[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.

[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.

[A comparative analysis of allele frequencies of rs1801133 and rs1801131 of MTHFR in patients with stroke and healthy people from the Moscow region]. / Sravnitel'nyi analiz chastot allel'nykh variantov rs1801133 i rs1801131 gena MTHFR v vyborke patsientov, perenesshikh ishemicheskii insul't, i u zdorovogo naseleniia v Moskovskom regione.

AIM: To study genetic characteristics of the population of the Moscow region and analyze the association of rs1801133 and rs1801131 of MTHFR with the risk of ischemic stroke (IS). MATERIAL AND METHODS: A sample of 170 and 115 patients with atherothrombotic and cardioembolic subtypes of IS and 360 residents of the Moscow region without IS were examined. MTHFR alleles were determined by a multiplex real-time polymerase chain reaction. RESULTS AND CONCLUSION: No association between the frequencies of MTHFR alleles and the risk of ischemic stroke was found. The comparison of allele frequencies with those in Caucasian populations published in the dbSNP (NCBI) and 1000 Genomes Project databases revealed significant differences for rs1801133 from the EUR 1000 Genomes Project. The allele frequency data for MTHFR could increase the accuracy and reliability of the individual risk calculation for multifactorial diseases in the Russian population.

[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.

[Cerebral atherosclerosis: a biomarker profile]. / Tserebral'nyi ateroskleroz: biomarkernyi profil'.

AIM: To assess the changes in several biomarkers in patients with atherosclerosis of brachiocephalic arteries and shape a biomarker profile of cerebral atherosclerosis as an integrative index. MATERIAL AND METHODS: The study included 124 patients with atherosclerotic lesions of internal carotid arteries (82 men and 42 women) aged from 37 to 73 years. The patients were stratified by history of prior stroke into 'asymptomatic' and 'symptomatic'. Along with general clinical and neurological examinations, ultrasound analysis of brachiocephalic arteries, neuroimaging, identification of biomarkers reflecting different stages of atherogenesis and evaluation of pathomorphological parameters of atherosclerotic plaques removed during carotid endarterectomy surgery were performed. RESULTS: Concentrations of NO2, NO3 and NO in blood plasma significantly differed between groups: 58.4, 43.3 and 15 mcmol/l, respectively, in the symptomatic group and 45, 19.2 and 25.8 mcmol/l in the asymptomatic group. The pro-inflammatory character of changes in atherosclerosis was confirmed by the increase in the concentration of lipoprotein-associated phospholipase A2 in patients with stroke (354.72±44.16 ng/ml versus 298.45±54.12 ng/ml). The level of the atheroprotective marker adiponectin decreased significantly in 'symptomatic' patients. Significant changes towards the prothrombotic state of blood were identified via levels of blood markers of fibrinolytic activity: plasminogen tissue activator and plasminogen activator inhibitor-1. CONCLUSION: Together with other diagnostic methods, identification of biomarkers can increase the accuracy of prognosis and prevention of sudden cardiovascular death. The authors have developed a scale of biomarker 'burdeness' of the patient with cerebral atherosclerosis that may be a first step to individualized prevention of associated ischemic complications.

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.

Multimodal approach to treatment of neurological complications of chronic brain ischemia.

AIM: The study of Actovegin effectin clinical presentations and hemorheological characteristics in patients with chronic cerebrovascular pathology (CCVP) and mild cognitive impairment. MATERIALS AND METHODS: The study group included 47 patients (25 male and 22 female), aged 61-75 years (mean age 63.8±5.4) with CCVP who were treated with Actovegin. The control group comprised 28 patients matched by gender and age, without associated cerebrovascular pathology. All patients along with thorough neurological examination underwent laboratory analyses (platelet and erythrocyte rheology), neurovisualization studies (functional magnetic resonance imaging of the brain). Depending on the dosage all patients were divided in two groups: Actovegin 1000 mg and 160 mg daily. RESULTS: Overall, with Actovegin treatment in 81% of cases positive dynamics both in subjective symptoms, and somatic status was observed. A favorable effect on cognitive function in patients with CCVP was noted. The dose-dependent drug effect was demonstrated. The effect of Actovegin on blood cell functioning included the formation of smaller (Tf and Ts; p=0.0096 and p=0.016) and less solid (γ dis) erythrocyte aggregates (p=0.0034) both in the study and control group. The increase in erythrocyte deformability during therapy was significantly associated with cognitive improvement (via MoCA test, r=0.28). CONCLUSION: Complex (including neuropsychological and neurovisualizational) examination may not only help determine the cognitive status in patients with CCVP, but also assess the efficacy of neurometabolic therapy. New facts of Actovegin's influence on erythrocyte aggregation and deformability have been identified, which may enhance micro- and macrocirculation. The acquired data may prove the wide spectrum of Actovegin's pharmacological effect, which allows to use it in all forms of cerebrovascular pathology.

[Complex assessment of the contribution of genetic factors to the risk of ischemic stroke]. / Kompleksnaia otsenka vklada geneticheskikh faktorov v razvitie ishemicheskogo insul'ta.

AIM: To develop a method of the complex assessment of genetic risk for ischemic stroke (IS) and evaluate its effectiveness. MATERIAL AND METHODS: Genotyping of 182 patients with atherothrombotic and cardioembolic subtypes of IS and 360 healthy individuals of 48 single nucleotide polymorphic loci (SNP) associated with the risk of II and its subtypes was performed. RESULTS AND CONCLUSION: In each group of SNPs, composite indicators of genetic risk of IS in groups of patients and healthy controls were identified. Differences between the calculated values of the genetic risk in these groups were significant (p <0,05). The quality of the binary classification validated by ROC-analysis confirmed the predictive potential of the proposed method of risk calculation for determining the genetic predisposition to the development of IS.