of the main group compared to those of the comparison group. CONCLUSION: The high efficacy and safety of treatment of CCI patients with mexidol using.

[The use of valdoxan in the treatment of post-stroke depression].

Forty patients, aged from 55 to 85 years, with post-stroke depression received valdoxan in dosage of 25 mg daily during 3 months. Patient's state was assessed with a battery of scales (The Hamilton depression scale, MMSE, Tinnetti scale etc). The high antidepressive effect and good tolerability of the drug were demonstrated. The improvement of movement and cognitive functions, together with the stabilization of the emotional state, was seen.

[Efficacy of cavinton in the treatment of patients with chronic blood flow insufficiency. Russian multicenter clinical-epidemiological program "CALIPSO"].

The multicenter clinical-epidemioilogical program "CALIPSO" included 4865 patients with chronic cerebrovascular insufficiency associated with arterial hypertension. Patients received cavinton in intravenous infusions in drops during one week in dosage (25 mg in the 1-4 days, 50 mg in the 5-7 days) and then perorally in dose 30 mg/day during 90 days. The data analysis of the first 1011 individual medical records revealed the significant decrease of patient's complaints (p<0,001) and severity of neurological symptoms (p<0,05) as well as the improvement in scores on the Tinnetti scale (p<0,001) and the MMSE (p<0,001). The safety profile of the drug was confirmed.

[A multicenter program on assessment of efficacy and safety of a new therapeutic scheme for patients with chronic cerebrovascular insufficiency].

An assessment of the complex multicenter prospective non-comparative program aimed at studying of efficacy and safety of a new scheme of therapy with cavinton in patients with chronic cerebrovascular insufficiency has been conducted. One hundred and forty-nine patients (46 male, 113 female), aged from 35 to 65 years, have been examined. The treatment started from intravenous infusions of the drug during 7 days as follows: 20, 30, 40, 50, 50, 50 and 50 mg of cavinton solution diluted in 500 ml of physiologic solution with the following peroral taking of cavinton forte in dose 10 mg 3 times daily during 11 weeks. Efficacy of drug was primarily assessed with MMSE and then by SF-36 and CGIC-PGIC. There were significant differences in scores on MMSE and SF-36 before and after treatment and on CGIC-PGIC on the 8th and 90th days of the study. The parenteral and peroral use of cavinton is well-tolerated and has a favorable safety profile.

[Cavinton in the complex treatment of patients with chronic cerebrovascular insufficiency].

A complex clinical-instrumental study included 138 patients with discirculatory encephalopathy (DE) who received cavinton perorally in dose 30 mg/day during 90 days (2 courses in a year) in addition to the basic therapy (hypotensive and antithrombotic drugs, neuroprotector glycine). A control group comprised 98 patients clinically matched with the main group. They received only basic therapy. Neurological status and results of neuropsychological tests were assessed before treatment and to the end of 3, 6 and 12 months. The improvement of all neurological syndromes studied was seen in the main group to the end of 12 months as compared to controls. The complex treatment using cavinton led to the significant decrease of risk of DE progression, development of transitory ischemic attacks and strokes compared to controls (relative risks were 0,01 and 0,14, respectively).