[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.

[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.

[Clinical characteristics and short-term outcomes of autoimmune encephalitis in adults]. / Klinicheskie kharakteristiki i kratkosrochnye iskhody autoimmunnogo entsefalita u vzroslykh.

OBJECTIVE: To characterize clinical, paraclinical features and short-term outcomes in different types of autoimmune encephalitis (AE) in a one-center cohort of Russian patients, as well as to evaluate the frequency and significance of the joint expression of antineuronal and anti-glial antibodies (Abs) in AE. MATERIAL AND METHODS: Forty-one patients were diagnosed with AE at the Research Center of Neurology from November 2020 to December 2022. Demographic, clinical characteristics, results of laboratory tests, MRI of brain, treatment and outcomes of disease were analyzed. The analysis of Abs to glial antigens (myelin-oligodendrocyte glycoprotein - MOG, glial fibrillar acidic protein - GFAP, aquaporin 4 - AQP-4) was performed by indirect immunofluorescence assay (Euroimmun, Germany). RESULTS: In 24 (58.5%) patients was established definite AE, confirmed by specific Abs detection; in 2 (4.9%) - definite limbic encephalitis, in 15 (36.6%) - seronegative probable AE (including 3 cases of Hashimoto's encephalitis). GFAP-Abs in cerebrospinal fluid (CSF) were detected only in two patients - with clinical and MRI-picture of autoimmune GFAP-astrocytopathy (A-GFAP-A). GFAP- and MOG-Abs in the blood were detected in 25.7% and 6%, respectively, AQP-4-Abs were not detected. There were no correlations between co-expression with glial Abs and clinical characteristics. Systemic and antithyroid Abs were present in 15% and 31%, respectively. Paraneoplastic AE accounted for 22%. For the first time in the Russian population, 2 cases of A-GFAP-A, 6 cases of AE associated with COVID-19 were described. The most common first syndrome were epileptic seizure (34%), psychiatric (29%) and cognitive (14%) disorders. Relapses of AE was observed in 22%. Inflammatory changes in CSF were detected in 41%, focal changes on MRI in 68%. First-line immune therapy was performed in all patients, 85% of cases received pulse therapy with methylprednisolone. Second-line immune therapy (rituximab or cyclophosphamide intravenously) was performed in 19.5%, 78% of patients achieved significant improvement during treatment (scores ≤2 on the modified Rankin scale). CONCLUSIONS: The results allow us to consider COVID-19 as a trigger of AE. The absence of detection of GFAP-Abs in CSF in patients with other types of AE contributes to the confirmation of the specificity of GFAP-seropositivity of CSF for the diagnosis of A-GFAP-A. The expression of GFAP- and MOG-Abs in AE can serve as confirmation of the immuno-mediated etiology of the disease, which is especially important for the AE diagnosis in the absence of antineuronal Abs.

[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.

[Chronic musculoskeletal pain in degenerative changes of the spine in young and middle-aged patients]. / Khronicheskaya skeletno-myshechnaya bol' pri degenerativnykh izmeneniyakh pozvonochnika u patsientov molodogo i srednego vozrasta.

