[Predictors of acute cerebral embolic lesions during carotid artery stenting]. / Prediktory ostrykh tserebral'nykh émbolicheskikh povrezhdenii pri stentirovanii sonnoi arterii.

The authors carried out a prospective study aimed at revealing predictors of acute embolic lesions of cerebral vessels during angioplasty with stenting of the internal carotid artery. The study enrolled a total of 54 patients who between May 2015 and December 2018 underwent carotid angioplasty with stenting performed at the Department of Vascular and Endovascular Surgery of the Research Centre of Neurology. The procedure of internal carotid artery stenting may be accompanied by intraoperative acute embolic lesions. In order to reveal intraoperative acute embolic lesions of cerebral vessels all patients before and 24 hours after the intervention were subjected to diffusion-weighted magnetic resonance imaging. Thirty-six patients received classical carotid stents (Xact and Acculink) and 18 patients received Casper stents. The patients of both groups were comparable by 24 characteristics studied, including the incidence of intraoperative acute cerebral embolic lesions (18/36 for the classical stents and 10/18 for the Casper stent), which made it possible to unite them into one group in order to increase the power of the study. All acute embolic lesions detected by the diffusion-weighted magnetic resonance imaging (prior to stenting and 24 hours thereafter) were clinically, asymptomatic with no perioperative stroke observed. In order to reveal predictors of intraoperative acute embolic lesions of cerebral vessels we analysed 22 characteristics of the patients, with the obtained findings demonstrating the following signs: a low-intensity (below 20 dB) ultrasonographic signal reflected from fragments of an atherosclerotic plaque during ultrasound examination prior to stenting (p=0.001) - a sign strongly associated with acute embolic lesions (sensitivity - 75%, specificity - 92%); symptomatic stenosis according to the anamnestic data (p=0.02) - a sign significantly associated with acute embolic lesions; female gender (p=0.06) - a sign moderately associated with acute embolic lesions; a history previously endured (according to the anamnestic data) operations on coronary and/or carotid arteries (p=0.09) - a sign weakly associated with acute embolic lesions. Based on the obtained findings we proposed a prognostic scale to assess the risk of acute embolic lesions of cerebral vessels during internal carotid artery stenting. Knowing the factors associated with intraoperative acute embolic lesions will allow the endovascular surgeon to single out the patients at increased risk of acute embolic lesions.

[Carotid revascularization in type 2 diabetes mellitus. Significance of chronic hyperglycaemia]. / Karotidnaia revaskuliarizatsiia u bol'nykh sakharnym diabetom 2 tipa. Znachenie khronicheskoi giperglikemii.

Patients with type 2 diabetes mellitus (type 2 DM) are typically prone to the development of cerebral atherosclerosis. Presented herein are the results of examination of patients suffering from ischaemic cerebrovascular diseases on the background of type 2 DM subjected to open surgical or endovascular interventions. In patients with cerebrovascular pathology and type 2 DM, atherosclerosis progresses on the background of chronic hyperglycaemia combined with dyslipidaemia, leading to increased incidence of the development of cerebral circulatory impairments and detection of the indications for carrying out angioreconstructive operations on the internal carotid arteries. The presence of type 2 DM is associated with increased risk for the development of ischaemic lesions of the brain matter while performing carotid endarterectomy and endovascular interventions which are associated with higher values of glycaemia (8.0 mmol/l) and glycated haemoglobin (7.8-8 %) prior to the operation.

[Prediction of ischaemic lesions of the brain in reconstructive operations on internal carotid arteries]. / Prognozirovanie ishemicheskikh povrezhdenii golovnogo mozga pri rekonstruktivnykh operatsiiakh na vnutrennikh sonnykh arteriiakh.

