[The structure of post/long COVID fatigue syndrome. Prospects for correction].

AIM: To study the features of post-COVID asthenic syndrome and evaluate the effectiveness of the drug containing the succinic acid complex with trimethylhydrazinium in its treatment. MATERIALS AND METHODS: A prospective, multicenter, comparative, randomized, double-blind, placebo-controlled study of the efficacy of sequential therapy with BRAINMAX® included 160 patients with a history of coronavirus infection within 12 to 16 weeks (not more than 12 months). The study was conducted at 6 healthcare centers in different regions of the Russian Federation. Testing was performed on the following scores: VAS for headache score, MFI-20 asthenia score, PSQI test, FAS-10 fatigue score, DHI dizziness score, MoCA cognitive impairment score, Beck anxiety score, vegetative index of Kerdo. RESULTS: PSQI questionnaire showed significant improvement in sleep quality in the study group: by -2.5 points [-4; -1] (p<0.001); there was a more pronounced significant decrease in the MFI-20 score of -19.5 points [-27; -11] (p<0.001); a significant decrease in the FAS-10 fatigue score by -9 [-13.5; -4] points (p<0.001); DHI dizziness score showed a decrease by -6 [-12; 0] points in the BRAINMAX® group (p=0.001); the score of Beck anxiety and depression scale decreased by -5 [-11; -2] points (p<0.001). Multiple linear regression data showed a significant increase of 0.56 (p=0.02) in the MoCA score. CONCLUSION: Our study convincingly showed the effectiveness of therapy with BRAINMAX® in a wide range of symptoms in patients with the post-COVID syndrome.

A prospective randomized, double-blind placebo-controlled study to evaluate the effectiveness of neuroprotective therapy using functional brain MRI in patients with post-covid chronic fatigue syndrome.

BACKGROUND AND PURPOSE: to assess executive network using resting-state fMRI and patterns of brain activation using task fMRI with a cognitive paradigm, against the background of taking the drug in comparison with placebo in patients with post-COVID asthenic syndrome. METHODS: The study employed a prospective, randomized, double-blind, placebo-controlled trial approach to assess the efficacy of utilizing functional MRI of the brain as a neuroprotective therapy for treating patients with chronic fatigue syndrome following COVID-19. The study included 30 patients matched by sex and age with post-COVID asthenic syndrome. All patients were examined with MFI-20, MoCA, FAS-10 scales, MRI using a Siemens MAGNETOM Prisma 3 T scanner before and after a course of therapy with coordination complex with succinate acid anion (CCSA) or placebo (15 patients each) using resting state fMRI and with cognitive paradigm. RESULTS: The changes obtained as a result of the treatment of post-Covid asthenic syndrome demonstrated clinical superiority in the reduction of asthenic symptoms for the group of patients treated with CCSA (MFI-20 scores: -20·0 points in the CCSA group compared to -12 points in the placebo group, p = 0·043). The data obtained also correlate with the analysis of task fMRI and resting state fMRI may indicate an increase in the functional cognitive status after a course of therapy with CCSA. Clinically, this correlates with a statistically significant improvement in the MoCA score (2 points in the CCSA group compared to 1 point in the placebo group, p < 0·05). CONCLUSIONS: the study demonstrates the potential effectiveness of CCSA therapy in relation to a wide range of symptoms (chronic fatigue syndrome/ asthenic syndrome and cognitive impairment) in patients with post-COVID syndrome. The first time demonstrated the effectiveness of neuroprotective therapy after post-COVID asthenic syndrome with the use of high-tech neuroimaging techniques.

[New opportunities for neuroprotective therapy of patients in the acute and early recovery period of ischemic stroke].

AIM: To evaluate the efficacy and safety of Brainmax in comparison with ethylmethylhydroxypyridine succinate and trimethylhydrazinium propionate in patients with ischemic stroke in the acute and early recovery period. MATERIALS AND METHODS: An open multicenter randomized study included 180 patients aged 1880 years (mean age 60.917.66 years, men 47.8%) with ischemic stroke in the acute and early recovery period (NIHSS from 3 to 15 points). Patients were randomized to receive Brainmax, ethylmethylhydroxypyridine succinate and trimethylhydrazinium propionate in an equal ratio (n=60). The drugs were administered intravenously for 10 days, followed by a transition to intramuscular injection for 14 days. Efficacy was assessed using the following scales: Modified Rankin Scale, NIHSS, Rivermead Mobility Index, Montreal Cognitive Assessment Scale (MoCA). Safety assessment was carried out according to the presence and structure of adverse events. RESULTS: The mean Modified Rankin Scale score for Visits 3 (day 10) and 5 (day 25) for the group treated with Brainmax was 2.410.85 and 1.440.91 points, for the group EMHPS 2.870.68 and 2.180.85 points, and for the group receiving trimethylhydrazinium propionate 2.870.50 and 2.550.70 points respectively, which reflects the best functional outcome in the Brainmax group (p0.05). Comparison of cognitive function indicators also showed statistically significant differences between the groups of drugs Brainmax and ethylmethylhydroxypyridine succinate. Evaluation according to the MoCA test showed that the use of Brainmax is 20% more effective in restoring cognitive functions (compared to monodrugs). CONCLUSION: The present study confirms the superiority of combination therapy with Brainmax over monotherapy with each of the components.

