Vol 12, No 1 (2018)

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Full Issue

Original articles

Risk factors for the development of the ischemic stroke in the carotid arterial system in males and females

Maksimova M.Y., Moskvicheva A.S., Chechetkin A.O.


Introduction. Biologically determined differences between males and females and different levels of sex hormones determine some specific features of their ischemic stroke (IS). Clinical studies aimed at identifying risk factors for the development of IS in persons of different sexes are considered to be necessary for elaborating strategies to increase life expectancy and to improve quality of life.

Objective: to study risk factors for the development of IS in the arteries of the carotid system in males and females.

Materials and methods. Risk factors for the development of IS in the arteries of the carotid system were analyzed in 268 patients for the period from 2010 to 2017. Among the patients, there were 148 (55%) men and 120 (45%) women aged from 47 to 79 years. MRI of the brain, duplex scanning of the cerebral arteries, and transthoracic and transesophageal echocardiography were used to establish the diagnosis of the stroke subtype.

Results. In the age group 47-79 years, females had more often cardioembolic and lacunar stroke, while males had predominantly atherothrombotic  stroke  and stroke with competing causes. Atrial fibrillation, diabetes mellitus, atherosclerotic cardiosclerosis, chronic heart failure, thyroid disease and excess body weight were also more common in females. In contrast, there were significantly more smokers and over-consumption of alcohol among males, and the same was true for small heart attacks and transient symptoms in the past history. Atherosclerosis of the extracranial part of the internal carotid artery (ICA) of high degree was found more often in males, while females with atherothrombotic stroke had significantly higher blood cholesterol level. The study of arterial hypertension (AH) revealed the following differences between groups: AH III degree (180/110 mm Hg or higher) was more often in females, and AH I degree (140-159 / 90-99 mm Hg) in males, while  the proportion of patients with grade II AH (160-179 / 100-109 mm Hg) and patients without AH  was approximately equal in the two groups.

Conclusions. The risk factors for the development of IS in the arteries of the carotid system in men are atherosclerotic carotid stenosis, smoking and excessive alcohol consumption. Development of stroke in men is preceded by small infarcts with transient symptoms. The risk factors for the development of IS in the arteries of the carotid system in women are atrial fibrillation, diabetes mellitus, atherosclerotic cardiosclerosis, chronic heart failure, thyroid disease, and excess body weight. As in men, despite of significantly higher cholesterol levels, there are more pronounced atherosclerotic carotid stenosis and more frequent ISs, one may suggest the existence of an additional factor leading to stroke (alternatively, women may have some gender-specific protective factor).

Annals of Clinical and Experimental Neurology. 2018;12(1):5-11
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Clinical-morphological features of hemodynamic strokes

Tanashyan M.M., Ablyakimov R.E., Gulevskaya T.S., Anufriev P.L., Evdokimenko A.N.


Introduction. An important objective of neurology is to clarify the pathogenesis of ischemic strokes and the diagnostic distinction of their pathogenetic subtypes that determines the possibility of targeted treatment and adequate prevention of strokes.
Objective: Definition of clinical and morphological features of the hemodynamic subtype of ischemic stroke.
Materials and methods. A clinical-pathological comparison in 32 cases of hemodynamic strokes.
Results. It was established that hemodynamic strokes were caused by the presence of factors reducing systemic and cerebral hemodynamics in combination with tandem atherostenosis of carotid arteries (40% of strokes) and vertebrobasilar arteries (43%), and, occasionally, stenosis of both brain arterial systems or isolated cerebral arterial stenosis (10% and 7%, respectively). The severity of tandem stenosis on the side of the cerebral infarction ranged from 50% to 90%, and some strokes developed with minimal stenosis of each of the vessels. Eighty eight percent of strokes developed in patients having combination of stenosis on the side of the infarction with significant contralateral stenosis. In 43% of strokes, single or multiple small-sized cortical or medium-sized cortical-subcortical infarctions in areas of adjacent blood supply of cerebral hemispheres, as well as lacunar or medium-sized infarctions in the white matter of the hemispheres were seen. Thirty nine percent of strokes were associated with infarctions in the areas of adjacent blood supply of the cerebellar and the brainstem arteries. Eighty percent of cases were associated with atypical for this stroke subtype large-sized and medium-sized cortical-subcortical infarctions outside the areas of adjacent blood supply, resulting from inability to compensate cerebral blood supply deficiency through arterial anastomoses because of severe insi- and contralateral stenoses.
Conclusions. Our clinical-pathological comparisons confirmed the previously established differential diagnostic criteria of hemodynamic strokes and, in addition, showed some specific features of their realization.