The present study was undertaken to examine the relationship between the level of the intensity of the ultrasonic signal reflected from atherosclerotic plaques (ATP) of carotid arteries and the risk for formation of an ischaemic lesion in the brain matter, detected during diffusion-weighted magnetic resonance imaging (DW-MRI) performed 24 hours after carotid endarterectomy (CEA) or carotid angioplasty and stenting (CAS). Our prospective study included a total of 78 patients presenting with stenosis of the sinus of the interior carotid artery. Of these, 42 patients were subjected to CEA and 36 subjects endured CAS. All patients in the preoperative period underwent ultrasonographic examination with determination of the degree of heterogeneity of ATPs and registration of the values of the intensity of acoustic characteristics of the signal. The condition of the brain matter before and 24 hours after the intervention was assesses by the findings of DW-MRI. None of the patients after the reconstructive intervention during the postoperative period demonstrated any evidence of acute cerebral circulation disorders. DW-MRI carried out 24 hours after the operation revealed acute ischaemia foci (AIF) in 9 (21.4%) patients after CEA and in 18 (50%) patients after CAS (p=0.05). It was revealed that the postoperative occurrence of AIF was related to the intensity of the ultrasonographic signal prior to the operation: in the CEA group patients the postoperative ischaemic foci were associated with high-intensity ultrasonographic signals (more than 25 dB), whereas in the CAS group patients, vice versa - with low-intensity signals (less than 25dB). For CEA, sensitivity and specificity of the preoperative ultrasonographic method of predicting postoperative embolic lesions of the brain appeared to be similar, amounting to 100% each (with the cut-off point of high- and low-intensity signals equaling 25 dB), and for CAS, sensitivity of the method turned out to be 75% and specificity - 100% (with the same cut-off point of 25 dB). A conclusion was drawn that quantitative characteristics of the intensity of an ultrasonographic signal from fragments of atherosclerotic plaques of the sinus of the internal carotid artery made it possible with high probability to predict the risk for the development of AIF in the brain matter after both CEA and CAS and may therefore serve as a reliable criterion for appropriate therapeutic decision-making with the lowest risk of inflicting lesions in a particular case. The threshold cut-off points of high- and low-intensity ultrasonographic signals, as well as their clinical significance are yet to be specified and verified with the growing number of cases.

[In vitro lipid-lowering and fibrinolytic effects of regulatory leucine-containing glyprolines in human blood].

The lipid-lowering, fibrinolytic, and anticoagulant effects of leucine-containing glyprolines, Pro-Gly-Pro-Leu and Leu-Pro-Gly-Pro, were studied in vitro in the blood of patients with disorders of lipid metabolism. The lipid-lowering impact of glyprolines and their ability to reduce the polymerization and to increase the depolymerization of fibrin in human blood were found. Possible mechanisms of lipolytic action of peptides by means of modulation of the lipid-dependent phospholipase A2 were proposed.

[Ischaemic lesions of cerebral after carotid stenting].

Carotid angioplasty with stenting is a reliable method of primary and secondary prevention of ischaemic stroke in patients with stenosing lesions of the internal carotid artery. However, carrying out such operations is sometimes associated with risk for the development of intraoperative impairments of cerebral circulation due to arterioarterial embolism in cerebral arteries, as well as vasospasm. Presented herein are the results of following up a total of 64 patients with pronounced atherosclerotic lesions of internal carotid arteries (>70%) - "symptomatic" and "asymptomatic", undergoing carotid stenting. Acute foci of ischaemia in the brain after stenting according to the findings of diffusion-weighted magnetic resonance tomography were revealed in 40% of cases, and in only 6% of patients they manifested themselves by symptoms of acute cerebral circulatory impairment. We revealed a direct correlation between the number, size of infarctions in the brain, and the appearance of neurological symptomatology. Intraoperative monitoring of blood flow in the middle cerebral artery during stenting makes it possible to predict the appearance of acute foci of cerebral ischaemia, to specify the genesis of perioperative stroke, as well as to evaluate clinical significance of vasospasm and material microembolism. The obtained findings should concentrate neurologists' attention on active postoperative follow up of patients subjected to carotid angioplasty with stenting in order to perform adequate personified neuroprotective correction, including preventive one.

