[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.

[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.

[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.

[Congenital hypopituitarism with monosomy of chromosome 18].

Congenital hypopituitarism is a rare disease. It can be caused by isolated inborn defects of the pituitary, gene mutations (PROP1, PIT1), and chromosomal abnormalities.Deletions of chromosome 18 (De Grouchy syndrome types 1 and 2) are a group of rare genetic diseases with a frequency of 1:50,000. Hypopituitarism in these syndromes is detected in from 13 to 56% of cases and depends on the size and location of the deleted segment.We have described a series of clinical cases of patients with congenital hypopituitarism due to deletions in chromosome 18. All children had a characteristic dysmorphic features and delayed mental and speech development. Within first months of life, patients developed muscular hypotension, dysphagia, and respiratory disorders. The patients had various congenital malformations in combination with hypopituitarism (isolated growth hormone deficiency and multiple pituitaryhormone deficiencies). In the neonatal period, there were the presence of hypoglycemia in combination with cholestasis.Hormone replacement therapy led to rapid relief of symptoms.Сhromosomal microarray analysis in 2 patients allowed us to identify exact location of deleted area and deleted genes and optimize further management for them.

[The role of arterial, venous blood and cerebrospinal fluid flow disturbances in forming cognitive impairment types in age-related cerebral microangiophathy]. / Rol' narushenii arterial'nogo, venoznogo krovotoka i likvorotoka v formirovanii kognitivnykh rasstroistv pri vozrastzavisimoi tserebral'noi mikroangiopatii.

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

[Executive functions: fMRI of healthy volunteers during Stroop test and the serial count test]. / Upravliaiushchie funktsii mozga: funktsional'naia magnitno-rezonansnaia tomografiia s ispol'zovaniem testa Strupa i testa seriinogo scheta pro sebia u zdorovykh.

AIM: To assess executive function in healthy adults using fMRI. MATERIAL AND METHODS: An analysis of fMRI activation and functional connectivity during a serial count task (as a shifting function test) and color-word Stroop test (classical inhibition function test) was made for 12 healthy adults. RESULTS AND CONCLUSION: The executive control network and salience network activation was comparable in both tasks. Nevertheless, there were differences between two tests in functional connectivity of the dorsolateral prefrontal cortex (DLPFC) and the supplementary motor area (SMA) with other brain regions, that can be explained by the differences in the regulatory mechanisms of task performance. Stroop test assumes its automatic performance, and control of program realization is performed mainly by executive-control network. The connectivity between the two DLPFCs with the lower parietal lobules and with each other and inhibition by SMA connectivity with only the right hemisphere regions support this notion. Serial count task excludes the process of monotonous learning, that was confirmed by widespread SMA connections in the absence of connectivity of the DLPFC with executive control network regions. This connectivity pattern allows assuming the leading role of SMA in certain brain regions choice and switching their activity for providing attention and executive control of cognitive operations shift during task performance. These findings allow us to consider the serial count task as the relevant fMRI test for executive functions with the special focus on set shifting, also in patients with executive function deficits. Furthermore, SMA region mapping with the serial count test paradigm could be considered as a potential target for navigated transcranial magnetic stimulation (nTMS) in these patients.

[Investigation of lymphocytes activation using a method of coherent phase microscopy].

Investigation of initial stages of T-lymphocytes activation was performed by coherent phase microscopy (CPM) based on the measurements of phase thickness and diameter of the cell and its organelles. Lymphocytes where activated in two ways: by addition of 2 10-6 g/ml phytohemagglutinin (PHA) and with He-Ne laser (lambda = 633 nm, 10-3 W) radiation. It was shown that phase thickness is proportional to refractivity (difference between refractive indices of an object and the surrounding medium) and geometrical thickness. Phase thickness decreased during activation independently of the nature of the stimuli. Phase thickness in healthy donors was 220 + 60 nm; decreased to 110 + 30 nm 1 h after addition of PHA. The same values were achieved 30 min after stimulation with the He-Ne laser. Characteristic changes in phase thickness in the nucleus and nucleolus were observed after lymphocytes were stimulated with the laser.