[Encephalopathy GNAO1]. / Entsefalopatiya GNAO1.

OBJECTIVE: To study the clinical picture of all patients with GNAO1 encephalopathy detected in the Russian Federation. This publication is a multicenter study combining data from epileptological centers in Moscow, Novosibirsk, St. Petersburg, Nizhny Novgorod, Tyumen. MATERIAL AND METHODS: Nine patients were included, aged 2 to 19 years, with 4 mutations. Male to female sex ratio = 5:4. RESULTS: 8 patients (5 with mutation c.607G>A (p.Gly203Arg), 1 - c.155A>G (Gln52Arg), 1 - c.485G>A (p.Arg162Gln)) had a variant of epileptic encephalopathy, developmental encephalopathy, 1 patient had torsion dystonia without epilepsy (mutation c.713A>G (p.Asp238Gly)). Epileptic seizures in 8 children with epileptic encephalopathy GNAO1 in 100% debuted at 1 month of life, becoming the earliest symptom of the disease. Motor development delayed in 100% of cases. Mental development was not affected only in the case of the dystonic variant. Hyperkinesis (dystonia, choreoathetosis, ballism) followed later, from 2 to 8 months. They were more severe than epilepsy. 4 patients with the c.607G>A (p.Gly203Arg) mutation developed repeated dystonic storms that were resistant to most drugs. CONCLUSION: Epilepsy in GNAO1 is difficult to treat, but temporary or complete remission is possible. Effective drug strategies for the treatment of hyperkinesis have not yet been developed. Expansion of indications for surgical therapy (DBS) of hyperkinesis in this syndrome is desirable.

Photoplethysmographic Imaging of Hemodynamics and Two-Dimensional Oximetry.

The review of recent papers devoted to actively developing methods of photoplethysmographic imaging (the PPGI) of blood volume pulsations in vessels and non-contact two-dimensional oximetry on the surface of a human body has been carried out. The physical fundamentals and technical aspects of the PPGI and oximetry have been considered. The manifold of the physiological parameters available for the analysis by the PPGI method has been shown. The prospects of the PPGI technology have been discussed. The possibilities of non-contact determination of blood oxygen saturation SpO2 (pulse saturation O2) have been described. The relevance of remote determination of the level of oxygenation in connection with the spread of a new coronavirus infection SARS-CoV-2 (COVID-19) has been emphasized. Most of the works under consideration cover the period 2010-2021.

[Epilepsy and other phenotypic features of X-linked intellectual disability caused by the mutations in the KIAA2022 gene]. / Epilepsiya i drugie fenotipicheskie osobennosti X-stseplennoi intellektual'noi nedostatochnosti, obuslovlennoi mutatsiyami gena KIAA2022.

OBJECTIVE: To study the literature data and a series of our cases regarding the epilepsy clinic, electroencephalographic changes and other phenotypic features in X-linked intellectual disability (ID) caused by KIAA2022 mutations. MATERIAL AND METHODS: We analyzed the anamnesis of the disease, using medical records from different Russian medical organizations, as well as the results of the genealogical anamnesis, clinical, genetic, electroencephalographic (EEG) and neuroimaging (brain MRI ) examinations of 7 patients (5 girls and 2 boys aged 5 to 13 years) with a confirmed diagnosis of X-linked ID caused by KIAA2022 mutations, in whom the clinical picture of the underlying disease was combined with epilepsy. RESULTS: The main common phenotypic features of patients with X-linked ID caused by the KIAA2022 mutations are mental retardation, lack of phrasal speech, motor developmental delay, and dysmorphism. The prominent epilepsy characteristics are myoclonic, atonic seizures with nods, flinches, body propulsions, atypical absences, and diffuse discharges «spike-polyspike-slow wave¼ on the EEG. No pathognomonic brain changes were found on MRI. In many cases, the absence of the effect of antiepileptic therapy was noted. CONCLUSION: The described cases of X-linked ID in combination with epilepsy show that this disease can be seen in males as well as in females, epilepsy is rather characterized by generalized seizures, and it is pharmacoresistant in many cases. There is a need for further research on this rare genetic syndrome.

