[Ischemic stroke associated with patent foramen ovale: hospital database analysis]. / Ishemicheskii insul't, assotsiirovannyi s otkrytym oval'nym oknom: analiz dannykh gospital'nykh registrov.

OBJECTIVE: To analyze clinical and instrumental characteristics of patients with ischemic stroke (IS) due to paradoxical embolism according to the data of hospital registers of Moscow and Perm. MATERIAL AND METHODS: A comprehensive study of 114 patients, aged 18 to 55 years, with IS by the mechanism of paradoxical embolism was carried out. All patients underwent clarification of the cause of IS (electrocardiography, ultrasound scanning of the brachiocephalic arteries, CT or MRI of the brain, CT or MR angiography, transthoracic and/or transesophageal echocardiography). The presence of right-left shunt blood flow (RLS) was confirmed by transcranial dopplerography with a bubble test. The clinical significance of patent foramen ovale (PFO) was assessed according to The PFO-Associated Stroke Causal Likelihood Classification System (PASCAL). RESULTS: Clinical and instrumental characteristics of patients with IS due to paradoxical embolism were obtained from two hospital registries. In both groups, the leading trigger for the development of IS was the Valsalva phenomen (>20%), the share of other provoking factors did not exceed 10%. Significant differences between the analyzed groups related to the ultrasonic characteristics of RLS/PFO: patients with a grade 4 shunt predominated in the Research Center of Neurology (RCN) population, while patients with a grade 3 shunt predominated in the City Clinical Hospital (CCH) №4 group. At the same time, there were twice as many patients with aneurysm of the interatrial septum in the CCH №4 group. In accordance with the PASCAL classification, in 93% of RCN patients, PFO can be considered as a probable cause of IS, while in the CCH No. 4 group, a probable causal relationship was traced only in 51% of cases, in 18% of patients, the role of an anomaly in the development of stroke was unlikely. CONCLUSION: The analysis showed that the primary screening of RLS in a regional vascular center allows classifying PFO as a probable cause of IS in only half of the patients. For a more accurate selection of patients for whom endovascular occlusion of the PFO will be most effective, an in-depth examination in a specialized hospital is recommended.

[Internal carotid artery dissection in patients with Turner's syndrome]. / Dissektsiya vnutrennei sonnoi arterii u bol'nykh s sindromom Shereshevskogo­Ternera.

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.

[Pulmonary arteriovenous shunt - a rare cause of recurrent stroke due to paradoxical embolism]. / Legochnyi arteriovenoznyi shunt ­ redkaya prichina retsidiviruyushchikh narushenii mozgovogo krovoobrashcheniya po mekhanizmu paradoksal'noi embolii.

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.

[Cognitive disorders in the middle-aged population and cerebrovascular risk factors]. / Kognitivnye narusheniia u lits srednego vozrasta i faktory riska tserebrovaskuliarnykh zabolevanii.

AIM: To study the frequency of subjective and objective cognitive disorders in the middle-aged population and their associations with main and additional cerebrovascular risk factors. MATERIAL AND METHODS: The authors examined 169 men and 239 women aged 40-59 years. Medical history study, blood tests, electrocardiography, brachiocephalic and common femoral arteries scan, echocardiography, magnetic resonance imaging of the brain (MRI) were performed. Luria and Munsterberg tests were done to assess cognitive dysfunction. Affective disorders were assessed by the Hospital scale of anxiety and depression. RESULTS AND CONCLUSION: Absence of subjective (SCI) and/or objective (OCI) cognitive impairments was found in 26,5%; 10% had purely SCI, more than 35,7% of complaints were accompanied by deviations in neuropsychological test results (OCI+), over 25% had only OCI-. The average age of patients with OCI+ was higher than in the control group. In women, the frequency of SCI was twice as high and OCI less frequent as in men. Absence of cognitive impairment and SCI were observed more frequently in individuals with higher education. The prevalence of multiple white matter lesions (WML) in MRI was 36%. Multiple WML and atherosclerosis of major arteries were more common in OCI+ group (47%). Mild affective disorders were more frequent in the studied groups. Anxiety disorders were more common than depressive ones. The amount of patients with affective disorders was highest in OCI+. Therefore, SCI is a common phenomenon among people aged 40-60 years. The use of simple neuropsychological tests in screening examination allows to identify individuals who are most appropriate for active search for vascular risk factors. Anxiety and depressive disorders cause a significant proportion of SCI among middle-aged people and are an important additional target for therapeutic measures.

