Vascular inflammation underlies the development of atherothrombotic stroke

Author:

A.V. ROMANENKO, I.P. AMELINA, E.YU. SOLOVYEVA
Pirogov Russian National Research Medical University, Moscow, Russia

Summary:
Atherothrombotic stroke is the one of the most common subtypes of ischemic cerebral circulatory disorders, the cause of which is atherosclerosis of the major arteries of the brain or their branches. The results of recent studies have shown that the atherosclerotic process is based on an inflammatory process in the vascular wall that leads to the initiation of atherosclerosis, endothelial dysfunction, oxidative stress, and the redistribution of various protein components in the blood-brain barrier. As a result, the progression of the described conditions leads to the manifestation of clinical symptoms and the formation of an acute vascular event. Understanding of the molecular components underlying functional disorders and damages of the cerebral vessels gives the key to modern therapy strategies. It is forming the foundation for the adequate, pathogenetically reasonable drug correction. For such patients, it should be aimed at the normalization of cerebral and central hemodynamics and incorporate the mechanisms of neuroplasticity. The drug 2-ethyl-6-methyl-3-oxypyridine-succinate (mexidol) can be considered as one of the pathogenetically justified agents in complex drug therapy of brain ischemia. Keywords: ischemic stroke, atherosclerosis, vascular inflammation, oxidative stress, endothelial dysfunction, ethylmethylhydroxypyridine succinate.


Treatment of alcohol withdrawal syndrome

Author:
Y.P. SIVOLAP
Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia

Summary:
Alcohol withdrawal arises in result of long-lasting or short, but massive, alcohol abuse, manifests itself with oppressive symptoms and in some cases is complicated by seizures, hallucinosis and delirium tremens that may be life-threatening for patients. The leading neurochemical factors underlying alcohol withdrawal syndrome and its complications are lack of GABA and excessive glutamate activity, which is important for therapy choice. The first-line drugs in the treatment of alcohol withdrawal syndrome and alcoholic delirium are benzodiazepines, which have the maximum pharmacological similarity with ethanol. Other medications, including barbiturates, anticonvulsants, propofol, dexmedetomidine, and antipsychotics, may be used as alternatives to and in addition to benzodiazepines, especially in the case of protracted delirium with therapeutic resistance. Certain prospects in the treatment of alcohol withdrawal syndrome are associated with ethylmethylhydroxypyridine succinate, which is a bit similar to benzodiazepines in its pharmacology.
Keywords: alcohol use disorders, alcohol withdrawal syndrome, alcohol seizures, alcohol hallucinosis, delirium tremens, benzodiazepines.


Features of responding to stress of elderly patients with chronic brain ischemia

Author:
T.A. SLYUSAR, YU.V. ABRAMENKO, S.S. RUBINA, R.V. MAYOROV, I.N. SLYUSAR

Tver State Medical University, Tver, Russia

Summary:
The aim of the study. To study the peculiarities of responding to stress, the stress resistance and adaptation of older men and women with chronic brain ischemia, as well as the stressboard effect of Mexidol. Material and methods. 124 patients aged 60–74 years old are surveyed: 72 men and 52 women (average age, respectively, 65.3 ± 0.4 and 64.7 ± 0.7 years) with Chronic Brain Ischemia I–II stage against the background of arterial hypertension and its combinations with atherosclerosis of cerebral vessels. The level of psychosocial stress was determined on the Holmes-Ray scale. Features of the response of patients to stress was studied using the methodology Scale of Psychological Stress PSM‑25 and S. Rogenzweig. Stress resistance was investigated using S. Kuhlen's stress resistance self-resistant test and Villianson. The level of anxiety was determined using a scale of Ch. D. Spilberger and Yu. L. Khanin, depressed – backup questionnaire. The type of adaptation reactions was studied in the leukocyte blood formula on the percentage ratio of lymphocytes and segmented neutrophils, taking into account the representation of other formed elements. Results. The level of stress in older women with Chronic Brain Ischemia was higher than in men. The predominance of the intrinsic orientation of the reaction to stress and resolving the type of response to men, and the extrapunitive or self-defense type among women, which may indicate the largerness of the latter. The level of stress resistance was lower in women than in men, which correlated with higher indicators of situational anxiety. Adverse adaptation reactions were more often registered in women than in men. The course of treatment with Mexidol of elderly patients with chemical leads to a decrease in the severity of subjective and objective symptoms, alarming disorders, increases the stress resistance and adaptive capabilities of the body, which is confirmed by an increase in the number of persons with favorable adaptation reactions. The high efficiency and safety of sequential therapy with Mexidol (injections, then the tableted form of Mexidol Forte 250) is shown. Keywords: chronic brain ischemia, sex, stress, stress resistance, emotional disorders, anxiety, depression, Mexidol, adaptation reactions.