[Cerebrovascular diseases and metabolic syndrome].

AIM: To study various aspects of cerebrovascular diseases (CVD) in the presence of metabolic syndrome (MS). SUBJECTS AND METHODS: A comprehensive clinical, laboratory, ultrasound, and neuroimaging study was conducted in 514 patients with symptomatic and asymptomatic atherosclerotic lesion of the internal carotid artery and MS. RESULTS: MS was found and proven to affect the following factors: a) the course and progression of carotid artery (CA) atherosclerotic lesion with transformation of its asymptomatic to symptomatic state; b) the structure and instability of an atherosclerotic plaque; c) the magnitude of blood theological changes; d) endothelial dysfunction; e) white matter changes; f) the clinical features of both acute and chronic CVD and the development of cognitive impairments. CONCLUSION: The association of the atherogenic activity of major components of MS, such as hyperinsulinemia, hypertension, dyslipidemia, and obesity, in the presence of dysregulated hemostasis and blood rheology substantially increases the risk of a progressive CA atherosclerotic process even in its asymptomatic course and accordingly favors the development and progression of different manifestations of CVD.

[Chronic cerebrovascular diseases associated with metabolic syndrome: new treatment approaches].

Metabolic syndrome is a risk factor for acute and chronic cerebrovascular diseases. The development of oxidative stress promotes the progression of cerebral ischemia and treatment of the biochemical disturbances is needed. Use of antioxidants in patients with cerebrovascular diseases and metabolic syndrome reduce such symptoms as insulin resistance, hyperglyceridemia, hyperglycemia. The authors present results of a clinical study of mexidol in 40 patients, aged from 50 to 70 years, with chronic cerebrovascular pathology. Perspectives of using this group of drugs as universal neuroprotectors are discussed.

[Two patterns of Ct-brain perfusion and Dc-potentials of the brain evoked cognitive task in discirculatory encephalopathy patients].

In patients with discirculatory encephalopathy the influence of verbal fluency test on the characteristics of cerebral perfusion, DC-potentials of the brain, as well as on blood pressure and heart rate was investigated. Two patterns of responses to the verbal fluency test were observed. The first one is the process of generalized activation, manifested by the reduction of the TTP (time to peak) parameters of brain perfusion, the rise of the DC-potentials in all areas of brain and the modulation of blood pressure and heart rate. The second process, directly connected with cognitive processing, was manifested by the shifts of local characteristics of brain perfusion and DC-potentials in the frontal, temporal and central cortex, especially in the left hemisphere. Correlations were found between the characteristics of cerebral perfusion and DC-potentials on the one hand and the number of words during the verbal fluency test performance on the other hand.

[Intraoperative monitoring of cerebral blood-flow and condition of cerebral at open and endovascular interventions in carotid system].

The aim of our research is to study hemodynamic and embolic situation during the carotid endarterectomy (CEA), carotid angioplastic and stenting (CAS), and to reveal the prognostic significance of the data provided by intraoperative monitoring of the brain blood flow in exposing acute ischemic lesions in brain. Intraoperative monitoring of blood flow in artery ophthalmic vas carried out with 60% of patients, in the middle cerebral artery-with 40% during the main stages of CEA, and with 64 patients in the middle cerebral artery during CAS. The comparison of the data of intraoperative monitoring of blood flow in middle cerebral artery with the result of brain diffusion-weighted magnetic resonance imaging (DW-MRI) 24 hours after the operation shows, that solid microembolic signals and vasospasm are prognostic signals (sensibility and specifics make up 95%) in the development of acute ischemic cerebral lesions. The monitoring of blood flow in artery ophthalmic is of the greatest diagnostic value in estimation of the hemodynamic situation, but it is of the lowest practical value in detecting microembolic signals. According to the data of the intraoperative blood flow monitoring in middle cerebral artery in group CEA the development of acute ischemic cerebral lesions were predicted with 11,1% of patients and the cause of postoperative stroke, developed by 2,9% of the patients, was specified. According to the result of DW-MRI, acute ischemic cerebral lesions were diagnosed with 21% of patients, that is, 18% of ischemic cerebral lesions were asymptomatic. In group CAS ischemic cerebral lesions were prognosed with 30% of patients, actually they were later detected with 40,6% of cases by means of DW-MRI. According to the data of intraoperative of blood flow monitoring the cause of the development of postoperative stroke was specified in 6,2% of cause; in 34,4% of cause the acute ischemic cerebral lesions were asymptomatic.

