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Hereditary and congenital pathologies make up a significant proportion in the structure of the general morbidity and mortality of the child population. In this regard, the problem of personalized medical care in multidisciplinary clinical centers seems very urgent. In the Scientific-Practical Center of specialized medical care for children the medical genetic service successfully functions since 1995. In 2017–2019, patients were consulted by geneticists, which accounted for 10,6% of all discharged patients; karyotype studies were performed in 463 (20,4%) consulted patients, chromosomal pathology was revealed in 28 (6,04%) of all karyotyped patients. DNA research was performed in 188 patients: exome sequencing – in 112; sequencing of exons of the SCN1A gene – in 39; search for mutations in the PHOX2B gene – in 17; search for frequent mutations in the FGFR1,2,3 genes – in 15 (the technique was introduced since September 2018); sequencing of SLC2A1 gene – in 5 patients. The high demand for medical genetic counseling and laboratory genetic diagnosis of hereditary and congenital diseases confirms the need for independent medical genetic units in multidisciplinary clinical hospitals, that should interact with medical genetic services at regional and federal levels.

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.

Introduction. Late and inaccurate diagnosis of tension-type headache (TTH) leads to the lack of timely rational treatment. In children and adolescents with TTH, the role of comorbid disorders that affect the course of TTH and can contribute to their chronification is not sufficiently taken into account. Meanwhile, with timely diagnosis and adequate treatment of TTH in many children and adolescents, a significant improvement in the disease’s course and the prognosis is achieved, and clinical remission is possible. Considering the high prevalence of TTH among children and adolescents, the decline in their quality of life, and the high frequency of comorbid disorders, it is reasonable to develop effective methods of preventive treatment for TTH in this age group. The aim of the study was to evaluate the effectiveness of monotherapy with γ-amino-β-phenyl butyric acid hydrochloride, amitriptyline, or breathing gymnastics (comparison group) indicated for two months as a preventive treatment of TTH in children and adolescents in the open randomized comparative study in three parallel groups of patients. Material and methods. In an open parallel study, 90 TTH patients aged 8-16 years were divided into three groups of 30 patients (each with 15 boys and 15 girls). Results. Significant differences with the comparison group in the individual response to therapy were confirmed. According to the criterion of a 50% or more reduction in the average number of headache attacks per month in group 1 (γ-amino-β-phenyl butyric acid hydrochloride), the improvement was achieved in 56.7% of patients, in group 2 (amitriptyline) - in 73.3%, in the 3rd group (breathing gymnastics) - in 30%. According to a more strict criterion for reducing the average number of headache attacks per month by 75% or more, the response to therapy was observed in group 1 in 30%. In group 2 - in 23.3%, in group 3 - in 3.3% of patients. In groups 1 and 2, along with a significant decrease in the frequency, duration, and intensity of TTH attacks, a significant improvement in daily activity, a favorable effect on the manifestations of fatigue, anxiety disorders, and sleep disorders associated with TTH was demonstrated. The therapeutic efficacy of breathing gymnastics exercises complex was confirmed in the prevention of TTH with frequency, duration, and intensity reduction of TTH, and diminishing its impact on daily activity, a moderate decrease in manifestations of fatigue, anxiety disorders (by patients’ self-assessment), and improvement in sleep quality.

Introduction. MRI revealing the epileptogenic foci is the central part of the presurgical evaluation of children with focal-resistant epilepsy. Besides that, MRI seems to be a reliable instrument of treatment optimization and good prognosis. Aim. To identify epileptogenic lesions in children with resistant focal epilepsy by high resolution (HR) MRI and comparing obtained data with postsurgical morphology. Materials and methods. We assessed the results of neuroimaging, EEG, clinical neurological status, and postsurgical morphological data in 65 children with focal epilepsy who had undergone antiepileptic surgery in Russian State Children Hospital, neurosurgery department (Moscow, Russia) from 2016 to 2020. Results. The broad spectrum of epileptogenic lesions was revealed by HR MRI, including focal and diffuse cortical dysplasias (44.6%), cortical post hypoxic gliosis (27.7%), glial tumors (7.7%), Rasmussen encephalitis (10.8%), tuberous sclerosis, and Sturge-Weber syndrome (3%), small angiodysplasias (4.6%) and other. Focal cerebral dysplasia had an obvious superiority as the main etiological factor in focal epilepsy and was approved in 33.8% of all patients. In all cases, epilepsy is characterized by frequent and resistant seizures, inflicting motor arrest, and psycho-emotional deterioration. Conclusion. HR MRI and multidisciplinary investigation have to be unchangeable standards in the presurgical evaluation of children with focal epilepsy. This approach’s effectiveness has reassuring confirmation by high level (95.2%) of total coincidence MRI and morphological results.

Merosin-deficient muscular dystrophy is the most common form of congenital muscular dystrophies (СMD), characterized by genetic heterogeneity and a severe course in most cases. CMD pathogenesis is associated with a partial or complete absence of laminin 2 chains in the basal membrane of muscle fiber caused by a mutation in theLAMA2gene. The clinical manifestations of LAMA2-associated muscular dystrophy vary from severe СMD (СMD 1A) with an early onset to a relatively mild course with a late onset and phenotype of limb-girdle muscular dystrophy. CMD type 1A is characterized by a delay in motor development from the first months of the life (while the vast majority of children do not master the ability to walk independently), facial muscles weakness, ptosis, ophthalmoplegia, spine rigidity, early occurrence of contractures in the shoulder, elbow, hip and knee joints, restrictive respiratory disorders, nutritional problems, such as disorders of swallowing and chewing, gastroesophageal reflux, low body weight; some children suffer from mental retardation and epilepsy.

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.