[Experience in the management of patients with genetic epilepsies and epileptic encephalopathies in the outpatient practice]. / Opyt vedeniya patsientov s geneticheskimi epilepsiyami i epilepticheskimi entsefalopatiyami v ambulatornoi praktike.

OBJECTIVE: To describe the spectrum of being detected gene mutations in patients with epilepsy in clinical practice of neurologists specializing in epilepsy with an analysis of diagnosed epileptic syndromes, the characteristics of seizures, the timing of a genetic diagnosis, options and treatment effectiveness. PATIENTS AND METHODS: The study included 100 patients (40 boys, 60 girls) with epilepsy and/or epileptic encephalopathy and a gene mutation identified. The average age was 6.9±5.1 years. Through remote access, epilepsy specialists filled out a specially designed unified table containing information from outpatient case history. RESULTS AND DISCUSSION: There are patients with a wide range of gene mutations, the leading of which is a mutation in the SCN1A gene (15%). The main method (85%) of detection remains the sequencing of the last generation in the «Hereditary Epilepsy¼ panel. Years pass from the onset of the disease to the genetic diagnosis (Me - 3 years). In most cases, patients with severe (52% have epileptic encephalopathy, 88% have developmental disorders) and pharmacoresistant (mean amount of anti-epileptic drugs - 3.8±2.2, multitherapy - 70%) syndromes have undergone genetic testing. In the treatment of these patients epileptologists are increasingly (52%) use alternative methods: steroids, ketogenic diet and others. The absence of seizures was observed only in 46% of patients. CONCLUSION: Thus, in the outpatient practice of epileptologists, patients with a wide range of gene mutations are found. As a rule, these are patients with severe, therapy-resistant epileptic syndromes.

[The impact of spinopelvic parameters on the rate of adjacent segment instability after short-segment spinal fusion]. / Vliianie pozvonochno-tazovykh parametrov na chastotu razvitiia nestabil'nosti smezhnogo segmenta pri monosegmentarnoi fiksatsii v poiasnichnom otdele.

AIM: The objective of this study is to determine the impact of postoperative spinopelvic parameters on the development of adjacent segment instability after single-level lumbar fusion. MATERIAL AND METHODS: A total of 116 patients with degenerative spine conditions after lumbar fusion were enrolled in this study and subdivided into two groups. Group I consisted of 24 patients with signs of adjacent segment instability; Group II included 92 patients without signs of instability. The minimal follow-up period was 24 months. RESULTS: The mean postoperative lumbar lordotic (LL) angle in both groups was within the normal range (-60.9±12); no statistically significant intergroup differences were revealed (56.6±12.1 and 58.4±11.2 for Groups I and II, respectively; p=0.314). In Group I patients, the mean pelvic incidence (PI) angle differed significantly from the mean PI values in Group II patients (70.4±7.6 and 53.2±8.4, respectively; p=0.006) and from the normal PI values (51.9±10). Therefore, the mean difference between PI and LL (PI-LL) angles in the Group I patients was significantly higher than in Group II (16.2±5.4 and 4.8±8.6, respectively; p=0.004). Significant PI-LL mismatch (PI-LL ≥10°) was observed in 22 (91.7%) patients in Group I and in 11 (11.95%) patients in Group II. According to regression analysis data, the PI-LL mismatch was identified as a risk factor for adjacent segment instability; the odds ratio =4.2; 95% confidence interval 1.46-12.25; and p=0.007. CONCLUSION: Patients with the high PI value and low LL value have a significantly higher risk of adjacent segment instability after short-segment spinal fusion.

[Diagnosis and interventional treatment of pain syndromes after surgery for degenerative lumbar spine diseases]. / Diagnostika i interventsionnoe lechenie bolevykh sindromov posle operativnykh vmeshatel'stv po povodu degenerativno-distroficheskikh zabolevanii poiasnichnogo otdela pozvonochnika.

