[Russian study on brain aneurysm surgery: a continuation (RIHA II)]. / Rossiiskoe issledovanie po khirurgii anevrizm golovnogo mozga: prodolzhenie (RIKhA II).

OBJECTIVE: To assess the main performance indicators of neurosurgical departments in surgical treatment of cerebral aneurysms in the Russian Federation. MATERIAL AND METHODS: We analyzed 22 neurosurgical departments (19 regional and 3 federal hospitals) in 2017 and 2021. The study enrolled 6.135 patients including 3.160 ones in 2017 and 2.975 ones in 2021. We studied the features of surgical treatment of cerebral aneurysms in different volume hospitals and factors influencing postoperative outcomes. RESULTS: The number of surgeries for cerebral aneurysms decreased from 2.950 in 2017 to 2.711 in 2021. Postoperative mortality rate was 6.3% and 5.6%, respectively. The number of microsurgical interventions decreased from 60% in 2017 to 48% in 2021. The share of endovascular interventions increased from 40% to 52%, respectively. Endovascular embolization was accompanied by stenting in 55% of cases. Simultaneous revascularization was carried out in 2% of cases. In 2021, the number of patients undergoing surgery in acute period of hemorrhage increased to 70% (in 2017 - 61%). The number of hospitals performing more than 50 surgical interventions for cerebral aneurysms annually increased from 14 in 2017 to 17 in 2021. CONCLUSION: Certain changes in neurosurgical service occurred in 2021 compared to 2017. Lower number of surgical interventions for cerebral aneurysms, most likely caused by the COVID-19 pandemic, is accompanied by lower postoperative mortality. Endovascular interventions and revascularization techniques became more common. The number of surgeries in acute period after aneurysm rupture and hospitals performing more than 50 surgical interventions for cerebral aneurysms annually increased.

[Long-term results of surgical treatment of patients with cerebral arterial aneurysms]. / Otdalennye rezul'taty khirurgicheskogo lecheniya patsientov s arterial'nymi anevrizmami golovnogo mozga.

OBJECTIVE: To study the long-term results of surgical treatment of patients operated on for cerebral aneurysms and their impact on functional recovery, independence and cognitive functions in the long-term period. MATERIAL AND METHODS: A multivariate regression analysis of long-term results of surgical treatment of 324 patients for cerebral aneurysms was performed (on average after 3.5 years). Upon admission of the patient to the hospital for surgical intervention, a clinical diagnostic examination was performed to confirm the diagnosis and determine the volume, timing and type of intervention. In the late period, a clinical neurological study was performed, which included an assessment of the degree of disability with the Barthel index and a modified Rankin scale, cognitive functions with MMSE, and the mental sphere with HADS. RESULTS: The severity of the condition at admission, corresponding to grade III-IV according to the Hunt-Hess classification, was the risk factor for an unfavorable prognosis for the recovery of patients in the long-term period of cerebral aneurysm surgery. The severe condition of patients at the onset of the disease increases the risk of disability by 1.9 times (p<0.05) and the risk of dementia by 6 times (p<0.05). An independent risk factor for the development of cognitive impairment is the patient's age: with an increase in age by 1 year, the MMSE score decreases by 0.27 (p<0.05). The prevalence of hemorrhage according to the Fisher classification, corresponding to grade III, is a predictor of the development of angiospasm in 91% of cases. In patients with established angiospasm, the risk of developing dementia and pre-dementia cognitive impairment was 57.3% (p<0.05). The best predictions for recovery of cognitive functions in the long-term period were observed in patients who underwent simultaneous aneurysm clipping with extra-intracranial anastomosis (mean MMSE score 25) compared with patients who underwent only aneurysm clipping (mean score 20), endovascular intervention (average score 21) or microsurgical intervention followed by intrathecal fibrinolytic injection (mean MMSE score of 20) (p<0.05). CONCLUSION: The predictors of unfavorable recovery of cognitive functions and the development of disability in the long-term period of surgical treatment of cerebral aneurysms were the severity of the condition at admission, corresponding to III-IV st. according to the Hunt-Hess classification, the age of the patient at the time of the intervention, the prevalence of hemorrhage according to Fisher, and the choice of surgical technique.

[Results of implementation of a 'Complex of measures to improve medical care for patients with stroke in the Russian Federation']. / Rezul'taty realizatsii 'Kompleksa meropriiatii po sovershenstvovaniiu meditsinskoi pomoshchi patsientam s ostrymi narusheniiami mozgovogo krovoobrashcheniia v Rossiiskoi Federatsii'.