Neovascularization of Carotid Atherosclerotic Plaque and Quantitative Methods of Its Dynamic Assessment in Vivo.

The study demonstrates significant variety of neovascularization degree and vessel diameter in the carotid atherosclerotic plaque. It is suggested that the increase in the number of vessels with a diameter <20 µ can be indicative of increased atherosclerosis activity, while the increase in the number of vessels with a diameter ≥40 µ indicates "reparative potential" of plaques. Duplex contrast-enhanced ultrasound scanning allows characterization of the localization and number of vessels with a diameter of ≥30 µ in the plaque, while even slight elevation of plasma concentration of basic fibroblast growth factor attests, first of all, to increased content of small vessels <30 µ in the plaque. The level of fibroblast growth factor >1.5 pg/ml is a reliable marker of increased number of both small and large vessels in the plaque.

[Identification of people at the latent stage of Parkinson's disease (the PARKINLAR study): first results and an optimization of the algorithm].

AIM: To work out an optimal algorithm to identify people at the latent stage of neurodegenerative process of «parkinsonian¼ type in the Russian population. MATERIAL AND METHODS: Authors launched a two-step study aimed at identifying people at the latent stage of Parkinson's disease (PD) in the Russian population - the PARKINLAR (PARKINsonism, LAtent stage, Russia). As the first step, we formed a group of «primary risk¼ by the identification in neurologically healthy people of at least one of the following confirmed PD risk factors: a) the substantia nigra hyperechogenicity (ultrasound screening was performed in 193 people); b) mutations in «parkinsonian¼ genes (genetic screening was performed in 29 relatives of PD patients from families with LRRK2, PARK2 and GBA mutations). Thereby, 37 people comprised the «primary risk¼ group, of whom 23 agreed to continue further examination (44±10.2 years). A matched group of people without the aforementioned primary biomarkers of PD served as control. As the second step, we undertook in the prescreened groups a complex of investigations assessing the presence of secondary («minor¼) biomarkers of PD: Sniffin' Sticks olfactory testing; color visual evoked potentials; analysis of goal-directed eye-head-hand movements with the use of a special neuro-cybernetic system; assessment of motor and non-motor symptoms with the use of UPDRS and NMSS scales. RESULTS: When comparing the «primary risk¼ group with controls, maximal differences in the occurrence of symptoms were seen for goal-directed eye movements (43.5% vs. 20.0%) and color vision (39.1% vs. 26.7%). Among these individuals, we found two people with 4 secondary biomarkers and one with 3, and no such observations in controls. People with the combination of a primary biomarker with several secondary biomarkers of PD comprised a group of «high risk¼ in our study. CONCLUSION: Optimization of this algorithm of population screening of people predisposed to the development of PD may be done by expanding the spectrum of biomarkers and assessing their validity in a long-term prospective observational study.

[No support for the hypothesis of chronic cerebrospinal venous insufficiency in multiple sclerosis]. / Nedokazannost' gipotezy khronicheskoi tserebrospinal'noi venoznoi nedostatochnosti pri rasseiannom skleroze.

Objective. To evaluate the jugular veins (IJV) using duplex sonography in patients with multiple sclerosis (MS). Material and methods. The study included 21 MS patients with different disease course, degree of disability and disease duration. A control group consisted of 8 healthy volunteers. Results. IJV changes that meet the CCSVI criteria have not been found. These findings are consistent with the results of recently published large studies. Possible reasons of non-confirmation of this hypothesis are discussed. Conclusion. Currently vascular intervention in MS is not recommended.

[Transcranial sonography in Parkinson's disease].

An abnormal hyperechogenecity of substantia nigra is thought to be the most characteristic sonographic feature in Parkinson's disease (PD). However specificity and sensitivity of the ultrasound method should be refined. Using transcranial sonography, authors have examined 168 patients with different clinical signs of parkinsonism, including 99 patients with idiopathic PD, and 56 patients without extrapyramidal disorders. Hyperechogenecity of substantia nigra was found in 93% of patients and in 14% of controls. It has been shown that this biomarker can successfully discriminate PD from a number of similar disorders (essential tremor, atypical parkinsonian syndromes). Sonographic features of late, early and genetically determined parkinsonism specifying some pathogenetic aspects of these pathologies are described. Taking into account the data obtained, transcranial sonography can be considered as a highly informative method in the differential and early diagnosis of PD.

