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The article deals with the investigation of the specific features of idiom interpretation at the eye-mindedness stage. The ability of a subject to perceive the external resemblance of objects makes their hidden features invisible. In the cognitive process the subject learns to perceive and to interpret the outside world as the complex of objects, situations as a whole for self-identity and developing the capability to identify himself regarding this reality. It is a matter of common observation that one of the most complex forms of metaphorical thinking is the subject ability to interpret a figurative meaning. In the course of the imagination intentional development the acquired ability to think metaphorically influences the comprehension of many aspects of language, including the correct interpretation of idioms. Integrated meaning of phraseological units and idioms causes serious problems in the process of the child language aquisition. Due to limited background knowledge and corresponding cognitive structures, the child tries to interpret each component separately, losing the figurativeness, but at the same time giving the idiom or phraseological unit an individual and unusual sense. Young researchers, relying on objective thinking, perceive idioms as sentences where words are freely combined. The study revealed that the idioms interpretation depends on a number of internal and external factors, as well as the background knowledge about the reality and the rules of successful speech interaction. Various language means reflect the children’s speech dynamics within the process of formation of the subject’s ability to interpret a figurative meaning. When interacting with the surrounding reality, the subject’s awareness of his personal “Ego” inevitably generates contradictions of the reality cognition priority and new information. Integration of the old and new information results in creation of a problem situation and its comprehension. Scarcely ever new facts fit the framework of known concepts and behavior algorithms. Efforts to resolve the problem situations by search and creation of the new ways and solution methods, images and senses discovering the outworld new features, show the subject’s cognitive activity.

The article is devoted to the investigation of the specific features of imagination at the stage of eye-mindedness during the cognitive activity of a subject. Human mind possesses the property of cognitive creativity, which means free combination of various images. Imagination is based on the creative processes. Perceiving the reality in the framework of his cognitive experience, a child tries to comprehend the surrounding «metaphorical reality», invoking his own interpretation and forming new meanings. The subject’s individual experience gives rise to a metaphor because of the response to the surrounding reality, as a method of solution of contradictions appearing during the cognition process and the reality representation. At the eye-mindedness, stage for search of solutions and language deficient meanings the child, using the available imagery, synthesizes new concepts, without thinking about logical laws or special compatibility regulations, easily transferring from one frame into another, activating fantasy and imagination. The investigation of the formation mechanism of the imagery on the rhyme discourse confirms that the reproductive representation is based on metaphorical transfers, which permit to abstract some feature of one subject and see it in another one. Emphasis of a feature specifies an image and makes it unforgettable at the expense of various stylistic means. Imagination as a method of imagery creation is connected with the subject’s emotional sphere, it opens the freedom to creative independency, fulfils the modeling function, creating unusual metaphors, implements new informative interpretation of features, phenomena. Being connected with thinking, it realizes its compensative function during the process of the subject’s cognitive activity, maintaining the correlation between available cognitive structures and new knowledge

The article is devoted to the essential problem – metaphorical aspects of imagination. An individual in the creative process uses experience, knowledge of the previous generations enriching own experience and adding the element of distinctiveness and individuality to the world’s experience. During the process of cognitive problem solution, spatial imagination helps an individual to create mental images without their visualization. At the eye-mindedness stage, the imagination plays a very important role in the cognitive activity of a child and makes its own contribution to the continuous process of the child’s world cognition. Cognizing the reality, communicating with adults a child tries to comprehend the surrounding «metaphorical reality» literally, in his own way and to the extent of his cognitive experience development, referring to his own interpretation and creating new meanings. A child’s cognitive experience is not as rich as an adult’s experience that is why the fantasy element is introduced into the cognitive process. A child compares his inconsiderable in number mental models with the reality objects, simulating his own reality based on the general typical features, «reading» (checking) the known information and filling in the informative gaps with new one. Everything that a child learns forms the basis for his games and stories that help him to appreciate new information. Children are able to build independently some metaphorical constructions, finding new functions for familiar objects, which allow establishing of inter-frame connections possessing heuristic power. Analysis of the subject’s linguistic worldview presented in the literary work fragment allows making the conclusion that metaphor is a universal tool of the intellection and the world cognition in all activity spheres

"The article approves the idea that the categories of space and time being basic categories of existence and cognition of the world; they form the structure of the worldview and sociocultural human experience and they are expressed in the linguistic worldview form. Investigation of the linguistic worldview of the literary work discourse to find out the way of its virtualization should be considered to be relevant. The aim of the work is to investigate the way of virtualization of the linguistic worldview of the literary work, which immersing us into absolutely different, weird and wonderful reality, causes our mind to perceive the events as virtually existing. Using mental models, language creates representations compared with those that originate from the experience of direct interaction with the world. Finally, they bridge words and the world.Analysis of the modelling of space-temporal relations in linguistic worldview of literary work allows imagining it in the form of complex of real or imaginary spaces – as mental model of space-temporal relations or cognitive map. It was concluded, that virtualization of the linguistic worldview is caused by alignment of mental model of space-temporal relations created by an author and mental model of a perceiving subject. Due to mental models existence in everyone’s mind we perceive the world described in fantastic story as real, imbedding it into our own mental models system to create common semantic field and using metaphor for searching of analogous cognitive structures and patterns as a means of world cognition and reality virtualization."

The article is devoted to the performance restoration technology development of the aluminum radiator of tractor «John Deer 7830». The distinctive feature of the suggested technology is cold gas spraying application, which provides air tightness restoration of the radiator made of thin‐walled aluminum parts and having complicated form that causes troubles to technological operation fulfilment. The carried out experimental investigations resulted in determining rational technological parameters of gas dynamic spraying: nozzle angle of the facility and the distance from the nozzle exit to the spraying surface, providing optimal mechanical characteristics of the repair coating.

Cervical artery dissection (CeAD) is the primary cause of ischemic stroke in young adults. Monogenic heritable connective tissue diseases account for fewer than 5% of cases of CeAD. The remaining sporadic cases have known risk factors. The clinical, radiological, and histological characteristics of systemic vasculopathy and undifferentiated connective tissue dysplasia are present in up to 70% of individuals with sporadic CeAD. Genome-wide association studies identified CeAD-associated genetic variants in the non-coding genomic regions that may impact the gene transcription and RNA processing. However, global gene expression profile analysis has not yet been carried out for CeAD patients. We conducted bulk RNA sequencing and differential gene expression analysis to investigate the expression profile of protein-coding genes in the peripheral blood of 19 CeAD patients and 18 healthy volunteers. This was followed by functional annotation, heatmap clustering, reports on gene-disease associations and protein-protein interactions, as well as gene set enrichment analysis. We found potential correlations between CeAD and the dysregulation of genes linked to nucleolar stress, senescence-associated secretory phenotype, mitochondrial malfunction, and epithelial-mesenchymal plasticity.

The article presents a case of a 54-year-old female patient who, over the course of 2 years, suffered 5 cerebrovascular accidents (CVA) due to infectious arteritis of both internal carotid arteries (ICA) and basilar artery as a complication of sphenoiditis and otitis. According to neuroimaging data, the steno-occlusive process in the ICA developed gradually, starting with the intracranial ICA narrowing with the contrast enhancement by vessel wall, the development of its occlusion six months later, and the detection of the extracranial ICA occlusion with the formation of «flame sign» at its mouth a year later. Repeated examination of the cerebrospinal liquid at an early stage of the disease revealed cytosis up to 367/3 and protein 0.66 g/l. The correct diagnosis was established only after 3 years with a retrospective analysis of clinical, neuroimaging, and laboratory data. Therefore, targeted antibiotic therapy was not carried out, which led to the progression of ICA occlusion and repeated strokes. Infectious arteritis should be taken into account in the differential diagnosis of the causes of the ICA occlusive process.

