[Identifying the neurostimulation target for treatment of cognitive impairment in aging and early cerebral small vessel disease]. / Vybor misheni neiromodulyatsii dlya korrektsii kognitivnykh rasstroistv pri starenii i rannei tserebral'noi mikroangiopatii.

OBJECTIVE: To develop individualized approaches to the use of neuromodulation as a non-pharmacological treatment of cognitive impairment (CI) based on the assessment of compensatory brain reserves in functional MRI (fMRI). MATERIAL AND METHODS: Twenty-one adults over 45 years of age, representing a continuum from healthy norm to mild cognitive impairment due to aging and early cerebral small vessel disease, were studied. All participants underwent fMRI while performing two executive tasks - a modified Stroop task and selective counting. To assess the ability to compensate for CI in real life, functional activation and connectivity were analyzed using the BRIEF-MoCA score as a covariate, which is the difference in ratings between the Behavior Rating Inventory of Executive Function (BRIEF) and the Montreal Cognitive Assessment Scale (MoCA). RESULTS: Both fMRI tasks were associated with activation of areas of the frontoparietal control network, as well as supplementary motor area (SMA) and the pre-SMA, the lateral premotor cortex, and the cerebellum. An increase in pre- SMA connectivity was observed during the tasks. The BRIEF-MoCA score correlated firstly with connectivity of the left dorsolateral prefrontal cortex (DLPFC) and secondly with involvement of the occipital cortex during the counting task. CONCLUSIONS: The developed technique allows identification of the functionally relevant target within the left DLPFC in patients with CI in aging and early cerebral microangiopathy.

[Pseudotumorous form of primary central nervous system vasculitis]. / Psevdotumoroznaya forma pervichnogo vaskulita tsentral'noi nervnoi sistemy.

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.

[Reversible cerebral vasoconstriction syndrome and ischemic stroke]. / Sindrom obratimogo tserebral'nogo vazospazma i ishemicheskii insul't.

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.

[Disruption of corpus callosum microstructural integrity by diffusion MRI as a predictor of progression of cerebral microangiopathy]. / Narushenie mikrostrukturnoi tselostnosti mozolistogo tela po dannym diffuzionnoi MRT kak prediktor progressirovaniya tserebral'noi mikroangiopatii.

OBJECTIVE: To assess the microstructural integrity of the corpus callosum in patients with cerebral small vessel disease (cSVD) using signal and biophysical diffusion MRI models and to identify the most sensitive markers of disease progression. MATERIAL AND METHODS: Diffusion MRI (3 Tesla) was performed in 166 patients (51.8% women; mean age 60.4±7.6) with cSVD and cognitive impairment of varying severity and in 44 healthy volunteers (65.9% women; mean age 59.6±6.8), followed by calculation of signal (diffusion tensor and diffusion kurtosis) and biophysical (WMTI, NODDI, MC-SMT) models, from which profiles of three corpus callosum segments were constructed. RESULTS: The best results were obtained for metrics in the forceps minor and body of the corpus callosum. Among the metrics of the signal models in the forceps minor, fraction anisotropy (FA) and mean diffusion (MD), which characterize the overall loss of microstructural integrity and increase in extra-axonal water, as well as indirect markers of demyelination when considering transverse diffusion parameters (radial diffusion and radial kurtosis), had the larger area under the curve according to the ROC analysis. Among the metrics of the biophysical models in the forceps minor, a larger area under the curve was found in the MC-SMT model for extra-axonal transverse diffusion (ETR), mean diffusion (EMD), and intra-axonal water fraction (INTRA), and in the WMTI model for intra-axonal water fraction (AWF). ETR had high inverse correlations with INTRA and AWF, while INTRA and AWF had high direct intercorrelations. CONCLUSION: Metrics of signaling (FA, MD, RD, RK) and biophysical patterns (ETR, EMD, INTRA, AWF) in the forceps minor and the corpus callosum body can be considered as indicators of cSVD progression. They indicate disease progression, mainly by an increase in extra-axonal water with the development of demyelination and tissue degeneration in the corpus callosum.

