Improvement of the efficacy of treatment of hypertensive encephalohathy by using mexidol

Author:
E.V. BOLOTOVA, N.YU. LUSHPAY, I.V. KOVRIGINA.
Kuban State Medical University under the Health Care Ministry of the Russia, Krasnodar, Russia; Reserch Institute - Territorial Clinical Hospital №1 med after Professor S.V. Ochapovski under the Health Ministry of the Russia, Krasnodar, Russia.

Summary:
Objective. To assess the efficacy and tolerability of mexidol used to improve cognitive impairment in patients with hypertension and clinical manifestations of chronic cerebral circulatory insufficiency. Material and methods. Forty-two patients with chronic cerebral circulatory insufficiency and cognitive impairment were examined. MMSE, МоСА and the clock drawing test were used to assess neuropsychological status. The Morisky-Green test was administered to evaluate medication adherence. Patients were stratified into two groups: patients of the first group (n=21) received standard treatment. Patients of the second group (n=21) received additionally mexidol in dose 200 mg (4 ml) in 100 ml of NaCl isotonic solution intravenously during 10 days and then in tablets (2 tablets 0,125 mg) twice a day during 8 weeks. Results. According to the 4-item Morisky Medication Adherence Scale (MMAS), 31% of respondents were not adherent to the treatment (MMAS score 0—2), 35.7% (n=15) of patients showed high adherence (MMAS score 4), 33.3% (n=14) demonstrated low adherence (MMAS score 3). The average score on the questionnaire was 2.85. In patients treated with mexidol, the absence of complaints increased by 3 times and headache regression increased by 90%. The improvement of memory, concentration and anxiety was observed in 50%, 55%, 67% of patients, respectively. Patients treated with mexidol demonstrated more significant changes during the clock drawing test. The average change in the scores increased by 0.95 compared to the control group, where the changes were 0.54 (p<0.02). The positive dynamics on MMSE and МоСА was shown in the mexidol group that indicated the positive effect of this drug on cognitive symptoms. Conclusion. The positive impact on cognitive symptoms and health in patients with chronic cerebral circulatory insufficiency allows to recommend mexidol as add-on to standard treatment of the main disease.

Keyword: mexidol, cognitive impairment, adherence.


Assessment of the efficacy of mexidol in the combination with hyperbaric oxygen in acute ischemic stroke

Author:
N.S. KULAI, E.YU. KOVALCHUK.
Saint-Petersburg I.I. Dzhanelidze research institute of emergency medicine, Saint-Petersburg, Russia.

Summary:
Objective. To study the efficacy of mexidol in the combination with hyperbaric oxygenation (HBO) in comparison with the standard HBO sessions in patients with acute ischemic stroke. Material and methods. One hundred and twelve patients were examined. In the main group, 48 patients underwent HBO and received treatment with mexidol. The control group consisted of 64 people who underwent the standard HBO sessions only. Results and conclusion. The use of combination therapy (HBO+mexidol) leads to the significantly more rapid normalization of acute phase indices which are correlated with neurological deficit reduction.

Keywords: ischemic stroke, hyperbaric oxygen therapy, mexidol.


The system stress-limiting action of mexidol in chronic cerebral ischemia

Author:
E.A. ANTIPENKO, A.V. DERUGINA, A.V. GUSTOV.
Nizhny Novgorod State Medical Academy of the Ministry of Public Health, Nizhny Novgorod; Lobachevsky Nizhny Novgorod State University, Nizhny Novgorod.