Vascular diseases of the brain and heart are the main cause of death and disability of the population of the Russian Federation. The social and economic burden of acute cerebral circulation disorders necessitated the development of a national program for the care of patients with acute vascular diseases. As a result of the implementation of a set of measures to improve medical care for patients with stroke over the past decade, the regions of the Russian Federation managed to create an 'insult network', equip the departments with high-tech diagnostic and therapeutic equipment, and train medical personnel. Due to the implementation of modern methods of treatment of stroke, the rates of disability and mortality from stroke have decreased.

[Surgical treatment of cerebral aneurysms in the Russian Federation]. / Khirurgicheskoe lechenie tserebral'nykh anevrizm v Rossiiskoi Federatsii.

OBJECTIVE: The objective of this study was to evaluate the results of surgical treatment of cerebral aneurysms in the Russian Federation. MATERIAL AND METHODS: We analyzed performance indicators in neurosurgical departments of regional and federal health institutions of the Russian Federation for 2017. The results of surgical treatment of cerebral aneurysms (CAs) were analyzed in 19 regional vascular centers (RVCs) in several federal districts and in 3 federal centers (FCs) with the most dynamically developing vascular neurosurgery and smoothly running system of statistical data processing. RESULTS: The study included 3160 patients hospitalized to 22 medical institutions in 2017. Of these, 1808 patients were treated in RVCs, and 1352 patients were treated in FCs. We analyzed factors affecting the treatment outcome in CA patients. We identified features of CA treatment in clinics with a different amount of surgical intervention. CONCLUSION: An increase in the surgical activity in centers and simultaneous development of microsurgical and endovascular treatments for cerebral aneurysms reduce postoperative mortality. Due to the presence of a RVC network in the Russian Federation, many patients could receive necessary specialized treatment. The number of operations for cerebral aneurysms has increased 6-fold for the past 10 years.

[Association of rs10912745 and rs4916375 polymorphisms located in the cluster of flavin-containing monooxygenase genes, with ischaemic cardioembolic stroke].

Twenty-one SNPs located in the cluster of genes FMO1-FMO2-FMO3-FMO4 and adjacent areas were analyzed in the patients with ischaemic cardioembolic stroke and in the control group. Significant differences between these samples were found in the distribution of genotype and allele differences in two polymorphic loci, rs10912745 and rs4916375. It was shown that these polymorphic loci are associated with the risk of ischaemic cardioembolic stroke development.

[Association study of polymorphic markers of F12, PON1, PON2, NOS2, PDE4D, HIF1a, GPIba, CYP11B2 genes with ischemic stroke in Russian patients].

Allele and genotype frequencies of 10 single nucleotide polymorphisms in F12, PON1, PON2, NOS2, PDE4D, HIF1a,GPIba, CYP11B2 genes were studied in a group of Russian patients with ischemic stroke (IS) from central regions of the Russian Federation and healthy donors matched for sex, age and ethnicity. The genotyping procedure included the amplification of selected DNA sequences with the following hybridization of fluorescently-labeled regions with allele-specific DNA-probes immobilized on a biochip. An analysis of allele and genotype frequencies for each gene in IS patients and controls did not reveal any significant differences. The pair-wise comparison of genes demonstrated that the frequency of the combination PON1A/-x PON2 GG was higher in the group of patients (p=0.044, OR=3.4 95% CI 1.06 − 10.4) compared to the controls and, thus, was associated with the higher risk for stroke.

[Dynamics of perfusion CT parameters in the early acute phase of ischemic stroke].

Perfusion computed tomography (CT) allows to evaluate brain perfusion and provides additional information about local cerebral hemodynamics in stroke patients. Twenty-seven patients underwent CT-perfusion in the early acute phase of ischemic stroke. Significant differences between ischemic lesion and contralateral hemisphere on CBF and MTT scans during the first 3 hours after stroke were revealed. In the following 24 h, the differences were seen in all perfusion parameters. CT-perfusion allows to reveal perfusion parameters associated with stroke severity and outcome that is relevant for prescription of reperfusion treatment beyond the boundaries of 3-4.5h "therapeutic window".

[The association between the DNA marker rs1842993 and risk for cardioembolic stroke in the Slavic population].

The analysis of association between DNA markers and total stroke risk was performed in 950 Slavonic patients. Patients with cardioembolic stroke were selected for a genome-wide association study. The HUMANCYTOSNP12 v.2 microchip was used to analyze all DNA samples on a panel of 301 000 single nucleotide polymorphisms. SNP rs1842993 on chromosome 7 was found to be associated with cardioembolic stroke risk.

[Association study of renin-angiotensin system genes and hemostasis system genes with ischemic stroke among Russians of Central Russia].