Objectives. To study the clinical and electroencephalographic characteristics of early infantile epileptic encephalopathy (EIEE) type 14, due to mutations in the KCNT1 gene. Materials and methods. Over the period 2017–2019, three unrelated girls (M.V. aged three years three months, T.V. aged nine months, and M.U. aged five months) with the clinical picture of infantile epilepsy with migrating focal seizures (IEMFS) were investigated and mutations in the KCNT1 gene were identified. New-generation DNA sequencing (Inherited Epilepsy panel) was run on an Illumina NextSeq 500 platform (USA). Video EEG monitoring was with an Encephalan Video system based on an Encephalan-RM RM-EEG-19/26 instrument (Medikom MTD, Russia). Results and conclusions. M.V. showed a previously undescribed mutation in exon 12 of the KCNT1 gene (chr9:138656907C>T) with amino acid substitution Arg356Trp. T.V. had a known mutation in chromosome 9, 138651532G>A with amino acid substitution of glycine by serine as position 288, i.e., Gly288Ser (OMIM: 608167.0010). M.U. showed a previously undescribed heterozygous mutation in exon 15 of the KCTN1 gene (chr9:138660712A>G), leading to an amino acid substitution in position 480 (Asp480Gly). In M.V., the onset of EIEE was at age four months with hypomotor dialeptic and tonic versive seizures. Epilepsy in T.V. started at age 4.5 months with hypomotor seizures with ophthalmoclonia and facial hyperemia. In M.V., neonatal convulsions were seen with bilateral tonic-clinic seizures and cyanosis, and subsequent development of status epilepticus with alternating hemiconvulsions. All girls went on to develop seizures of multiregional genesis to the level of migrating status epilepticus with the typical electroclinical picture of IEMFS. Thus, these findings lead to the conclusion that the KCNT1 gene may be the main gene determining the development of EIEE.

Tuberous sclerosis is one of the genetically determined neurodermal syndromes, characterized by focal epilepsy, which is resistant to drug therapy in most cases. Tuberous sclerosis has not been surgically treated for a long time due to the multifocal nature of brain damage. However, using new instrumental methods the surgeon can isolate tuber – “drivers”, responsible for epileptic induction, which, therefore, can be a target for surgical removal. The article presents a clinical case of the treatment of pharmacoresistant epilepsy in a 17-year-old girl with tuberous sclerosis and normal neuropsychiatric and cognitive status; the surgeon managed to achieve a complete regression of seizures after the surgical removal of one of the tubers. Using a multimodal complex of examinations, including high-resolution magnetic resonance imaging and invasive electroencephalographic monitoring, the surgeon managed to identify the “inductor” tuber associated with the epileptic initiation zone among multiple cortical tubers. This section of the cerebral cortex was subjected to surgical resection. For the entire postoperative period (16 months) there were no seizures and antiepileptic drugs were canceled; cognitive processes, memory were improved. Thus, active surgical tactics may be effective in more than 50% of patients with tuberous sclerosis and pharmacoresistant epilepsy. This case confirms the need for a multidisciplinary examination prior to the surgery in patients with tuberous sclerosis.

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 Results. The rate of detection of small-size cortical malformations, such as nodular heterotopies or focal cortical dysplasias was significantly higher in groups of patients whose brains (according to MR images) were at the infantile or adult phases of myelination. In children with the isointensive phase myelination, only large cortical dysplasias could be identified. In the first phase, the focal malformations had low amplitude signals in T2-weighted images and high amplitude signals in T1, unlike those in adult patients. In the isointensive phase, the quality of visualization was significantly reduced and provided poor diagnostic information.Conclusion. The results confirm the diagnostic significance of early (before age of 5 months) MRI testing in cases with suspected CD-associated focal epilepsy. However, at the period between 5 and 12 months of age, MR imaging was ineffective for CD diagnosing. Later, in the period from 12 to 15 months, the MRI ability to identify the CDs gradually increased. We consider the standard T2 weighted images with high TR values, the most effective MR modality for diagnosing CDs in young children.

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. С onclusion . 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.

On the example of the diagnosis of the structural basis of focal epilepsy in an adult patient, the possibilities of a multimodal and interdisciplinary approach to diagnosis, combining the latest methods of neuroimaging with the results of neurophysiological examinations, are considered. The interaction and high qualification of specialists in epileptology, neuroradiology and pathomorphology provide a high probability to determine the cause of the focal forms of epilepsy. Along with the introduction of super-inductive MR systems, it is important to use their capabilities correctly and optimize the scanning protocol for the individual characteristics of the patient. With a long-term pharmacoresistant course of focal epilepsy, accompanied by low quality of life, the progression of neurological deficits and the aggravation of cognitive and personality problems in patients, it becomes obvious that these patients, even with negative results of standard MRI, are candidates for a more in-depth comprehensive examination to identify the structural basis of epileptogenesis and subsequent epileptic surgery. However, the problem of epilepsy pseudoresistance should be considered, when a patient with uncontrolled seizures takes antiepileptic drugs for a long time in inadequate dosages. Modern comprehensive diagnostics offers new rational approaches to antiepileptic therapy indication on the part of the doctor, as well as to improve the patient's compliance to the treatment.На примере диагностики структурной основы фокальной эпилепсии у взрослого пациента рассматриваются возможности мультимодального и междисциплинарного подхода к диагностике, совмещающего новейшие методы нейровизуализации с результатами нейрофизиологических обследований. Взаимодействие и высокая квалификация специалистов в области эпилептологии, нейрорадиологии и патоморфологии с большой вероятностью позволяет установить причину развития фокальных форм эпилепсии. Наряду с внедрением супериндуктивных МР-систем важное значение имеет правильное использование их возможностей и оптимизация протокола сканирования под индивидуальные особенности пациента. При длительном фармакорезистентном течении фокальной эпилепсии, особенно на фоне низкого качества жизни, прогрессирования неврологического дефицита и усугубления когнитивных и личностных проблем у пациентов, становится очевидным факт, что эти пациенты даже при негативных результатах стандартной МРТ являются кандидатами для более углубленного комплексного обследования с целью идентификации структурной основы эпилептогенеза и последующей эпилептической хирургии. Однако следует отметить так называемую проблему псевдорезистентности эпилепсии, когда пациент с неконтролируемыми приступами длительное время принимает противоэпилептические препараты в неадекватных дозах. Современная комплексная диагностика позволяет предложить новые рациональные режимы противоэпилептической терапии, а также улучшить комплаентность пациента.

