[The relationship between the development of post-stroke cognitive impairment and changes in the coagulation component of hemostasis]. / Svyaz' postinsul'tnykh kognitivnykh narushenii i izmenenii koagulyatsionnogo zvena gemostaza.

OBJECTIVE: To evaluate the relationship between the severity of post-stroke cognitive impairment (PSCI) and coagulation parameters assessed using the dynamic thrombophotometry. MATERIAL AND METHODS: Thirty-five patients with hemispheric ischemic stroke (IS) with moderate neurological deficit at admission were included. All patients underwent a comprehensive clinical and instrumental assessment according to the current guidelines. On days 10-14, the cognitive status of patients was assessed using the Montreal Cognitive Assessment (MoCA). Coagulation parameters were assessed using the dynamic thrombophotometry at admission, on 6-8th days and 13-15th days from the onset of the disease. A database of laboratory studies of 30 apparently healthy volunteers was used as a comparison group. RESULTS: Data analysis revealed that a number of spatial and temporal parameters were within the reference values, and there were no significant changes over time. Nevertheless, though the optical density of the fibrin clot (D) was within the reference values, it showed a steady increase from the admission by the end of the 1st week of the disease (p=0.007) and by 13-15th days (p=0.009). Correlation and multivariate linear regression, including baseline stroke symptom severity, showed significant associations (p<0.01 in all tests) between the higher optical density of the fibrin clot (D) on days 6-8 and 13-15 and lower MoCA score, confirming the negative effect of altered hemostatic parameters on cognitive function in IS patients. CONCLUSION: The increase of optical density of the fibrin clot (D) by 6-8th and 13-15th days is a potential prognostic biomarker for the early development of PSCI.

[Efficacy and safety of the drug Cellex for the treatment of patients with cognitive impairment with chronic cerebral ischemia - results of a multicenter randomized double-blind placebo-controlled clinical trial]. / Effektivnost' i bezopasnost' primeneniya preparata Tselleks dlya lecheniya patsientov s kognitivnymi narusheniyami s khronicheskoi ishemiei golovnogo mozga ­ rezul'taty mnogotsentrovogo randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo klinicheskogo issledovaniya.

OBJECTIVE: To evaluate the efficacy and safety of using Cellex for the treatment of cognitive impairment as part of the complex therapy of patients with chronic cerebral ischemia (CCI) compared with placebo. MATERIAL AND METHODS: The study randomized 300 patients with a reliable diagnosis of CCI stage 1-2, all participants were divided into two groups, 150 participants in each - main and control. The study drug Cellex or placebo was administered as two 10-day treatment courses, 1 ml once a day. The duration of the study was 90±5 days for each participant. The primary end point for evaluating the effectiveness of the therapy was the degree of improvement in the state of cognitive functions relative to the initial state according to the Montreal Cognitive Dysfunction Scale (MoCA) on the 31st and 60th days from the start of therapy in the compared groups. Secondary endpoints were the assessment of the degree of improvement in the state of cognitive functions according to psychometric testing scales (MoCA, Correction Test, Frontal Dysfunction Test Battery) relative to the initial state on the 31st, 60th and 90th days from the start of therapy. Also, a dynamic assessment of the systemic concentration of markers of brain damage - S100ß, GFAP, MMP9 and neurotrophins - BDNF and GDNF was carried out. RESULTS: The primary endpoint of the study was achieved-the MoCA score in each group increased uniformly after baseline. However, in the main group, this indicator was significantly higher starting from visit 3 - 23.4±2.8 points in the main group, in the placebo group 22.7±2.3 (p<0.001), a statistically significant difference also remained at visit 5 (p<0.001). When analyzing the secondary endpoints according to the battery of frontal dysfunction tests and the correction test, a more pronounced positive trend was also noted in the main group. Changes in the emotional sphere in both groups remained within the normal range. The dynamics of the systemic concentration of markers of brain damage and neurotrophins was multidirectional, the assessment of which was possible only at the trend level. CONCLUSION: Based on the statistical analysis of the results of the study, Cellex was confirmed to be superior to Placebo in the degree of improvement in cognitive functions measured by the MoCA scale after the 1st and 2nd treatment courses.

COVID-19-Associated Stroke.