The efficacy of antioxidant treatment with mexidol forte in 250 patients with chronic cerebral venous insufficiency

Author:
E.I. CHUKANOVA, A.S. CHUKANOVA, KH.I. MAMAEVA
Pirogov Russian National Research Medical University, Moscow, Russia

Summary:
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. Keywords: chronic cerebral venous insufficiency, antioxidants, mexidol forte 250, venotonic drugs, L-lysine aescinat, diosmin/hesperidin.


Possibilities of improving the effectiveness of therapy in patients with chronic cerebral ischemia against the background of COVID-19

Author:
V.V. KOVALCHUK, I.I. ERSHOVA, N.V. MOLODOVSKAYA
Semashko City Hospital No. 38, St. Petersburg, Russia

Summary:
Objective. To study the possibility of improving the efficacy of treatment with mexidol in COVID‑19 patients with chronic cerebral ischemia (CCI). Material and methods. Three hundred and four patients with CCI and COVID‑19 were observed, group 1 (n=152) consisted of patients receiving basic therapy and mexidol, group 2 (n=152) received only basic therapy. Mexidol was administered intravenously for 14 days, 500 mg (10 ml) per 400 ml of saline solution, then Mexidol FORTE 250 was administered in a dose of 250 mg 3 times a day for 2 months. The state of cognitive functions (MoCA scale), sleep (Spiegel questionnaire), asthenia (MFI-20 scale), and quality of life (SIP questionnaire) were evaluated. Examinations were performed before treatment, 30 and 75 days after start of treatment. Results. In group 1, there was a more complete and earlier recovery of the state of cognitive functions (an increase in indicators on the MoCA scale, p<0.01), a regression of asthenia (p<0.05), and normalization of sleep (p<0.01). By the end of the study, there were significantly more patients in group 1 with complete or significant recovery of all quality of life indicators. Conclusion. Long-term sequential therapy with mexidol provides a more complete recovery of impaired functions in patients with CCI and COVID-19. Keywords: COVID-19, SARS-CoV-2, chronic cerebral ischemia, asthenia, cognitive disorders, dementia, quality of life, mexidol.


Role of antioxidant therapy in patients with moderate and severe COVID-19

Author:
E.K. SHAVAROVA1,2, E.R. CAZAKHMEDOV1, M.V. ALEKSEEVA1, L.G. EZHOVA2, Zh.D. KOBALAVA1

1Peoples' Friendship University of Russia (RUDN), Moscow, Russian Federation;

2V.V.Vinogradov City Clinical Hospital, Moscow Healthcare Department, Moscow, Russian Federation