[Resistance to antiplatelet drugs in patients with cerebrovascular disorders].

This review concerns clinical and laboratory resistance to antiplatelet drugs (aspirin and clopidogrel) in patients with cerebrovascular disorders. Results of certain clinical trials showed that laboratory resistance to antiaggregants is associated with recurrent thromboembolic vascular events. The commonest causes of aspirin resistance are production of arachidonic acid metabolites via the lipoxygenase pathway, poor compliance with the treatment, polymorphism of the genes encoding for cyclooxygenase and glycoprotein (GP) IIb/IIIa, endothelial dysfunction. The causes of clopidogrel resistance include inadequate doses of the drug, its low absorption, poor compliance with the treatment, polymorphism of ADP receptors, GP IIb/IIIa and cytochrome P450 genes, acute coronary syndrome and stroke, metabolic syndrome. Therapeutic efficacy of antiaggregants can be improved by increasing their doses, using membranotropic agents, correcting endothelial dysfunction, etc. Because the apparent variability of antiplatelet drug resistance is currently due to the use of different test-systems by different authors, the evaluation of individual sensitivity to a given drug showing laboratory resistance and the choice of alternative therapy are thus far possible only in the framework of clinical studies. Large-scale prospective multicenter trials of antiplatelet drug resistance are needed along with research for better understanding mechanisms of individual platelet sensitivity and resistance to antiaggregants and developing efficacious methods for their correction.

[Association between changes in characteristics of local cerebral blood flow and slow brain electrical activity in patients with dyscirculatory encephalopathy].

Associated changes in the characteristics of local cerebral blood flow (CBF) and slow brain electrical activity were studied in 40 patients with dyscirculatory encephalopathy. CBF and CBV (cerebral blood volume) values for the frontal and temporal cortex and basal ganglia positively correlated with the constant potential values in the central lead influenced by the blood flow rate in the upper sagittal sinus.

[The complex energy correction of chronic brain ischemia].

Considerable disturbance of all quality of life domains that worsens social adaptation and daily living and results in an asthenic-neurotic syndrome, along with neurologic and mnestic-intellectual disturbances, was revealed in patients with chronic brain ischemia (stages I, II, III). Based on the results of the double blind placebo-controlled trial, the high clinical efficacy of cytoflavin in patients with chronic brain ischemia has been shown. The treatment with cytoflavin decreases the severity of subjective symptoms and complaints thus increasing the working ability of patients, improves balance and gait, decreases the severity of asthenic and neurotic syndromes, improves cognitive and memory functions (information storage, reasoning and attention), positively effects on quality of sleep and all aspects of quality of life, in particular, on physical activity, self-rating of health and viability as well as social activity, mental health and emotional lability.

[Interhemisphere asymmetry of regulation of the local brain blood flow in patients with dyscirculatory encephalopathy].

Patients with dyscirculatory encephalopathy (DE) were examined to elucidate interhemisphere relationships by recording brain constant potential (CP) and perfusion CT. Electrophysiological characteristics were shown to relate to local brain blood flow. Dispersion of intrehemisphere CP level in DE patients proved more pronounced than in healthy subjects. Interhemisphere CP difference in temporal region significantly (p < 0.001) correlated with the time needed to reach maximum concentration of contrast agent in the frontal and temporal cortex, basal ganglia, and thalamus. Left temporal CP level positively correlated with contrast agent concentration in the above brain structures of both hemispheres and negatively with that in the right hemisphere. It is concluded that intertemporal relationships may influence vegetative nervous system that in turn changes cardiovascular function.