The article describes a 45-year-old female patient with recurrent transient ischemic attacks and ischemic stroke due to spontaneous spasm of the middle cerebral artery, the anterior cerebral artery and distal part of the internal cerebral artery on the left, verified by MR angiography and CT angiography. It is assumed that the spasm caused damage to the vascular wall, an increase in its permeability, the development of edema, inflammation and subsequent fibrosis, therefore a complete restoration of the arterial lumen did not occur.

Moyamoya disease (MMD) is a rare disease characterized by progressive stenosis of the terminal part of the internal carotid arteries (ICA) and the proximal part of their branches, which is accompanied by the formation of collateral network that look like smoke clouds on angiography (Japanese terminology - moyamoya). If the disease is comorbid to other diseases, usually associated with acute or chronic inflammation, including autoimmune processes, it is designated as moyamoy syndrome (MMS). MMD and MMS are one of the causes of ischemic stroke and chronic cerebrovascular insufficiency in young and middle age, less often they lead to hemorrhages. The review presents data on epidemiology, morphology, pathogenesis (the role of genetic predisposition, inflammation, proangiogenic factors and immune disorders), clinical manifestations, instrumental diagnostics and treatment.

A 23-year-old female patient with primary vasculitis of the central nervous system simulating a brain tumor is described. The clinical picture was represented by migraine-like headaches, ataxia, transient numbness of the right leg, the lips, double vision, a slight decrease of cognitive functions. MRI of the brain revealed a tumor-like focus in the cerebellum, intensively accumulating contrast, containing micro-hemorrhages (SWI mode). Small single ischemic foci in the brain hemispheres and brain stem were also found. MR angiography (3T) did not found any pathology. Examination of the cerebrospinal fluid revealed a small cytosis (mainly T-lymphocytes) and a slight increase in protein. The results of the analysis of cerebrospinal fluid for syphilis, tuberculosis and the herpetic group of viruses were negative, type 1 oligoclonal synthesis was found. Blood tests for toxoplasmosis, antibodies to aquaporin, anti-neutrophil antibodies, markers of systemic inflammation were within normal limits. Different diagnoses were assumed: demyelinating disease, encephalitis, multiple encephalomyelitis, lymphoma. The diagnosis was established only by a brain biopsy - lymphocytic vasculitis was revealed. According to the immunohistochemical study, T-helpers predominated in the infiltrates. After pulse therapy with Metylprednisolon (1000 mg intravenously drip №. 5), the patient's condition almost returned to normal. It was recommended to take prednisolone per os (starting dose 60 mg) for 7 months.

Objective: To evaluate transforming growth factor beta (TGF-β) in patients with cervical artery dissection (CeAD)., Material and Methods: TGF-β was studied by enzyme immunoassay in 74 of 336 patients with CeAD observed at the Research Center of Neurology (Moscow) from 2000 to 2021. The average patient's age at the time of TGF-β study was 41.6±9.8 years; the proportion of women was 51%. TGF-β was studied in the first month of the disease ( n =9), for 2-3 months ( n =12) and at a later period (mean - 4.3±5.03 years) ( n =53). The control group consisted of 20 healthy volunteers, matched for age and sex. Dissection occurred in internal carotid artery (ICA) ( n =42), vertebral artery (VA) ( n =29), ICA+VA ( n =3) and involved 1 artery ( n =58) or 2-3 arteries ( n =16). Clinical manifestations included ischemic stroke (IS) ( n =49), isolated cervical-cephalic headache ( n =23), lower cranial nerve palsy ( n =2). Pathological CeAD tortuosity was detected by angiography in 13 patients, and a dissecting aneurysm in 15 patients., Results: TGF-β1 and TGF-β2 were elevated in patients with CeAD patients compared with the control: TGF-β1 - 4990 [3950; 7900] pg/ml vs. 3645 [3230; 4250] pg/ml, p =0.001; TGF-β2 - 6120 [4680; 7900] pg/ml vs. 3155 [2605; 4605] pg/ml, p =0.001. The highest TGF-β1 and TGF-β2 levels were noted at 2-3 months of the disease. There was no correlation between the TGF-β level and various clinical and angiographic parameters., Conclusion: Increased TGF-β level confirms that CeAD patients have connective tissue disorder that underlies the arterial wall weakness. A higher TGF-β level at 2-3 months of CeAD seems to be connected with an active reparative process in arterial wall after dissection. TGF-β can be used as a biomarker of connective tissue dysplasia in patients with CeAD.

Objectives: Cerebral small vessel disease (SVD) associated with age and vascular risk factors is one of the leading causes of cognitive disorders as well as ischemic and hemorrhagic strokes. The pathogenesis of this disease has not been fully understood yet. The previously established association of the antibodies against the NR2 subunit of the NMDA receptor (NR2ab) with the mechanisms of SVD such as ischemia and blood-brain barrier (BBB) disruption, might suggest their importance in the brain damage., Design & Methods: We studied the NR2ab serum level in 70 patients (45 females, 61.1 ± 6.3 y.o.) with different severity of cognitive impairment and MRI features of SVD and 20 healthy volunteers (12 females, 58.5 ± 6.4 y.o.)., Results: The elevated level of NR2ab was associated with subjective cognitive impairment (SCI) (p = 0.028) and mild cognitive impairment (MCI) (p = 0.017), Fazekas grade (F) 2 (p = 0,002) and F3 (p = 0,009) of white matter hyperintensities (WMH) and the numbers of lacunes in the cerebral white matter (less than 5) (p = 0,039)., Conclusion: The detected increase in serum NR2ab level in patients with SCI, as well as the minimal amount of white matter lacunes, is most likely caused by hypoxia-induced endothelial damage in the early stage of SVD. Normal NR2ab values in patients with F1 WMH, the increased NR2ab level in patients with F2 and F3 WMH and those with the minimal number of lacunes can indicate that NR2bs are involved in diffuse brain damage due to hypoxia-induced loss of BBB integrity., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective: To study the frequency of CeAD that developed during pregnancy or in post partum period among all CeADs in women; to study the course of pregnancy in women with prior CeAD., Material and Methods: 162 women (mean age 37.1±4.1 years) with CeAD we examined at the Research Center of Neurology (Moscow), 98% women were studied during last 15 years. 140 women were of childbearing age (≤45 years, mean age - 35±2.8 years). All patients were interviewed whether or not CeAD occurred during pregnancy or in post partum period (CeADPPP). Obstetric history before and after CeAD was studied in 57 women of childbearing age (average age - 35.9±7.3 years at CeAD development)., Results: CeADPPP developed in 6 out of 162 all female patients (3.7%) or of 140 childbearing age patients (4.3%). It occurred 2-6 months (4 patients) and 10 days after delivery (1 patient), or on the 25 th week of pregnancy (1 patient). CeADPPP patients were younger than patients with CeAD out of pregnancy or postpartum period (29.8±8 years vs 35.1±6.7 years, p >0.05). CeADPPP in comparison with CeAD outside these periods more often involved internal carotid artery (ICA) (50% vs 35%, p =0.666), more often occurred in 2-3 arteries (50% vs 31%, p =0.386) and more often was accompanied by dissecting aneurysm development (50% vs 8%, p =0.013). After CeAD, 18 out of 57 patients in whom obstetric history was studied, including 3 patients with postpartum dissection had 29 pregnancies. The pregnancy outcomes were as follows: childbirth (17 pregnancies, 59%), fetal loss (8 pregnancies, 27%) and medical abortion (4 pregnancies, 14%). Delivery occurred on average 4.5±2.061 years after CeAD in women aged 33.0±4.25 years (cesarean section - 15 patients). Fetal loss occurred at 7.4±3.5 weeks of pregnancy in women aged 37.6±3.13 years on average 2.7±1.4 years after CeAD. Fetal loss frequency after CeAD was higher than before it (27% vs 7%, p =0.016). There were no CeAD recurrences during pregnancy and postpartum period in women who had previously undergone CeAD., Conclusion: CeADPPP frequency among all dissections in women is 3.7-4.3%. The risk of CeAD recurrence during pregnancy or the postpartum period after prior CeAD is very low. The risk of fetal loss during 2.7±1.4 years after CeAD is higher than before it (27% vs 7%). Hormonal and growth factors associated with pregnancy and the postpartum period is suggested to contribute to cervical artery wall damage. It is possible that the prolonged action of some of these factors may disrupt the placental vessels formation, predisposing to miscarriage.

