[Intrathecal chemotherapy for leptomeningeal metastases in patients with breast cancer]. / Intratekal'naya khimioterapiya pri leptomeningeal'nom metastazirovanii u bol'nykh rakom molochnoi zhelezy.

Leptomeningeal metastases are lesions of brain and/or spinal cord sheaths by tumor cells. They occur in 5% of patients with solid tumors, although autopsies reveal these lesions much more often (10-20% of cases). Leptomengeal metastases are an unfavorable prognostic factor. Despite the modern NCCN treatment standards, including intrathecal therapy (ITT), such patients receive only irradiation of the entire brain and/or spinal cord in most cases. OBJECTIVE: To evaluate the effectiveness of ITT in patients with leptomeningeal metastases in breast cancer. MATERIAL AND METHODS: Twenty-five patients with breast cancer and leptomeningeal metastases underwent intrathecal administration of methotrexate between 2016 and 2022. Intrathecal chemotherapy was administered through lumbar puncture. We performed an intensive course (intrathecal methotrexate 15 mg 2 times a week for 1 month (8 injections), then intrathecal methotrexate 15 mg 1 time a week (4 injections), and then 15 mg 1 time a month until progression or unacceptable toxicity). RESULTS: The median duration of ITT was 2.5 months. Complete neurological responses were observed in 3 out of 25 (12%) patients, partial neurological response - in 15 out of 25 (60%) patients, progression of neurological symptoms - in 7 (28%) patients. The number of complete cytological responses was observed in 6 out of 25 (24%) patients. The median overall survival after ITT was 6.7 months. CONCLUSION: Effectiveness of ITT is confirmed by higher quality of life (72% of patients), complete cytological responses (24%) and improvement in neuroimaging data. This is an important criterion for severe patients with limited treatment options. First-stage ITT before whole-brain irradiation is preferable, as this approach increases overall survival by 3 months. Undoubtedly, ITT is a treatment option that can be used in routine clinical practice for lesions of brain and spinal cord sheaths.

[Validation of screening method based on EEG analysis for the risk assessment of psychiatric and behavioral disorders: a pilot study]. / Validatsiya skriningovogo metoda na osnove analiza EEG dlya otsenki riskov psikhicheskikh i povedencheskikh rasstroistv: pilotnoe issledovanie.

OBJECTIVE: To assess the validity of the screening method based on EEG analysis using predictive analytics algorithms with the calculation of linear discriminant functions (LDFs), in comparison with a classification system based on psychometric self-report scales. MATERIAL AND METHODS: A comparative cross-sectional study with partial blinding involving healthy volunteers was conducted at two investigational sites. The calculated scores of LDFs used to assess risks of impulsivity, depression and anxiety acted as quantitative characteristics of subjects' mental state. Testing included completing psychometric scales. RESULTS: As a result of the performed validation of the original screening method based on EEG analysis in comparison with the scores of psychometric scales chosen as a reference method, satisfactory results were obtained with the best parameters of sensitivity, specificity, and accuracy for detecting high levels of impulsivity associated with pronounced aggressiveness. Of considerable interest is also the direct correlation found between high levels of LDF impulsivity scores and high levels of self-rated aggression on a psychometric scale (BPAQ-24). CONCLUSION: The results open up the possibility of using the proposed method to predict a number of emotional and behavioral characteristics of subjects, including a high risk of aggressive behavior as part of professional selection.

Effect of the type of N-substituent in the benzo-18-azacrown-6 compound on copper(II) chelation: complexation, radiolabeling, stability in vitro, and biodistribution in vivo.

In this work, we synthesized two new benzo-18-azacrown-6 ethers bearing picolinate and pyridine pendant arms and studied the copper complexes of these ligands, as well as those of an acetate analog. All considered ligands were capable of forming mono- and dinuclear complexes due to their large size and large number of donor sites. Among all forms of complexes, the coordination of cations inside the macrocycle has only been shown for the mononuclear form of the acetate complex, while out-cage coordination has been observed for other forms. Electrochemical studies have shown the instability of the mononuclear form of the complex with the pyridine ligand to the reduction in the range of redox potentials of bioreductants. The stabilities of labeled acetate complexes with "in-cage" coordination of the cation and picolinate with "out-cage" coordination were compared in an excess of serum and superoxide dismutase; while the former turned out to be unstable to transchelation, the latter was stable throughout the experiment. Additional studies in biologically relevant media were performed for the picolinate complex and demonstrated its stability in vitro. The biodistribution of this complex in mice after 6 hours post-injection demonstrates a slow excretion from the body; however, the accumulation is noticeably lower than that of free copper cations.