Annals of Clinical and Experimental Neurology. 2018;12(1):12-18
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Neurosurgical aspects of hemorrhagic stroke

Mustafin M.S., Novikova L.B., Akopyan A.R., Shakirov R.R.


Introduction. The occurrence of hemorrhagic stroke (HS) is about 1/5 of that of ischemic stroke, but HS represents an important problem of neurology because of high mortality and disability rates. HS can manifest as spontaneous subarachnoid hemorrhage (SAH), intracerebral hematoma (ICH), spontaneous (non-traumatic) extradural and subdural hematomas, or as a combination of these conditions. HS is characterized by a high percentage of complications, most severe of which is intraventricular hemorrhage (IVH).

Objective. To analyze the structure of HS, its complications and various methods of neurosurgical treatment.

Materials and methods. We studied medical histories of 84 patients with HS were who were treated in the Neurosurgical Department of GBUZ RB Hospital ambulance Ufa for the 6-month period in 2016. All patients underwent neurological, instrumental and laboratory examination, CT scan and CT angiography, brain MRI and, if necessary, cerebral angiography (CAG). To assess the severity and outcome of IVH, we used the Graeb criteria of the ventricular system involvement and the Hounsfieid characteristics of the ventricular clot density.

Results. The main causes of HS were arterial hypertension (54,7%) and aneurysmal disease of the brain (44%). Most of patients (63,8%) had putaminal ICH. Rupture of the aneurysm was the cause of SAH in 24 (28.6%) of patients. Aneurysms were located mostly in the basin of the middle cerebral artery. Surgical treatment was undertaken in 76 patients (90.4%t). IVH as a complication occurred in 21.4% of patients, main cause of this complication was massive SAH.

Discussion. In most of our cases of HS, the clinical picture of SAH was seen – 59.5% of patients. Among all methods of neurosurgical treatment of ICH, we predominantly used minimally invasive high-tech techniques proven to be most effective: needle aspiration, endoscopic removal of hematomas under the control of neuronavigation, and fibrinolysis; these technologies were used in 52.5% of patients. 

Annals of Clinical and Experimental Neurology. 2018;12(1):19-23
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Adhesion molecules in patients with severe atherothrombotic stroke

Okhtova F.R., Mikhal'chenko V.N., Maksimova M.Y.



Introduction. Atherothrombotic stroke represents 34% of stroke cases among all the subtypes of ischemic stroke. Adhesion molecules are proteins associated with the basal membrane. They contribute to the intensification of adhesion processes, hyperaggregation of blood cells and microcirculation disorders.

Objective. To investigate the blood levels of adhesion molecules in patients with severe atherothrombotic stroke.

Materials and methods. For the study, we recruited 21 patients (mean age, 67 [61; 73] years) with atherothrombotic stroke in the  carotid system who were observed for the initial 48 hours since the development of neurological symptoms. The patients were categorized as severe stroke based on the total NIHSS score (Me 15 [14; 18]) at the time of admission. The spectrum of soluble cellular adhesion molecules as immunological markers of endothelial dysfunction was studied.

Results. Increased levels of sICAM-1, sPECAM-1, sР-selectin, sЕ-selectin and sVCAM-1 were revealed at the beginning of the acute period of atherothrombotic stroke. By the day 21, a decrease of sPselectin, sE-selectin and sVCAM-1 was seen, and this phenomenon was probably caused by effects of blood antiplatelet therapy and statins on cellular adhesion. Positive correlation was established between the VCAM-1 during the first 48 hours of atherothrombotic stroke and the severity of neurologic deficit by the day 21. In the subgroup of patients with lethal outcomes, sICAM-1 and sVCAM-1 levels were higher in comparison with patients with severe disability.