To study the therapeutic efficacy of two treatment modes of peptidergic nootropic medication cortexin in children with developmental dysphasia aged 3-4 years.Ninety-four children with developmental dysphasia were divided into three groups. In group 1 (27 patients), cortexin was administered once a day intramuscularly for 10 days. After this course, the children were not prescribed drug therapy, a second examination was carried out 2 months after the start of treatment. In group 2 (40 patients), two courses of cortexin were administered at 1-month intervals, and the children were also followed up for two months. Control group 3 (27 patients) did not receive medication, but was also followed up for two months. All the parents were provided with recommendations for the stimulation of speech development in children. Before the study and two months later, speech development was assessed with special scales and questionnaires for parents.The increase ratio of the active vocabulary volume by 2 times or more was observed in group 2 (two courses of cortexin treatment) in 80.0% of patients (significant differences with groups 1 and 3,The results of the study confirm the higher effectiveness of two courses of the peptidergic nootropic medication cortexin in the pharmacotherapy of developmental dysphasia in children, aged 3-4 years, conducted over two months, compared with the indication of one treatment course.Оценить терапевтическую эффективность двух режимов терапии пептидергическим ноотропным препаратом Кортексин при дисфазии развития у детей в возрасте 3—4 лет.Обследованы 94 ребенка с дисфазией, распределенных на три группы. В 1-й группе (27 пациентов) проводился курс лечения Кортексином: 1 раз в сутки внутримышечно ежедневно в течение 10 дней. После этого курса детям не назначалась лекарственная терапия, повторное обследование осуществлялось через 2 мес от начала курса Кортексина. Во 2-й группе (40 пациентов) проведено два курса Кортексина с интервалом 1 мес, дети также наблюдались в течение 2 мес. Третья группа сравнения (27 пациентов) не получала медикаментозной терапии, но также наблюдалась в динамике в течение 2 мес. Родители всех пациентов получали рекомендации по стимуляции речевого развития у детей. Перед началом лечения и через 2 мес оценивали состояние речи детей по шкалам речевого развития и специальным опросникам для родителей.Кратность увеличения объема активного словаря в 2 раза и более отмечена во 2-й группе (2 курса лечения Кортексином) у 80,0% пациентов (значимые различия с 1-й и 3-й группами

The number of COVID-19 patients is increasing worldwide and the number of patients with neurological manifestations of a new coronavirus infection is increasing as well. Pathognomonic for COVID-19 is the presence of cephalgic syndrome, infectious-toxic encephalopathy, hypo- and anosmia and ageusia. Inducing of pathological autoimmune response contributes to the development of Miller Fischer and Guillain-Barré syndrome. Hyperergic reaction with the generation of the so-called «cytokine storm» provokes multisystem hemorrhagic complications such as Kawasaki disease and acute necrotizing hemorrhagic encephalopathy. There is also a special form of COVID-19-associated stroke. Almost all post-COVID-19 patients complain of severe fatigue, emotional lability, and sometimes have features of asthenic-neurotic, anxiety-phobic disorders and apato-abulic syndromes, which require rehabilitation measures, as well as courses of restorative neurotrophic and nootropic therapy.Во всем мире нарастает число пациентов с COVID-19, среди которых больные с неврологическими проявлениями новой коронавирусной инфекции. Увеличивается и количество верифицированных педиатрических случаев с неврологическими осложениями. Патогномоничным для COVID-19 является наличие цефалгического синдрома, инфекционно-токсической энцефалопатии, гипо- и аносмии и агевзии. Индуцирование патологического аутоиммунного ответа способствует развитию синдромов Миллера Фишера и Гийена—Барре. Гиперергическая реакция организма с развитием так называемого цитокинового шторма провоцирует мультисистемные геморрагические осложнения по типу болезни Кавасаки и острой некротизирующей геморрагической энцефалопатии. Выделяют также особую форму COVID-19-связанную с инсультом. Практически все пациенты, перенесшие COVID-19, жалуются на выраженную астенизацию, эмоциональную лабильность, а также порой имеют черты астеноневротического, тревожно-фобического расстройств и апатико-абулического синдрома, что требует реабилитационных мероприятий, а также курсов восстановительной нейротрофической и ноотропной терапии.

Objectives. To assess the efficacy and safety of hopantenic acid (Pantogam) compared with placebo in the treatment of ADHD for four months in children aged 6–12 years during a prospective, multicenter, comparative, double-blind, placebo-controlled, parallel-group trial. Materials and methods. The study included 100 patients constituting the safety population (50 in the Pantogam group and 50 in the placebo group). A total of 89 patients completing the study in compliance with the protocol entered the efficacy evaluation population: 45 in the Pantogam group (group 1) and 44 in the placebo group (group 2). Pantogam was given as tablets containing 250 mg at the pediatric therapeutic dose of 30 mg/kg, divided into two split doses, for four months. Assessment of patients’ statements at follow-up addressed the total points scores on the DSM-IV ADHD, the CGI-S Clinical Global Impression scale, the WFIRS-P functional impairments scale, and the results of a correction test (the Toulouse–Pieron test). Results and conclusions. The efficacy of Pantogam in ADHD in children aged 6–12 years as compared with placebo showed a marked tendency to an increase in the proportion of patients with improvements (decreases in total points scores on the DSM-IV ADHD scale by more than 25%) by the ends of the third and fourth months of treatment: treatment responses were achieved in 66.7% and 68.9%, respectively, compared with 52.3% and 61.4% in the placebo group. Pantogam therapy also produced a decrease in disease severity from the placebo level on the CGI-S scale. At four months of Pantogam treatment, there were decreases in the severity of functional impairments on sections 4 and 6 of the WFIRES-P “Family,” “School and learning,” “Child’s self-concept,” and “Risky activities” scales. Pantogam also improved the maintenance of attention in children with ADHD, as measured using the Toulouse–Pieron test (quality and rate of performance) as compared with placebo. Treatment with Pantogam at a mean daily dose of 30 mg/kg for four months demonstrated a favorable safety profile, no different from that of placebo.

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.

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.

This article describes 9 clinical cases of Aicardi–Goutieres syndrome (AGS) in children admitted to the hospital of the Scientific and Practical Center of Medical Care for Children with Resistant Multifocal Epilepsy. Epilepsy, psychomotor retardation, and a loss of previously acquired skills were diagnosed during the investigation. Targeted exome sequencing in one child revealed a mutation in the RNASEH2B gene responsible for the development of this disease. AGS is an early-onset progressive encephalopathy with basal ganglia calcification, leukodystrophy, lymphocytosis, elevated interferon-alfa levels in the cerebrospinal fluid, and no evidence of viral infection. Noninfectious leukoencephalopathy concurrent with multifocal epilepsy in early childhood suggest that the syndrome is an inherited disease.