The COVID-19 pandemic has had significant influences on the incidence of acute cerebrovascular accidents and the structure of mortality. SARS-CoV-2 increases the risks of developing both ischemic and hemorrhagic stroke. The key pathogenetic element underlying the development of cerebral stroke in COVID-19 consists of impairments to the operation of angiotensin 2 receptors, which are accompanied by accumulation of excess quantities of angiotensin 2, endothelial dysfunction, hypercoagulation, overproduction of proinflammatory cytokines, and an oxidative storm. In patients with stroke and COVID-19, lesion severity is associated with dual mechanisms of ischemia - systemic and cerebral. The possibilities of medication-based correction of both systemic impairments associated with coronavirus infection and local impairments due to ischemic or hemorrhagic brain damage, are limited. Substances with antioxidant activity may potentially be effective in patients with stroke and COVID-19. Data from a number of clinical rials indicate that Mexidol significantly improves functional outcomes in ischemic stroke. Use of Mexidol in patients with stroke and COVID-19 is advised.

[Ofatumumab - a new drug for the treatment of multiple sclerosis]. / Ofatumumab ­ novyi preparat dlya lecheniya rasseyannogo skleroza.

Recently anti-B-cell therapy has been increasingly integrated into the treatment of multiple sclerosis (MS). This review is devoted to ofatumumab, a new drug of this line. Ofatumumab, an all-human monoclonal antibody used to treat chronic leukemia, binds to a different region than the binding site of other CD20 antibodies, including both a small and large loop in the CD20 receptor structure. This monoclonal antibody provides favorable results for MS by reducing the frequency of exacerbations and the risk of disability progression, significantly more pronounced when compared with teriflunomide. The drug can be used in patients with active relapsing MS and SPMS with exacerbations, with the ineffectiveness of first-line drugs as one of the options for second-line therapy, in patients with highly active MS, especially with a high risk of PML (transfer from natalizumab), as well as if there are difficulties in organizing intravenous courses in day hospitals (produced as outpatient injections).

[Treatment of multiple sclerosis with glatiramer acetate: a new look]. / Lechenie rasseyannogo skleroza preparatami glatiramera atsetat ­ novyi vzglyad.

In recent years, the use of a new dosage (40 mg) of glatiramer acetate (GA), which is administered 3 times weekly has become widespread. In Russia, the drug Timexon (produced by the company BIOCAD) was developed and passed successful clinical trials. The final efficacy analysis included 150 patients treated for 12 months. The convenience of using a double dose of GA in 40 mg, which is registered on the territory of the Russian Federation by two manufacturing companies: CJSC BIOCAD and Teva Pharmaceutical Enterprises Ltd., has been proven.

[COVID-19 related stroke]. / Insul't, assotsiirovannyi s COVID-19.

The COVID-19 pandemic had a significant impact on both the incidence of acute cerebral circulatory disorders and the structure of mortality. SARS-CoV-2 increases the risk of both ischemic and hemorrhagic stroke. The key pathogenetic links underlying the development of cerebral stroke in COVID-19 are impaired functioning of angiotensin 2 receptors, accompanied by the accumulation of excess angiotensin 2, endothelial dysfunction, hypercoagulation, hyperproduction of proinflammatory cytokines and oxidative storm. In patients with stroke and COVID-19, the severity of the lesion is associated with a dual mechanism of ischemia - systemic and cerebral. The possibilities of medical correction of systemic disorders associated with coronavirus infection, as well as local ones caused by ischemic or hemorrhagic brain damage, are limited. Substances with antioxidant activity could potentially be effective in patients with stroke and COVID-1.

[Efficacy and safety of ethylmethylhydroxypyridine succinate in patients with ischemic stroke]. / Effektivnost' i bezopasnost' primeneniya etilmetilgidroksipiridina suktsinata u patsientov s ostrym ishemicheskim insul'tom.

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.

[The efficacy and safety of siponimod in the Russian population of patients with secondary progressive multiple sclerosis]. / Éffektivnost' i bezopasnost' siponimoda u patsientov s vtorichno-progressiruiushchim rasseiannym sklerozom v rossiiskoi populiatsii.

AIM: To study the efficacy and safety of siponimod in patients with secondary progressive multiple sclerosis (SPMS) in the Russian population of the EXPAND study. MATERIAL AND METHODS: Ninety-four patients with SPMS from Russia were included in the analysis. Sixty-three patients received siponimod and 31 patients received placebo. The primary endpoint of the study was time to 3-month confirmed disability progression (3m-CDP) events, other clinical and radiological endpoints were also evaluated. RESULTS: The siponimod group showed a 54% reduction in the risk of 3m-CDP compared with the placebo group (p=0.0334). Secondary endpoints also showed the advantage of the drug over placebo. In the siponimod group, mild adverse events associated with impaired liver function, as well as arterial hypertension, were more common. No patient left the study due to an adverse event. CONCLUSION: The use of siponimod in patients with SPMS in the Russian population reduced the risk of disability progression. Siponimod showed a favorable safety profile.