OBJECTIVE: To identify clinical and laboratory indicators associated with the development of chronic musculoskeletal pain syndrome in young and middle-aged patients with degenerative changes of the spine. MATERIAL AND METHODS: The study included 103 patients (59 women and 44 men) with a mean age 42 [36; 47] years with chronic musculoskeletal back pain. To verify degenerative changes of the spine, MRI was performed using Magnetom Symphony (Siemens; Germany), Magnetom Verio (Siemens; Germany) devices. The intensity of the pain syndrome, the neuropathic component of pain sensations, and affective disorders were assessed. Blood levels of osteocalcin, parathyroid hormone, thyroid stimulating hormone were determined using an immunochemiluminescent analyzer Immulite 2000 (Siemens, USA), vitamin D - using an immunochemical analyzer Architect i2000SR (Abbott, USA), vitamin PP and 17-hydroxyprogesterone by sandwich-type ELISA on a plate reader VICTOR 2 (Perken Elmer, USA). The levels of interleukin-1ß, interleukin-6 and interleukin-8 and tumor necrosis factor alpha (TNF-α) in the blood were determined by enzyme-linked immunosorbent assay (ELISA) on a Real-best plate ELISA analyzer (Russia) using Cloud Clone Corparation kits (USA, China). RESULTS: The main causes of musculoskeletal pain in the main group (83 patients) with a mean age of 42 [38; 46] years, were degenerative changes of the spine without signs of compression of the spinal nerves and spinal canal stenosis. In the control group (20 patients) with a mean age of 41 [34; 47] years, main causes were static and functional disorders. Patients with degenerative changes of the spine often led a sedentary lifestyle and had an increased body mass index. Tobacco smoking was noted in 48.2% of patients of the main group and 25% of patients in the control group (p=0.080). The intensity of pain in patients in both groups had a moderate degree, the neuropathic component of pain was not detected. Asthenia, situational and personal anxiety were mild or elevated in both groups In the main group, there was an increase in the levels of pro-inflammatory factors (C-reactive protein, TNF-α, IL-1ß, IL-6 and IL-8), as well as a decrease in the level of osteocalcin. CONCLUSION: The revealed increase in the levels of pro-inflammatory factors (C-reactive protein, TNF-α, IL-1ß, IL-6 and IL-8) in the blood confirms the role of inflammatory reactions in the pathogenesis of degenerative changes of the spine and the associated musculoskeletal pain syndrome. A decrease in the level of osteocalcin with a normal content of parathyroid hormone in the blood in patients of main group may be associated with desorganized bone remodeling and increased bone resorbtion.

[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.

[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.

[Chronic cerebrovascular diseases and neuroprotection: the clinical efficacy of meldonium (Mildronat)]. / Khronicheskie formy narushenii mozgovogo krovoobrashcheniya i neiroprotektsiya: klinicheskaya effektivnost' primeneniya mel'doniya (Mildronat).

OBJECTIVE: To evaluate the efficacy of meldonium (mildronat) in patients with chronic cerebral vascular disease (CVD). MATERIAL AND METHODS: An open comparative study of the clinical efficacy of meldonium (mildronat) in patients with chronic CVD caused by arterial hypertension and atherosclerosis was conducted. The main group included 30 (60%) patients who were prescribed meldonium (mildronat) at a dose of 1000 mg per day in addition to routine basic therapy. The control group was consisted of 20 (40%) patients who received routine basic therapy only. The duration of the study was 60 days. To evaluate the clinical efficacy of the meldonium (mildronat), the main subjective clinical symptoms, neurological, psychoemotional and cognitive status, quality of life were assessed when patients were included in the study (before treatment), on the 11th and 60th days from the start of treatment. To assess the meldonium (mildronat) effect on the endothelium vascular wall, asymmetric dimethylarginine (ADMA), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and endothelin-1 were determined in the blood when patients were included in the study, on the 11th and 60th days from the start of treatment. RESULTS: Meldonium (mildronat) has a positive therapeutic effect on the main clinical symptoms and cognitive functions which appears in increasing the quickness of mental activity, improving short-term and operative memory, increasing the resistance of mental processes and memory traces to interfering influences, and improving cognitive evoked potentials P300 results. Meldonium (mildronat) therapy leads to the decrease in the level of state and trait anxiety. The quality of life of patients treated with meldonium (mildronat) increases due to the physical and mental components. The effect of meldonium (mildronat) on the decrease in endothelin-1 and PAI-1 levels, which indicates the antitrombogenic effect of the drug, has been identified. CONCLUSION: Nootropic, anxiolytic and antitrombogenic effects of meldonium (mildronat) in patients with chronic CVD are demonstrated that makes it possible to recommend this drug for widespread use by specialists in clinical practice.