The analysis of alleles and genotypes frequencies of 14 SNP in genes of rennin-angiotensin system (REN, AGT, AGTR1, AGTR2, BKR2, ADRB2) and hemostasis system (FGB, F2, F5, F7, ITGB3, SERPINE1, MTHFR), as well as ACE insertion-deletion polymorphism in patients with stroke comparing to healthy controls matched by age, sex and ethnicity has been carried out. The genotyping procedure included the amplification of selected gene sequences following by hybridization of fluorescently labeled fragments with SNP-specific DNA probes. The analysis of allele frequencies of each gene separately revealed no statistically significant differences between groups of patients with stroke and healthy donors. Also the complex study has been performed to estimate the contribution of rennin-angiotensin system and hemostasis system genes to the genetic susceptibility to ischemic stroke among Russians from Central Russia using method MDR (Multifactor Dimensionality Reduction). The combination with increased risk for development of ischemic stroke was presented by complex genotype FGB G/- x ACE I/- x MTHFR C/- x SERPINE1 5G/5G (p = 0.03, OR = 2.4, 95% CI 1.1-5.3), which frequency was statistically significant higher in patients with stroke compared to healthy control.

[Analysis of the polymorphic variants of the PDE4D gene in patients with acute stroke in the Moldavian population].

The risk of the ischemic stroke is mediated by both environmental and genetic factors. Recent studies of DeCode group identified the risk of polymorphisms for ischemic stroke in the phosphodiesterase 4D gene (PDE4D). The goal of this study was to explore the role of two variants of the gene encoding PDE4D [SNP41 (rs152312) and SNP87 (rs2910829)] in the Moldavian patients with ischemic stroke and in control. No significant association with ischemic stroke was observed with SNP41 and 87.

[Polymorphic variants of ALOX5AP gene and the risk of acute stroke development in the Russian population].

A protein capable of activating 5-lipoxygenase (ALOX5AP) is considered a presumable risk factor of acute stroke development. Polymorphic variants of the ALOX5AP gene were examined. Two ALOX5AP gene polymorphisms (SG13S114 (rs10507391) and SG13S32 (rs9551963)), which previously had shown association with the risk of ischemic stroke in other populations, were studied. These single nucleotide polymorphisms were analyzed using a sample of acute stroke patients (N = 1320) and a control sample (N = 467). No statistically significant associations were found between acute stroke and the ALOX5AP gene polymorphisms examined.

[Clinical-electrophysiological characteristics of the cognitive sphere in patients in the acute period of the first cerebral ischemic stroke].

A neuropsychological and neurophysiological study using computed EEG was carried out in 31 stroke patients who did not have a cognitive impairment according to MMSE. Thirty age-matched patients with the same risk factors without a history of stroke were included into the control group. The examination of the control group was performed only once. The examination of stroke patients was performed on days 1, 7 and 21. It was shown that cognitive neurodynamic disturbances (memory disorders and the visual memory decrease) and bioelectrical brain activity disturbances (the decrease in a- and beta band activities and the increase of theta-band power) occurred from the first day and lasted during the acute stroke period even after the improvement of neurological status.

[Analysis association of acute ischemic stroke and DNA markers in Russian and Moldavian populations].

Polymorphisms c.202G > A of prothrombin F2 gene, c.1691G > A of coagulation factor V F5 gene, c.675delinsG of plasminogen activator1 gene, and (-5)T > C Kozak gene of thrombocytic receptor were studied in the Russian and Moldavian ethnic groups. We have found no association between these polymorphisms and the risk of ischemic stroke development in both ethnic groups. No association was revealed between the risk of stroke development and various combinations of the single nucleotide polymorphisms examined in the sample of ischemic stroke patients from Russia.

[Association of cerebral stroke with a phosphodiesterase 4D (PDE4D) gene polymorphism in the Moscow population].

We studied SNP41 (rs152312) and SNP87 (rs2910829) of the PDE4D gene in 577 stroke patients and 270 healthy controls. The significant differences in the distribution of genotype and allele frequencies of the SNP41 between patients and controls were revealed. Genotypes AA and AG were associated with the higher risk of stroke in the Moscow population (OR 1,6). No association between SNP87 and stroke was found.

[Association of factors of vascular tone regulation with the development of hemorrhagic transformation in patients with ischemic stroke].