[Prospects of use of research results for drugs with anitihypoxic and antioxidative properties in neuroprotective treatment strategies (Opinion of the Council of Experts dated 26 March 2022)]. / Perspektiva ispol'zovaniya rezul'tatov issledovaniya preparatov s anitigipoksantnymi i antioksidantnymi svoistvami v neiroprotektivnoi strategii lecheniya (Zaklyuchenie soveta ekspertov ot 26 marta 2022 g.).

Cerebrovascular diseases are one of the main causes of death and permanent disability. Effective and timely neuroprotective therapy can reduce the burden of cerebrovascular disease. The possibilities of neuroprotection as a method of prevention and medical rehabilitation of acute and chronic cerebrovascular diseases are addressed.

[Prospects and possibilities for the treatment of patients with long COVID-19 syndrome].

AIM: To study the efficacy and safety of a drug product based on the succinic acid complex with trimethylhydrazine used to treat patients with asthenic syndrome after a new coronavirus infection (COVID-19). MATERIALS AND METHODS: A prospective, multicenter, comparative, randomized, double-blind, placebo-controlled study of the safety and efficacy of sequential therapy with Brainmax® enrolled 160 patients 12-16 weeks after coronavirus infection (no more than 12 months). The study was conducted at 6 healthcare centers in different regions of the Russian Federation. At the enrollment, clinical and neurological examination and the following tests were performed: complete blood count, urinalysis, blood chemistry, coagulation test, pulse oximetry, electrocardiography, glomerular filtration rate calculation (according to Cockcroft-Gault formula) were performed. Also, the patients were assessed using the following tools: VAS headache rating scale, MFI-20 asthenia scale, PSQI index, FAS-10 fatigue assessment scale, Dizziness Handicap Inventory (DHI), MoCA-test for cognitive impairment assessment, Beck Anxiety Inventory, Kérdö Autonomic Index. RESULTS: The primary endpoint was the mean reduction in the MFI-20 asthenia scale score after the therapy (Visit 5, 41st day of therapy) compared to data from Visit 0 (beginning of therapy). A clinically significant advantage of the study drug versus the placebo was demonstrated, with a median absolute change in the MFI-20 score of -19.5 [-27; -11] points in the Brainmax® drug group and -3 [-7; 1] score in the placebo group (p<0.001). A significant sleep quality improvement according to the PSQI index was shown in the study group: by -2.5 [-4; -1] points versus no improvement in the placebo group (0 [-3; 0], p<0,001). Significant differences were also noted for the following secondary endpoints: PSQI sleep quality scale, FAS-10 fatigue assessment scale, DHI, and Beck Anxiety and Depression Inventory. There was also a decrease in patients' complaints of cognitive deterioration according to the CGI scale. CONCLUSION: Our study clearly demonstrated the efficacy and high safety profile of Brainmax® in a representative sample of patients with the post-COVID syndrome.

[Expanding the possibilities of antithrombotic therapy of cerebrovascular pathology]. / Rasshirenie vozmozhnostei antitromboticheskoi terapii tserebrovaskulyarnoi patologii.

The paper provides an overview of the current state of the problem of antithrombotic therapy in angioneurology. Given the importance and prevalence of cerebral atherosclerosis as one of the leading etiological factors of acute and chronic cerebrovascular disorders (CCD), the paper focuses mainly on antiplatelet therapy. The most recent recommendations for the use of acetylsalicylic acid and clopidogrel, the main antiplatelet drugs, are highlighted. The clinical failure of primary or secondary prevention of cerebrovascular diseases, one of the reasons for which is resistance to the therapy, is considered separately. The authors discuss the causes of aspirin resistance and ways to overcome it, one of which may be a switch to another drug. The well-known medication dipyridamole is proposed as a possible alternative and/or addition to the treatment regimen. The most modern ideas about the mechanisms of its action are described, the pleiotropy of its effects is emphasized. The results of own studies on assessment of the effectiveness and safety of dipyridamole (curantil) in patients with various forms of CCD are presented. The results of the CCD pilot project to study the antiplatelet profile of dipyridamole in patients with such a cause of ischemic NMC as Ph-negative myeloproliferative diseases are discussed separately. It is noted that when prescribing both dipyridamole and acetylsalicylic acid preparations, comparable platelet aggregation levels are determined. In conclusion, the need to follow the paradigm of personalized therapy is emphasized, in which individually selected therapy is prescribed (including) taking into account resistance to a particular drug.

[Adie syndrome]. / Sindrom Éidi.

Disorders and abnormalities of pupil reactions comprise important part in the clinical practice of both ophthalmologists and neurologists. The present article presents a historical perspective on one of such pathologies - Adie syndrome, and discusses its etiology, pathogenesis and clinical symptomatology. The article also describes a clinical case of one patient with comorbidity.