Postoperative pain accompanies up to 20% of interventions for degenerative spine diseases (DSDs). The epidemiologic data are contradictory; clinical and radiological diagnostics is often low efficient; capabilities of interventional diagnosis and treatment techniques are poorly understood. PURPOSE: The study purpose was to investigate the structure of pain syndromes after surgery for DSDs of the lumbar spine, based on complex diagnostics, as well as to evaluate the capabilities of interventional treatment. MATERIAL AND METHODS: We examined 310 patients with postoperative pain syndromes. Patients with obvious indications for repeated surgery were excluded from the analysis; the remaining patients underwent selective diagnostic blockades followed by interventional (puncture) treatment. A positive outcome was defined as a reduction in pain by 50% on the numerical rating scale (NRS-11), by 20% in the Oswestry index (ODI), and by 8 points in the sciatica bothersomeness index (SBI), with the effect lasting for 12 months. Predictive factors for the risk of pain syndromes were analyzed. RESULTS: Out of 310 patients, 162 (52.6%) patients had no obvious indications for surgery. Radicular pain was detected in 56 (18.6%) of 310 patients; the positive treatment outcome was achieved in 38 (67.86%) of 56 patients. Facet pain was present in 29 (9.35%) patients; the positive treatment outcome was achieved in 23 (79.31%) patients. Discogenic pain was found in 12 (3.87%) patients; the positive treatment outcome was achieved in 5 (41.63%) patients. sacroiliac joint (SIJ) pain was present in 42 (13.55%) patients; the positive treatment outcome was achieved in 36 (85.71%) patients. Myofascial and competing pain was detected in 12 (3.87%) patients; the causes were not identified in 11 (3.55%) cases. The main risk factors were sagittal balance parameters. CONCLUSION: Complex diagnostics revealed postoperative pain not associated with surgical causes in 52.6% of cases; the origin of pain was identified in 49.95% of cases. Interventional treatment was effective in 64.81% of cases; failed back surgery syndrome was diagnosed in 16.13% of patients.

[THE PATIENTS QUALITY OF LIFE ESTlMATION IN PRESENCE OF METASTASIS OF A RENAL-CELL CANCER IN THE BONES ON BACKGROUND OF THE BISPHOSPHONATES APPLICATION].

Results of the patients quality of life (QL) estimation, while presence of a renal-cell cancer metastasis in the bones, using questionnaire QLQ-C30 and Karnofsky index, as well as the pain visual-analogue scale on background of treatment with bisphosphonates (BPH), were adduced. After conclusion of the combined treatment the general state improvement, a trustworthy reduction of the pain syndrome severity, as well as the patients' psychoemotional and social state, were noted. Complex treatment of patients, using BPH, have promoted a positive impact on their QL as well as a reduction of a skeleton complications rate.

[The children health centers: first results of functioning and perspectives of development].

The article presents analysis of functioning of children health centers organized in allsubjects of the Russian Federation. For the first time, according data of report form 68, the information are received concerning visits of children in following age groups: 0-4 years, 5-9 years, 10-14 years, 15 and 16-17 years. The average Russian indicators of visits of children health centers are calculated that can be applied in territories as markers of their effectiveness. The main flows of arrival of children population to health centers and determining factors are established. The particular attention is paid to analysis of repeated visits. The regional experience of their payments in the system of mandatory medical insurance is presented. The experience of implementation of Internet resources in propaganda of healthy life-style in adolescents and young parents is examined. The results of the carried out study were used as a basis to establish in n prevention activities of children health centers problem zones of medical organizational, technological and informational character. The proposals are given concerning enhancement of children health centers functioning.

Functional connection between posterior superior temporal gyrus and ventrolateral prefrontal cortex in human.

The connection between auditory fields of the temporal lobe and prefrontal cortex has been well characterized in nonhuman primates. Little is known of temporofrontal connectivity in humans, however, due largely to the fact that invasive experimental approaches used so successfully to trace anatomical pathways in laboratory animals cannot be used in humans. Instead, we used a functional tract-tracing method in 12 neurosurgical patients with multicontact electrode arrays chronically implanted over the left (n = 7) or right (n = 5) perisylvian temporal auditory cortex (area PLST) and the ventrolateral prefrontal cortex (VLPFC) of the inferior frontal gyrus (IFG) for diagnosis and treatment of medically intractable epilepsy. Area PLST was identified by the distribution of average auditory-evoked potentials obtained in response to simple and complex sounds. The same sounds evoked little if there is any activity in VLPFC. A single bipolar electrical pulse (0.2 ms, charge-balanced) applied between contacts within physiologically identified PLST resulted in polyphasic evoked potentials clustered in VLPFC, with greatest activation being in pars triangularis of the IFG. The average peak latency of the earliest negative deflection of the evoked potential on VLPFC was 13.48 ms (range: 9.0-18.5 ms), providing evidence for a rapidly conducting pathway between area PLST and VLPFC.