Objective: To study the frequency, angiographic and clinical features of aneurysms and tortuosity (T) in patients with internal carotid artery (ICA) and vertebral artery (VA) dissection., Material and Methods: Three hundred and twenty-seven patients (average age - 37.8±9.1 years, women - 57%) with ICA/VA dissection verified by neuroimaging were studied. Repeated neuroimaging in 2.4±3.3 years was performed in 254 patients. In one case, tortuous ICA fragment resected at the surgery complicated by dissection was histologically studied., Results: ICA/VA aneurysms were found in 46 (14%) patients. At repeated neuroimaging aneurysms did not change (38%), increased (11%) or decreased in size (8%), were not detected (38%) or were detected for the first time (5%). Patients with aneurysms compared with those without aneurysms more often had multiple dissections (44% vs. 20%, p =0.001) and T (35% vs. 13%, p =0.001), but less frequently the artery lumen occlusion in the acute period (15% vs. 40%, p =0.001). T was found in 53 (16%) patients. Patients with T compared with patients without T were older (40.6±8.1 vs. 37.3±9.3 years, p =0.039), more often had aneurysms (30% vs. 11%, p =0.001) and recanalization of occlusion observed in the acute period (89% vs. 54%, p =0.006). Dissection more often occurred in tortuous than in non-tortuous artery (79% vs 21%, p =0.001). During 4.8±3.6 years of follow-up, TIA developed inone patient (2%) with an aneurysm. Histological examination of tortuous ICA fragment, which also contained a small aneurysm, revealed dysplastic changes., Conclusion: The association between aneurism and T in patients with ICA/VA dissection suggests their common basis - the arterial wall weakness due to dysplasia. Age-related changes are also important for T development. T is a risk factor for ICA/VA dissection. Aneurysms formed after ICA/VA dissection have a benign course.

Objective: To study clinical/laboratory signs of primary vasculitis (PV) of the internal carotid artery (ICA) and vertebral artery (VA)., Material and Methods: We examined 31 patients (23 men, 74%, mean age - 36.2±5.7 years) with ICA/VA PV verified by vessel wall contrast enhancement on black blood MRI (T1-weighted fat and blood suppressed sequences with- and without contrast injection) at the Research Center of Neurology (Moscow) from January 2012 to September 2019. Systemic vasculitis was excluded in all cases. Interleukins (IL-1β, IL-2, IL-6, IL-17), TNF-a, transforming growth factor beta 1 (TGF-β1) and basic fibroblast growth factor (bFGF) were analyzed by ELISA in 25 patients. Control group consisted of 21 healthy volunteers (12 men, 57%; mean age - 35.3±10.2 years)., Results: Clinical manifestations of ICA/VA PV included: ischemic stroke (IS) (94%), which combined with transient ischemic attacks (TIA) in 35%; isolated TIA (3%); Tolosa-Hunt syndrome (3%). Recurrent strokes were observed in 41% of patients on average in 5.3±2.1 months. Carotid artery was involved in 77%, VA - in 16%, both arteries - in 7%. Concomitant involvement of ICA/VA branches was in 19% patients. The level of arterial damage was follows: Intracranial part of arteries involved in 55%, intra-extracranial - in 35%, extracranial - in 10%. Bilateral involvement was found in 26%. Headache/neck pain in the acute IS period was observed in 21%. IS severity (NIHSS) was as follows: moderate (59%), mild (34%), moderately severe (7%). Disability after 3 months according to mRankin scale was as follows: mild (72%) moderate (21%), none (7%). The laboratory study revealed an increased levels of IL-6 (8.19±3.89 pg/ml vs 4.7±1.48 in control, p =0.000), IL-2 (5.64±1.82 pg/ml vs 4.30±1.65, p =0.013), TNF-a (36.9±33.66 pg/ml vs 12.68±5.93, p =0.000), TGF β1 (2.77±1.60 pg/ml vs 1.63±0.64, p =0.006) and bFGF (417.67±132.68 pg/ml vs 335.71±105.08, p =0.018). The levels of IL-1β and IL-17 did not differ significantly from the control., Conclusion: ICA/VA PV has a number of clinical peculiarities. Proinflammatory cytokines produced by Th17 and Th1 CD4+ lymphocytes as well as bFGF and TGR-β1 play a role in its pathogenesis. Normal levels of IL-1β and IL-17 suggest that they are not significant in the development of isolated inflammation in ICA/PA, in contrast to systemic inflammation in giant cell arteritis, in which, according to literature data, their level increases. Isolated ICA/PA inflammation seems to be caused by transaxonal (trigeminal nerve, upper-cervical roots, autonomic nerves) spread of pathogens that initiate immune inflammation in the ICA/PA wall.

Aim/: To assess individual values of salt sensitivity and osmotic fragility on the patient's erythrocytes and evaluate predictive ability of these parameters in the development of cerebral small vessel disease (CSVD)., Material and Methods: The study included 73 patients with CSVD (48 women, mean age 60.1±6.5 years) and 19 volunteers (14 women, mean age 56.9±5.4 years). Their erythrocytes were used for the measurement of salt-sensitivity by a modified salt blood test and of osmotic fragility by the classical osmotic fragility test. Binary logistic regression was used to assess the ability of salt-sensitivity and osmotic fragility to predict CSVD development. ROC analysis was used to find out the optimal threshold values of these predictors, their sensitivity and specificity., Results: An increase in salt sensitivity (cut-off: 8.5 mm/h; sensitivity 64%, specificity 74%) and osmotic fragility (cut-off: 0.62 u.a.; sensitivity 52%, specificity 90%) or their simultaneous use ( p of the model <0.000001, cut-off 0.62; sensitivity 88%, specificity 68%) are the independent predictors of CSVD. An increase in salt sensitivity and osmotic fragility is also independently associated with the acceleration of severity of white matter hyperintensities according to Fazekas stages ( p =0.019 and 0.004, respectively)., Conclusion: The possibility of prediction of CSVD according to an increase in salt sensitivity and osmotic fragility allows us to consider them as the risk factors of CSVD. The standardization of these tests for use in clinical practice is necessary to identify the risk group for CSVD and its individual prevention.