[Giant petrosal meningioma invading the fourth ventricle: total removal of a recurrent tumor after eighteen years. Neurosurgical nuances. Case report and literature review]. / Gigantskaya meningioma zadnei poverkhnosti piramidy visochnoi kosti s porazheniem IV zheludochka: total'noe udalenie retsidiviruyushchei opukholi cherez 18 let. Neirokhirurgicheskie nyuansy. Sluchai iz praktiki i obzor literatury.

The authors present a patient and neurosurgical nuances of total resection of recurrent meningioma of posterior surface of petrous bone 65´35´30 mm. The tumor captured two critical zones of posterior cranial fossa with unusual frontal growth and spread from the surface of petrous bone to the fourth ventricle. The neoplasm filled the ventricle without lesion of ependyma. Extensive fibrous meningioma of posterior surface of petrous bone was totally excised 18 years ago. MRI was annually carried out for 5 years. Surgical nuances that ensured total extraction of tumor without cytoreduction were as follows: 1) en-bloc resection of tumor from the fourth ventricle due to smooth surface of tumor and minimum number of adhesions with cerebellum; MR-confirmed CSF strip between the tumor edges and walls of the ventricle; no signs of hydrocephalus in subtotal ventricular tamponade; 2) unusual frontal tumor growth under 45º required appropriate angular traction of tumor with minimal rotation; 3) traction was followed by sequential appearance of 3 segments of tumor: petrous, apertural and ventricular; 4) topography of the area of lateral eversion of the fourth ventricle was established by identifying the narrowing (constriction) of tumor; 5) in extracting the tumor from the fourth ventricle, we performed minimal rotation to avoid damage to ventricular walls and lateral aperture due to difference between the larger and smaller diameters (by 6 mm) of ovoid ventricular segment of tumor; 6) no CSF leakage following appearance of ventricular segment (tumor enlargement) indicated integrity of ependyma of the fourth ventricle. Histological examination confirmed fibrous meningioma. Fast and complete regression of focal symptoms was observed after surgery. A 3-year follow-up after surgery revealed no signs of tumor recurrence.

[Surgical management of brain metastases following female reproductive system cancers: analysis of 37 cases]. / Opyt khirurgicheskogo lecheniya tserebral'nykh metastazov opukholei organov zhenskoi reproduktivnoi sistemy: analiz 37 sluchaev.

Background. Previously, treatment of women with brain metastases following reproductive system cancers was palliative and included whole brain radiotherapy. Currently, treatment approaches have changed and life expectancy has increased. Nevertheless, the role of surgical treatment in these patients is still discussed. OBJECTIVE: To demonstrate an appropriateness and role of neurosurgical care in the complex management of women with brain metastases following reproductive system cancers. MATERIAL AND METHODS: There were 78 women with brain metastases following reproductive system cancer. All patients were treated at the Blokhin National Cancer Medical Research Center for the period 2004-2019. We have also reviewed the literature data for the last 30 years.Results and discussion. Resection of brain metastases in complex treatment of endometrial, ovarian and cervical cancer ensured favorable long-term survival in our material. Thus, mean life expectancy after resection of brain metastases was 16.3 months in patients with ovarian cancer, uterine cancer - 15.6 months, cervical cancer - 10.25 months. Obviously, surgery is not indicated in all cases. However, this approach improves local control and should be used in combination with other treatment methods for improvement of life expectancy and its quality in certain patients. CONCLUSION: Selective surgical approach should be essential in the treatment of patients with brain metastases following reproductive system cancer. A multidisciplinary approach ensures the best treatment outcomes.

[Electroencephalographic markers of alexithymia in patients with moderate depression]. / Elektroentsefalograficheskie markery aleksitimii u bol'nykh depressiyami umerennoi stepeni tyazhesti.