Summary:
Objective. To clarify the mechanisms of the action of anti-stress antioxidant agent (mexidol) in patients with chronic cerebral ischemia. Material and methods. Sixty-seven patients with chronic cerebral ischemia (TE stage II), 48 women and 19 men, mean age 48.2 years, were examined. To assess the state of multilevel stress system, the level of anxiety and depression, degree of autonomic imbalance, adaptive reactions of the blood and functional properties of erythrocyte membranes, level of average weight molecules in the blood plasma were studied. Therapeutic complexes consisted of standard therapy (vinpocetine and piracetam) and mexidol (10 ml intravenous drip 200 ml of physiological solution once a day every day for 10 days with subsequent transition to the oral ingestion of the drug (1 tablet (125 mg) 3 times a day for three months). Results and conclusion. In group 1 treated with additional antioxidant mexidol, the more pronounced and prolonged positive effect on the clinical symptoms of TE was observed. There were the persistent decrease in the level of anxiety and reduction of autonomic imbalance in the main group. The dynamics of adaptive reactions of blood indicated the activation of the adrenal cortex. There was a decrease in the content of average weight molecules and recovery of the sorption capacity of red blood cells. The results indicate the multi-component multi-level stress-limiting effect of mexidol in patients with chronic cerebral ischemia stage II.

Keywords: mexidol, chronic cerebral ischemia, treatment, stress.


An influence of submaximal (submineximal) doses of mexidol on oxidant stress and inflammation in the acute period of ischemic stroke

Author:
A.R. GODUNOVA, A.A. RAKHIMOVA, O.I. LEONTYEVA, I.G. TALIPOVA, R.M. YAKHIN, SH.G. MUSIN.
Emergency Hospital, Naberezhnye Chelny, Russia.

Summary:
Objective. To study an effect of submaximal doses of mexidol on the dynamics of biochemical markers of inflammation and damage to brain tissue in the acute period of ischemic stroke. Material and methods. A total of 60 patients admitted in the first 6h after disease onset with a verified ischemic stroke (7-9 points on the ASPECT scale) were enrolled in the study. Thirty patients in the study group received submaximal doses of mexidol: 750 mg infusion dropwise in 250 ml of 0.9% NaCl solution for 6 days. Thirty patients of the control group received standard therapy. Biomarkers and neurological status were evaluated within 60 minutes from the time of admission to the hospital and after 6 days. Results and conclusion. In both groups, the changes in CRP, IL-6, and fibrinogen did not contribute to the efficacy of mexidol. The brain natriuretic peptide (BNP) biomarker, plasma-A-associated pregnancy (PAPP-A) biomarker, average NIHSS score and mean cerebroasthenia score on the MFI-20 scale in the study group were significantly reduced compared to the control group. This study indicates a decrease in oxidative stress and signs of inflammation, a reduction of the severity of neurological deficit and an increase in physical activity of patients treated with submaximal doses of mexidol. Given the activation time of the damaged antioxidant system of the body, the recommended period of treatment is 3 months.

Keywords: antioxidant stress, inflammation, acute period, ischemic stroke, mexidol.


Mexidol effect on the factor induced by hypoxia HIF-1α expression in the rat cerebral cortex in its ischemia

Author:
E.N. YAKUSHEVA, P.YU. MYLNIKOV, I.V. CHERNYKH, A.V. SHCHULKIN.
Pavlov Ryazan State Medical University, Ryazan, Russia.

Summary:
The aim of the research – to study the Mexidol (ethylmethylhydroxypyridine succinate) effect on the factor induced by hypoxia (HIF-1α) expression in the frontal cortex of the brain in its ischemia. Material and methods. The work was performed on the 64 male Wistar rats. The expression of HIF-1α was determined immunohistochemically. Results and discussion. It is determined that single intraperitoneal administration of Mexidol at a dose 120 mg/kg and oral administration at a dose 100 mg/kg three times a day for 14 days is not affected the expression of HIF-1α. Unilateral occlusion of the common carotid artery increases the expression of HIF-1α at 4 hours after the occlusion. Oral administration of Mexidol at a dose 100 mg/kg three times a day for 14 days before and after ischemia increases the expression of HIF-1α after 4 and 12 hours in comparison with the norm, on the 5th day in comparison with occlusion control. Thus, it has been established that Mexidol increases the expression of HIF-1α in the frontal cortex of rat brain not under normal conditions, but in unilateral occlusion of the common carotid artery.

Keywords: mexidol, ethylmethylhydroxypyridine succinate, ischemia, occlusion of common carotid artery.