[Neurological disorders in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)]. / Nevrologicheskie rasstroistva pri éozinofil'nom granulematoze s poliangiitom (sindrom Cherdzha-Strossa).

Eosinophilic granulomatosis with polyangiitis - EGPA (Churg-Strauss syndrome) is a rare autoimmune disorder. The pathogenesis of the disease includes production of anti-neutrophil cytoplasmic antibodies directed against myeloperoxidase with the development of small-vessel necrotizing vasculitis and eosinophilic infiltration of organs. The involvement of peripheral and central nervous system is observed in more than 3/4 of cases. The authors describe three patients with EGPA. In a 53-year-old male patient, EGPA manifested with multiple neuropathies, which regressed after treatment with corticosteroids and cytostatics. In a 34-year-old woman, cerebral sinus thrombosis and cerebral infarction developed in the non-active period of long-term EGPA. The patient was treated with anticoagulants. A 77-year-old woman with a newly diagnosed EGPA, confirmed by bone marrow examination for eosinophilia, developed ischemic stroke and polyneuropathy. The causes and mechanisms of development as well as dynamics and outcomes of neurological disorders, differential diagnosis, treatment and prognosis of eosinophilic granulomatosis with polyangiitis are discussed.

[Asthenia, emotional disorders and quality of life of patients with multiple sclerosis]. / Asteniia, émotsional'nye rasstroistva i kachestvo zhizni u patsientov s rasseiannym sklerozom.

Objective. The evaluation of the dynamics of asthenia, chronic fatigue syndrome, emotional disorders and quality of life of patients with multiple sclerosis (MS) and to explore the possibility of using idebenon (noben) in treatment of these impairments. Material and methods. We studied 35 patients, 18 men and 17 women, with MS (mean age 36.4±8.86 years, mean disease duration 10.33±6.07 years); 83% of patients had remitting type and others - secondary progressive type. Along with neurological examination, we used the Modified Fatigue Impact Scale (MFIS 21), the Hospital Anxiety and Depression Scale and a quality of life questionnaire (EQ5D). Patients had marked asthenia and chronic fatigue at baseline. The old age of the patients and duration of MS and its severity according to EDSS predicted the higher levels of asthenia, chronic fatigue and anxiety with depression and lower quality of life on EQ5D. All patients received noben in dosage 90 mg daily (30 mg 3 times a day) during 6 months. Results and conclusion. Idebenon (noben) reduced the severity of chronic fatigue syndrome, asthenia and depression in MS patients. The dose used in the study may be regarded as the optimal dose that provides best efficacy with minimal side-effects.

[Possibilities of medical correction of moderate cognitive impairment].

Thirty-four outpatients with moderate cognitive impairment were treated with one of standard extracts of Ginkgo Biloba - EGb761 (memoplant). Memoplant was used in high dosages (240 mg daily) twice a day during three months. Patients were assessed using the Montreal Cognitive Assessment (MoCA), the hospital depression scale and QoL questionnaire EQ5d as well as standard neurological and somatic examination. A statistical analysis of data revealed a significant improvement in most measures, mostly in attention, memory, orientation and visual-spatial/ executive functions as well as in anxiety and depression. The drug is well-tolerated and is recommended for practical use.

[Emotional disorders and quality of life in patients with post stroke asthenia].

An aim of the study was to assess the severity of asthenic syndrome, emotional disorders and quality of life indicators in post stroke patients treated with idebenone (noben). We studied 35 patients aged from 47 to 76 years, mean age 58,85±7,99 years, 21 men and 14 women. The time after stroke was 1-8 years (mean 2,63±1,51 years). The duration of follow-up was 6 months. Patients were examined at baseline and 3 and 6 months after treatment with noben in dose 90 mg daily (30 mg 3 times a day). Patients were examined clinically, the following scales were used as well: the Scandinavian stroke scale, the modified MFIS-21, the hospital anxiety and depression scale (HADS) and EQ5D including VAS. It has been shown that asthenic syndrome negatively influenced quality of life and emotional sphere thus impeding the recovery of daily activities. The follow-up study revealed that the treatment with idebenone in dose 90 mg daily decreased the severity of asthenia and emotional disorders and significantly improved quality of life.

[Neuroprotective treatment with citicoline (ceraxon) in patients with ischemic stroke].

