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PACS1 neurodevelopmental disorder (Schuurs-Hoeijmakers syndrome; MIM #615009) is a rare autosomal dominant genetic syndrome characterized by developmental delay, intellectual disability, dysmorphic features, and rare seizures. The article describes a clinical case of PACS1 syndrome in a female patient with developmental delay, speech disorder, motor development delay and epilepsy coupled to described variants in PACS1 gene (rs398123009, chr11:6621120, c.607C>T, p.Arg203Trp). Knowing PACS1 syndrome molecular mechanisms is important not only for genotype-phenotypic correlation, but also for developing new therapeutic approaches that could improve the quality of patients’ life.

In most cases, variants of nucleotide sequence in the SEMA6B gene account for developing the phenotype of progressive myoclonus epilepsy and, to a lesser extent, developmental encephalopathy with or without epilepsy. Loss-of-function variants in nucleotide sequence localized mainly in exon 17 of the SEMA6B gene contribute to production of aberrant proteins with “toxic” functions. A clinical case of status epilepsy in a patient with a variant in the SEMA6B gene (c.2506delС; p.His836ThrfsTer136; NM_032108.4) is described in the article that expands our knowledge regarding the SEMA6B gene variants resulting in progressive myoclonus epilepsy.

Focal epilepsy is the most common type of epilepsy accounting for 60–70% of all cases of this pathology. We present two familial cases of focal epilepsy associated with a nucleotide sequence variant in DEPDC5 gene. Clinical and ancestry examination was performed by using instrumental (magnetic resonance imaging, video-electroencephalography) and genetic testing methods. The nucleotide sequence variants in DEPDC5 gene were found in two probands and paired fathers with epilepsy. Focal cortical dysplasia was detected only in the father of Proband 1 as well as Proband 2 with resistant epilepsy and severe cognitive deficit. Hence, such clinical cases confirm that pathogenic variants in DEPDC5 gene are related with familial focal epilepsy, which clinical manifestation may depend on the type of identified mutation. The study of genotype-phenotype correlations is necessary to apply proper therapy. Before surgical treatment of epilepsy, the genetic testing by whole exome or whole genome sequencing should be performed.

The article presents the clinical cases of 6 patients with epilepsy, psychomotor and speech developmental delay. The heterozygous variants of the nucleotide sequence in SPTAN1 gene were detected by whole exome sequencing. Mutations in SPTAN1 gene have been described in patients with developmental and epileptic encephalopathy 5 (ОMIM: 613477). The clinical history, electroencephalographic and magnetic resonance imaging data of our patients are similar in children with variants in SPTAN1 gene described previously. It was shown that variants in SPTAN1 gene located closer to the C-terminal region are associated with a more severe phenotype, whereas the variants near the N-region – with a milder course of the disease without structural brain anomalies. However, further research is necessary in the future to better understand genotype-phenotypic correlations in SPTAN1-associated encephalopathy.

The clinical case of a patient with congenital contractures of the lower and upper limbs, face, seizures, facial dysmorphias, motor disorders and psychomotor development delay is presented. The proband with Freeman–Sheldon syndrome had no mutations in genes associated with distal arthrogryposis. Chromosomal microarray analysis revealed terminal duplication of the long arm of chromosome 9 and terminal microdeletions of the short arm of chromosome 20 – 46,XX.arr[hg38]9q33.3q34.3 (127016168_138124666) x3,20p13 (259113_1003183)x1 in the de novo status. This clinical observation demonstrates an opportunity of using innovative molecular cytogenetic technologies in the search for disease-related genetic causes in the absence of mutations detected by whole exome sequencing.

We present the clinical case of patient with epilepsy, developmental retardation and hearing loss. The whole exome sequencing allowed to reveal compound heterozygous variants of the nucleotide sequence in SPATA5 gene (c.1714+1G>A, c.1678G>A). Mutations in the SPATA5 gene have been described in patients with epilepsy, hearing loss and mental retardation syndrome (MIM 616577). Paired parents were carriers of one heterozygous gene variant. Such mutations lead to the development of epileptic disorders in 3% of cases, and should be considered in patients not only as a possible cause of neurodegenerative diseases, but also leading to pathology with clinical manifestations mimicking mitochondrial disease.