[A role of altered inflammation-related gene expression in cerebral small vessel disease with cognitive impairment]. / Rol' izmeneniya ekspressii genov, assotsiirovannykh s vospaleniem, pri tserebral'noi mikroangiopatii s kognitivnymi rasstroistvami.

OBJECTIVE: To identify the role of changes in the expression of inflammation-related genes in cerebral microangiopathy/cerebral small vessel disease (cSVD). MATERIAL AND METHODS: Forty-four cSVD patients (mean age 61.4±9.2) and 11 controls (mean age 57.3±9.7) were studied. Gene expression was assessed on an individual NanoString nCounter panel of 58 inflammation-related genes and 4 reference genes. A set of genes was generated based on converging results of complete genome-wide association studies (GWAS) in cSVD and Alzheimer's disease (AD) and circulating markers associated with vascular wall and Brain lesions in cSVD. RNA was isolated from blood leukocytes and analyzed with the nCounter Analysis System, followed by analysis in nSolver 4.0. Results were verified by real-time PCR. RESULTS: CSVD patients had a significant decrease in BIN1 (log2FC=-1.272; p=0.039) and VEGFA (log2FC=-1.441; p=0.038) expression compared to controls, which showed predictive ability for cSVD. The cut-off for BIN1 expression was 5.76 a.u. (sensitivity 73%; specificity 75%) and the cut-off for VEGFA expression was 9.27 a.u. (sensitivity 64%; specificity 86%). Reduced expression of VEGFA (p=0.011), VEGFC (p=0.017), CD2AP (p=0.044) was associated with cognitive impairment (CI). There was a significant direct correlation between VEGFC expression and the scores on the Montreal Cognitive Assessment test and between BIN1 and VEGFC expression and delayed memory. CONCLUSION: The possible prediction of cSVD by reduced expression levels of BIN1, VEGFA and the association of clinically significant CI with reduced VEGFA and VEGFC expression indicate their importance in the development and progression of the disease. The established importance of these genes in the pathogenesis of AD suggests that similar changes in their expression profile in cSVD may be one of the conditions for the comorbidity of the two pathologies.

[Nitric oxide availability in cerebral microangiopathy]. / Dostupnost' oksida azota pri tserebral'noi mikroangiopatii.

OBJECTIVE: To develop a test of individual nitric oxide (NO) availability based on changes in erythrocyte rheological properties after incubation with a NO donor and to evaluate the role of these disorders in brain damage and development of cognitive impairment (CI) in cerebral small vessel disease (cSVD). MATERIAL AND METHODS: In 73 cSVD patients (48 (65.8%) women, mean age 60.1±6.5), the rheological properties of erythrocytes before and after incubation with 10 µmol/L L-arginine-NO donor were evaluated using a laser-optical rotating cell analyzer, and the blood-brain barrier (BBB) permeability by MRI-T1 dynamic contrast. RESULTS: Among the studied parameters of erythrocyte rheological properties, the best characteristic by ROC analysis was the rate of erythrocyte disaggregation (y-dis) after incubation with L-arginine (area under the curve 0.733 (0.609-0.856), sensitivity 67%, specificity 79%). Patients with a y-dis threshold >113 sec-1 had more severe CI, arterial hypertension, white matter lesions, and increased BBB permeability in gray matter and normal-appearing white matter. CONCLUSION: The prolonged rate of erythrocyte disaggregation in cSVD patients after incubation with L-arginine indicates the risk for disease progression due to decreased NO bioavailability/disruption of the functional L-arginine-eNOS-NO system. This test can be used to assess individual NO bioavailability and potentially identify indications for modifying therapy with NO donors such as L-arginine. Clinical trials are needed to standardize and evaluate the efficacy of NO donor therapy in patients with cSVD and CI.

[Controlled arterial hypertension and blood-brain barrier damage in patients with age-related cerebral small vessel disease and cognitive impairments]. / Kontroliruemaya arterial'naya gipertenziya i povrezhdenie gematoentsefalicheskogo bar'era u bol'nykh s vozrastzavisimoi tserebral'noi mikroangiopatiei i kognitivnymi narusheniyami.

