[Epilepsy with PCDH19 mutation: polypharmacy as a consequence of the complexity and diversity of pathogenesis mechanisms]. / Epilepsiya pri mutatsii gena PCDH19: polipragmaziya kak sledstvie slozhnosti i mnogoobraziya mekhanizmov patogeneza.

Mutations in the human PCDH19 gene lead to epileptic encephalopathy of early childhood. It is characterized by the early onset of serial seizures, cognitive impairment and behavioral disorders (including autistic personality traits). In most cases, difficulties arise in selecting therapy due to pharmacoresistance. The pathogenesis of the disease is complex. The data available to us at the moment from numerous studies present the pathogenesis of «PCDH19 syndrome¼ as multi-level, affecting both the epigenetic support of cell life, and development of stem cells and progenitor cells in the process of neuroontogenesis, and the influence on the neurotransmitter mechanisms of the brain, and disruption of the formation of neural networks with an inevitable increase in the excitability of the cerebral cortex as a whole, and local changes in the highly labile regulatory structures of the hippocampal region. And it is not surprising that all these changes entail not only (and perhaps not so much) epileptization, but a profound disruption of the regulation of brain activity, accompanied by autism spectrum disorders, more profound disorders in the form of schizophrenia or cyclothymia, and the formation of delayed psychomotor development. A «side branch¼ of these pathogenetic processes can also be considered the participation of PCDH19 dysfunctions in certain variants of oncogenesis. The need for polypharmacy (in most cases) confirms the diversity of mechanisms involved in the pathogenesis of the disease and makes the prospects for the development of effective and rational treatment regimens very vague. Cautious optimism is caused only by attempts at relatively specific treatment with ganaxolone.

[Epigenetic influences and brain development]. / Epigeneticheskie vliyaniya i razvitie mozga.

In recent years, the amount of scientific data on the involvement of epigenetic processes in the regulation of brain development in postnatal ontogenesis has been rapidly growing. The article provides an overview of scientific research on the mechanisms of epigenetic influences on brain development. Information was searched in the Scopus, Web of Science, MedLine, The Cochrane Library, PubMed, Pedro, Scholar, eLibrary, CyberLeninka and RSCI databases for the period 1940-2022 by keywords: brain development, epigenetics, neuroontogenesis, methylation, histone modifications, chromatin remodeling, non-coding RNAs. Today, the mechanisms of epigenetic influence on the genome include DNA and RNA methylation, covalent modification of histones, chromatin remodeling, and the influence of non-coding RNAs. Epigenetic modifications are often reversible and provide the necessary plasticity for the response of progenitor cells to environmental signals. The influence of each of these factors on the neurodevelopment is considered. The possibility of transsynaptic transmission of hereditary material by means of circular RNA is indicated. The main ways of microRNA influence on brain development are presented and their universality as an «overgenic¼ regulator of organism adaptation to external conditions is indicated. Data on the relationship of long non-coding RNAs with the regulation of the functional activity of oligodendroglia are presented. Also, the data presented indicate the paths to the pathogenetically determined prevention of congenital brain pathology.

[Epileptic syndromes associated with focal clonic seizures]. / Epilepticheskie sindromy, assotsiirovannye s fokal'nymi klonicheskimi pristupami.

OBJECTIVE: To study clinical, electroencephalographic and neuroimaging features in children with epileptic syndromes associated with focal clonic seizures (FCS). MATERIAL AND METHODS: We examined 1258 patients with various forms of epilepsy with the onset of seizures from the first day of life to 18 years. RESULTS: FCS was identified in 263 patients (20.9%). FCS were included in the structure of 13 different epileptic syndromes: Rolandic epilepsy (28.1%), structural focal epilepsy (27.5%), structural focal epilepsy associated with benign epileptiform discharges of childhood (SFE-BEDC) (20.6%), focal epilepsy of unknown etiology (7.5%), epilepsia partialis continua (4.6%), pseudo-Lennox syndrome (3.4%), ESES syndrome (2.7%), Landau-Kleffner syndrome (1.5%), Dravet syndrome (1.1%), benign occipital epilepsy (1.1%), benign focal epilepsy in infancy (0.8%), MISF syndrome (0.8%), cognitive epileptiform disintegration (0.8%). In 50% of cases, epilepsy associated with FCS debuts before the age of 5 years (from 1 month to 18 years, average age 4.26±3.9). CONCLUSION: The groups of syndromes associated with FCS have different prognosis for remission of seizures. Prognostic predictors of seizure remission are: epileptic syndromes associated with BEDC, the presence of periventricular leukomalacia. A severe prognosis for the course of epilepsy is associated with local structural changes in the neocortex. Despite a favorable prognosis for seizures, continued diffuse interictal epileptiform activity with BEDC on the electroencephalogram is a predictor of the onset of cognitive impairment in children.