Aim. To approve of diagnostic effectiveness of SWAN (SWI) images in revealing of calcium containing epileptogenic substrates in children with resistant focal epilepsy.Materials and methods. The results of MRI in children with refractory focal epilepsy obtained in the Radiology Department of the Russian State Children Hospital in the period from 2018 to 2020 were observed retrospectively. High-resolution epileptological MR protocol used for investigation of 67 children. SWAN was applied in all cases for identification of calcium containing epileptogenic substrates, including cavernomas, DVA syndrome, cortical gangliogliomas, Sturge-Weber syndrome and tuberous sclerosis complex. All images were received by using MRI 3T 750 W Discovery GE.Results. In 17 cases (25%) SWAN provided important diagnostic information about the nature of the of epileptogenic lesion, its prevalence and borders. Additional earlier invisible structural changes were revealed in 2 cases of SWS and 1 cases of FCD; and in 13 cases SWAN gave us possibility to avoid CT for approving calcium in epileptogenic focus.Conclusion. We believe that adding SWAN in to the epileptological MR protocol is the necessary step for optimizing calcium and blood degradation products identification in the structure of potential epileptogenic focuses. Moreover, it would be very effective instrument for differential diagnosis of cerebral structural changes, specifying its etiology and, hence, would have influence on the therapeutic tactic and surgical strategy in children with focal epilepsy.

Introduction. Cortical dysplasias (CDs) encompass a wide variety of disorders that in most cases lead to epilepsy, especially in infants and young children. MRI diagnosis of CDs is a major part of presurgical examination of pediatric patients with resistant focal epilepsy.Aim. To identify MR markers of CD in the immature brain and develop an MRI protocol for early diagnosis of CDs.Materials and methods. Children aged

Objective: to analyse the clinical and neurophysiological data from a case of early infantile epileptic encephalopathy type 16 in a child with homozygous mutation in TBC1D24 gene.Material and methods. Female child M. aged 1 year and 2 months, with identified mutations in TBC1D24 gene was examined. The whole exome sequencing was performed (Next Generation Sequencing with the Illumina HiSeq 1500 platform, USA). Dynamic video-EEG monitoring was conducted with a “Encephalan-Video” RM-19/26 instrument (“Medicom MTD”, Russia).Results. According to the patient history, on the 22nd day of life, the child developed vocalisms with tonic tension of the limbs. At her 2 months of life, focal myoclonia and myoclono-clonies were noted; at her 4 months – return of tonic seizures with vocalisms followed by eyelid myoclonus, perioral myoclonus, ophthalmoclonia, alternating hemiconvulsions and tonic-clonic seizures. The family history of epilepsy was negative; the parents denied any consanguinity, but admitted a chance of being distant relatives. Neurological examination revealed hypotonic-astatic syndrome and psycho-motor retardation. A video EEG monitoring test detected multiple EEG negative multifocal myoclonic episodes in combination with dystonic hyperkinesia and motor automatism. Although typical epileptiform spike-wave discharges were rare, a focus of low-index spike-wave complexes was identified in the left temporal zone. Therapy with valproates, barbiturates and levetiracetam did not produce any significant effect but benzodiazepines (clonazepam) caused a moderate improvement; a switch to clobazam therapy was then recommended. This case of inherited developmental and epileptic encephalopathy was defined as early infantile epileptic encephalopathy type 16 (OMIM#615338) with autosomal recessive inheritance associated with a previously not described homozygous mutation of the TBC1D24 gene, chr:16:2546775 A>C that caused Tyr209Ser amino acid substitution. Pre-conception testing of the TBC1D24 gene under the IVF condition is recommended to the parents.Discussion. Since 2010, a few variants of early infantile epileptic encephalopathy type 16 caused by homozygous mutation of the TBC1D24 gene have been described in the literature. This clinical case is closer to progressive myoclonic epilepsy with dystonia (PMED), which indicates the nosological autonomy of this form of epilepsy.Сonclusion. Children with pharmacoresistant epilepsy and epileptic encephalopathies, as well as those with unusual course of these diseases need genetic assessment with the new generation exom sequencing techniques – such as the “hereditary epilepsy” panel, as well as clinical and full-exom sequencing.All authors contributed equally to this publication.