Concentrations of plasma vascular tone regulation markers that are indicators of endothelium dysfunction in the acute phase of ischemic stroke and their effect on the development of hemorrhagic transformation (HT) of the lesion focus have been studied. Concentrations of renin, endothelin 1-21, neuron-specific enolase, NT-proCNP, soluble adhesion molecules (sICAM) were measured in 67 patients on days 1, 3-4. Significantly higher concentrations of renin, endothelin 1-21, neuron-specific enolase were found in patients with HT in the first day compared to patients without HT. The level of NT-proCNP was lower in patients with HT; the increase in the severity of hemorrhagic component led to the elevation of neuron-specific enolase and sICAM concentrations. In conclusion, both markers of blood-brain barrier damage and regulating factors of vascular tone may play a predictive role in the development of HT in ischemic stroke.

[The role of polymorphic variants of gene of inducible NO-synthase NOS2 in brain infarction in patients with acute ischemic stroke].

Cerebrovascular diseases including stroke are an important problem of public health. Stroke development depends on external factors and individual genetic specificity of patient. Excessive NO production by inducible NO-synthase (iNOS) damages brain tissue at various stages of the disease. The goal of this work was to study the role of 4 polymorphic variants of gene of inducible NO-synthase iNOS (-2447C/G, -1659C/T, -0,7(OTTA)n I/D, S608L (150C/T)) in brain infarction in patients with acute ischemic stroke. A statistically significant correlation between S608L (150C/T) polymorphism and infarction dynamics was observed during days 1-3 and 7-21 after infarction. These parameters correlated with neurological status estimated using the Orgogozo scale during days 1-7 of the disease development. It was demonstrated that genotype N150N was associated with ischemic focus propagation regardless of its volume and neurological status by Orgogozo scale in patients with acute stroke. It was also observed that genotype N150N had effect on ischemic damage during days 1-3 in case of low initial volume.

[Phosphodiesterase 4D (PDE4D) gene polymorphism in patients with acute stroke from Moscow].

Two PDE4D gene polymorphisms [SNP41 (rs152312 and SNP87 (rs 2910829)] were studied in patients with acute stroke (n = 577) and in control sample (n = 270). Significant differences in the genotype and allele frequency distribution were found between these samples for polymorphism SNP41. We showed that the AA and AG genotypes of SNP41 polymorphism were associated with higher risk of acute stroke development in the Moscow population (OR = 1.6). No association of SNP87 polymorphism with the disease was observed.

[Efficacy and safety of the combined therapy with citicholine and actovegin in the acute period of ischemic stroke].

One hundred and four patients with acute carotid ischemic stroke were included in the study. Patients were divided into 4 groups. Patients of control group (group 1) were treated with equal basic and reperfusional therapy without any cytoprotectors. Patients of the 2nd group received citicholine in dose 1000 mg per day. Patients of the 3rd group were treated with 250 ml actovegin per day. The NIH stroke scale, the modified Rankin scale and the Barthel index were used to assess neurological status dynamics. The significant decrease of neurological deficit and improvement of functional recovery were seen in patients treated both with citicholine and actovegin (p < 0.005) to the 30th day compared to the control group. There was a trend towards the decrease of brain infarction volume within 5 days after stroke in patients of the 4th group. No side-effects of citicholine and actovegin were found.

[The use of citicoline in the acute cerebral stroke].

Data on the mechanism of action of the neuroprotector citicoline, its effectiveness in the experimental models of cerebral ischemia and in patients with ischemic and hemorrhagic stroke are reviewed. Citicoline is a unique drug with neuroprotective properties that demonstrated the positive results in patients with stroke. The effectiveness of the combined thrombolytic and citicoline therapy was demonstrated in the experimental model of ischemic stroke.

[Genome-wide scanning in the study of risk for cerebral stroke].

The role of genetic predisposition to the formation of most multifactorial diseases, including stroke, was demonstrated in a number of investigations. To determine the individual genetic risk of a polygenic disease, the candidate gene approach is used most often. It is based on the analysis of polymorphic variants of certain genes taking into consideration the function of their protein product. But this approach is limited by the analysis of defined genes and does not detect new groups of genes, which involved in the pathogenesis of cerebral stroke. Genome-wide association study is a wide-range analysis of whole-genome polymorphisms, which allows to compare the distribution of allele frequencies in stroke patients and healthy individuals. The use of this method for the determination of individual genetic risk of acute stroke allows to perform molecular-genetic screening of most significant markers of stroke predisposition; to determine patients with the highest risk of stroke and to perform the mass health examination with preventive therapy prescription. The genome-wide association study to determine the individual genetic risk of stroke, taking into account ethnic origin, is performed in the Russian Federation since 2008 on the basis of the Neurological clinic of the Russian State Medical University in collaboration with the Institute of Molecular Genetics, Russian Academy of Sciences.