Тhе possibility of treatment of cognitive impairment in the complex therapy of patients with the consequences of cerebral infarction

Author:
Е.В. KUZNETSOVA, Е.А. SALINA, I.I. SHOLOMOV.
Saratov State Medical University of the Russian Health Protection, Neurology Chair.

Summary:
Objective. То study neuropsychological status of inpatients with the consequences of сеrеbrаl infarction treated with cortexin аnd mexidol. Material аnd methods. We carried out а neurological аnd neuropsychological examination of 62 patients with the consequences of cerebral infarction treated with cortexin in the dose of 10 mg and mexidol in the dose of 5 ml of 5% solution intravenously during 15 days. Results аnd conclusion. It has bееn shown that the use of this drug combination decreases complaints аnd neurological symptoms аnd significantly improves cognitive аnd emotional status as well. The more positive changes аrе related to attention, speed of mental reactions, anxiety аnd verbal activity. The complextherapy with cortexin аnd mexidol decreased neurological deficit аnd improve cognitive functioning and psychoemotional status thus increasing quality of life аnd rehabilitation potential of the patients.

Keywords: consequences of сеrеbral infarction, cognitive impairment, emotional status, cortexin, mexidol.


Modern strategies of protection of hypoxic-ischemic brain damage

Author:
S.N. YANISHEVSKY, N.V. TSYGAN, S.YU. GOLOKHVASTOV, R.V. ANDREEV, I.V. LITVINENKO, O.S. KARPOVA, V.A. YAKOVLEVA.
Kirov Military Medical Academy, St. Petersburg, Russia.

Summary:
Nowadays, there are two complementary approaches to treatment of patients with ischemic stroke: reperfusion and neuroprotection. The main purpose of neuroprotection is to intervene ischemic cascade at every stage of the pathological process and thus avoid the death of nerve cells and expand the therapeutic window for reperfusion therapy. The use of drugs with neurotrophic, antioxidant and neuroregenerative effects is pathogenically explained at all stages of post stroke rehabilitation. Ethylmethylhydroxypyridine succinate (mexidol) is a derivative of succinic acid with antihypoxic, membrane protective, nootropic, anticonvulsant and sedative action. The majority of researchers confirmed the positive effect of mexidol expressed as the marked regression of neurological deficit and wider opportunities for further early rehabilitation. The results of the randomized double blind multicenter placebo-controlled, parallel-group trial of the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (EPICA) were published in 2017. The results of the study showed the best positive dynamics of neurological function recovery in case of timely treatment with mexidol with the following two month therapy. The safety of the long-term use of mexidol was confirmed.

Keywords: stroke, acute period, neuroprotection, succinate, efficacy of treatment, safety of therapy.


A comparative study of the effects of mexidolum and mildronatum on the physical performance of experimental animals

Author:
Т.А. VORONINA, I.G. KAPITSA, Е.А. IVANOVA.
Zakusov Institute of Pharmacology, Moscow, Russia.

Summary:
Objective. To evaluate the effects of mexidolum on physical performance using acute and subchronic administration in experimental animals. Materials and methods. The investigation was carried out using 123 male white outbred mice. The forced swim test was used to assess the effects of the drugs on the physical performance of mice. Results and conclusion. A single intraperitoneal administration of 50 and 100 mg/kg mexidolum and subchronic intraperitoneal administration of 100 mg/kg mexidolum significantly enhances the physical performance of animals in the forced swim test. Subchronic intraperitoneal administration of 100 mg/kg of the comparison drug mildronatum enhances the physical performance of animals, while intraperitoneal administration at a lower dose (50 mg/kg) has no effect. The effect of mexidolum at a dose of 50 and 100 mg/kg is comparable with the effect of mildronatum in a dose of 100 mg/kg.

Keywords: physical performance, mexidolum, mildronatum, mice.


Тhе neuroprotective therapy of outpatient treatment of chronic cerebral ischemia

Author:
S.V. BEREZHNAYA, E.Z. YAKUPOV.
Kazan, Municipal health саrе «City hospital №6»; Kazan State Medical University.