OBJECTIVE: To search for electroencephalographic markers of alexithymia in patients with moderate depression. MATERIAL AND METHODS: Sixty-four right-handed inpatients (20 men and 44 women, mean age 29.3+10.7 years), were studied. The level of alexithymia was assessed by the Russian version of the Toronto Alexithymia Scale (TAS-20-R). Patients were stratified into 4 groups by TAS-20-R scores. Two main groups of 22 patients each included people with high (>60 scores) and low (20-51 scores) levels of alexithymia. Control groups included 10 patients with 60-85 scores and 10 patients with 52-54 scores. Current methods of electroencephalographic analysis were used. RESULTS: Alexithymia in patients with moderate depression is characterized by a restructuring of the integrative activity of the brain detected by electroencephalography at rest. Patients with high alexithymia differ from those with low alexithymia by (1) lower values of the real part of the coherence between the frontal and anterior temporal leads of the left hemisphere in the band 28-30 Hz; (2) lower values of the imaginary part of coherence in the band 11-12 Hz between the posterior temporal and parietal as well as the posterior temporal and occipital cortical zones of the right hemisphere; (3) higher rates of the real part of the coherence between the right frontal and central leads in the frequency ranges 12-14 and 6-7 Hz; (4) large values of the imaginary part of the coherence between the left parietal and right posterior temporal cortex in the band 24-26 Hz; (5) higher values of the square of the coherence modulus between the left frontal and anterior temporal cortical zones in the band 17-18 Hz. CONCLUSION: Large cortical representations with involvement of theta, alpha, beta-1 and beta-2 rhythms can contribute to the pathogenesis of alexithymia.

[Discriminant EEG analysis for differential diagnosis of schizophrenia. Methodological aspects]. / Ispol'zovanie diskriminantnogo analiza EEG dlya differentsial'noi diagnostiki shizofrenii. Metodologicheskie aspekty.

BACKGROUND: A search for accurate linear discriminant function (LDF) allowing the diagnosis of schizophrenia and estimation of treatment effectiveness according to EEG is an urgent problem. OBJECTIVE: To develop a methodology for discriminant EEG analysis for minimizing the overlearning effect, selection of optimal LDF model and evaluation of its generalizing ability. MATERIAL AND METHODS: Two hundred and twenty patients with schizophrenia and 1400 people without psychiatric diseases, who were comparable in basic characteristics, were enrolled. EEG was recorded using 16 leads, 10-20 system and aural reference electrodes. EEG was processed by spectral and coherent analysis. RESULTS: After linear discriminant analysis, LDF was obtained to differentiate people with schizophrenia from healthy subjects and a formula was selected from LDF that included 8 predictors (spectral and coherent parameters of standard EEG ranges theta, alpha and beta) with 90% sensitivity and 80% specificity, significance level for Wilks' lambda p<3.9E-28 and the Mahalanobis distance between training set centroids 4,6. CONCLUSION: A method for obtaining optimal LDF models and selection the best one with further LDF generalizing ability assessment is suggested.

Glial Fibrillary Acidic Protein in the Diagnosis and Prognosis of Malignant Glial Tumors.

Serum levels of glial fibrillar acidic protein (GFAP) were analyzed in 317 patients with primary and metastatic tumors of the brain, 78 patients with neurological diseases, and 66 normal subjects. A significant increase in the basal level of GFAP was typical of patients with glioblastomas in comparison with other groups (patients with astrocytomas, cerebral metastases, benign tumors, non-tumor diseases, and healthy subjects). An association of GFAP levels with unfavorable prognosis of overall survival in patients with glioblastoma was revealed. The data attest to high specificity and sensitivity of GFAP as a biochemical marker of glioblastoma.

[The use of eeg discriminant analysis in the diagnosis of schizophrenia]. / Ispol'zovanie diskriminantnogo analiza élektroéntsefalogrammy v diagnostike shizofrenii.