OBJECTIVE: To evaluate the relationship between blood pressure (BP) profile and blood-brain barrier (BBB) permeability in age-related cerebral microangiopathy (CMA) in patients with- and without controlled arterial hypertension (AH). MATERIAL AND METHODS: 24-hour ambulatory BP monitoring (ABPM), brain MRI, including T1-weighted dynamic contrast images, were performed in 53 patients with CMA (age 60.1±6.8, women 69.8%, controlled hypertension/normal BP 84.8%/15.2%) and 17 healthy volunteers. RESULTS: ABPM showed good control of AH with most of the assessed parameters associated with the severity of white matter hyperintensity (WMH). The permeability of the BBB in normal-appearing white matter (NAWM) and gray matter in patients with CMA was significantly higher than in the control group and was associated with ABPM parameters. The permeability of the BBB in WMH decreased with an increase in its severity. CONCLUSION: BBB permeability is a universal mechanism of NAWM and gray matter damage that supports the progression of WMH in CMA patients with controlled AH and without AH. The relationship of increased BBB permeability with slight deviations of ABPM can be explained by common mechanisms of their development due to endothelial dysfunction due to CMA and also points to the utility of more aggressive AH treatment. It is advisable to study the effect of antihypertensive and vascular drugs on BBB permeability with a view to their potential use in CMA.

[Transforming growth factor beta in patients with cervical artery dissection]. / Transformiruyushchii faktor rosta beta u bol'nykh s dissektsiei vnutrennikh sonnykh i pozvonochnykh arterii.

OBJECTIVE: To evaluate transforming growth factor beta (TGF-ß) in patients with cervical artery dissection (CeAD). MATERIAL AND METHODS: TGF-ß 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-ß study was 41.6±9.8 years; the proportion of women was 51%. TGF-ß 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-ß1 and TGF-ß2 were elevated in patients with CeAD patients compared with the control: TGF-ß1 - 4990 [3950; 7900] pg/ml vs. 3645 [3230; 4250] pg/ml, p=0.001; TGF-ß2 - 6120 [4680; 7900] pg/ml vs. 3155 [2605; 4605] pg/ml, p=0.001. The highest TGF-ß1 and TGF-ß2 levels were noted at 2-3 months of the disease. There was no correlation between the TGF-ß level and various clinical and angiographic parameters. CONCLUSION: Increased TGF-ß level confirms that CeAD patients have connective tissue disorder that underlies the arterial wall weakness. A higher TGF-ß level at 2-3 months of CeAD seems to be connected with an active reparative process in arterial wall after dissection. TGF-ß can be used as a biomarker of connective tissue dysplasia in patients with CeAD.

Daily blood pressure profile and blood-brain barrier permeability in patients with cerebral small vessel disease.

Cerebral small vessel disease (CSVD) plays an important role in cognitive impairment, stroke, disability, and death. Hypertension is the main risk factor for CSVD. The use of antihypertensive therapy has not resulted in the expected decrease in CSVD complications, which may be related to the underestimation of significance of daily blood pressure profile for blood-brain barrier (BBB) permeability. 53 patients with CSVD of varying severity (mean age 60.08 ± 6.8 years, 69.8% women, subjects with treated long-standing hypertension vs. normotensive subjects - 84.8% vs. 15.2%) and 17 healthy volunteers underwent ambulatory blood pressure monitoring (ABPM) and MRI, including T1-weighted dynamic contrast-enhanced magnetic resonance imaging for assessing BBB permeability. Most of ABPM parameters in CSVD patients did not differ from controls, but were associated with the severity of white matter hyperintensity (WMH) and the total CSVD score. BBB permeability in normal-appearing white matter (NAWM) and grey matter (GM) was significantly higher in CSVD patients, and the severity of BBB permeability remained similar in patients with different stages of WMH. Among BBB permeability parameters, the area under the curve, corresponding to an increase in the contrast transit time in NAWM, had the greatest number of correlations with deviations of ABPM parameters. BBB permeability in CSVD is a universal mechanism of NAWM and GM damage associated with a slight increase in ABPM parameters. It is obvious that the treatment of hypertension in patients with not severe WMH should be more aggressive and carried out under the control of ABPM.