Cervical artery dissection (CeAD) due to arterial wall weakness (dysplasia) is one of the most common causes of ischemic stroke (IS) at a young age. A rare and little known cause of CeAD is Turner's syndrome (TS)-is an inherited disease caused by completely or partially missing X chromosome. In this paper, we describe 2 female patients, aged 27 and 33 years, with genetically confirmed TS (karyotype 45X0) and internal carotid artery dissection(ICAD).TS frequency among our 304 patients with CeAD was 0.07%. Both patients had short stature, received hormone replacement therapy from the age of 14 and had arterial hypertension. In addition, the first patient suffered from hypothyroidism, osteoporosis and survived a nephrectomy for hydronephrosis. ICAD in first patient manifested by IS. MRI of the neck arteries, MRA and CTA revealed intramural hematoma, hemodynamically significant stenosis, which regressed in 4 months. In the second patient, dissection was manifested by local symptoms (Horner's syndrome, cervicocephalic pain on the dissection side). MRA and CTA revealed a precranial dissected aneurysm of the left ICA (on the side of local symptoms), fusiform expansion of the right ICA, and pathological tortuosity of both ICA. The paper discusses the cause of vasculopathy in TS. It is assumed that connective tissue damage is associated with a deficiency of biglycan - extracellular matrix protein, which interacts with collagen and elastin to strengthen the arterial wall. Biglycan gene is linked to X-chromosome which is completely or partlially missing in TS resulting in a biglycan deficiency. The role of sex hormone deficiency as a cause of arterial wall weakness is unlikely.

Introduction: Cerebral small vessel disease (CSVD) is the leading cause of vascular and mixed degenerative cognitive impairment (CI). The variability in the rate of progression of CSVD justifies the search for sensitive predictors of CI., Materials: A total of 74 patients (48 women, average age 60.6 ± 6.9 years) with CSVD and CI of varying severity were examined using 3T MRI. The results of diffusion tensor imaging with a region of interest (ROI) analysis were used to construct a predictive model of CI using binary logistic regression, while phase-contrast magnetic resonance imaging and voxel-based morphometry were used to clarify the conditions for the formation of CI predictors., Results: According to the constructed model, the predictors of CI are axial diffusivity (AD) of the posterior frontal periventricular normal-appearing white matter (pvNAWM), right middle cingulum bundle (CB), and mid-posterior corpus callosum (CC). These predictors showed a significant correlation with the volume of white matter hyperintensity; arterial and venous blood flow, pulsatility index, and aqueduct cerebrospinal fluid (CSF) flow; and surface area of the aqueduct, volume of the lateral ventricles and CSF, and gray matter volume., Conclusion: Disturbances in the AD of pvNAWM, CB, and CC, associated with axonal damage, are a predominant factor in the development of CI in CSVD. The relationship between AD predictors and both blood flow and CSF flow indicates a disturbance in their relationship, while their location near the floor of the lateral ventricle and their link with indicators of internal atrophy, CSF volume, and aqueduct CSF flow suggest the importance of transependymal CSF transudation when these regions are damaged.

The evaluation of the clustering of magnetic resonance imaging (MRI) signs into MRI types and their relationship with circulating markers of vascular wall damage were performed in 96 patients with cerebral small vessel disease (cSVD) (31 men and 65 women; mean age, 60.91 ± 6.57 years). The serum concentrations of the tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor-A (VEGF-A), and hypoxia-inducible factor 1-α (HIF-1α) were investigated in 70 patients with Fazekas stages 2 and 3 of white matter hyperintensities (WMH) and 21 age- and sex-matched volunteers with normal brain MRI using ELISA. The cluster analysis excluded two patients from the further analysis due to restrictions in their scanning protocol. MRI signs of 94 patients were distributed into two clusters. In the first group there were 18 patients with Fazekas 3 stage WMH. The second group consisted of 76 patients with WMH of different stages. The uneven distribution of patients between clusters limited the subsequent steps of statistical analysis; therefore, a cluster comparison was performed in patients with Fazekas stage 3 WMH, designated as MRI type 1 and type 2 of Fazekas 3 stage. There were no differences in age, sex, degree of hypertension, or other risk factors. MRI type 1 had significantly more widespread WMH, lacunes in many areas, microbleeds, atrophy, severe cognitive and gait impairments, and was associated with downregulation of VEGF-A compared with MRI type 2. MRI type 2 had more severe deep WMH, lacunes in the white matter, no microbleeds or atrophy, and less severe clinical manifestations and was associated with upregulation of TNF-α compared with MRI type 1. The established differences reflect the pathogenetic heterogeneity of cSVD and explain the variations in the clinical manifestations observed in Fazekas stage 3 of this disease.

Paradoxical embolism is one of the mechanisms of ischemic stroke in patients younger than 45 years of age, due to opening between the right and left chambers of the heart through a patent foramen ovale, an atrial or ventricular septal defect, pulmonary arteriovenous malformations (PAVMs), etc. The PAVMs are structurally abnormal vessels that provide direct capillary-free communication between the pulmonary and systemic circulations, and hence an anatomic "right-to-left" shunt. Most pulmonary malformations are congenital and associated with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease). This publication highlights the issues of pathogenesis, clinical presentation, diagnosis and treatment of this pathology, and also describes a clinical case in which multiple PAVMs caused repeated ischemic strokes.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disease of the central nervous system, mainly affecting the brain stem, cerebellum and spinal cord. The clinical picture includes gradually developing ataxia, double vision, dysarthria, pyramidal and cognitive impairment. Morphological examination reveals T-cell perivascular lymphocytic infiltration with CD4 lymphocytes predominance over CD8 lymphocytes. The cause of the disease is unknown. The article describes two patients (a 18-year-old woman and a 40-year-old man) with typical clinical and MRI manifestations of CLIPPERS, which was confirmed by brain biopsy in the female patient. The duration of follow-up was 3 and 7 years, respectively. Both patients survived an infection 2-3 weeks before the onset of disease that allows one to discuss its role in CLIPPERS pathogenesis. Both patients had a clear clinical and MRI responsiveness to steroids. In the female patient, steroids were replaced by intramuscular administration of the TNF-α blocker adalimumab. During 1,5 years of its use, there were no clinical relapses and pathological brain changes on MRI.