[Brain MRI-findings in Ph - negative myeloproliferative disorders].

Myeloproliferative disorders (MPD) are accompanied by a high proportion of thrombotic complications, which may lead to cerebrovascular disease (CVD). AIM: To describe MRI-findings in patients with Ph - negative MPD and evaluate any cerebrovascular disease. MATERIALS AND METHODS: We included 104 patients with Ph - negative MPD (age varied between 20 and 58) with clinical correlates of cerebrovascular pathology. RESULTS: Brain MRI showed post - stroke lesions in 20% of patients (7 hemispheric infarcts due to thrombotic occlusion of one of the large cerebral arteries, 14 - cortical infarcts). 37 patients (36%) had vascular cerebral lesions. Cerebral venous sinus thrombosis occurred in 5 patients - in 7% (n=3) of patients with polycythemia vera and 5% (n=2) - in patients with essential thrombocythemia. The incidence of vascular cerebral lesions was associated with higher levels of the following: erythrocyte, platelet count, fibrinogen, and with the decrease in fibrinolytic activity, as well. CONCLUSION: The pioneering results of the study include the description and analysis of brain MRI-findings in patients with Ph - negative MPD. The underlying mechanisms of cerebrovascular pathology in these patients are associated with certain blood alterations (particularly, hemorheology) which present a major risk factor.

Acute ischemic stroke in the setting of essential thrombocytemia (clinical cases).

This article describes several clinical cases of acute ischemic stroke among patients suffering from essential thrombocytemia. Ambiguity of etiological factors of stroke is demonstrated among patients with this pathology. Thrombocytosis and high allele load in the Jak2 gene play an important role (even with normal platelet count) in progression of cerebrovascular disease. Also the question of effectiveness of preventive and etiological therapy is considered.

[Diagnosis of latent polycythemia vera: A clinician's opinion]. / Diagnostika latentnoi istinnoi politsitemii (vzglyad klinitsista).

AIM: to identify the clinical features of latent polycythemia vera (PV) as an independent nosological entity. SUBJECTS AND METHODS: The investigation enrolled 81 patients (50 with extensive (manifest) PV and 31 with latent PV) who had visited the Outpatient Department, Hematology Research Center, Ministry of Health of Russia, in 2014 to October 2015. RESULTS: The gender distribution of the patients was statistically comparable in the analyzed groups. The patients with manifest PV were slightly older than those with latent PV: the median age in the compared groups was 56 and 44 years, respectively. Red blood cell counts, hemoglobin concentrations, and packed cell volume were higher in the patients with manifest PV. Blood platelet counts were higher in the latent PV group. There were no differences in the number of white blood cells in the compared groups. All the patients were JAK2 V617F mutation carriers. The JAK2 allele load was significantly higher in the manifest PV group than in the latent PV group. The compared patient groups differed in the rate of thromboses in the history or at diagnosis. In the patients with latent PV, thromboses were detected in 38% of cases versus 16% in those with manifest PV. In latent PV, there were mainly venous thromboses; abdominal vascular thromboses were diagnosed with a high frequency. Arterial thromboses were revealed in only 2 cases. CONCLUSION: Chronic myeloproliferative disease that is characterized by the JAK2 V617F mutation, borderline hemoglobin counts, and morphological features of a bone marrow trephine biopsy specimen, which are specific for PV, is an independent PV variant, namely: latent PV.

[Characteristics of health status of children-orphans and the effectiveness of health promotion in a preventive sanatorium]. / Kharakteristika sostoianiia zdorov'ia detei-sirot i éffektivnost' ikh ozdorovleniia v usloviiakh sanatoriia-profilaktoriia.

The data are provided on the health status of 850 children-orphans and effectiveness of their health promotion under conditions of sanatorium dispensary. The following results were obtained: the abnormalities in physical development were identified in 22 percent of children, high incidence of ENT diseases (18.8%), visual disturbance (18.8%), deviations in the somatic status (18.7%) and in neuropsychic development (12%). The children of the I group health constituted 7 percent. The experience is summarized of health promoting activities among children from 4 boarding schools. It is indicated that health promotion has a favourable effect on child neuropsychic status, with the rate of acute diseases per year being declined by 2.2 times and the incidence of chronic diseases aggravations--by 1.5. The high efficiency of health promotion under conditions of sanatorium-dispensary permits to recommend this method for wide introduction into the practical performance of curative and preventive institutions.

[Determination of the enzyme activity in tissue homogenates and biological liquids]. / Opredelenie fermentativnoi aktivnosti v gomogenatakh tkanei i biologicheskikh zhidkostiakh.

The described method for measuring the enzymic activities in tissue homogenates and biological fluids is based on the separation of the space with the biological fluid, where the enzymic reaction takes place, from the space with the substrate solution, where the analytical effect is measured, by a semipermeable membrane. The authors present the results of measurements of monoamine oxidase activity in rat liver mitochondria homogenate, of acetylcholinesterase activity in mouse brain homogenate, and of cholinesterase activity in cow blood serum.