AIM: There have been no criteria found so far to quantify the wide range of EEG spectral and coherent indicators, which would allow discrimination between schizophrenia disorders and healthy human states. The goal of this research is to find objective EEG-based schizophrenia criteria through a discriminant analysis and to obtain a linear discriminant function (LDF) with sensitivity and specificity of at least 85%. MATERIAL AND METHODS: The study covered 83 schizophrenia patients and 116 healthy individuals, with similar major characteristics. EEGs were recorded in EDF format using 16 leads under the 10-20 system and ear reference electrodes, with further spectral and coherent analysis. RESULTS: A discriminant analysis has provided LDFs from which a formula with 5 predictors was extracted. The most valuable diagnostic predictors were beta2 and theta rhythm powers in the F3 lead. In the same manner, interhemispheric theta rhythm coherence in the pair T5-T6 and interhemispheric beta rhythm coherence in the pairs F3-C3 and T3-C3 were significant predictors. All of them being negative, the EEG supplied thereby most likely relates to the schizophrenia class. CONCLUSION: The novel methods used for selecting EEG features and choosing their combinations to obtain LDFs and verify the outcomes will give the researcher a powerful and flexible tool to perform an EEG discriminant analysis which allows obtaining linear discriminant functions in short terms without routine procedures, performance of preliminary diagnosis using an expert system based on the obtained LDF, evaluation of treatment efficacy by the LDF score dynamics. During treatment and changes of predicting modules function, variables may increase or decrease depending on the direction of predictors that may serve as an indicator of treatment efficacy.

Connection between Proliferation Rate and Temozolomide Sensitivity of Primary Glioblastoma Cell Culture and Expression of YB-1 and LRP/MVP.

Glioblastomas (GBL) are the most common and aggressive brain tumors. They are distinguished by high resistance to radiation and chemotherapy. To find novel approaches for GBL classification, we obtained 16 primary GBL cell cultures and tested them with real-time PCR for mRNA expression of several genes (YB-1, MGMT, MELK, MVP, MDR1, BCRP) involved in controlling cell proliferation and drug resistance. The primary GBL cultures differed in terms of proliferation rate, wherein a group of GBL cell cultures with low proliferation rate demonstrated higher resistance to temozolomide. We found that GBL primary cell cultures characterized by high proliferation rate and lower resistance to temozolomide expressed higher mRNA level of the YB-1 and MDR1 genes, whereas upregulated expression of MVP/LRP mRNA was a marker in the group of GBL with low proliferation rate and high resistance. A moderate correlation between expression of YB-1 and MELK as well as YB-1 and MDR1 was found. In the case of YB-1 and MGMT expression, no correlation was found. A significant negative correlation was revealed between mRNA expression of MVP/LRP and MELK, MDR1, and BCRP. No correlation in expression of YB-1 and MVP/LRP genes was observed. It seems that mRNA expression of YB-1 and MVP/LRP may serve as a marker for GBL cell cultures belonging to distinct groups, each of which is characterized by a unique pattern of gene activity.

[Hemodynamic and biochemical characteristics of the prefrontal cortex after the first episode of juvenile schizophrenia].

Authors analyzed biochemical (data obtained by proton MR spectroscopy) and hemodynamic ( data of fMRI) characteristics of the prefrontal cortex in 7 patients with juvenile shift-like schizophrenia examined during remission after the first episode and in 8 mentally healthy subjects matched for sex and age. The between-group differences in the tested parameters were not found, however, the neurobiological features of the prefrontal cortex were correlated with the psychopathological symptoms assessed with the PANSS.

[EEG, ERP in selective attention paradigm and the level of some metabolites in brain prefrontal cortex].

The preliminary analysis at the first stage of the research has revealed the statistically significant correlations between electrophysiological parameters and the level of several metabolites (determined by magnetic-resonance spectroscopy) in the left dorsolateral prefrontal cortex. The findings are assumed to be due to the individually specific peculiarities of activation of this brain region and its impact on the information processing. The neurophysiological markers of decreased brain functional state are associated with the lower N-acetyl aspartate and choline and higher level of creatin/phosphocreatin in the tested region of prefrontal cortex.

Interhemispheric asymmetry in EEG photic driving coherence in childhood autism.