[The proinsulin level in the blood of children with type 1 diabetes mellitus of various duration].

Proinsulin content was measured in the serum of 82 children (aged from 3 to 14 years) with type 1 diabetes mellitus of various duration. Three groups of patients characterized by low (54%), normal (42%) and high (4%) levels of this prohormone were recognized. No dependence the proinsulin level on the disease term was found. The serum proinsulin level may be used as a parameter specifying the pathogenesis of type 1 diabetes mellitus.

[Distal polyneuropathy in children with diabetes mellitus type 1].

To identify the association between distal peripheral neuropathy (DPN) and type 1 diabetes mellitus (T1D), 62 children and adolescents with different duration of T1D have been studied using electromyography (EMG). Subclinical symptoms of DPN occur with equal frequency in 74% of children with short duration of T1D (group 1) and in 72% of children with long duration of disease. In both groups, the highest frequency of disturbances of the neurophysiological parameters was found in the sural sensory nerve and the lowest frequency in the median motor nerve. Correlations between HbAlc levels and compound muscle action potential were revealed only in tibial and peroneal nerves and only in the early stages of T1D. However, this dependence disappears with increasing duration of the disease.

[Age-related transformation of infantile spasms into drug-resistant forms of epilepsy].

An objective of this paper was to study treatment outcomes in patients with infantile spasms (IS) in the evolutionary aspects and from the point of view of drug resistance. We have treated 124 children with IS. Standard therapy included hormones synacthen depot (0.03-0.05 mg/kg) or dexasone (0.3-0.5 mg.kg). The drug regimen was as follows: 10 injections daily initially, following with 5 injections every other day, then 5 injections every two days, plus a valproate in dose 30-40 mg/kg/day. Seventy-three patients were followed up: 21 patients continued to manifest spasms despite the use of several adequate and well-tolerated antiepileptic drugs (AEDs) as a monotherapy, as well as a combination therapy. The patients were divided into 2 groups. In Group 1 (n=12) the remission period was from 0 to 4 months, while in Group 2 (n=9) remission lasted from 7 months up to 4 years. The patients demonstrated all types of IS and modified hypsarrhythmia. In Group 1, the patients were relieved of IS in 66% of the cases and the EEGs showed no epileptic activity in 58%. 83% of the patients then experienced a return of IS and 50% of the patients had hypsarrhythmia. Adding 2 and 3 AEDs to the treatment did not bring any change. A transformation of hypsarrhythmia was observed as the patients grew older. All patients in Group 2 had a cessation of IS, and 77% of the patients had no hypsarrhythmia. In one third of the cases, the IS returned while the other two thirds had focal seizures. EEGs predominantly demonstrated the focal epileptic activity. Adding 2 AEDs had positive effect on seizures in 66% of the cases and EEGs improved in 88% of the cases. Adding 3 AEDs had no effect on the course of the condition in one third of the cases, and in most cases the EEGs did not change. In Group 1, the condition was of drug-resistant nature, and in Group 2 we saw a remission in the condition. After the hormone regimen was completed, a relief of the epileptic activity was achieved for most patients in Group 2. In Group 1, the recurrence of IS was in correlation with the persistence of hypsarrhythmia. We have not found any obvious benefit from the use of any one AED or a combination of AEDs. 78% of the patients in Group 1 demonstrated further persistence of IS for several years. In Group 2, the return of seizures and the EEGs were age-dependent and the treatment had a more positive outcome.

[Intestinal endotoxin in induction of type 1 diabetes].