[Chronic cerebrovascular diseases, metabolic syndrome and the status of hemorrheological and hemostatic systems].

AIM: to study an association between metabolic syndrome and endothelial dysfunction as a regulator of hemorrheological and hemostatic processes in patients with chronic forms of cerebral circulatory insufficiency. SUBJECTS AND METHODS: Forty-six patients with chronic cerebrovascular diseases (CCVD) were examined; of them 23 patients were diagnosed as having metabolic syndrome (MS). Clinical manifestations and major hemorrheological and hemostatic parameters, such as platelet and erythrocyte aggregation, fibrinogen, hematocrit, von Willebrand factor, antithrombin III, intercellular adhesion molecules (IAM), etc., were estimated. Endothelial dysfunction was studied from the data of cuff test (CT). RESULTS: MS promotes a higher degree of clinical symptomatology in patients with CCVD and more significant impairments in the hemorrheological and hemostatic systems. CT has shown that all the patients have an inadequate endothelial reaction - the antiaggregatory, fibrinolytic, and anticoagulant activities of the endothelium are lowered. There was endothelium-dependent hyperproduction of IAM. CONCLUSION: The found changes suggest that MS has a considerable impact on the formation of a significant procoagulant state of the hemorrheological and hemostatic systems in patients with CCVD.

[A multicenter program on assessment of efficacy and safety of a new therapeutic scheme for patients with chronic cerebrovascular insufficiency].

An assessment of the complex multicenter prospective non-comparative program aimed at studying of efficacy and safety of a new scheme of therapy with cavinton in patients with chronic cerebrovascular insufficiency has been conducted. One hundred and forty-nine patients (46 male, 113 female), aged from 35 to 65 years, have been examined. The treatment started from intravenous infusions of the drug during 7 days as follows: 20, 30, 40, 50, 50, 50 and 50 mg of cavinton solution diluted in 500 ml of physiologic solution with the following peroral taking of cavinton forte in dose 10 mg 3 times daily during 11 weeks. Efficacy of drug was primarily assessed with MMSE and then by SF-36 and CGIC-PGIC. There were significant differences in scores on MMSE and SF-36 before and after treatment and on CGIC-PGIC on the 8th and 90th days of the study. The parenteral and peroral use of cavinton is well-tolerated and has a favorable safety profile.

[Hemorheology and hemostasis in patients suffering from ischemic cerebral stroke and metabolic syndrome].

A high level of mortality and disability makes study of various aspects of ischemic cerebral stroke (ICS) an extremely important problem. Presently, combination of various cardiovascular risk factors significantly increases the probability of such life-threatening conditions as ICS. Such risk factors as arterial hypertension, dyslipoproteinemia, excessive body weight, glucose intolerance or diabetes are often combined, which led to a suggestion to consider them together as one symptom complex, metabolic syndrome (MS). It is evident that MS affects the functioning of different organs and systems, including the systems of hemorheology and hemostasis. These are changes in hemorheological and hemostatic parameters that play a leading (in some cases decisive) role in the development of ICS. The present study found that the presence of MS in ICS patients hindered improvement in hemorheological and hemostatic parameters in the course of the disease. This was manifested by the absence of positive changes in thrombocyte aggregation, as well as fibrinogen level elevation in patients with MS in the course of treatment. Elevated blood level of D-dimers within the whole acute period in most MS patients also reflected more active thrombus formation. The development of ICS is very unfavorable to the condition of vascular wall athrombogenic activity in all patients. At the same time, worsening in all the chains of endothelial wall athrombogenic ability was more prominent in MS patients. Significant influence of MS on the forming of prothrombotic condition, which determines unfavorable clinical course of ICS, was demonstrated.

[Diffusion- and perfusion-weighted magnetic resonance imaging: possibilities and perspectives].