OBJECTIVE: Examination of the EEG photic driving coherence during intermittent photic stimulation in autistic patients with relatively intact verbal and intellectual functions in order to enhance the likely latent interhemispheric asymmetry in neural connectivity. METHODS: Fourteen autistic boys, aged 6-14years, free of drug treatment, with I.Q. 91.4+/-22.8, and 19 normally developing boys were subject to stimulation of 12 fixed frequencies of 3-27Hz. The number of high coherent connections (HCC) (coherence >0.6-0.8) was estimated among 7 leads in each hemisphere. RESULTS: In contrast to the spectral characteristics showing the right hemisphere deficit in the photic driving reactivity, the number of HCC differentiated the groups only in the left hemisphere where it was higher in autistics at the EEG frequencies corresponding to those of stimulation at 6-27Hz without asymmetry at other frequencies, the left-side prevalence increasing with frequency. No asymmetry was observed in the resting state. CONCLUSIONS: Spectral and coherence characteristics of the EEG photic driving show different aspects of latent abnormal interhemispheric asymmetry in autistics: the right hemisphere "hyporeactivity" and potential "hyperconectivity" of likely compensatory nature in the left hemisphere. SIGNIFICANCE: The EEG photic driving can reveal functional topographic alterations not present in the spontaneous EEG.

[A psychophysiological approach toward the problem of consciousness].

Psychophysiological analysis of the relationship between the level of consciousness and the brain activation permitted an identification of three levels of consciousness at the transition from wakefulness to sleep. A change in the intensity and quality of involuntarily mental processes served as an index of the level of consciousness according to subjects' self-reports. It was found that a certain EEG profile corresponds to each level of consciousness under study. Data obtained showed that the lowest level of activation corresponds to a state in which a subject notes an inhibition of "internal speech", "failure of thoughts". At this case the dynamics of the EEG high frequency rhythm changes which is possibly related to the mechanism of transmission of cognitive information.

[Effect of carbamazepine on the structure-function relations in the development of the epileptic structure]. / Vliianie karbamazepina na strukturno-funktsional'nye sviazi v razvitii épilepticheskoi sistemy.

The experiments on white outbred male rats with cobalt-induced epileptogenic focus in the left sensomotor cortical region showed that the anticonvulsant effect of carbamazepine (20 mg/kg) depends on the functional state of the epileptic system (ES). In various stages of the ES development, the drug effect is related to the influence upon the determinant focus generating the epileptic activity. In the initial stage, carbamazepine primarily affects epileptic activity of the cortical foci (ipsi- and contralateral hemisphere). In the second (generalization) stage, the drug decreases the epileptic activity in all structures, but to a greater extent, in the dorsal hippocampus and lateral hypothalamus.

[Spatial organization of bioelectrical brain activity in epilepsy and amenorrhea of central genesis]. / Prostranstvennaia organizatsiia bioélektricheskoi aktivnosti golovnogo mozga pri épilepsii i amenoree tsentral'nogo geneza.

The study aimed at modification of co-herent analysis (CA), as a mathematical method for EEG data processing for objective evaluation of bioelectric brain activity spatial organization in women with epilepsy and secondary amenorrhea of central genesis. One hundred sixty one women (30 with epilepsy, 116 with amenorrhea and 115 controls aged 15 to 41 years) have been examined. Characteristic changes of cortico-cortical inter- and intra-hemisphere relations for patients with catamenial (CTM) and noncatamenial (NCTM) epilepsy in different menstrual cycle terms were found. The most distinct changes were detected in theta-activity analysis. In the beginning of menstrual cycle, the patients with CTM epilepsy exhibited higher CA indices in theta-rhythm range in all right hemisphere pairs studied. On the contrary, patients with NCTM epilepsy exhibited lower CA indices mainly in the right brain hemisphere. alpha-rhythm spatial organization analysis in the same patients showed similar correlations, but they were better expressed in alpha-rhythm generation zone: in the beginning of menstrual cycle CA indices were high in patients with CTM epilepsy and low in those with NCTM epilepsy. Comparing to controls, patients with secondary amenorrhea of central genesis showed most distinct changes in theta-activity towards the CA indices increase in the majority of the leads. In patients with epilepsy and amenorrhea, CA indices of right brain hemisphere and intra-central temporal lead pairs were lower than in patients with amenorrhea without epilepsy by both alpha- and theta-rhythms.

[Azo derivatives of levorin]. / Azoproizvodnye levorina.

Levorin, an aromatic heptaenic antibiotic and sodium nitrite in solution of acetic acid formed a diazo compound. In the diazo reaction this compound interacted with beta-napthol or H-acid. The resulting azo compounds were readily soluble in organic solvents. In water their nitrites formed true solutions. The biological activity of the azo levorins was 100-200 times lower than that of the initial levorin. The physico-chemical characteristics of the azo levorins are presented.