Summary:
The coronavirus disease COVID-19 is characterized by high mortality and the lack of effective etiotropic therapy. Activation of oxidative stress may be one of the links in the pathogenesis of organ damage of this infection. Objective. To assess the ability of Mexidol® to influence the rate of clinical improvement in pneumonia caused by the SARSCoV-2 virus in hospitalized patients with the novel coronavirus disease COVID-19 and concomitant discirculatory encephalopathy. 62 patients over the age of 18 years with confirmed new coronavirus disease COVID-19 according to computed tomography (CT) of the lungs (stages CT1, CT2, CT3) and PCR of a swab from the nasopharynx and oropharynx for SARS-CoV-2 virus RNA were included. After randomization patients of group 1 received an infusion of Mexidol® at a dose of 1000 mg/day, patients of group 2 – an infusion of isotonic sodium chloride solution for 7 days. Compared with the control group, the patients receiving Mexidol® therapy showed a significantly more pronounced decrease in body temperature, a tendency towards a decrease in the severity of shortness of breath. In the Mexidol® group, the concentration of superoxidedismutase did not change, while in the control group there was a tendency to its decrease, C-reactive protein decreased 2.2 times more than in the control group (p = 0.09). There was a tendency for a more rapid decrease in ferritin in the active intervention group. Mexidol® therapy can have a positive effect on the clinical manifestations and severity of laboratory-inflammatory syndrome in patients with the new coronavirus disease COVID-19. Key words: coronavirus disease COVID-19, oxidative stress, Mexidol.


Efficacy and safety of ethylmethylhydroxypyridine succinate in patients with ischemic stroke

Author:

M.V. ZHURAVLEVA1,2, I.A. SHCHUKIN3, M.S. FIDLER3, A.B. PROKOFIEV2, S.YU. SEREBROVA2, N.S. VASYUKOVA4, E.YU. DEMCHENKOVA1, V.V. ARKHIPOV1,2
1Research Centre for Examination of Medical Devices, Moscow, Russia;
2Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
3Pirogov Russian National Research Medical University, Moscow, Russia;
4Federal Scientific Center — All-Russian Scientific Research Institute of Experimental Veterinary Medicine named after K.I. Skryabin and Ya.R. Kovalenko, Moscow, Russia

Summary:
Stroke is still the most significant problem of the modern medicine and the leading cause of mortality and morbidity. There is the great experience of neuroprotection in patients with stroke in the Russian Federation. In clinical practice it’s important to follow conditions, where neuroprotection will have maximum safety and effectiveness. The clinical trials of ethylmethylhydroxypyridine succinate (mexidol) in patients with acute ischemic stroke are described in the present review. Early management (in the first 6 hours) with mexidol significantly improve recovery dynamic and stroke outcome. Therapy with mexidol increases neurological recovery, improves vital activity and quality of life of patients with stroke. Furthermore, mexidol demonstrates high safety profile. Keywords: ischemic stroke, thrombolytic therapy, clinical trial, disability, antioxidant system, ethylmethylhydroxypyridine succinate, Mexidol.


The efficacy of ethylmethylhydroxypyridine succinate in patients with cerebrovascular pathology complicated with diabetes mellitus and metabolic syndrome

Author:
E.V. EKUSHEVA1,2, E.V. BIRYUKOVA3
1Academy of Postgraduate Education under the Federal State Budgetary Unit «Federal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of the Federal Medical Biological Agency», Moscow, Russia;
2Belgorod State National Research University, Belgorod, Russia;
3Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia

Summary:
Arterial hypertension, diabetes mellitus, obesity and dyslipidemia continue to be the main risk factors for diseases of the circulatory system and the leading causes of mortality in the world, the combination of these diseases significantly increases the likelihood of the development and more rapid progression of cardiovascular and cerebrovascular pathology. Improving approaches to the diagnosis and treatment of these diseases is a priority problem in modern medicine. Currently, there is no universal drug that can influence all stages of pathological process in both cerebrovascular diseases and diabetes mellitus, and the problem of rational use of drugs in patients with comorbid pathology has not been completely resolved. A difficult clinical task includes not only the timely detection of the disease and the correct diagnosis, but also the choice of the safest and most effective medicine. A number of clinical studies have demonstrated the efficacy of mexidol in the treatment of this category of patients, which is determined by its complex, pleiotropic and multimodal mechanisms of action. Keywords: cerebrovascular diseases, diabetes mellitus, metabolic syndrome, antioxidant therapy, mexidol.