Objective: To perform cluster analysis of MRI signs of cerebral microangiopathy (small vessel disease, SVD) and to clarify the relationship between the isolated groups and circulating markers of inflammation and angiogenesis., Material and Methods: The identification of groups of MRI signs (MRI types) using cluster hierarchical agglomerative analysis and iterative algorithm of k-means and assessment of their relationship with serum concentrations of tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor-A (VEGF-A), hypoxia-inducible factor 1-α (HIF1-α) determined by ELISA were performed in 96 patients with SVD (STRIVE, 2013) (65 women, average age 60.91±6.57 years)., Results: Cluster analysis of MRI signs identified two MRI types of SVD with Fazekas grade 3 of white matter hyperintensity (WMH). MRI type 1 ( n =18; 6 women, mean age 59.1±6.8 years) and MRI type 2 ( n =22, 15 f., mean age 63.5±6.2 years) did not differ by age, sex, severity of hypertension, presence of other risk factors. MRI type 1 had a statistically significantly more pronounced WMH in the periventricular regions, multiple lacunes and microbleeds, atrophy, severe cognitive impairment and gait disorders compared with MRI type 2. Its formation was associated with a decrease in VEGF-A level. MRI type 2 had the significantly more pronounced juxtacortical WMH, white matter lacunes, in the absence of microbleeds and atrophy, and less severe clinical manifestations compared with MRI type 1. Its formation was associated with an increase in TNF-α level., Conclusion: Clustering of diagnostic MRI signs into MRI types of SVD with significant differences in the severity of clinical manifestations suggests the pathogenetic heterogeneity of age-related SVD. The relationship of MRI types with circulating markers of different mechanisms of vascular wall and brain damage indicates the dominant role of depletion of angiogenesis in the formation of MRI type 1 and increased inflammation in the formation of MRI type 2. Further studies are needed to clarify the criteria and diagnostic value of differentiation of MRI types of SVD, and also their mechanisms with the definition of pathogenetically justified prevention and treatment of various forms of SVD.

The authors present the current data on the classification, epidemiology, etiology, neurological manifestations, prognosis, diagnosis, and treatment of patients with fibromuscular dysplasia (FMD). The review is based on the selection of publications by searching PubMed for keywords from the first sources until March 2019. FMD is a segmental non-atherosclerotic and non-inflammatory disease of large- and medium-caliber arteries leading to their stenosis. The disease occurs mostly in women (90%), and manifests itself in the 5th decade of life. In the cerebrovascular form of FMD, the extracranial internal carotid artery and the vertebral artery are usually affected. Diagnosis is based on the identification of alternation of narrowing and dilation of arteries using angiography (the string of beads sign (multifocal form)). Neurological manifestations include headache, tinnitus, and ischemic stroke, usually due to the dissection or stenosis, rarely, intracerebral or subarachnoid hemorrhages. The prognosis in most cases is favorable, relapses of strokes are rare. Treatment includes antiplatelet agents, if they are ineffective to prevent recurrence of ischemic stroke, endovascular treatment is carried out. Approaches to the treatment of intracranial aneurysms do not differ from those in patients without FMD.

Cerebral small vessel disease (SVD) is one of the leading causes of cognitive impairment and stroke. The importance of endothelial dysfunction and high blood-brain barrier (BBB) permeability in pathogenesis, together with ischemia, is under discussion. The aim of this study was to clarify the relationship between tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), and magnetic resonance imaging (MRI) signs of SVD. We examined 71 patients (23 men and 48 women; mean age: 60.5 ± 6.9 years) with clinical and MRI signs of SVD, and 21 healthy volunteers with normal MRIs. All subjects underwent 3T MRI and measurements of t-PA and PAI-1 levels. An increase in t-PA level is correlated with the volume of white matter hyperintensities (WMH) ( R = 0.289, p = 0.034), severity on the Fazekas scale ( p = 0.000), and with the size of subcortical ( p = 0.002) and semiovale ( p = 0.008) perivascular spaces. The PAI-1 level is not correlated with the t-PA level or MRI signs of SVD. The correlation between t-PA and the degree of WMH and perivascular spaces' enlargement, without a correlation with PAI-1 and lacunes, is consistent with the importance of t-PA in BBB disruption and its role in causing brain damage in SVD., Competing Interests: The authors declare no conflict of interest.

Background: Age-related cerebral microangiopathy (small vessel disease, SVD) is the main cause of vascular and mixed cognitive impairment (CI) with a complex neuropsychological profile., Aim: To investigate the role of arterial and venous blood flow and cerebrospinal fluid (CSF) flow, as well as their interrelation, in the forming of CI types in patients with SVD., Material and Methods: Fifty patients (31 f., mean age 61.2±6,2) with SVD (STRIVE, 2013), including 37 with mild CI and 13 with dementia, were examined. A type of CI was determined based on combination of standard deviations from normal results on memory and executive function tests: isolated dysexecutive (13) and predominantly dysexecutive (6), predominantly amnestic (12), mixed, equal impairment of EF and memory, (19). In the statistical analysis, groups of the isolated and predominantly dysexecutive types were merged according to the dominance of deviations in the EF into the dysexecutive type of CI (19). Phase contrast MRI (PhC-MRI) was used to assess characteristics of arterial and venous blood flow and CSF flow on different levels. Indexes of pulse and intracranial compliance and surface of the cerebral aqueduct were calculated., Results: Patients with all CI types had a CSF flow systolic peak delay at the cervical level. Mixed and dysexecutive CI types as compared with predominantly amnestic type and control were defined by blood flow reduction in the sinus rectus, and mixed type by the additional decrease in its pulse wave width, blood flow reduction in an internal jugular artery and maximal blood flow velocity in the inner carotid artery, the increase in the intracranial compliance index and surface of the cerebral aqueduct., Conclusion: The neuropsychological CI type in SVD is defined by features of pathophysiological mechanisms conditioned on differences in blood flow and CSF flow impairment severity and formed hydrodynamic interaction between them. Differential features of CI types in SVD defined by PhC-MRI might become important predictive indicators of potential interaction between SVD and degeneration, improve understanding of risk factors, pathogenesis, prevention and treatment of age-related brain damage.

Cervical artery dissection is the common cause of ischemic stroke in young and middle-age patients. According to our previous studies, dissection is related to arterial wall dysplastic changes, which in their turn are due to mitochondrial cytopathy. The authors describe three male patients who at the age of 53, 25 and 35 years underwent internal artery (ICA) dissection with occlusion of its lumen and subsequent recanalization in one of them. In 3.5 months, 13.5 years and 3 years respectively, patients developed intracerebral hemorrhage (IСH), which was not related to arterial hypertension, cerebral arterial aneurysms and anticoagulants. IСH were located on the side of ICA occluded after dissection (2 patients) or bilaterally in the territory of patent ICA (1 patient). Multivoxel 1 H-MR spectroscopy performed in one patient on 40 and 48 days after ICH revealed a high lactate peak in the externally unchanged hemispheric white matter. It is assumed that mitochondrial cytopathy in patients with dissection may involve large as well as small intracerebral arteries (mitochondrial microangiopathy), which could be the cause of ICH.

Primary vasculitis (angiitis) of the central nervous system (PACNS) is a rare disease targeting the vessels of the brain, spinal cord and leptomeninges without systemic involvement. The etiology is not clear enough. The authors review clinical, laboratory and radiological features of PACNS. Clinical manifestations are variable and depend on the caliber of affected vessels. The main clinical manifestations of small sized vessel vasculitis include encephalopathy (cognitive disorders, epileptic seizures), headache and transient cerebral ischemia. The main clinical presentation of vasculitis of medium/large cerebral arteries is ischemic strokes, which usually develop in different vascular territories. CSF findings in the majority of patients show modest lymphocytic pleocytosis, elevated protein level and occasionally the presence of oligoclonal bands. MRI data are not specific and include infarcts, hyperintensity (FLAIR) and sometimes tumor-like lesions. The gold standard for the verification of PACNS affected small-sized arteries is brain and leptomeningeal biopsy. Cerebral angiography allows the verification of vasculitis of medium and large cerebral arteries revealing segmental narrowings (beading). High resolution black blood MRI before and after contrast injection may visualize intracranial vessel wall contrast enhancement - the sign of inflammation in intracranial arteries. Treatment of PACNS includes corticosteroids and cyclophosphamide. In the case of patient intolerance, rituximab and blockers of tumor necrosis factor may be used.