Objective. Study the clinical and neurophysiological evolution of early infantile epileptic encephalopathy type 4 (EIEE4) caused by a STXBP1 gene mutation.Material and methods. During 2016-2019, we conducted dynamic observation and treatment of a girl with EIEE4 combined with a mutation in the STXBP1 gene. DNA sequencing was performed using the "Hereditary epilepsies" panel (Next Generation Sequencing on the platform of Illumina HiSeq 2500, USA). Dynamic video-EEG monitoring was performed with an “Encephalan-Video" RM-19/26 ("Medicom MTD“, Russia).Results. In this 3.5 y.o. patient with infantile epileptic encephalopathy, a heterozygous autosomal dominant de novo mutation in the STXBP1 gene was found. This mutation (not described previously) is located in chromosome 9, specifically, in the 20th exon with genome coordinates Chr9:130453 (C.*96T>A). This child suffered from severe neonatal hypoxic-ischemic encephalopathy, which led to spastic cerebral palsy. In addition, she developed seizures as early as at the age of 6 month; the seizures (flexor tonic spasms) were paralleled with EEG changes similar to the Mar-kand-Blume-Ohtahara syndrome, namely, multiple independent spike-wave foci in combination with the partial attenuation pattern (kind of the "burst-suppression" pattern). Valproate monotherapy had little effect, and hormonal treatment caused a temporary improvement. Permanent clinical remission with no seizures was achieved by including leveti-racetam in the therapeutic combination. A number of studies demonstrated a high efficacy of levetiracetam in cases of STXBP1 gene mutations. At the age of 2,5years, the girl demonstrated changes in her EEG records toward the continuous spike-wave during sleep (CSWS) pattern with the morphology of "benign epileptiform discharges of childhood" ("BEDC").Conclusions. In spite of the aggravated perinatal anamnesis, children with epileptic encephalopathy need genetic examination using the Next Generation Sequencing (NGS) methods (such as "Hereditary epilepsies" panel), combined with full exome sequencing. Such genetic examinations are helpful for establishing the exact etiology of epilepsy and developing a personalized approach to antiepileptic therapy.

Consequences of traumatic brain injury (TBI) in children and adolescents pose a major medical and social problem, as TBI interferes with neuro ontogenesis. Among these consequences, paroxysmal disorders that manifest in the long-term after TBI represent an important issue. These disorders include posttraumatic headaches, posttraumatic epilepsy and subclinical epileptiform EEG activity. In this review, clinical manifestations, pathophysiology and management of the long-term post-TBI paroxysmal disorders in children and adolescents are discussed.

Aim: To determine main etiologies and clinical features of neonatal seizures (NS) in groups of newborns of different gestational age (GA).Materials and Methods. Main etiologies of NS were evaluated in 165 newborns divided into four groups: I – 84 early preterm newborns with GA of 28 weeks or less, II – 52 newborns with 29-32 weeks GA, III – 12 newborns with 33-36 weeks GA, and IV – 17 term infants with GA between 37 and 41 wks.Results. In the above 165 infants, the following causes of NS were found: perinatal hypoxia-ischemia – 72.1% of cases, grade III-IV intracranial hemorrhage – 6.1%, congenital infections in 9.7%, CNS infections (bacterial meningitis and viral meningoencephalitis) – 9.7%, сerebral dysgenesis – 1.2%, and inborn errors of metabolism and neurodegenerative diseases accounted for 1.2%. Intracranial hemorrhage (grade III-IV) was detected in newborns with GA less than 32 wks only. The etiological role of CNS infections was higher in term newborns (23.5%) than in the other groups.Conclusion. In examining newborns with NS, genetic mechanisms should be taken into consideration, especially when no indications of early brain damage are apparent. This approach is important today as targeted therapies of gene-associated epileptic syndromes are becoming feasible. In the present article, the use of levetiracetam in infants with NS and early onset epilepsy is discussed.

ASL (Arterial Spin Labeling) – a novel modality of MR angiography – is based on radio-frequency labeling of aqueous protons in the arterial blood; the method is used to monitor blood supply to organs, including the brain. So far there has been little information on the use of ASL in children with focal epilepsy, especially in the pre-surgery period.Aim: to evaluate the perfusion patterns in seizure-free children with drug resistant focal epilepsy (FE) using the ASL mode of MRI.Materials and methods. We studied the ASL data of 54 (23-boys/31 girls) patients with FE treated in the Dpt. of Neurology at the Russian State Children Hospital from 2015 to 2018. The patients’ age varied from 4 months to 17 years. All images were produced with a 3T GE Discovery 750W system.Results. We found several brain perfusion patterns in children with FE; among other factors, those patterns depended on the clinical status of the patient, i. e. the interictal period or the early post- seizure period. The main pattern of the interictal period was characterized by a focal decrease in perfusion located around a structural focus identified on MRI scans. In the early post-seizure period, there was an increase in the arterial perfusion in the area of a structural epileptogenic lesion.Conclusion. ASL-MRI is an effective diagnostic method providing more information on children with FE during their pre-surgery phase. The ASL modality needs further research to rationalize its wider use as a preferred diagnostic tool or as a combination with the more complex PET and SPECT.