Effectiveness and safety of mexidol forte 250 in the sequential therapy in patients with chronic ischemia

Author:
N.G. KATAEVA1, T.A. ZAMOSHCHINA1,2, M.V. SVETLIK1,2
1 Siberian State Medical University , Tomsk, Russia;
2 National Research Tomsk State University , Tomsk, Russia

Summary:
Objective. To study of efficacy and safety of mexidol used as intravenous infusion for 14 days, followed by per os treatment with mexidol FORTE 250 for 60 days in patients with chronic brain ischemia (CHM) complicated with arterial hypertension and atherosclerosis. Material and methods. The mexidol group included 27 patients (24 women and 3 men) with CHM I—II gr and the combination of arterial hypertension and atherosclerosis who received intravenous infusions of mexidol (500 mg once daily) within 14 days, with the subsequent per os treatment with mexidol FORTE 250 in a daily dose of 750 mg (1 tablet 3 times a day) for 60 days. The comparison group consisted of 30 patients (22 women and 8 men) with CHM I—II gr, comparable in age, nature of risk factors and expression of neurological manifestations. Patients in both groups received basic medications to treat their risk factors. Motor activity (Tinetti test), cognitive functions (MoCa test), anxiety and depression (Hamilton anxiety and depression scale), clinical condition (General Clinical Impression scale) were assessed. Results and conclusion. Inclusion of mexidol (500 mg iv infusion once a day within 14 days with the subsequent oral administration of 750 mg (1 tablet 3 times a day) for 60 days) in standard therapy of arterial hypertension with atherosclerosis and chronic brain ischemia is expedient. The results show greater clinical efficacy and sufficient safety of such combination therapy. By the end of therapy (day 74), patients in the mexidol group have a reliable improvement in motor activity, cognitive function and psychoemotional sphere, as well as a decrease in fatigue and neurological manifestations compared with the comparison group. Keywords: chronic ischemia of a brain, mexidol, mexidol FORTE 250.


Efficacy and safety of Mexidol across age groups in the acute and early recovery stages of hemispheric ischemic stroke (results of additional sub-analysis of a randomized double blind multicenter placebo-controlled study, in parallel groups trial EPICA)

Author:

L.V. STAKHOVSKAYA1, E.A. MKHITARYAN2, O.N. TKACHEVA1,2, T.M. OSTROUMOVA3, O.D. OSTROUMOVA3,4

1Pirogov Russian National Research Medical University, Moscow, Russia;
2Russian Clinical and Research Center of Gerontology of Pirogov Russian National Research Medical University, Moscow, Russia;
3Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical (Sechenov University),
Moscow, Russia;
4Russian Medical Academy of Continuous Professional Education, Moscow, 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) across age groups according to the World Health Organization classification. Material and methods. The study is an additional analysis across age groups among patients participated in the randomized double blind multicenter placebo-controlled, in parallel groups trial EPICA. All subjects (62 men and 88 women) were subdivided into age groups: younger than 60 years, 60—65 years, 76—90 years. Additionally, all participants were divided into 2 populations: ITT (Intent to treat population, patients who received at least one treatment/placebo dose) and PP (Per protocol population, patients who received treatment per study protocol). Results of Modified Rankin scale (mRs) at the end of treatment period, Barthel index, Beck depression inventory, European Quality of Life Questionnaire were assessed. Results. The efficacy of mexidol assessed with all the scales did not differ depending on the age group. By the end of treatment, the mean mRS score was lower in the 76-90 years subgroup (in both populations), compared to placebo (p<0,001). The decrease in mean mRS score (Visit 1—5) was more prominent in patients aged 60—65 years (p=0,025), including patients with diabetes mellitus (DM). Patients aged 76—90 years and patients with DM, compared to placebo, had a decrease of the severity of cognitive-affective depression symptoms (p=0,049 and p=0,02) and an increase in patients without problems with everyday activities (p=0,007 and p=0,02). Patients with DM, compared to placebo, also had the higher levels of everyday activity (p=0,023) and quality of life (p=0,045). There were no statistically significant differences in the frequency of side-effects in patients of all groups. Conclusion. It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages in all age groups, including patients with DM. Keywords: ischemic stroke, mexidol, ethylmethylhydroxypyridine succinate, efficacy and safety, ischemic stroke, acute period, acute rehabilitation period, EPICA.