The dynamics of neurological symptoms assessed with the Scandinavian stroke scale, the Barthel index and the modified Rankin scale was studied in 89 patients with moderate ischemic stroke who received citicoline (ceraxone) intravenously and orally. The results were compared to a group of 52 age-, sex- and stroke-matched patients who did not receive citicoline. To the date of discharge from the hospital (days 21-24), the full restoration (p<0.05) was noted in patients of the main group. Efficacy of citicoline was significantly (p<0.05) higher in patients younger than 70 years and when the drug was used in the first hours of disease.

[Characteristics of serum albumin in patients with intracerebral hemorrhagic stroke].

Authors studied the influence of the psychoemotional stress preceding the stroke on the dynamics of neurological symptoms (Glasgo coma scale, Scandinavian stroke scale and Barthel index) and on the conformational changes of albumin in 59 patients with intracerebral hemorrhage due to arterial hypertension. The psychoemotional stress was associated with less favorable clinical course and outcome of intracerebral hemorrhage. Conformational properties of albumin were changed in all patients with intracerebral hemorrhage compared to controls. Psychoemotional stress preceding stroke aggravated changes in albumin molecule.

[Dynamics of clinical and laboratory parameters in patients with severe ischemic stroke of hemispheric localization and different variants of nutrition support].

We studied an effect of different nutrition algorithms on the outcome of neurological symptoms and laboratory data in patients with ischemic stroke. The active nutrition support included in the basic therapy from the beginning of the disease has a positive effect on the patient's state. The mixed artificial nutrition (enteral + intravenous) was more effective compared to the intravenous or enteral nutrition alone in improving the clinical state, shortening the duration of staying in intensive care wards and complete compensation of disturbances of protein and energy metabolism during the first day of disease.

[Pathophysiological mechanisms of hemorrhagic stroke and the ways of differential therapy].

The changes developing in the perifocal area of hematoma and perspectives of antioxidant and chelate therapy were studied on the model of experimental hemorrhagic stroke and in clinical conditions. Microcirculatory, ischemic and inflammation disturbances with a certain time sequence were found in the perifocal areas. These changes, along with hypostasis and oxidative stress, form the pathobiochemical cascade of changes in hemorrhagic stroke and are potential therapeutic targets. Administering of an antioxidant and chelate drug histochrome reduces the intensity of changes in the perifocal area in the experimental conditions. In clinical conditions, it accelerates the dynamics of brain and meningeal symptoms regression and improves the blood rheological properties.

[An influence of histochrome on the dynamics of neurological disorders and MRT-picture in experimental hemorrhagic stroke].

Presented are the results of the use of histochrome in animals with experimental hemorrhagic stroke. An influence of the compound on cerebral edema and the dynamics of hemoglobulin converting as well as a role of MRT in diagnostic of experimental hemorrhagic stroke in different periods of the disease are discussed.

[Lipoxins: study of various biosynthesis pathways]. / Lipoksiny. Issledovanie razlichnykh putei biosinteza.

Lipoxins A4 and B4 were obtained by using soybean lipoxygenase and blood cells as a source of enzymatic activity. The conditions facilitating lipoxin biosynthesis from arachidonic acid catalyzed by soybean 15-lipoxygenase were selected. A comparative analysis of lipoxin biosynthesis with the use of cell suspensions containing only granulocytes and of mixed suspensions (platelets + granulocytes and platelets + total fraction of blood leucocytes) was carried out.

[Arachidonic acid metabolism in the neutrophilic granulocytes in lymphogranulomatosis]. / Obmen arakhidonovoi kisloty v neitrofil'nykh granulotsitakh pri limfogranulematoze.

Metabolism of arachidonic acid in neutrophils was studied in vitro in blood samples obtained from 36 patients with Hodgkin's disease of various stage and histology and 32 healthy donors. The basic metabolites were: leucotriene B4, such products of its omega-oxidation as 20-hydroxy-leucotriene B4 (20-OH-LTB4) and 20-carboxy-leucotriene B4 (20-COOH-LTB4), and 5-hydroxyeicosatetraenic acid. Their profile proved identical in patients with Hodgkin's disease and healthy donors. Most patients with Hodgkin's disease showed a decrease in leucotriene B4 and 5-hydroxyeicosatetraenic acid and an increase in the level of omega oxidation of leucotriene B4 as assessed by omega catabolite/leucotriene B4 ratio. The levels of 5-hydroxyeicosatetraenic acid and leucotriene B4 omega-oxidation were found to depend upon histology and stage of Hodgkin's disease. They were nearly normal in patients with stage III, mixed cellular disease, B-symptoms and signs of biologic activity of tumor. A direct correlation was established between the level of leucotriene B4 omega oxidation in neutrophils and that of ceruloplasmin in blood serum of patients with various stages of Hodgkin's disease.