[Predictors and integrative index of severity of cognitive disorders in cerebral microangiopathy]. / Prediktory i integrativnyi pokazatel' tyazhesti kognitivnykh rasstroistv pri tserebral'noi mikroangiopatii.

OBJECTIVE: To search for sensitive predictors of cognitive impairment (CI) and an integrative index of their severity. MATERIAL AND METHODS: We assessed CI and diffusion-tensor MRI (DT-MRI) in the regions of interest (ROI) significant for CI in 74 patients (48 women, mean age 60.6±6.9 years) with cerebral small vessel disease (CSVD). The results of DT-MRI were used to construct a predictive model of CI using binary logistic regression and to calculate an integrative index of CI severity. RESULTS: According to the constructed model, the predictors of CI were axial diffusivity (AD) of posterior frontal periventricular normal-appearing white matter (pvNAWM), right middle cingulum bundle (CB) and mid-posterior corpus callosum (CC). ROC analysis showed strong model predictive power for CI in cSVD (AUC (95% CI): 0.845 (0.740-0.950)). The threshold value of the AD predictors model for CI in cSVD was 0.53 (sensitivity 84%, specificity 76%). AD predictors of CI showed significant correlations with white matter hyperintensities volume and MoCA scores. The presence of CI as measured by neuropsychological testing and regression equation solution was corresponded to individual AD predictors of patients exceeding the CI model's threshold. CONCLUSION: Disturbances in the AD of pvNAWM, right middle CB and mid-posterior CC associated with axonal damage are a predominant factor in the development of CI in CSVD. The predictors of CI and the integrative index of CI severity calculated on their basis can potentially be used as a tool for assessing the severity of CI and the effectiveness of treatment, as well as in clarifying the interaction between vascular and degenerative pathology and in developing measures for the prevention of CI in patients with MRI signs of cSVD.

[Resting state functional MRI in neurology and psychiatry]. / Funktsional'naya MRT pokoya v nevrologii i psikhiatrii.

Resting state functional magnetic resonance imaging (fMRI) is a neuroimaging technique based on analyzing spontaneous, low frequency fluctuations in the activity of brain areas by measuring by their MRI signal to investigate the functional architecture of the brain during rest. The use of resting state fMRI opens up possibilities for assessing brain functional relationships in both normal conditions and in different CNS pathologies in order to clarify the disturbed mechanisms of brain functioning and develop approaches for therapeutic non-invasive neuromodulation. Understanding the acquisition of data, the features of their preprocessing and analysis is very important for clinicians who use resting state fMRI in their studies, since it is neurologists, psychiatrists, and neurosurgeons who set research tasks and are the final consumers of the results. The article details the methodological features of obtaining and analyzing resting state fMRI data, the advantages and disadvantages of the method. The article is intended for a wide range of specialists using this method in their work or planning to include it in their research.

[The efficacy and safety of Erenumab in patients with high-frequency episodic migraine according to the first Russian real-life study of the Research Center of Neurology]. / Effektivnost' i bezopasnost' erenumaba u patsientov s chastoi epizodicheskoi migren'yu po dannym rossiiskogo issledovaniya real'noi klinicheskoi praktiki Nauchnogo tsentra nevrologii.