Hypertension (HT) and its cerebral complications are extremely vexing medical and social problems. Despite the obvious association between hypertension and the clinical and neuroimaging features of cerebral microangiopathy (CMA) (also known as cerebral small vessel disease), the causal links between them remain ambiguous. Besides, antihypertensive therapy as the only way to manage these patients does not always prevent brain damage. Knowledge about the key factors and mechanisms involved in HT and CMA development is important for predicting the risk of cerebral complications and developing new approaches to their prevention and treatment. At present, genome-wide association studies and other approaches are used to investigate the common hereditary mechanisms of HT and CMA development, which will explain a large number of CMA cases not associated with hypertension, lack of a correlation between HT severity and the degree of cerebral injury, and failure of antihypertensive therapy to prevent CMA progression. Epigenetic markers likely play a modulating role in the development of these diseases.

Cerebral microangiopathy (small vessels disease) is a cause of diffuse changes of brain tissue (encephalopathy) denoted in Russian literature by the term dyscirculatory encephalopathy (DE). The main cause of microangiopathy leading to encephalopathy is arterial hypertension, less frequently - cerebral amyloid angiopathy and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. The diagnosis of encephalopathy in patients with microangiopathy is based on the combination of clinical manifestations (mainly, cognitive impairment of varying severity and disorders of gait) with the neuroimaging changes (white matter hyperintensity, multiple lacunar infarcts on MRI). The causes of DE hyperdiagnosis in Russia, its differential diagnosis with the consequences of recurrent strokes as well as the question of the terminology are considered. The term 'microangioencephalopathy' (instead of DE) to denote encephalopathy in patients with the cerebral small vessel disease is proposed, as more fully reflecting morphological changes of the brain.

Aim: To study the frequency and characteristics of headache which is in the past history (HPH) of patients with cervical artery dissection (CeAD) and evaluate with the help of EEG and visual evoked potentials (VEP) the role of central mechanisms in its development., Material and Methods: Two hundred and twenty-seven patients with CeAD verified by neuroimaging were studied. All patients were interviewed about the presence of a headache in the past history and its features. The comparison group comprised 35 patients (mean age - 32,3±8,9 years, 77% female) with migraine. Thirty-five patients with HPH and 35 patients of the comparison group underwent EEG and VEP., Results: HPH was found in 101 patients (average age of 38.5±8.5 years, 70% female) (44.5%) out of 227 patients. In 35 patients (15.4%), HPH met the International Criteria for migraine (with aura - 3.1%, without aura - 12.3%) and in 66 patients (29.1%) did not (non-migraine headache). The latter started at the age of 24.5±10.2 years, had mild/ moderate intensity (95%), diffuse localization (68%), dull/pressing/squeezing character (53%), never accompanied by vomiting and rarely by nausea (8%), photo- phonophobia (11%). HPH, which met the migraine criteria unlike migraine in the comparison group began at a later age (19.9±9.6 vs 16.2±4.4 years, p<0.03), more frequently did not have aura (80% vs 48%, p<0.003), less often was unilateral (31% vs 71%, p<0,004) and had less intensity. The visual EEG analysis less often found rhythmic disorganization in CeAD patients with HPH than in comparison group with migraine. The hyperventilation caused a slight increase in the spectral power of Teta, Delta waves in HPH patients and significant enhancement in comparison group with migraine (p<0.05). Pattern reversal VEP in patients with HPH had a greater latency and smaller amplitude of cortical responses than in comparison group with migraine (p=0.028 and =0.037, respectively). The flash VEP amplitude was lower in HPH patients than in migraine (p=0.01)., Conclusion: HPH in patients with CeAD meets criteria of migraine in 15.4% (with aura - 3.1%, without aura - 12.3%), 29.1% patients have nonmigraine HPH. Central mechanisms, namely, the hypersensitivity of the cerebral cortex playing the main role in migraine pathogenesis, are not significant in HPH genesis. The main role appears to have peripheral mechanisms - dysplastic changes in the wall of extra- and intracranial arteries that predispose both to headache and dissection.

The authors present a clinical-morphological observation of the 47-year old man with a severe fatal ischemic stroke due to middle cerebral artery thrombosis which developed at the site of intimal rupture. The cause of intimal rupture was the arterial wall dysplastic changes. There were no signs of atherosclerosis and hypercoagulation. As the intima rupture did not lead to blood input into arterial wall, but was accompanied by superimposed thrombosis, we suggested to denote such cases as incomplete dissection.

Aim: To determine indicators of homeostasis, inflammation and homocysteine in the young-aged patients with ischemic stroke (IS) of different genesis in the subacute and chronic stages., Material and Methods: Out of 218 patients with IS (mean age 34.7±8.7 years), 55 had stroke due to dissection of the inner carotid or the spinal artery, 28 due to cardioembolia, 38 due to antiphospholipid syndrome (APS), 16 due to cerebral arteritis; 85 patients were classified as having cryptogenic stroke, including 23 with noncerebral thrombosis (coagulopathy of unknown etiology) and 62 with no thrombosis. The control group included 28 healthy people matched for age and sex., Results: There were 1) an increase in von Willebrand factor and coagulation factor VIII as well as a decrease in plasminogen and an increase in plasmin-inhibitor in IS caused by thrombosis (APS, cardioembolia, coagulopathy of unknown etiology); 2) alterations in erythrocyte aggregation and deformity in cryptogenic stroke; 3) mild or moderate hyperhomocysteinemia, with the exception of patients with APS and arteritis. Linear regression analysis confirmed these relationships. Discriminant analysis identified the clusters of parameters characteristic of APS (an increase in (aPTT), plasminogen, blood sedimentation rate, C-reactive protein) and cardioembolia (decreased protein C and increased hematocrit)., Conclusion: The laboratory markers associated with cerebral thrombosis can be used for identification of a prothrombotic state as a cause of IS in the young age. Moderate hyperhomocysteinemia is a risk factor but not a cause of IS. The increase of inflammatory markers in APS suggests a role of infection in its development.

The authors have analyzed the causes of ischemic stroke (IS) in more than 600 young patients examined in the cerebrovascular department of the Neurological Research Center (Moscow) during the period 2003-2016 years. It has been suggested that a wider use of high-resolution MRI and T1 weighted db-fs images as well as intracranial CTA will help to verify more often intracranial dissection and primary cerebral vasculitis that will result in a decrease of cryptogenic IS frequency.

Afemale patient with recurrent posterior reversible encephalopathy syndrome, severe hypocalcemia due to extirpation of the parathyroid glands is described. The disease was characterized by the acute development of headache, seizures, cognitive and behavioral disorders, mental confusion, transitory blood pressure increasing. The vasogenic edema in the posterior parts of the brain, detected by CT at the first exacerbation,was completely regressed. The residual neurological deficit and MRI changes remained after the recurrent exacerbations. Main clinical features of PRESare explained by hypocalcemia and accompanying electrolyte disturbances.The reported case shows the necessity to study blood electrolytes in patients with PRES to clarify their pathogenic role and the necessity of drug correction.