The aim of the study was to study the effect of the drug recognan (citicoline) on the neurodynamic characteristics of mental activity in patients with mild cognitive impairment.A survey of 58 subjects (17 of them male and 41 female) aged 18-45 years (average age 27.2±12.5 years) was conducted. Clinical diagnosis according to ICD-10 «Mild cognitive impairment» (F06.7). The main subgroup included29 people received oral recognan therapy (in solution, 100 mg in 1 ml) for 30 days, with a daily dosage of 500 mg (5 ml of solution). In the control group (29 people) drug therapy was not performed. Tests were used: «Graphic sample», the sample on the reciprocal coordination of the hands (Ozeretsky test), test for the compression of fingers, the test «number series». The follow-up period was 30 days. All subjects were examined three times (initially, in the middle of the study - on day 15, at the end of the study - on day 30).The results obtained showed that the use of the drug recognan (citicoline) has a positive effect on the indicators of visual-motor coordination and spatial representations, neurodynamic characteristics of movement, and cognitive functions. After a 2-week treatment with recognan improved graphical sample, 84% of patients, with reliable improvement according to the Wilcoxon (Изучение влияния препарата Рекогнан (цитиколин) на нейродинамические характеристики психической деятельности у пациентов с легкими когнитивными нарушениями.Проведено обследование 58 пациентов (17 мужчин и 41 женщина) в возрасте 18—45 лет (средний возраст 27,2±12,5 года) с клиническим диагнозом по МКБ-10 «Легкое когнитивное расстройство» (F06.7). В основную группу вошли 29 пациентов, которые получали пероральную терапию Рекогнаном (в растворе, 100 мг в 1 мл) в течение 30 дней, при этом суточная дозировка препарата составляла 500 мг (5 мл раствора). В группе сравнения (29 человек) медикаментозная терапия не проводилась. Использовались тесты «Графическая проба», проба на реципрокную координацию рук (проба Озерецкого), проба на сжимание пальцев, тест «Числовые ряды». Все пациенты обследовались трижды (до начала терапии, на 15-й день терапии, после лечения — на 30-й день).Полученные результаты показали, что применение препарата Рекогнан (цитиколин) оказывает положительное влияние на показатели зрительно-моторной координации и пространственных представлений, нейродинамические характеристики движения, когнитивные функции. После 2 нед лечения Рекогнаном отмечалось улучшение выполнения графической пробы у 84% обследованных, с достоверным улучшением (

OBJECTIVE The aim of the observational program was to study the effect of the use of the drug recognan (citicoline) on the state of higher mental functions (memory, attention, visual-motor coordination, dynamic praxis,verbal thinking and imagination) in patients with mild cognitive impairment. MATERIAL AND METHODS A survey of 54 subjects (16 of them male and 38 female) aged 18-50 years (average age 28.5±10.5 years) was conducted with a diagnosis of «Mild cognitive impairment» («F06.7»). The group was randomized into 2 subgroups: the main subgroup (26 people) received oral therapy with the drug Recognan, for 30 days, with the daily dosage of the drug being 500 mg. In the control group (28 people), nootropic drug therapy was not performed. Standard psychometric techniques were used to study higher mental functions. All subjects were examined three times (initially, in the middle of the study - on day 15, at the end of the study - on day 30). RESULTS AND CONCLUSION After 2 weeks of treatment with recognan, there was an improvement in concentration in 81.9%, memory in 50% (p=0.008), verbal imagination productivity in 68.2% (p=0.015), counting functions in 60% (p=0.015), visual-motor coordination and dynamic praxis - in 86.4% (p=0.003), increased speed and efficiency of mental work (p=0.001). After a 30-day course of treatment with recognan, there was an improvement in memory in 58.3% of patients (p=0.007), an increase in concentration in 64%, an improvement in counting functions in 64.3% (p=0.011), verbal imagination productivity in 63.3%, visual-motor coordination and dynamic praxis in 86.4% (p=0.007), speed and efficiency of mental work (p=0.006), which indicates a complex positive effect of recognan on higher mental functions in patients with mild cognitive impairment cognitive impairment.

On June 25-26, 2021, a round table was held in Kazan with the participation of leading neurologists of Russia, where the issues of treatment of patients with cognitive impairment due to cerebrovascular diseases were discussed. Cognitive disorders of vascular genesis (VCD) are widespread in the population, are a common cause of a decrease in the quality of life and restriction of daily activity. The cause of VCD is both acute and chronic cerebrovascular diseases. An effective way to prevent VCD is to control cardiovascular risk factors, ensure a sufficient level of cognitive and physical activity throughout life. The role of drug therapy, aimed, among other things, at normalizing metabolic processes in the brain, is extremely important. The data on the mechanisms of action of the new domestic drug prospecta, the results of its clinical trials in patients with VCD are presented.25—26 июня 2021 г. в Казани состоялся круглый стол с участием ведущих неврологов России, на котором обсуждались вопросы лечения пациентов с когнитивными нарушениями вследствие цереброваскулярных заболеваний. Когнитивные нарушения сосудистого генеза (СКН) широко распространены в популяции, являются частой причиной снижения качества жизни и ограничения повседневной активности. Причиной СКН являются как острые, так и хронические цереброваскулярные заболевания. Эффективный способ предупреждения СКН — контроль факторов сердечно-сосудистого риска, обеспечение достаточного уровня когнитивных и физических нагрузок на протяжении жизни. Исключительно важна роль медикаментозной терапии, направленной в том числе на нормализацию обменных процессов в головном мозге. Приведены данные о механизмах действия нового отечественного препарата Проспекта, результатах его клинических испытаний у пациентов с СКН.