[Results of proximal vertebral arteries endovascular interventions].

OBJECTIVE: To evaluate immediate and long-term clinical and ultrasound efficacy of proximal vertebral arteries stenting. We studied 74 subjects (age 61+/-10 years) who underwent transluminal balloon angioplasty with stenting of vertebral arteries (77 vessels). Technical success (i.e., residual stenosis < 20%) was achieved in 95% patients. No events (acute stroke, myocardial infarction, or death) were recorded during the procedure or in early postoperative period. Clinical improvement was seen in 81% patients presented with symptoms of vetebrobasilar insufficiency at the baseline (n = 52). Sixty six patients (89%) were followed up in the late postoperative period (6 to 54 months after the intervention). No events of acute stroke were recorded in the vertebrobasilar circulation. Relapse of vertebrobasilar symptoms after temporary improvement was seen in 13% patients. Stent restenosis/occlusion was diagnosed in 36% patients although no relationship was revealed between the alteration of stent patency and relapse of clinical symptoms. Restenosis correlated with initial stenosis of > or = 70% (p < 0.05) and type of stent material. Use of cobalt chromium stents was associated with 2-fold decrease of restenosis rate vs non cobalt chromium stents (24% vs 50%, respectively, p < 0.05). Therefore, stenting of proximal vertebral arteries yields good technical and clinical results. High restenosis rate is a major problem of endovascular treatment of atherosclerosis and needs further evaluation.

[Comparative clinical and anatomic characteristic of patients with patent foramen ovale in cryptogenic and noncryptogenic stroke].

In order to study anatomical and functional characteristics of patent foramen ovale (PFO) in patients with cryptogenic stroke and with other stroke subtypes we examined 56 stroke patients (male--35, female--21, age 46.7 +/- 16.5 years) with PFO and ischemic stroke. Diagnosis of PFO was made by transesophageal echocardiography (TEE), contrast transcranial Doppler monitoring (C-TCD), contrast transthoracic echocardiography (C-TTE). Group 1 was made up of patients with definite stroke cause (cardioembolic, lacunar, atherotrombotic) (n=40), and group 2--of patients with cryptogenic stroke (n=16). Patients in group 2 were younger than patients in group 1 (38.7 +/- 13.4 and 50.4 +/- 16.5 years, p < 0.05) and had slight neurological symptoms. These patients also more frequently had avalvular, or "window-like" anatomic types of PFO (2 [13%] and 4 [27%] patients, respectively), combination of large anatomic size (3 mm and larger) and functional level of PFO (3 degree of the right-to-left shunt by C-TCD) (p < 0.05).

[Haemodynamic role of blood-plasma circulating cell-free DNA and contained therein high-molecular-weight CpG-rich fraction in pathogenesis of arterial hypertension and atherosclerosis obliterans of carotid arteries].