Authors describe a 7-year-old boy, who developed a severe right-sided hemiparesis, aphasia, seizure, and confusion state during sport games. There was no headache. Allergic dermatitis in the past medical history and influenza vaccination 2 weeks before stroke were recorded. On the 12th day of disease, MRI of the brain revealed an acute infarction in the territory of left anterior and middle cerebral arteries with hemorrhagic transformation. MPA (15 day) showed occlusion of the left ACA and MCA. HR-MRI T1&#95;db&#95;fs weighted imaging (36 day) found intramural hematoma (IMH) in ACA and MCA with marked stenosis of the lumen. After 3 months, HR-MRI/MRA showed the complete regression of IMH, recanalization of the arterial lumen, prolonged irregular MCA stenosis. Neurological deficit regressed significantly.

Objective: To analyze clinical and neuroimaging data in patients with neck pain and headache as the only manifestation of the internal carotid artery (ICA) dissection (ICAD) and vertebral artery (VA) dissection (VAD)., Material and Methods: One hundred and sixty-one patients (mean age - 37.4±4,99 years, 84 women, 52%) with cervical artery dissection (CAD) verified by magnetic resonance imaging (MRI) were enrolled. Neck pain and headache were the only CAD manifestation in 33 patients (mean age 37,3±7,4 yars, 28 women, 85%)., Results: The localization of the dissections in these patients was the following: one VA (15 patients), two VA (9), one ICA (7), two ICA (1), one ICA + two VA (1). The whole number of dissected arteries was 45: extracranial localization - 38, extra-intracranial - 6, intracranial - 1. Dissection led to stenosis of the arterial lumen in 41 arteries, to occlusion - in 2 and to dual lumen in 2 arteries. Small aneurism was found in 4 arteries. Combination of headache and the neck pain was observed in 26 out of 33 patients (79%), the only headache in 4 patients, the only neck pain in 3 patients. Along with this, 9 out of 24 VAD patients had the shoulder and/or arm pain. Headache in VAD patients was located more often in the occipital region (18 out of 24) that had never been observed in ICAD patients (p=0.0009). Fronto-temporal pain was observed more often in ICAD patients (5 out of 8 patients) than in VAD (2 out of 24 patients) (p=0.003). Neck pain in all VAD patients in comparison with 3 out ofI8 [CAD patients had posterior localization (p=0,007). Anterolateral neck pain was observed in 4 out ofI8 ICAD patients and in no patients with VAD (p=0.0009). The pain appearance was abrupt in all ICAD patients and most of the VAD patients. In 8 VAD patients the pain has been increasing during several hours. The pain intensity was severe in 19 patients, moderate in 12 and mild in 2. The characteristics of the pain were as following: constrictive/dull (26 patients), throbbing (1 patient) or combined (6 patients). Pain was increasing in a stepwise manner during the first days in 14 out of 24 VAD patients and in no one of ICAD patients (p=0.008). The mean pain duration period was 31 8 ± 15,7 days. Pain relief drugs were ineffective or had a short effect in 97% of patient., Conclusion: Isolated pain is more characteristic for women with VAD. Usually pain is presented as a combination of headache and neck pain. Pain localization, mode of appearance and the course are different in VAD and ICAD. The rarity of occlusion among patients with <> manifestation let to suggest that the intramural hematoma in this group of patients spreads to the adventitia that can reflect media weakness. Arterial wall changes underlying its weakness seem to be sex-hormone dependent taking into consideration the high predominace of women in cad manifested by isolated pain.

We present a medical history of a 30-year old male patient with fatal ischemic stroke, resulting from the right internal carotid artery (ICA) dissection provoked by repeated head tilts and verified by magnetic resonance imaging and pathomorphological examination. At admission, the high level of creatine phosphokinase (5284 un/ml, normal level<171) in the blood was found, the coagulation parameters were normal. Autopsy revealed intramural hematoma (IMH), which was located between the media and adventitia of the arterial wall, began at 3 cm above the common carotid artery bifurcation and extended to the base of the skull. The lumen of the ICA at the level of the IMG and intracranial parts as well as of the middle cerebral artery was occluded by the thrombus. The histological examination of the right ICA wall found splitting, thinning, fragmentation, disrupters of internal elastic membrane, severe media fibrosis, myocyte necrosis at the site of the dissection with the surrounding leukocyte infiltration, as well as lymphocytic infiltrates, clusters of eosinophils in adventitia. Similar changes, except myocyte necrosis, were also found in intact (non-dissected) brain supplying arteries. In general, they were similar to those in fibromuscular dysplasia (FMD). Histochemical and electron microscopic studies of skeletal muscles showed signs of mitochondrial cytopathy. The authors discuss the relationship between the dissection, FMD and mitochondrial pathology.

Objective: To compare demographic, clinical, and imaging characteristics of patients with internal carotid artery dissection (ICAD) and vertebral artery dissection (VAD) in a Russian population., Material and Methods: One hundred fifty-two consecutive patients (74 males, 49%; mean age - 37.0±10.3 years) with cervical artery dissection (ICAD - 85 patients, 56%; VA - 62 patients, 41%; ICA+VA - 5 patients - 3%) verified by MRI/MRA were studied. Five patients with both ICAD and VAD were excluded from analysis., Results: Patients with ICAD more often were men (63%, p<0.0001), while patients with VAD were women (69%, p<0.0001), age distribution was similar (37.4±11.2 and 36.2±9.4 years, p>0.05). The main precipitating events for VADs were neck movements, prolonged static turning of the head, physical exertion (57% vs 28% in ICAD, p=0.0009). Head trauma within the previous month was more often reported by ICAD patients than VAD patients (21% vs 7%, p=0.0295). Clinically ICADs more frequently manifested by ischemic stroke (IS) then VADs (82% vs 55% p=0.0004), but more rarely by isolated cervical pain/headache (10% vs 35%, p<0.0001). 85% patients with dissections had neck/headache preceding cerebral ischemia: isolated neck pain (27%, p=0.0001) or a combination of neck pain with headache (55%, p=0.0004) were characteristic of VADs while headache was typical for ICADs (71%, р=0.0001). According to MRI, bilateral ICADs were found more rarely than bilateral VADs (10% vs 31% p=0.0029). Arterial occlusion was more common for ICADs (61% vs 20%, p<0.0001), double lumen was found only in VAD patients (6%, p=0.0121), and aneurysms were revealed with similar frequency (ICAD 7%, VAD 5%)., Conclusion: There were significant differences between patients with ICAD and VAD in terms of gender distribution, precipitating events, clinical and imaging features. Different embryonic origin of ICA and VA, their anatomical differences, and intramural hematoma location in relation to intima and adventitia may underlay these differences.