To evaluate the characteristics of neurodevelopment by the age of 5-8 years in children who were born very preterm with extremely low body weight (ELBW) and very low body weight (VLBW).Seventy-two patients, aged from 5 years to 8 years were examined. Patients were divided into group I (36 patients born preterm with ELBW (16 boys, 20 girls)) and group II (36 patients born with VLBW (16 boys, 20 girls)). The control group included 30 healthy peers (16 boys, 14 girls). All children were assessed by means of the Griffiths Mental Development Scales, Extended Revised: 2 to 8 years (GMDS-ER 2-8).The value of general quotient (GQ) in patients born with ELBW (73.4±2.1) was significantly lower compared to their healthy peers (80.9±2.1; p=0.036). The same tendency was found in patients born with VLBW who's GQ was decreased by 73.1±3.0 (p=0.101). Concurrently the patients demonstrated lower scores on all six scales, which achieved significant difference with the controls for the 'Locomotor' and 'Performance' scales in group I, and for the 'Performance' and 'Practical reasoning' scales in group II. The boys born with ELBW tended to demonstrate lower results on all six scales and received significantly lower scores on the 'Locomotor' and 'Language' scales. The boys born with VLBW demonstrated significantly lower scores on the 'Language', 'Eye and hand co-ordination' and 'Practical reasoning' scales. In girls significantly lower score on the 'Performance' scale only was shown for those, who were born with ELBW.Early diagnosis and characterization of developmental delays in children born very preterm determine the effectiveness of therapeutic measures based on the individual approach and comprehensive medical-psychological-pedagogical support.Цель исследования. Оценка нарушений нервно-психического развития у детей в возрасте 5-8 лет, родившихся глубоко недоношенными с экстремально низкой (ЭНМТ) или очень низкой (ОНМТ) массой тела. Материал и методы. Обследовали 72 пациентов в возрасте от 5 до 8 лет. Детей разделили на две группы: по 16 мальчиков и 20 девочек в каждой. В 1-ю группу вошли дети, которые были рождены глубоко недоношенными с ЭНМТ, во 2-ю - с ОНМТ. Группу контроля составили 30 (16 мальчиков, 14 девочек) здоровых, сопоставимых по возрасту. Для оценки нервно-психического развития всех детей применяли шкалу Гриффитс (GMDS-ER 2-8), состоящую из 6 субшкал. Результаты. Значения общего показателя нервно-психического развития (GQ) были статистически значимо более низкими у детей 1-й группы по сравнению с контролем (73,4±2,1 и 80,9±2,1 соответственно; р=0,036). У пациентов 2-й группы GQ также имел тенденцию к снижению и составил 73,1±3,0 (р=0,101). При дифференцированном анализе шкалы Гриффитс в 1-й группе снижение показателей достигало статистически значимых различий по субшкалам 'двигательная активность' и 'выполнение действий', во 2-й - по субшкалам 'выполнение действий' и 'практическое мышление'. У мальчиков 1-й группы статистически значимым было снижение баллов по субшкалам 'двигательная активность' и 'речь', 2-й группы - по субшкалам 'речь', 'зрительно-моторная координация', 'практическое мышление'. Среди девочек значимое снижение показателей было выявлено только в 1-й группе по субшкале 'выполнение действий'. Заключение. Ранняя диагностика и определение характера отставаний в развитии детей, родившихся глубоко недоношенными, определяет эффективность лечебно-реабилитационных мероприятий, при этом необходимы индивидуальный подход и комплексное медико-психолого-педагогическое сопровождение.

The problem of epilepsy comorbidity with autism spectrum disorders in children is discussed. The incidence data of autism spectrum disorders in epilepsy, epileptiform discharges on the EEG in autism spectrum disorders and epilepsy in autism spectrum disorders are reviewed. The following types of epilepsy and autism co-occurrence are discussed: both conditions are independent, have different causes and may co-occur by chance; epilepsy and autism are associated, both being independent consequences of the same genetic disorder or early cerebral damage; autism is caused by the epileptic process which interferes with the function of specific brain networks involved in the development of communication and social behavior; autism is a result of the withdrawal reaction in the epileptic child. The known genetic causes of epilepsy and autism spectrum disorders comorbidity are provided. The practical issues are discussed, in particular the rational indication of antiepileptic drugs to the children suffering autism spectrum disorders.Рассматривается проблема коморбидности расстройств аутистического спектра (РАС) с эпилепсией у детей. Приводятся данные о встречаемости РАС при эпилепсии, эпилептиформных разрядов на ЭЭГ при РАС, а также эпилепсии при РАС. Рассматриваются возможные варианты ассоциации эпилепсии и РАС: РАС и эпилепсия могут развиться одновременно, но независимо, и вызываются разными причинами; РАС и эпилепсия взаимосвязаны, являются проявлением одного и того же генетического дефекта или раннего повреждения ЦНС; РАС - следствие эпилепсии, начинающейся или распространяющейся на развивающиеся нейронные сети, ответственные за коммуникацию и социальное поведение; РАС - результат реакции на изоляцию у детей с эпилепсией. Приводятся примеры сочетания эпилепсии и РАС, которые имеют общую генетическую природу. Обсуждаются практические аспекты проблемы коморбидности эпилепсии и РАС, в частности целесообразность назначения антиэпилептических препаратов детям с РАС.

Study aim. To investigate the dynamics of measures of behavior, attention, and memory during treatment with Noofen (250-mg capsules) in children with attention deficit hyperactivity disorder (ADHD). Materials and methods. A total of 50 patients taking part in an open study were divided into two groups of 25 patients: patients of group 1 received Noofen while patients of group 2 (controls) received only low doses of multivitamins. Treatment lasted one month. Noofen was given at doses of 15–20 mg/kg (500–750 mg) per day using 250-mg capsules, as two or three doses. Results and conclusions. Neuropsychological test results at the end of one month of treatment demonstrated improvements in cognitive functions, including measures of self-control, sustained, focused, and distributed attention, and auditory verbal memory. It is suggested that the initial positive changes may provide a base for attaining more significant clinical outcomes with longer-lasting treatment.

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 article describes the main clinical forms and causes of speech delay in children. It presents modern data on the role of neurobiological factors in the speech delay pathogenesis, including early organic damage to the central nervous system due to the pregnancy and childbirth pathology, as well as genetic mechanisms. For early and accurate diagnosis of speech disorders in children, you need to consider normal patterns of speech development. The article presents indicators of pre-speech and speech development in children and describes the screening method for determining the speech delay. The main areas of complex correction are speech therapy, psycho-pedagogical and psychotherapeutic assistance, as well as pharmaceutical treatment. The capabilities of drug therapy for dysphasia (alalia) are shown.

The article is devoted to the actual problem of modern pediatrics and neurology ― a comprehensive diagnosis and correction of sleep disorders in children. Detail the features of the clinical manifestations of sleep disorders in childhood (insomnia and parasomnia), great attention is paid to sleep apnea syndrome as a risk factor for somatic and psychopathological disorders in children. Highlight the current capabilities of complex instrumental diagnosis of sleep disorders with the use of highly effective methods of polysomnography and pulse oximetry. The actual dimensions as non-drug and drug treatment of sleep disorders in children, taking into account the pathogenetic features of their occurrence. From the standpoint of evidence-based medicine demonstrate efficient methods of herbal medicine, developed on the basis of traditional Chinese recipes, as well as modern nootropics and magnesium preparations. It is shown that sleep disorders in children not only lead to a deterioration of emotional mood, cognitive function, health and school performance, but also are associated with increasing risk of somatic disorders, which determines the need for timely diagnosis and comprehensive differentiated medical and psychological data correction of pathological conditions, taking into account the neurophysiological and biochemical mechanisms of their development, as well as polymorphism of clinical manifestations, in order to increase the effectiveness of treatment and quality of life of patients.