[Myelin oligodendrocyte glycoprotein immunoglobulin G-associated encephalomyelitis]. / Entsefalomielity, assotsiirovannye s antitelami k mielin-oligodendrotsitarnomu glikoproteinu.

The article discusses the role of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) in demyelinating diseases of the central nervous system. Clinical phenotypes of demyelinating syndromes associated with MOG-IgG that are currently included into neuromyelitis optica spectrum disorders (NMOSD) are described. However, it has been shown that encephalomyelitis associated with MOG-IgG (MOG-EM) has certain clinical, radiological, immunological and histopathological features that make it possible to single out these syndromes into a separate nosological form. We provide International recommendations that establish indications for testing MOG-IgG using cell-based assay. We discuss epidemiological issues and classification challenges of the disease. Various approaches to treatment and prevention of relapses of MOG-EM are analyzed.

[Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids]. / Khronicheskoe limfotsitarnoe vospalenie s perivaskulyarnym nakopleniem kontrastnogo veshchestva v mostu golovnogo mozga, otvechayushchee na lechenie steroidami.

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.

[Clustering of diagnostic MRI signs of cerebral microangiopathy and its relationship with markers of inflammation and angiogenesis]. / Klasterizatsiya diagnosticheskikh MRT-priznakov tserebral'noi mikroangiopatii i ee svyaz' s markerami vospaleniya i angiogeneza.

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-ß1 (TGF-ß1), 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.

[Diagnostic value of antibodies to myelin oligodendrocyte glycoprotein in demyelinating diseases of the central nervous system]. / Diagnosticheskoe znachenie antitel k mielin-oligodendrotsitarnomu glikoproteinu pri demieliniziruiushchikh zabolevaniiakh tsentral'noi nervnoi sistemy.

AIM: To evaluate the diagnostic value of MOG-IgG antibodies in multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). MATERIAL AND METHODS: Twenty-nine patients with definitive MS according to the criteria of McDonald, 2010 (21 with relapse-remitting MS and 8 with secondary progressive MS), 7 patients with ADEM confirmed by clinical and instrumental data and 27 healthy volunteers were included in the study. Serum MOG-IgG levels were evaluated in all patients. MOG-IgG levels in the cerebrospinal fluid (CSF) were evaluated in 22 cases with MS, 6 cases with ADEM, and 8 healthy volunteers using ELISA. RESULTS AND CONCLUSIONS: Serum MOG-IgG levels are significantly higher in patients with MS and ADEM compared to the control group. No statistically significant differences in the serum MOG-IgG levels were found between MS and ADEM groups. When analyzing the level of MOG-IgG in CSF, no statistically significant between-group differences were obtained. The sensitivity and specificity of the determination of MOG-IgG in serum in patients with MS are 75,8% and 92.59%, respectively. MOG-IgG is detected in serum and CSF in patients with demyelinating diseases that indicates its pathogenetic significance in the development of MS and ADEM. Serum MOG-IgG may be a valuable biomarker for demyelinating diseases. Further research in a large population of patients is required.

[Brain MRI-findings in Ph - negative myeloproliferative disorders].

Myeloproliferative disorders (MPD) are accompanied by a high proportion of thrombotic complications, which may lead to cerebrovascular disease (CVD). AIM: To describe MRI-findings in patients with Ph - negative MPD and evaluate any cerebrovascular disease. MATERIALS AND METHODS: We included 104 patients with Ph - negative MPD (age varied between 20 and 58) with clinical correlates of cerebrovascular pathology. RESULTS: Brain MRI showed post - stroke lesions in 20% of patients (7 hemispheric infarcts due to thrombotic occlusion of one of the large cerebral arteries, 14 - cortical infarcts). 37 patients (36%) had vascular cerebral lesions. Cerebral venous sinus thrombosis occurred in 5 patients - in 7% (n=3) of patients with polycythemia vera and 5% (n=2) - in patients with essential thrombocythemia. The incidence of vascular cerebral lesions was associated with higher levels of the following: erythrocyte, platelet count, fibrinogen, and with the decrease in fibrinolytic activity, as well. CONCLUSION: The pioneering results of the study include the description and analysis of brain MRI-findings in patients with Ph - negative MPD. The underlying mechanisms of cerebrovascular pathology in these patients are associated with certain blood alterations (particularly, hemorheology) which present a major risk factor.