We studied serum level of intestinal flora endotoxin (LPS) in 45 children and adolescents aged 3-17 years old with diabetes mellitus type 1. Levels of endotoxin, were significantly elevated in type 1 diabetic patients (2.89 +/- 0.33 Eu/ml) compared with control (0.4 +/- 0.03 Eu/ml). There was significant difference in serum LPS levels in patients with type 1 diabetes onset (3.93 +/- 0.79 Eu/ml) compared with children and adolescent with old time diabetes (2.37 +/- 0.27 Eu/ml). These results have a major implication on our understanding of the role of gut flora endotoxin in pathogenesis of type 1 diabetes.

Statistical analysis of clone formation in cultures of human stem cells.

We performed a statistical analysis of clone formation from aneuploid cells (chromosomes 6, 8, 11, X) in cultures of bone marrow-derived human multipotent mesenchymal stromal cells by spontaneous level of aneuploidy at different terms of culturing (from 2 to 19 cell cycles). It was found that the duration of cell cycle increased from 65.6 h at passages 2-3 to 164.5 h at passage 12. The expected ratio of aneuploid cells was calculated using modeled 5, 10, 20 and 30% selective preference in reproduction. The size of samples for detecting 10, 25, and 50% increased level of aneuploidy was calculated. The presented principles for evaluation of aneuploid clone formation may be used to distinguish clones of any abnormal cells.

Phenotypic differences in viral immune escape explained by linking within-host dynamics to host-population immunity.

Viruses that do not cause life-long immunity persist by evolving rapidly in response to prevailing host immunity. The immune-escape mutants emerge frequently, displacing or co-circulating with native strains even though mutations conferring immune evasion are often detrimental to viral replication. The epidemiological dynamics of immune-escape in acute-infection viruses with high transmissibility have been interpreted mainly through immunity dynamics at the host population level, despite the fact that immune-escape evolution involves dynamical processes that feedback across the within- and between-host scales. To address this gap, we use a nested model of within- and between-host infection dynamics to examine how the interaction of viral replication rate and cross-immunity imprint host population immunity, which in turn determines viral immune escape. Our explicit consideration of direct and immune-mediated competitive interactions between strains within-hosts revealed three insights pertaining to risk and control of viral immune-escape: (1) replication rate and immune-stimulation deficiencies (i.e., original antigenic sin) act synergistically to increase immune escape, (2) immune-escape mutants with replication deficiencies relative to their wildtype progenitor are most successful under moderate cross-immunity and frequent re-infections, and (3) the immunity profile along short host-transmission chains (local host-network structure) is a key determinant of immune escape.

Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes: experience of the PedPump Study in 17 countries.

AIMS/HYPOTHESIS: To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome. METHODS: Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European countries and Israel were recorded during routine clinical visits. HbA(1c) was measured centrally. RESULTS: A total of 1,041 patients (age: 11.8 +/- 4.2 years; diabetes duration: 6.0 +/- 3.6 years; average CSII duration: 2.0 +/- 1.3 years; HbA(1c): 8.0 +/- 1.3% [means +/- SD]) participated. Glycaemic control was better in preschool (n = 142; 7.5 +/- 0.9%) and pre-adolescent (6-11 years, n = 321; 7.7 +/- 1.0%) children than in adolescent patients (12-18 years, n = 578; 8.3 +/- 1.4%). There was a significant negative correlation between HbA(1c) and daily bolus number, but not between HbA(1c) and total daily insulin dose. The use of <6.7 daily boluses was a significant predictor of an HbA(1c) level >7.5%. The incidence of severe hypoglycaemia and ketoacidosis was 6.63 and 6.26 events per 100 patient-years, respectively. CONCLUSIONS/INTERPRETATION: This large paediatric survey of CSII shows that glycaemic targets can be frequently achieved, particularly in young children, and the incidence of acute complications is low. Adequate substitution of basal and prandial insulin is associated with a better HbA(1c).

[The influence of drainage and plasty of the epidural space on the results of lumbar diskectomies].

The nearest and long-term results of microdiskectomies were analyzed in 185 patients. The methods of decreasing the postoperative epidural fibrosis - drainage of the postoperative wound, plasty of the epidural space with fat or different artificial materials were used. No statistically reliable dependence on using the methods concerning the dynamics of the neurological status, pain syndrome and quality of life was noted.