The article is dedicated to an urgent issue of modern pediatrics and neurology — complex treatment of stroke consequences in children. The article details etiological aspects, pathophysiological mechanisms and clinical peculiarities of stroke consequences in children, the primary among which are asthenic syndrome (73–86% of the patients), movement disorders (33–58%), cognitive disorders (60%), paroxysmal conditions (30%), sensory disorders (14%), emotional-volitional and behavioral disorders (17–38%), vegetative dysfunction syndrome (60–74%), pain syndrome (53–74%) and syncopal conditions (12%). The article details the main spheres of complex rehabilitation of children with stroke consequences, including use of innovative medical rehabilitation technologies — kinesitherapy, dynamic proprioceptive correction, mechanotherapy using robotic systems, physiotherapy and drug correction. The article demonstrates that diagnosis and treatment of stroke consequences in children is a difficult problem, which requires a differential complex approach in order to improve effectiveness of both drug therapy and rehabilitation and quality of life of the patients.

To assess the efficacy of noophen (γ-amino-β-phenylbutyric acid hydrochloride) in the preventive treatment of tension-type headache (TTH) in children and adolescents.The study included 30 patients with TTH, aged from 8 to 16 years, treated with noophen in dose of 15-20 mg/kg per day (2-3 times perorally) during 2 month. Before and during the treatment characteristics of headache, its influence on daily activities were assessed with HIT-6 and PedMIDAS, anxiety disorders were assessed with SCAS, the dynamics of sleep disturbances in children were evaluated.A significant decrease in the frequency, duration and intensity of TTH as well as positive changes in daily life activities and reduction of anxiety and sleep disorders manifestations, which are the risk factors for TTH, were demonstrated during the treatment with noophen. Starting from the first month of treatment, there was a significant decrease in the number of days completely lost because of headache and days with the reduced activity (a decrease in the productivity by50%).Цель исследования. Оценка эффективности препарата ноофен (γ-амино-β-фенилмасляной кислоты гидрохлорид) в профилактической терапии головной боли напряжения (ГБН) у детей и подростков. Материал и методы. Обследованы 30 пациентов 8-16 лет с ГБН, которые принимали ноофен в течение 2 мес в дозе 15-20 мг/кг в день перорально в 2-3 приема. Контрольную группу составили 30 пациентов того же возраста, которым была назначена дыхательная гимнастика. До и во время лечения оценивали характеристики головной боли, ее влияние на повседневную активность по методикам HIT-6 и PedMIDAS, проявления тревожных расстройств по шкале детской тревоги SCAS, динамику по детской шкале нарушений сна. Результаты и заключение. На фоне терапии препаратом ноофен наряду с существенным уменьшением частоты, продолжительности и интенсивности ГБН установлена положительная динамика в повседневной активности пациентов, а также регресс проявлений тревожности и расстройств сна, которые относятся к факторам риска ГБН. Начиная с 1-го месяца терапии наблюдалось значительное уменьшение количества полностью 'потерянных' из-за головной боли дней и дней со сниженной активностью (снижение продуктивности более чем на 50%).

Neurodevelopmental disorders, including intellectual disability, autistic-spectrum disorders, speech disorders, attention deficit hyperactivity disorder (ADHD), learning disabilities, are more prevalent in children with epilepsy compared with the general population. Marked developmental delay and regression of acquired skills are characteristic of epileptic encephalopathies. Conditions, in which neurodevelopmental disorders are associated with the marked epileptiform EEG activity, while clinical epileptic seizures are absent, represent a serious problem. The authors consider the features of epilepsy with electrical status epilepticus during slow-wave sleep, pseudo-Lennox syndrome, Landau-Kleffner syndrome, children autistic epileptiform regression, autosomal-dominant rolandic epilepsy with verbal dispraxy and a combination of epilepsy and subclinical epileptiform EEG activity with developmental dysphasia and ADHD. In addition to the optimization of basic treatment with antiepileptic drugs (AEDs), nootropic drugs which do not increase epileptiform activity (hopantenic acid), are recommended.У детей с эпилепсией значительно чаще, чем в общей детской популяции, встречаются нарушения нервно-психического развития: общая интеллектуальная недостаточность, расстройства аутистического спектра, нарушения развития речи, синдром дефицита внимания и гиперактивности (СДВГ), расстройства обучения. Выраженное отставание в развитии, а также регресс ранее приобретенных навыков характерны для эпилептических энцефалопатий. Серьезную проблему представляют состояния, при которых нарушения нервно-психического развития ассоциированы с выраженной эпилептиформной активностью на ЭЭГ, а клинические эпилептические приступы отсутствуют. Рассматриваются особенности проявлений таких состояний, как эпилепсия с электрическим эпилептическим статусом медленноволнового сна, синдром псевдо-Леннокса, синдром Ландау-Клеффнера, детский аутистический эпилептиформный регресс, аутосомно-доминантная роландическая эпилепсия с речевой диспраксией, а также сочетание с эпилепсией и субклинической эпилептиформной активностью на ЭЭГ дисфазии развития и СДВГ. Помимо оптимизации основной терапии антиэпилептическими препаратами (АЭП) в случаях сочетания эпилепсии с нарушениями развития рекомендуются ноотропные препараты, которые не вызывают нарастания эпилептиформной активности (гопантеновая кислота).