[Clinical and biochemical characteristics of atypical variants of multiple sclerosis]. / Kliniko-biokhimicheskie kharakteristiki atipichnykh variantov rasseiannogo skleroza.

AIM: To study the clinical and biochemical features of atypical variants of multiple sclerosis (MS) (tumefactive demyelination (TD), Balo's concentric sclerosis (BCS)) and acute disseminated encephalomyelitis (ADEM)). MATERIAL AND METHODS: Forty-two patients were studied, including 32 patients with atypical variants of MS (6 patients with BCS and 26 patients with TD) and 10 patients with ADEM. The control group included 20 healthy volunteers. Clinical characteristics and EDSS scores were evaluated. Antibodies to aquaporin 1 (AQP1-IgG), aquaporin 4 (AQP4-IgG), antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) and aquaporin 1 (AQP1) in serum and cerebrospinal fluid (CSF) were detected using ELISA. RESULTS AND CONCLUSION: BCS and TD occurred both in isolation and comorbid with MS (in 50% of cases with BCS, 50% of cases with TD). Atypical symptoms of MS were detected in 50% of cases of CFS, 15.4% of cases of PD. The levels of CSF cytosis and CSF protein were not significantly different between the groups. The levels of AQP1-IgG, AQP4-IgG, AQP1, MOG-IgG in serum with BCS, TD and ADEM were significantly higher than in the control group. No significant differences were found between atypical variants of MS. A correlation between a high level of MOG-IgG and the EDSS score in BCS was shown. MOG-IgG may have a pathogenetic significance in BCS. Further studies of AQP1-IgG, AQP4-IgG and MOG-IgG in patients with atypical variants of MS are needed.

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.

[Cerebral atherosclerosis: a biomarker profile]. / Tserebral'nyi ateroskleroz: biomarkernyi profil'.

AIM: To assess the changes in several biomarkers in patients with atherosclerosis of brachiocephalic arteries and shape a biomarker profile of cerebral atherosclerosis as an integrative index. MATERIAL AND METHODS: The study included 124 patients with atherosclerotic lesions of internal carotid arteries (82 men and 42 women) aged from 37 to 73 years. The patients were stratified by history of prior stroke into 'asymptomatic' and 'symptomatic'. Along with general clinical and neurological examinations, ultrasound analysis of brachiocephalic arteries, neuroimaging, identification of biomarkers reflecting different stages of atherogenesis and evaluation of pathomorphological parameters of atherosclerotic plaques removed during carotid endarterectomy surgery were performed. RESULTS: Concentrations of NO2, NO3 and NO in blood plasma significantly differed between groups: 58.4, 43.3 and 15 mcmol/l, respectively, in the symptomatic group and 45, 19.2 and 25.8 mcmol/l in the asymptomatic group. The pro-inflammatory character of changes in atherosclerosis was confirmed by the increase in the concentration of lipoprotein-associated phospholipase A2 in patients with stroke (354.72±44.16 ng/ml versus 298.45±54.12 ng/ml). The level of the atheroprotective marker adiponectin decreased significantly in 'symptomatic' patients. Significant changes towards the prothrombotic state of blood were identified via levels of blood markers of fibrinolytic activity: plasminogen tissue activator and plasminogen activator inhibitor-1. CONCLUSION: Together with other diagnostic methods, identification of biomarkers can increase the accuracy of prognosis and prevention of sudden cardiovascular death. The authors have developed a scale of biomarker 'burdeness' of the patient with cerebral atherosclerosis that may be a first step to individualized prevention of associated ischemic complications.