OBJECTIVE: To assess the effectiveness and safety of Erenumab, a monoclonal antibody to calcitonin gene-related peptide receptors, in patients with high-frequency episodic migraine (HFEM) in real-life study. MATERIAL AND METHODS: 35 patients with HFEM without aura (≥8-14 attacks per month) (30 females, mean age 32.4±8.1) received monthly subcutaneous administration of Erenumab 70 mg for 3 months. The primary endpoint was the change in monthly migraine days (MMDs) from baseline, the secondary endpoint was the proportion of patients who achieved a 50% reduction in the number of days with headache. The change in pain intensity, change in the number of days of use of acute migraine-specific medication, the effect on daily activity (HIT-6 scale, MIDAS), anxiety and depression (the Hospital Anxiety and Depression Scale) were assessed. RESULTS: At the end of the third month Erenumab decreased MMDs by 5±3.6 (p=0.00000). A 50% reduction in the mean number of migraine days per month was achieved for 60% of patients, the intensity of headache according to the visual analogue scale from 8±1.2 points to 5±2 points (p=0.00000), monthly analgesics intake passed from 11±7 to 4.5±3.7 (p=0.000001). 25.7% of patients did not respond to treatment, showing less than a 30% decrease in the number of days with headache. A decrease in pain intensity correlated with a decrease in anxiety (from 8±4 to 6±4 points (p=0.003)) and depression (from 6±4 to 4±3 points (p=0.0004)) according to HADS, reduced HIT-6 scale from 65±6 to 55±7 points (p=0.00000) and MIDAS from 45 [33; 67] points to 16 [5; 33] (p=0.000004)). Patients reported good tolerability of Erenumab. 25.7% of patients noted a tendency to constipation. No patient discontinued treatment due to adverse events. CONCLUSION: Real-life study confirmed the efficacy and safety of Erenumab in the treatment of HFEM, a decrease in the severity of comorbid anxiety and depression, and social maladjustment.

[Cervical artery dissection in women: relationships with pregnancy and postpartum period]. / Dissektsiya vnutrennei sonnoi i pozvonochnoi arterii u zhenshchin: vzaimootnoshenie s beremennost'yu i poslerodovym periodom.

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 25th 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.

[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.

[Primary vasculitis of internal carotid and vertebral arteries: a role of cytokines, transforming growth factor beta 1 and basic fibroblast growth factor]. / Pervichnyi vaskulit vnutrennei sonnoi i pozvonochnoi arterii: rol' tsitokinov, transformiruyushchego faktora rosta ß1 i osnovnogo faktora rosta fibroblastov.

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-1ß, IL-2, IL-6, IL-17), TNF-a, transforming growth factor beta 1 (TGF-ß1) 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 ß1 (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-1ß 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-ß1 play a role in its pathogenesis. Normal levels of IL-1ß 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.

White matter hyperintensity in different migraine subtypes.

The diagnostic value of white matter hyperintensities (WMH) in different types of migraineare unknown. To evaluate the WMH pattern of different subtypes in migraine patients with no vascular risk factors. 92 migraine patients (73 females, mean age 34.6 ± 8.9; 61 episodic migraine, 31 chronic migraine, 36 migraine with aura, 56 migraine without aura) without vascular risk factors underwent brain MRI (3 T). We also included a matched healthy control group with no migraine (n = 24). The prevalence of WMH in different types of migraine was similar and ranged from 38.7 to 44.4%; the control group showed no WMH at all. Lesions were located within frontal, parietal and temporal lobes (in order of decreasing incidence) in juxtacortical and/or deep white matter. WMH appeared as round or slightly elongated foci with a median size of 2.5 mm [1.5; 3]. Total number, size and prevalence of WMH by lobes and white matter regions were similar between groups, and no interaction with age or sex was found. The number of lesions within the frontal lobe juxtacortical white matter correlated with the age of patients (r = 0.331, p = 0.001) and the duration since migraine onset (r = 0.264, p = 0.012). Patients with different migraine subtypes and without vascular risk factors are characterized by a similar pattern of WMH in the absence of subclinical infarctions or microbleedings. Therefore, WMH have no relevant prognostic value regarding the course of migraine and vascular complications. WMH pattern may be used to differentiate migraine as a primary disorder and other disorders with migraine-like headache and WMH.

[Salt sensitivity and osmotic fragility are newly specified risk factors for age-related cerebral microangiopathy]. / Sol'-chuvstvitel'nost' i osmorezistentnost' ­ faktory riska vozrast-zavisimoi tserebral'noi mikroangiopatii.

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.

[Aneurysms and pathological tortuosity of the internal carotid and vertebral arteries in patients with dissection of these vessels: a results of long-term study]. / Anevrizmy i patologicheskaya izvitost' vnutrennikh sonnykh i pozvonochnykh arterii u bol'nykh s dissektsiei etikh sosudov: rezul'taty dolgosrochnogo issledovaniya.

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.

[Fibromuscular dysplasia and its neurological manifestations]. / Fibromyshechnaya displaziya i ee nevrologicheskie proyavleniya.

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.

[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.