To analyze the images obtained during pre-surgical neuroimaging in patients with gangliomas for the presence of specific signs and verification of the neoplastic process.The results of presurgical MRI (3.0, 1.5 Tesla) of 20 patients with gangliomas were analyzed to identify specific signs of a neuronal-glial tumor and verify the neoplastic process based on the results obtained and a review of the literature. In addition to high-resolution MRI (HR MRI), various protocol modifications were applied to patients with epileptogenic pathological substrates of unclear etiology, including tractography (DTI) and contrast-free MR perfusion (ASL). In 5 cases, a multi-modal study was performed that combined the results of CT, routine MRI, HR MRI, functional MRI (fMRI) in various combinations and PET CT.In 17 cases, patients underwent epileptic surgery. Three patients without epilepsy were operated on for a tumor diagnosed by radiological examination. In all 20 cases, gangliogliomas were verified, including 1 anaplastic, 1 infantile desmoplastic, and another patient had histological samples showing signs of a composite tumor. Combination with FCD IIIb was observed in 3 cases. Two patients had a double pathology (cases of tumors combination with lissencephaly and neuronal heterotopia) and another had a composite neuronal-glial tumor. In 15 cases, gangliogliomas showed neuroradiological features typical for dysembryoplastic neuroepithelial tumor (DNT) such as multicystic, nodular, and diffuse (dysplastic) described in the literature. In addition, in 9 cases, they had significant signs of neoplastic process such as contrast enhancement, continued growth and remodeling of the underlying bone. Verification of the neoplastic process based on the results of neuroradiological studies was difficult in 6 cases. In 2 cases, it was not possible to confirm the presence of neoplasm by radiological methods, and in 1 patient, the verification of the tumor during differential diagnosis took more than 8 years. The most common differential diagnosis was performed with DNT and FCD type IIb, which have a number of similar neuroradiological features.Анализ изображений, полученных при прехирургической нейровизуализации у пациентов с ганглиоглиомами, на предмет наличия специфических признаков и верификации неопластического процесса.Проанализированы результаты прехирургических МРТ 20 пациентов с ганглиоглиомами на томографах 3,0, 1,5 тесла (Т) для выявления специфических признаков нейронально-глиальной опухоли и верификации неопластического процесса, основываясь на полученных результатах и обзоре литературы. Пациентам с эпилептогенными патологическими субстратами неясной этиологии дополнительно к МРТ с высоким разрешением (МРТ ВР) применялись различные модификации протокола с включением трактографии (DTI), бесконтрастной МР — перфузии (ASL). В 5 случаях проводилось мультимодальное исследование, совмещавшее в различных комбинациях результаты КТ, рутинной МРТ, МРТ ВР, функциональной МРТ (фМРТ) и позитронно-эмиссионной КТ.В 17 случаях пациенты были подвергнуты хирургическому лечению по поводу эпилепсии. Три пациента без эпилепсии были прооперированы по поводу опухоли, диагностированной с помощью радиологического обследования. Во всех 20 случаях были верифицированы ганглиоглиомы, из них 1 анапластическая, 1 инфантильная десмопластическая, еще у 1 пациента гистологические образцы имели признаки композитной опухоли. Сочетание с фокальной кортикальной дисплазией IIIb отмечено в 3 случаях. У 2 пациентов отмечалась двойная патология (случаи сочетания опухолей с лиссэнцефалией и нейрональной гетеротопией) и еще у 1 — композитная нейронально-глиальная опухоль. В 15 случаях ганглиоглиомы демонстрировали характерные для дизэмбриопластических нейроэпителиальных опухолей нейрорадиологические признаки: мультикистозный, узловой и диффузный (диспластический), описанные в литературе. Помимо этого, в 9 случаях они имели достоверные признаки неопластического процесса, такие как контрастное усиление, продолженный рост и ремоделирование подлежащей кости. Верификация неопластического процесса по результатам нейрорадиологических исследований была затруднена в 6 случаях. В 2 случаях не удалось подтвердить наличие опухоли лучевыми методами исследования, еще у 1 пациента верификация опухоли при проведении дифференциального диагноза заняла более 8 лет. Наиболее часто дифференциальный диагноз проводился с дизэмбриопластическими нейроэпителиальными опухолями и фокальной кортикальной дисплазией IIb типа.

To evaluate the efficacy and safety of tenoten for children in the treatment of specific developmental disorders of academic skills in children of 1-3 grades.Two hundred and forty children, aged 7-9 years, (Total set, Safety population) with verified specific reading disorder (F81.0), specific spelling disorder (F81.1), specific disorder of arithmetical skills (F81.2), mixed disorder of scholastic skills (F81.3; F81.2+F81.0, or F81.2+F81.1, or F81.2+F81.0+F81.1), diagnosed with the use of logopedic or psychological testing (15-35 scores in Fotekova T.A. and Akhutina T.V. reading and writing tests; 5-15 scores in arithmetical subscale of the Wechsler Intelligence Scale for Children) were enrolled in the study. CT was conducted in 10 clinical centers in Russian Federation in 2015- 2019. Patients were randomized into two groups. The first one (The mean total academic skills score increased by 18.55±15.87 points. The significant total difference between the median changes in the total score in the tenoten and placebo groups was 5 points. There was a trend towards positive changes in reading and spelling mean scores in tests that didn't reach statistical significance due to lack of normal distribution of points in samples. There were 73 adverse events (AEs) in 42 patients of the tenoten group and 95 AEs in 31 children of the placebo group. No serious or severe AEs were registered in the tenoten group. No AEs definitely related to the study treatment were registered. No negative drug interactions were observed in the tenoten group.Tenoten for children is an effective and safe treatment for specific developmental disorders of academic skills in primary school children. Tenoten for children is well tolerated. The treatment is characterized by a high level of adherence of children and their parents to therapy.Изучение эффективности и безопасности Тенотена детского в терапии специфических расстройств развития учебных навыков у учащихся 1—3-го классов.В многоцентровое двойное слепое рандомизированное плацебо-контролируемое клиническое исследование были включены 240 детей в возрасте 7—9 лет с диагностированными расстройствами чтения (F81.0), спеллингования (F81.1), арифметических навыков (F81.2), смешанными расстройствами учебных навыков (F81.3; расстройство, одновременно отвечающее критериям подрубрик F81.2+F81.0, либо F81.2+F81.1, либо F81.2+F81.0+F81.1), подтвержденными результатами логопедического и психолого-педагогического тестирования (15—35 баллов при оценке чтения и 15—30 баллов при оценке письма по методу Т.А. Фотековой, Т.В. Ахутиной; 5—15 баллов по результатам субтеста №3 «Арифметический» теста Векслера). Клиническое исследование проведено в 10 клинических центрах в РФ в 2015—2019 гг. Пациенты были рандомизированы в 2 группы. Первая группа (В результате лечения Тенотеном детским суммарный балл сформированности учебных навыков увеличился на 18,55±15,87 балла. Статистически значимая итоговая разница между медианными изменениями суммарного балла в группах Тенотена детского и плацебо составила 5 баллов. Отмечена тенденция к положительному влиянию терапии на средние баллы чтения и письма по результатам тестов, однако отсутствие нормального распределения баллов в выборках не позволило получить статистически значимые различия между группами. В ходе исследования было зарегистрировано 73 нежелательных явления (НЯ) у 42 пациентов группы Тенотена детского и 95 НЯ у 31 пациента группы плацебо. В группе Тенотена детского не выявлены НЯ тяжелой степени и серьезные НЯ. Не выявлено ни одного НЯ, достоверно связанного с применением исследуемого препарата, и не зарегистрировано случаев взаимодействия Тенотена детского с лекарственными средствами различных классов.Применение препарата Тенотен детский в лечении специфических расстройств развития учебных навыков у детей младшего школьного возраста является эффективным и безопасным, хорошо переносится и сочетается с высоким уровнем приверженности терапии детей и их родителей.