The hydrodynamic resistance (HR) of blood is one of the components of the total peripheral resistance. High-molecular-weight DNA appears to decrease the HR in accordance with the Toms's effect. The present study was undertaken to investigate the HR and properties of cell-free DNA circulating in the blood plasma (hereinafter referred to as pDNA) of the control donors, patients suffering from either arterial hypertension (AH) alone or that combined with atherosclerotic lesions of the carotid arteries (CAs). Within the normal concentrations of pDNA, we revealed an inverse dependence of the HR thereupon and upon the content in pDNA of the high-molecular-weight CpG-rich fraction (CpG-DNA), i. e., a transcribed region of the ribosomal repeat (rDNA). A decrease or an increase in the pDNA concentration in all the patients examined was accompanied by an elevation of the rDNA concentration in the blood plasma. Exceeding a certain level thereof appeared to give rise to an increase in both the HR and arterial pressure (AP). Patients presenting with degree I essential AH were found to have a decreased endonuclease activity of the blood plasma, with the pDNA concentration being more than two-fold higher with no change in the rDNA content. Their HR appeared to be increased (p<0.01). Patients diagnosed as having degree II AH were characterized by a normal or decreased level of pDNA and an elevated content of pDNA, with the HR being slightly lowered. In patients presenting with atherosclerosis obliterans of the ACs, the initial manifestations of the lesions of the carotid arteries were typically revealed on the background of a lowered HR (p<0.05). All patients suffering from atherosclerotic lesions of the ACs could be subdivided into two groups, which in our opinion is probably associated with different various mechanisms of destructive damage to the arterial intima. In some of them, the pDNA concentration does not differ from the normal values, but in its composition, there is an increased content of rDNA, elevating as obliteration of the vessels' lumen increases, with the HR being decreased. The majority of them have degree II AH. In others, the pDNA concentration is by an order of magnitude higher than the normal values, while the rDNA content in pDNA is decreased, with the HR being elevated. Most of them have degree III AH. Pronounced and rough stenoses take an asymptomatic course in patients with decreased values of the HR and a slightly elevated level of pDNA and/or rDNA in the blood plasma. A higher level thereof leads to a rise in the HR and to the appearance of neurological symptomatology. Hence, CpG-DNA circulating in the composition of pDNA is a constantly acting endogenous blood factor decreasing the HR (the Toms's effect) and normalizing AP under physiological conditions, being however a cause of their increase and impairment of blood circulation in the pathogenesis of AH and atherosclerosis obliterans of the CAs.

[Pathogenetic significance of patent foramen ovale in patients with the determined cause of ischemic insult].

The prevalence of open oval window (OOW) in patients with different types of ischemic insult and the possibility of independent pathogenetic contribution of OOW to brain injury were evaluated by examining 85 patients (mean age 53 +/- 14 yr) with cardioembolic (CES), lacunar (LS), and other subtypes of ischemic insult. CT and MRT of the head, duplex scanning of head arteries, contrast transcranial monitoring middle cerebral arteries, standard and contrast transthoracic and transoesophageal echocardiography revealed OOW in 40% of the patients. It had small anatomic and functional size and a tunnel-like shape. The presence of an interatrial shunt was unrelated to the degree of neurologic deficit, the size and location of brain injuries, the number of ischemic foci. It is concluded that OOW has no pathogenetic significance of its own and makes no contribution to brain injury in stroke-affected patients.

[Epidemiology, clinical features and betaserc therapy of vertigo in initial and reversible cerebrovascular pathology].

The study comprised two sections: epidemiologic and clinical. The aim of the epidemiologic investigation was to determine prevalence of vertigo, including its mild cases, in patients with initial and reversible forms of cerebrovascular pathology. While screening an open population, 726 men and women aged 35-60 years have been examined using uniform program. Vertigo was detected in 30%, frequent and long-lasting one in 14.6% cases (8.1% men and 21.9% women, p < 0.001). A clinical section included a profound examination of 40 patients. Along with duplex scanning of major brain arteries, neurologic and otoneurologic examination of the patients, aucoustic stem evoked potentials have been registered. Marked dysfunctions of autonomic nervous system and changes in functioning of different vestibular analyzer regions were revealed. High efficacy of betaserk used during 2 months in dosage 16 mg three times a day was demonstrated by improvement of the patient's state in 97% cases.

[Association analysis of polymorphism in angiotensin-converting enzyme gene in ischemic stroke]. / Analiz assotsiatsii polimorfizma v gene angiotenzinprevrashchaiushchego fermenta pri ishemicheskom insul'te.

Family and twins study demonstrated that genetic factors may be involved in stroke. Previously, insertion/deletion (I/D) Alu-polymorphism in the angiotensin-converting enzyme (ACE) gene has been suggested as a risk factor for some cardiovascular diseases. There fore, cardiovascular factors are well-known risk factors for ischemic stroke. We selected patients with ischemic stroke and with no evidence for arterial hypertension and carried out ACE polymorphism analysis. Association study of I/D polymorphism in group of these patients (52 individuals) and 80 control persons from the same population of Russian descent demonstrated no evidence for statistically significant differences in frequencies of I/D alleles or II/DD/ID genotypes between these groups. Thus, it suggests that ACE I/D polymorphism alone is not risk factor for stroke in non-hypertension patients. We cannot, however, exclude possible interaction between ACE-D/D genotype and sex.