Summary:
Objective. То perform а differential analysis of the efficacy of combination therapy bу the drugs with different modalities (mexidol, aescusan, halidorum) in outpatients with chronic cerebral ischemia (CCI), stages I-III. Material and methods. А study included 50 patients with CCI of atherosclerotic, hypertensive and mixed genesis (stage I-20, stage II-20, stage III-10 patients). In addition to somatic therapy, patients received three courses of mexidol, halidorum and aescusan combination therapy during 6 weeks with а 3 month interval between the courses. The changes in subjective complaints and objective clinical manifestations were evaluated after each course. Results and conclusion. The therapeutic efficacy after durable complex therapy bу repeated courses of antioxidants is supported bу the results of clinical and neurological examinations. Mexidol in the combination with aescusan and halidorum contributed to the improvement of cognitive, adaptive, motor functions of the patients with CCI, stages I and II. То increase treatment efficacy in patients with CCI, stage III, we recommend to use the drugs that improve cognitive functions of the patients.

Keywords: chronic cerebral ischemia, mexidol, combination therapy.


Results of a randomized double blind multicenter placebo-controlled, in parallel groups trial of the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (EPICA)

Author:
L.V. STAKHOVSKAYA, N.A. SHAMALOV, D.R. KHASANOVA, E.V. MELNIKOVA, A.S. AGAFIINA, K.V. GOLIKOV, E.I. BOGDANOV, A.A. YAKUPOVA, L.V. ROSHKOVSKAYA, L.V. LUKINYKH, T.M. LOKSHTANOVA, I.E. POVERENNOVA, L.A. SHEPANKEVICH.
Pirogov Russian National Research Medical University, Moscow, Russia; Research Institute of Cerebrovascular Pathology and Stroke of Pirogov Russian National Research Medical University, Moscow, Russia; Interregional Clinical-Diagnostic Center, Kazan, Russia; City Hospital №26, St. Petersburg, Russia; City Hospital №40, St. Petersburg, Russia; City General Hospital №2, St. Petersburg, Russia; Kazan State Medical University, Kazan, Russia; Nikolaev Hospital, St. Petersburg, Russia; Vsevolga Clinical Interregional Hospital, Leningrad Region, Russia; Pirogov City Clinical Hospital №1, Samara, Russia; Seredavin Samara Regional Clinical Hospital, Samara, Russia; Research Institute Experimental and Clinical Medicine, Novosibirsk, Russia.

Summary:
Aim. To evaluate the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (IS). Material and methods. A randomized double blind multicenter placebo-controlled, in parallel groups trial included 151 patients (62 men and 89 women) with hemispheric IS. Using a method of simple randomization, 150 patients (62 men and 88 women), aged 40-79 years, were randomized into two groups. Patients of Group I were treated with mexidol: 500 mg/day IV infusion for 10 days, followed by 125 mg tid (375 mg/day) PO for 8 weeks. Patients of Group II received the placebo according to the same scheme. The total duration of patients’ participation in trial ranged from 67 to 71 days. Results. By the end of treatment, the mean score on the modified Rankin scale (mRS) was lower in Group I compared to Group II (p=0.04). In Group I, the decrease in mRS mean score (Visit 1-5) was more prominent (p=0.023), percentage of patients with 0-2 scores by mRS scale (Visit 5) was higher (p=0.039), mean NIHSS score lower (p=0.035) in Visit 5 compared to group II. By the end of treatment, the decrease in mean NIHSS score in patients with diabetes mellitus was more prominent in Group I in comparison with Group II (p=0.038). In Group I, the dynamic of improvement of quality of life was more prominent and started from Visit 2 in general population and subpopulation of patients with diabetes mellitus. The share of patients with no problems with movement in space was higher in Group I (p=0.022). There were no statistically significant differences in frequency of side effects in patients of both groups. Conclusion. It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages.

Keywords: acute disturbances of cerebral circulation, mexidol, ethylmethylhydroxypyridine succinate, efficacy and safety, ischemic stroke, acute period, acute rehabilitation period, EPICA.