Conclusion. Elevated expression of sVCAM-1 in the first 48 hours of atherothrombotic stroke is associated with severe neurologic deficit by the day 21 of stroke. The high levels of sICAM-1 and sVCAM-1 upon admission may be regarded as risk factors for lethal outcomes.

Annals of Clinical and Experimental Neurology. 2018;12(1):24-30
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Pharmacological correction of cerebrovascular disorders in various experimental pathological conditions

Mirzoyan R.S., Gan,shina T.S., Kim G.A., Kurdyumov I.N., Maslennikov D.V., Kurza E.V.



Introduction. In the treatment of patients with cerebrovascular disorders, pharmacological correction of cerebral circulation largely depends on the character and the state of the pathological process. This determines the need to study the pharmacological regulation of the cerebral blood supply in various pathological conditions.

Objective. To study the effects of oxymethylethylpiridine succinate, nicotinoyl gamma-aminobutiric acid, nimodipine, amlodipine besylate and S-amlodipin nicotinate on the cerebral circulation of intact and ischemic rats, and to assess the effects of oxymethylethylpiridine succinate and nimodipine in experimental myocardial infarction and combined vascular pathology of the brain and heart.

Materials and methods. The cerebral circulation was evaluated using the laser Doppler flowmetry technique. Global transient ischemia was caused by occlusion of both common carotid arteries with simultaneous decrease in arterial pressure by bleeding and subsequent reinfusion. Experimental myocardial infarction was modeled by occlusion of the left coronary artery.

Results. Oxymethylethylpiridine succinate significantly increases blood supply to the brain in rats under conditions of global transient ischemia of the brain and combined vascular pathology of the brain and heart, in contrast with intact animals and animals with experimental myocardial infarction. Nicotinoyl gamma-aminobutiric acid equally increased blood circulation of the intact and the ischemic brain. Nimodipine equally increased cerebral blood flow in intact rats and in rats underwent brain ischemia, whereas this effect was significantly weakened in experimental myocardial infarction and disappeared in combined vascular pathology. S-amlodipin nicotinate and, to a lesser extent, amlodipine bisilate increased blood supply to the ischemic brain. The vasodilating effects of oxymethylethylpiridine succinate, nicotinoyl gamma-aminobutiric acid and S-amlodipin nicotinate, but not of nimodipine, were eliminated by GABAA receptor blockers.

Conclusions. The dependence of the vasodilating effect of the studied drugs on the initial state of the organism was revealed. This phenomenon should be taken into account in prescribing target pathogenetic therapy of ischemic stroke.

Annals of Clinical and Experimental Neurology. 2018;12(1):31-37
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Carnosine restores the activation of signaling cascades and the ratio of apoptosis-regulating proteins in the penumbra zone after a permanent focal cerebral ischemia in rats

Lopacheva O.M., Lopachev A.V., Kulichenkova K.N., Devyatov A.A., Berezhnoy D.S., Stvolinsky S.L., Kulikova O.I., Gavrilova S.A., Morozova M.P., Fedorova T.N.



Introduction. Ischemic stroke is one of the most common and socially significant diseases, and its pathogenesis is associated with oxidative stress. The study of mechanisms of the neuroprotective action of the natural antioxidant carnosine is promising in the context of carnosine-based drug development.

Objective. To study the effect of carnosine on the level of apoptosis-regulating proteins of the Bcl-2 family and the level of activation of protein kinase B (Akt) and MAP kinases ERK1/2, p38 and JNK in the rat brain after a 24-hour permanent focal cerebral ischemia.

Materials and methods. In the model of permanent focal cerebral ischemia caused by the occlusion of the middle cerebral artery in Wistar rats, we assessed, using Western blotting, the level of expression of Bcl-2 family proteins and the phosphorylation of Akt, ERK1/2, p38 and JNK in the penumbra zone of the cortex in the ischemic hemisphere and in the symmetrical region of the contralateral hemisphere, as well as in similar areas of the brain of intact animals. Carnosine was administered to animals intraperitoneally at doses of 50 mg/kg and 500 mg/kg of body weight in the postischemic period.