The majority of epilepsy cases have their onset in childhood. Compared to their peers, many more children with epilepsy suffer from severe neurodevelopmental disorders, including intellectual disability and autism spectrum disorders. In the present report, the incidence of intellectual disability and autism spectrum disorders among children with epilepsy is reviewed. Four types of connection between epilepsy and autism are discussed: these two conditions are independent as they have different etiologies and may co-occur just by chance; epilepsy and autism are associated because both originate from the same genetic defect or from an early CNS damage; autism is caused by the epileptic process, which interferes with the developing brain networks involved in communication and social behavior. Studies demonstrating positive effects of levetiracetam on the behavioral and cognitive functions (memory, attention) in epileptic children are cited.

Electrical status epilepticus during slow-wave sleep (ESES) is an EEG pattern of continuous (85-100%) diffuse epileptiform activity in the sleep EEG. The morphology of the epileptiform complexes is identical to benign epileptiform discharges of childhood (BEDC). Epilepsy with ESES (or “Penelope Syndrome”) is a form of age-dependent epileptic encephalopathies with the phenomenon of continuous spike-waves during slow wave sleep. This group of epilepsies also includes Pseudo-Lennox syndrome, Landau-Kleffner syndrome, autistic epileptiform regression and some others. In most cases, the ESES pattern correlates with the severity of cognitive deficit in this population of epileptic children. The aim of this study was to evaluate the efficacy and safety of levetiracetam in children with the ESES pattern in the EEG. Materials and Methods. During the period of 2010-2016, 34 epileptic children with ESES patterns in the EEG (14 boys and 20 girls) treated with levetiracetam (33 in combined and 1 in monotherapy) were studied. Results. Twenty eight of the patients with ESES patterns in the sleep EEG were diagnosed with the ESES form of epilepsy. Among them, 7 idiopathic, 13 symptomatic, and 8 “symptomatic” cases of ESES (the latter resulted from “double pathology” of idiopathic + hypoxic-ischemic factors and these children had cerebral palsy). Among other ESES patients, 3 cases were of Pseudo-Lennox syndrome, 2 cases of Landau-Kleffner syndrome and one girl with autistic epileptiform regression. All 28 children received levetiracetam at therapeutic doses of 20-80 mg/kg/daily. Levetiracetam was highly effective in 67.6% of patients (n=23); of those, 2 children showed full clinical and electroencephalographic remission before reaching puberty, 9 children had clinical remission and 12 children had a significant decrease in seizures and epileptiform discharges. A low efficacy of levetiracetam was seen in 20.6% (n=7) of patients. Disease aggravation (seizures and epileptiform discharges) was found in 11.8% (n=4) of patients. Other negative effects were observed in only 4 (11.8%) children (3 cases of agitation and sleep disturbance and one case of allergic rash). In conclusion, levetiracetam is a highly effective medication (67.6% of cases) in combined antiepileptic therapy in children with ESES. However, the risk of exacerbation was as high as 11.8%. The most effective combinations of levetiracetam were those with valproates and ethosuximide.

Childhood absence epilepsy (CAE) is an idiopathic generalized epilepsy, which could be attributed to genetic forms according to the latest proposals of the Commission on Classification and Terminology of the International League Against Epilepsy (2016). CAE has specific clinical and encephalographic characteristics. Data regarding cognitive impairment in children with CAE is still controversial. There are some attempts to introduce more strict diagnostic criteria to be able to define the disease course and prognosis of this form of epilepsy. These are the criteria proposed by Panayiotopoulos C. P. in 2005. Objective. To asses specific features of CAE taking into account the criteria of Panayiotopoulos C. P. (2005). Materials and methods. We have retrospectively analyzed 186 cases of CAE in children; study participants were divided into groups according to Panayiotopoulos’s criteria (2005). Results. Children from the group allocated in accordance with Panayiotopoulos’s criteria had neither generalized tonic-clonic seizures (GTCS) nor myoclonic seizures; control of absence seizures was achieved in 94.3% of the cases; almost 90% of children in this group received monotherapy with mean treatment duration of 2.8 years. Conclusions. The use of more precise diagnostic criteria for CAE will help to predict clinical course of this form of epilepsy and its outcome.