[Biomarkers and mechanisms of early vascular damage]. / Biomarkery i mekhanizmy rannego povrezhdeniia sosudistoi stenki.

AIM: To assess the association of classic vascular risk factors, indicators of cerebral arteries wall damage and stress induction, and their role in early vascular and brain damage in middle age subjects without vascular events. MATERIAL AND METHODS: 87 patients were evaluated (49 women, 38 men, mean age 51.2±6.5). The following vascular risk factors were assessed: hypertension, diabetes, total cholesterol and low density lipoproteins levels, obesity and smoking. Patients underwent ultrasound of neck arteries, brain MRI and laboratory testing of blood parameters, probably associated with vascular wall damage: CRP, TNF-α, sICAM-1, sVCAM, HIF1-α, NO, VAP-1, VEGF-A, VEGF-C, sVEGF-R1, sVEGF-R2, TGF-ß1, general antioxidant status. RESULTS AND CONCLUSION: Mediating role of stress parameters in risk factors formation, initiation and maintenance of mechanisms of vascular damage was demonstrated. Hypercortisolemia suggested the association with age, atheromatosis, local inflammatory reactions via the TGF-ß1-HIF-1-VEGF family, systemic inflammation response via CRP, and elevated epinephrine levels were associated with TNF-α-mediated systemic inflammation. The association of TNF-α and MRI signs of cerebral small vessel disease (SVD) in non-hypertensive patients may indicate that TNF-α-mediated inflammation and increased permeability of vessel wall is an independent cause and potential biomarker of early small vessel damage. Influence of hypertension on age-dependent SVD is probably maintained by local vascular wall damage mechanisms via the TGF-ß1-HIF-1-VEGF family. However, hypertension heterogeneity and association of early cerebral vessels damage with various protective reactions require further clarification of the conditions for using these parameters as possible biomarkers of early SVD.

Multimodal approach to treatment of neurological complications of chronic brain ischemia.

AIM: The study of Actovegin effectin clinical presentations and hemorheological characteristics in patients with chronic cerebrovascular pathology (CCVP) and mild cognitive impairment. MATERIALS AND METHODS: The study group included 47 patients (25 male and 22 female), aged 61-75 years (mean age 63.8±5.4) with CCVP who were treated with Actovegin. The control group comprised 28 patients matched by gender and age, without associated cerebrovascular pathology. All patients along with thorough neurological examination underwent laboratory analyses (platelet and erythrocyte rheology), neurovisualization studies (functional magnetic resonance imaging of the brain). Depending on the dosage all patients were divided in two groups: Actovegin 1000 mg and 160 mg daily. RESULTS: Overall, with Actovegin treatment in 81% of cases positive dynamics both in subjective symptoms, and somatic status was observed. A favorable effect on cognitive function in patients with CCVP was noted. The dose-dependent drug effect was demonstrated. The effect of Actovegin on blood cell functioning included the formation of smaller (Tf and Ts; p=0.0096 and p=0.016) and less solid (γ dis) erythrocyte aggregates (p=0.0034) both in the study and control group. The increase in erythrocyte deformability during therapy was significantly associated with cognitive improvement (via MoCA test, r=0.28). CONCLUSION: Complex (including neuropsychological and neurovisualizational) examination may not only help determine the cognitive status in patients with CCVP, but also assess the efficacy of neurometabolic therapy. New facts of Actovegin's influence on erythrocyte aggregation and deformability have been identified, which may enhance micro- and macrocirculation. The acquired data may prove the wide spectrum of Actovegin's pharmacological effect, which allows to use it in all forms of cerebrovascular pathology.

[Indicators of homeostasis, inflammation and homocysteine in ischemic stroke in the young age]. / Pokazateli gemostaza, vospaleniia i gomotsistein pri ishemicheskom insul'te v molodom vozraste.

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.