Results. In permanent focal cerebral ischemia in rats, the amount of Bax and, to a lesser extent, of Bcl-2 increased in the penumbra zone shifting the Bcl-2/Bax ratio towards the pro-apoptotic signal; a decreased Akt activation and an increased ERK1/2 activation was observed. The administration of carnosine rescued the activation of Akt and the Bcl-2/Bax ratio but did not affect an increased activation of ERK1/2. No significant changes in the level of Bak, Bcl-xL and Bcl-w, and no activation of p38 and JNK were observed in the penumbra zone.

Annals of Clinical and Experimental Neurology. 2018;12(1):38-49
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MRI in the assessment of cerebral small vessel disease

Gnedovskaya E.V., Dobrynina L.A., Krotenkova M.V., Sergeeva A.N.



Cerebral small vessel disease (cSVD) is a leading cause of vascular cognitive impairment and dementia, cerebral hemorrhages, and lacunar strokes. It is considered to be the most common clinically silent vascular brain disorder. Major forms of cSVD are age- and hypertension-associated arteriolosclerosis and cerebral amyloid angiopathy. For most types of cSVD causes and mechanisms of disease development and progression remain unknown. Detailed research of cSVD is hindered by lack of technical approaches to an in vivo assessment of microvasculature. MRI equivalents of pathological changes in cSVD might serve as surrogate markers of vascular damage and might be associated with clinical signs and symptoms. We review studies that demonstrated clinical significance of the primary MR signs of cSVD, i.e. white matter hyperintensity (formerly known as leukoareosis), lacunes, enlarged perivascular spaces and cerebral microbleeds, as well as their role in the disease progression. Recently introduced STRIVE standards established MRI changes as diagnostic criteria for cSVD. These standards may significantly improve our understanding of the role of various factors in the development of cSVD and its heterogeneity. However, individual prognostication and assessment of short-term and long-term treatment efficacy is still lacking. The use of diffusion-weighted MRI techniques for the assessment of microstructural changes of visually normal bran tissue might be helpful. Strong association between microstructural changes and clinical manifestation of cSVD supports the need for multimodal MRI studies for the assessment of pathophysiological mechanisms of the disease progression even on preclinical stages.

Annals of Clinical and Experimental Neurology. 2018;12(1):61-68
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Multimodal studies of the human brain using functional magnetic resonance imaging and magnetic resonance spectroscopy

Ublinskiy M.V., Manzhurtsev A.V., Men'shchikov P.E., Akhadov T.A., Semenova N.A.



Studying the brain structure and function in health and disease is one of the most important and intensively developing fields of neuroscience in the new century. Nowdays, in vivo studies of brain structure, metabolism, blood flow and function are mostly performed using safe imaging technologies not requiring ionizing radiation and based on magnetic resonance imaging (MRI). In this review, the detailed description of the principles of commonly used techniques that provide high-quality information about the brain, such as functional MRI (fMRI) and magnetic resonance spectroscopy (MRS), is presented. The potential and advantages of these methods including their use in combination with other imaging techniques (MR-tractography etc.) are outlined. The authors believe that combining all MRI options in one study may produce a complex approach for exploring physical-chemical mechanisms underlying brain function which may be of value for basic and applied research.

Annals of Clinical and Experimental Neurology. 2018;12(1):54-60
pages 54-60 views

Clinical analysis

Difficulties in managing patients with hepatolenticular degeneration

Proskokova T.N., Vyalova N.V., Serdyuk N.B., Khelimsky A.M.


In this paper, we present some typical problems of managing patients with hepatolenticular degeneration (HLD), a severe hereditary disorder of cupper metabolism requiring permanent cupper-eliminating therapy. Special attention should be paid the following questions: choice of combined treatment with D-penicillamine (D-PAM) and zinc vs. monotherapy with either of these medications; the possibility of temporary worsening of neurologic symptoms induced by massive increase in free copper level in the blood following therapy with D-PAM; the need for special psychological support of patients and their relatives; strict adherence to a regimen prohibiting physical exercises and the need for following a special diet. Two clinical cases have been described: a fatal case of many-year compensated HLD after a physical load during a travel to the seaside, and a case of an infected foot wound in a HLD patient with the development of septicopyaemia (lower leg phlegmon and osteomyelitis of the lumbar vertebrae) following a physical activity and violation of the dietary pattern. 

Annals of Clinical and Experimental Neurology. 2018;12(1):50-53
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