Mitochondrial diseases (MD) represent a large clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain. The article discusses clinical features of the MD, accompanying by epilepsy. Two case reports are presented of MELAS syndrome and Alpers-Huttenlocher syndrome. The genetic background of MD is discussed as well as methods for establishing the diagnosis of MD and peculiarities of antiepileptic therapy

Neurodevelopmental disorders, including intellectual disability, autistic-spectrum disorders, speech and language disorders, attention deficit hyperactivity disorder (ADHD), learning disabilities, are more prevalent in children with epilepsy compared with their peers. Marked developmental delay and regression of acquired skills are typical for epileptic encephalopathies. On the other hand, neurodevelopmental disorders associated with epileptiform activity on the EEG without any clinical manifestations of epileptic fits, represent a serious problem. The causes of neurodevelopmental disorders in children with epilepsy are discussed, as well as clinical features of some epilepsies, associated with neurodevelopmental disorders.

The frequency of detection of stroke in children has increased over the last 25 years (from 1.3 to 13/100 000). The children identified more than 100 risk factors for stroke, but more than a third of cases the cause is not identified. We have analyzed the incidence of epilepsy in children with stroke and risk factors to evaluate the possibility of occurrence of epileptic seizures. It handled 280 case histories of children who had a stroke in the period from 2013 to August 2015 (excluding children with perinatal stroke and bleeding with severe brain injuries) treated at the Morozov Children'sClinicalHospital. All children held in the dynamics of EEG, psychological testing, repeat MRI. The diagnosis of epilepsy had 24 children (8.6%) of the treated patient records. Ischemic stroke was diagnosed in 62%, hemorrhagic – 38%. In HS, prevailed children aged up to 3 years, with ischemic from 6 to 14 years. The most common attacks made their debut from 12 to 24 months after a stroke, some earlier occurrence of attacks observed in hemorrhagic stroke, from 1 month to 12 months (77%). Only 3/24 (12.5%) children seizures were observed in the acute phase stroke. In 71% was a combination of several types of attacks. Two of the children diagnosed with idiopathic forms epilepsy – childhood absence and juvenile myoclonic. Evaluation of the outcome of stroke scale PSOM-SNE and pathopsychological evaluation by the Achenbach revealed more severe neuropsychological problems in children with stroke with epileptic seizures than those without epilepsy.

Abstract: the aim of the study was to analyst the efficiency and safety of topiramate in children and adult epileptic populations depending on the patient’s age and forms of epilepsy. 597 epileptic patients receiving topiramate (302 males, 295 females) aged from 2 up 57 years were followed with video-EEG control during the period of 2002-2012. Topiramate was effective at 66,2% of patients (n=395). Low efficiency was seen at 26,8% (n=160) patients. The aggravation effect has been noted at 7% (n=42) of patients. Drug compliance (for >1 year) was 61,8% (n=369). High efficiency in group 2-3 year (n=134) was 53,8% (n=72), low efficiency in 34,3% (n=46), aggravation – in 11,9% cases (n=16); in group >3-7 years (n=253) high efficiency 59,7% (n=151), low 32% (n=81), aggravation in 8,3% (n=21); in pediatric population >7 years (n=132) high efficiency 81,8% (n=108), low effect in 15,2% (n=20), and 3% aggravation (n=4); in adult population >18 years (n=78) the efficiency was 82,1% (n=64), low effect 16,6% (n=13) and aggravation in 1,3% (n=1). So, topiramate is highly effective medication in the therapy of idiopathic generalized epilepsies without absences and in symptomatic/cryptogenic focal forms of epilepsy. Topiramate could also be useful additional drug in the therapy of epileptic encephalopathies. With the increasing of patients’ age the efficiency of topiramate raised, while the aggravation risks decreased. Peak of aggravation potential was seen in early childhood population and maximal effectiveness – in children up 7 years and adult population.

Abstract: the article presents the clinical observation of outpatients with a diagnosis of epilepsy in the children’s neurological department Morozovsky Children Hospital translation from the original on generic drug valproic acid. Such changes in anticonvulsant therapy in patients quarter led to a deterioration of the disease in the form of clinical remission failure, impairment at lectroencephalography, as well as the emergence of side effects from the gastrointestinal tract and deterioration of cognitive functions. On the basis of this observation can be confirmed by the fact that patients with epilepsyin remission is not recommended translated from the original drug to a generic.

Hypoglycemia in congenital hyperinsulinism (WGI) in children increases the risk of brain damage, seizures and development delay. The aim of our study was to evaluate the clinical manifestations in children with CHI. Hypoglycemia is often manifests with seizures, which are sometimes in the future may lead to the development of epilepsy. Seizures in CHI do not always require a diagnosis of epilepsy and prescription of anticonvulsants. EEG changes in these children may be observed in the absence of epileptic seizures. Developmental delay was more common in children with neurological abnormalities and MRI changes. Children with ABCC8 gene mutations have more complicated for CHI and more prominent developmental delay.