The aim of this study was to analyze clinical and neuroimaging manifestations of vertebral artery (VA) dissection. Twenty seven patients (19 men, 8 women, mean age 34.1±6.1) with the VA dissection were enrolled. All the patients underwent MRA, neck MRI (T1 f-s, T2 f-s) and head MRI. Twenty six of 27 patients had follow-up MRA/MRT studies: during the acute period and after 2 months or later. Clinical manifestations of VA dissection included ischemic stroke (IS, 52%), transient ischemic attack (TIA, 4%) and isolated neck pain/headache (44%). Ninety two percent of patients in the group of patients with isolated pain and 53% in the group with brain ischemia were women. Bilateral dissection of VA was found in 10 of 27 patients (37%), concomitant internal carotid artery dissection -- in 2 patient (7,4%). In 93% of the patients, IS/TIA was associated with neck pain and/or headache. In 64% patients, the pain occurred after neck movements or mild head trauma. The pain preceded brain ischemia symptoms by a few days/2--3 weeks (80%) or appeared simultaneously with them (13%). Symptoms of brain ischemia developed abruptly (82%) usually in wakeful state (80%) during rotation/ bending of the head. Most patients (93%) had complete or good regress of neurological deficit. MRA/MRI revealed hemodynamically insignificant VA stenosis (92%), VA occlusion (5%), increasing of the external VA diameter (100%), dual lumen (8%) and small dissecting aneurysm (11%). In 4 of 6 stroke patients studied within the first week, the signs of arterial embolism were found. The follow up MRA/MRI showed the regress of all stenosis and recanalization of one of two occlusions. In patients with isolated pain, dissections occurred more often in the V1--V2 segments of VA (83%), while in patients with IS/TIA the dissections were mostly found in the V3--V4 segments (47%) (р<0.05). The patients with IS/TIA had more prominent VA stenosis and smaller external arterial diameters in comparison with patients with isolated pain. This suggests the subintimal localization of intramural hematoma (IMH) in the group of ischemic manifestation and subadventicial localization of IMH in patients with isolated head/neck pain. Clinical manifestations of VA dissection depend on the IMH localization. The main mechanism of brain ischemia appears to be an arterial embolism by clotted IMH fragments from the secondary intimal tear. It is suggested that in patients with isolated pain, the media may be weaker than in patients with brain ischemia that in turn promotes subadventicial IMH propagation.

Skin and muscles biopsy specimens of a patient harboring A3243G mutation in mitochondrial DNA, with dissection of internal carotid and vertebral arteries, associated with MELAS were studied using histochemical and electron-microscopy techniques. Ragged red fibers, regional variability of SDH histochemical reaction, two types of morphologically atypical mitochondria and their aggregation were found in muscle. There was correlation between SDH histochemical staining and number of mitochondria revealed by electron microscopy in muscle tissue. Similar mitochondrial abnormality, their distribution and cell lesions followed by extra-cellular matrix mineralization were found in the blood vessel walls. In line with generalization of cytopathy process caused by gene mutation it can be supposed that changes found in skin and muscle microvessels also exist in large cerebral vessels causing the vessel wall "weakness", predisposing them to dissection.

The study included 142 patients (87 women, 55 men) (mean age 36.2 +/- 8.3 yr) after ischemic stroke caused by dissection of cerebral arteries (D) (n = 37), anti-phospholipid syndrome (APS) (n = 55) or cardiogenic embolism (CE) (n = 11). Stroke of unknown origin (cryptogenic) was diagnosed in 39 patients. Mutations of 5,10-methylenetetrahydropholate reductase (MTGPR), prothrombin, and coagulation factor V genes were documented by PCR in 38, 0, 3% of D cases, 55.9, 9, 13% of APS cases, 73, 9, 0 CE cases, 57, 5, 0% of cases with cryptogenic stroke compared with 43, 0, 0% in controls. Mutations in MTGPR gene in CE cases, prothrombin gene in APS and CE cases, coagulation factor V gene in APS cases occurred more frequently than in control (p < 0.05). They, were more frequent in APS/CE than in D (p < 0.05). Mutation rate in cryptogenic stroke was not significantly different from that in control (p < 0.05). It is concluded that the above mutations are not involved in pathogenesis of cryptogenic stroke, whereas those of prothrombin and coagulation factor V genes may enhance the thrombogenic potential in APS and CE patients. The role of MTGPR gene mutation in pathogenesis of cardiogenic stroke needs clarification.

Spontaneous cerebral artery dissection is a common cause of ischemic stroke in young adults and children. Dissection is often related to arterial wall weakness the cause of which is unknown. An aim of the present paper was to carry out an electron microscopic study of skin arteries and arterioles in patients with ischemic stroke caused by cerebral artery dissection. Skin biopsy samples from 3 patients (2 men and one women, 15, 25 and 43 years of age, respectively) were studied. Electron microscopy revealed changes of endothelial, smooth muscle cells and fibroblasts in the skin microvessels. These changes included the decrease in the number of mitochondria and their alterations (vacuolization, destruction of the cristae, the presence of the needle-shaped crystals and crystal-like inclusions) and swelling of the endoplasmic reticulum. Some of these changes were characteristic of mitochondrial diseases. The changes in the extracellular matrix (thickening of the subendothelial layer and deposition of microcalcificats) were also detected. It is assumed that the mitochondrial cytopathy found in the skin microvessels may be also present in large cerebral arteries. This could underlie dysplastic changes in the cerebral artery wall and predispose to its dissection.

To clarify the mechanism of the development of cerebral infarcts in the internal carotid artery (ICA) dissection, the data of neuroimaging (localization of infarcts) and angiography have been analyzed in 49 patients (19 females 30 males, mean age 35,6 +/- 11,3 years). Four variants of infarct localization have been distinguished: 1 - the whole ICA territory (middle and anterior cerebral arteries - MCA, ACA) - 10%, 2 - the territory of superficial and deep branches of MCA- 37%, 3- the territory of superficial MCA branches and cortical-medullar arteries - 31% (the cortex and underlying white matter - 19%, the periventricular white matter and semiovale center - 6%, combined localization - 6%); 4 - the territory of deep (perforating) MCA branches (the basal ganglia and adjacent white matter) - 22%. In most of patients (92%) the dissection resulted in the occlusion or severe stenosis of intracranial ICA which in a half of cases extended to MCA and/or ACA. In 72% patients dissection involved the extracranial ICA. The marked obstructive process in the dissected ICA allows to assume that the hemodynamic, but not embolic, mechanism plays a key role in the development of infarcts. This is in line with the frequent infarct localization in the end or border zones (superficial and deep) of brain blood supply (31%) and the development of stroke during a sleep (49%). Arterio-arterial embolism as a mechanism of ischemic stroke development was found in 8% of patients with the isolated extracranial ICA dissection. It caused stenosis of the lumenand in 6% accompanied by the pseudoaneurism formation. Thrombi formed inside the aneurism could be the origin of the embolism.

We studied 203 patients (116 male, 87 female, mean age 34,6±8,2 years) with ischemic stroke (IS). The study was carried out in one week - 14 months after the development of stroke. All patients underwent MRT/CT of the brain, cerebral angiography (MRA, rarely - CTA or conventional angiography), duplex ultrasound and echocardiography. Antiphospholipid antibodies, homocysteine, platelet aggregation, blood clotting, methylenetetrahydrofolate reductase, prothrombin and factor V Leiden gene mutations were also studied along with routine clinical and biochemical blood tests. When it was indicated, antinuclear antibodies, DNA antibodies, antibodies to some viruses were studied and muscle biopsy was performed. The causes of IS were as follows: cerebral artery dissections (25%), cardioembolism (12%), antiphospholipid syndrome (11%), coagulography (7%), arterial hypertension (8%), atherosclerosis (3%), mitochondrial cytopathy (3%), cerebral vasculitis (1%), Moya-moya disease (0,5%), cerebral artery spasm after the aneurysm disruption (0,5%). The cause of IS remained unknown (cryptogenic stroke) in 29%. In a half of these cases, clinical presentations suggest the cerebral artery dissection as a cause of IS. However in the acute period the diagnosis was not verified by angiography which was conducted only in the late stage of stroke (3 months or more after stroke development).