The article addresses theoretical and practical issues of using diffusion- (DW-MRI) and perfusion-weighted (PW-MRI) magnetic resonance tomography in acute period of ischemic stroke. The authors consider prognostic value of the results obtained with both methods of MRI-diagnosis and possibilities of their usage in pathophysiological studies of ischemic stroke. Prognostic value of DW-MRI in measuring of final size of stroke used at the first day of stroke is higher compared to standard regimes. A ratio between clinical and MRI data has been analyzed. A conception comparing a ratio between the presence of lesion and its size using DW-MRI and PW-MRI is presented. A longer duration of the penumbra comparing to conventional terms was described. The results of DW-MRI and PW-MRI study are suggested to be used for prognostic purpose as well as for elaboration of an optimal treatment tactics. Some controversial issues of using DW-MRI and PW-MRI, are discussed.

[Ischemic stroke: hemostasis and factors of cerebral embolism].

Hemorheology and hemostasis in patients with ischemic stroke in comparison to the process of cerebral embolism are considered. Results of transcranial Doppler monitoring of microembolic signals and indices of coagulation and anticoagulation blood systems are analyzed. The changes of both hemorheology and hemostasis in ischemic disturbances of blood circulation are characterized by an increase of coagulation blood activity and suppression of anti-coagulation activity. In ischemic stroke, as compared to transitory ischemic attacks, the markers of thrombinemia were increased significantly that was most pronounced in cases of lacunar and cardioembolic genesis. Cerebral microembolism was associated with imbalance of hemostasis systems. The results of the study may be used in elaboration of recommendations for optimization of therapeutic arrangements in ischemic disturbances of cerebral blood circulation.

[Neuromuscular electrostimulation in acute ischemic stroke].

Efficacy of poststroke rehabilitation depends on intensity of afferent current from the paretic limb to the lesion. The afferentation course is represented by neuromuscular electrostimulation (NMES) of the paretic hand's finger and hand extensors. The procedure's effect on the focus of acute ischemic lesion was analysed with MRT imaging including diffusion-perfusion-weighted MRT which can assess bioenergetic condition of the focus and brain perfusion. The analysis shows that NMES in acute ischemic stroke does not result in enlargement of the lesion and deterioration of brain circulation. Motor function seems to recover faster in the group given NMES.

[Effects of extrastimulation on morphofunctional state of cochlear stria vascularis]. / Osobennosti spontannogo nistagma pri supratentorial'nykh ishemicheskikh ochagakh golovnogo mozga.

An electron-microscopic study of the response of cochlear stria vascularis (CSV) cells to an electric impact of physiotherapeutic parameters was made in 26 guinea-pigs. Twelve guinea-pigs (group 1) have undergone 9 sessions of bilateral endaural electrostimulation with square bipolar impulses (4 ms, 0.1-0.4 mA, 50 Hz, 20 min). Fourteen guinea-pigs of group 2 have undergone a 12-18-day course of intramuscular ototoxic antibiotic canamycin in a dose 200-400 mg/day followed by the above electrostimulation. Nine anesthesized guinea-pigs of group 3 were inserted an electrode into the niche of the round window of the right ear. After a 10-day course of canamycin (200 mg/day) they were exposed to electrostimulation (8 sessions) with impulsed alternative current (100 Hz, 1 ms, 0.08 mA, 30 min). Five guinea-pigs served control. Morphofunctional state of CSV was assessed at electronograms by analyzing cell ultrastructure and counting the number of secretory vacuoles in the apical region of marginal cell cytoplasm. In group 1 there was intensification of biosynthetic processes in all CSV cells and a significant (p<0.01) increase of vacuole number in the marginal cells (53.9+/-3.8) vs normal value (33.9+/-1.5). In group 2 ultrastructure of all CSV cells was less affected and secretory activity was almost normal (31.4+/-2.9). CSV cell condition was similar to ultrastructure of the cells in group 2. The number of vacuoles in CSV marginal cells of the right (28.9+/-1.98) and left (29.1+/-5.4) cochleas was similar. Thus, electrostimulation activates biosynthetic processes in CSV structures and enhances secretory activity of marginal cells.