A total of 722 patients (374 men and 348 women, aged from three months to 57 years) were treated with topiramate during the period 2002–2012. Epilepsy was diagnosed and antiepileptic treatment was evaluated using follow-up video-EEG monitoring. Topiramate was effective in 465 patients (64.4%), the efficacy of monotherapy (72.2%) being greater than that of combined therapy (61.9%). Low efficacy was noted in 198 patients (27.4%). Aggravation was seen in 59 cases (8.2%). Compliance (remaining on treatment for more than one year) was 60.79%. High efficacy in children aged less than one year was seen in 55.2% of cases, while low efficacy was seen in 34.5% and aggravation in 10.3%; among children aged 1–3 years, high efficacy was seen in 54.8% and low efficacy was seen in 31.8%, with aggravation in 13.4%; in children aged over three years, efficacy was high in 67.3% and low in 26.2%, with aggravation in 6.5%; in the adult population aged over 18 years, the agent was effective in 82.1% of patients, with low efficacy in 16.6%, and aggravation in just one patient. Topiramate demonstrated high efficacy in the treatment of idiopathic generalized forms of epilepsy (IGE) without absences, as well as in symptomatic/cryptogenic focal forms of epilepsy. Increases in patients’ age were associated with increases in the efficacy of topiramate, while the risk of aggravation decreased significantly.

One of 20 modern children and teenagers has attention deficit hyperactivity disorder (ADHD). New diagnostic criteria of ADHD according to DSM-V classification which contain the following main changes are considered in the article: age of onset — to 12 years; the requirement to cross-situational character of symptoms is strengthened; the ADHD age dynamics is reflected and the threshold number of symptoms for adult patients is entered; the comorbidity with autism spectrum disorders is allowed. Peculiarities of examination of children and teenagers with ADHD are discussed. Treatment of a syndrome must be complex and should include methods of behavior correction, psychotherapy, neuropsychological correction. Medicinal therapy demands the sufficient duration as the improvement of a state has to extend not only on the main manifestations of ADHD, but also on a social psychological aspect of patients' life. As the examination of a group of children with ADHD showed, during long courses of treatment by hopantenic acid for overcoming not only the main symptoms, but also violations of adaptation and social psychological functioning (improvement of a self-assessment, communication with people around and social activity) treatment terms must be not less than 4–6 months. The development and application of complex correction under ADHD should be carried out in due time and have individual character.

The article is dedicated to the relevant aspects of complex diagnosis and treatment of cognitive disorders in children and adolescents with traumatic brain injury (TBI) sequelae in the long term. Traumatic brain injury is one of the most important issues of the modern neuroscience due to high incidence rate and incapacitation severity. A steady increase in TBI sequelae, many of which are cognitive disorders (cerebro-asthenic and psychoorganic syndromes, post‑traumatic dementia) accompanied by various symptoms of vegetative dysfunction syndrome, has been observed in children in the recent years. The factors affecting severity of TBI sequelae in children are severity of the injury, age at the injury, time elapsed since the injury and localization of the lesion. Disturbances of memory and attention (75%), hand-eye coordination, cerebro-asthenic disorders (88%) and chronic headaches (95%) are prevalent in the structure of cognitive disorders after a minor TBI. Severer cognitive dysfunctions accompanied by pathological neurological symptoms resulting in difficulties in learning, self‑service and negatively affecting social adaptation in general are observed in 94-100% of the children having suffered moderate or severe TBI. The article discusses the modern methods of complex diagnosis and pathogenetically substantiated techniques of drug therapy of cognitive disorders in patients with traumatic brain injury sequelae in detail.

Treatment of developmental disorders, correction of learning disabilities and behavioral problems in children should be prompt, complex and include pharmacotherapy with nootropic agents. The results of recent studies shown in this review proved effectiveness of pharmacotherapy with pyritinol in children with perinatal injury of central nervous system and its consequences, psychomotor and speech development delay, dyslexia, attention deficit/hyperactivity disorder, cognitive disorders and learning disabilities (including manifestations of epilepsy, chronic tic disorders and Tourette syndrome). Due to its ability to optimize metabolic processes in central nervous system, pyritinol is used in treatment of vegetative dysfunction in children and adolescents, especially associated with asthenical manifestations, as well as in complex therapy of exertion headache and migraine. The drug is effective in treatment of cognitive disorders in children and adolescents with epilepsy, pyritinol was administered without changing of the basic anticonvulsive therapy and no deterioration (increase of severity of seizures or intensity of epileptiform activity on electroencephalogramms) was observed. Significant nootropic effect of pyritinol, including neurometabolic, neuroprotective, neurodynamic and other mechanisms, in association with safety and rare side effects of this drug determines its wide usage in pediatric neurology.

A total of 32 children aged 6–12 years with attention deficit hyperactivity disorder (ADHD) were monitored during prolonged (6–8 months) treatment with Pantogam (homopantothenic acid) at daily doses of 500–1000 mg. Treatment results were assessed using the DSM-IV core ADHD symptom scales and the WFIRS-P (parental) scale every two months. Decreases in core symptoms on the DSM-IV core ADHD symptom scale were seen at two months of treatment. Significant changes on the WFIRS-P scale took longer: improvements in self-concept, socialization, and social activity were seen at four months and in behavior and schoolwork, basic life skills, along with decreases in risk-associated behavior, at six months. Thus, in contrast to regression of core ADHD symptoms, overcoming impairments in social-psychological adaptation required longer treatment periods.

The author considers causes, clinical variants and diagnostic principles of speech development in children. A role of neurobiological factors in the genesis of speech disorders and developmental dysphasia including early organic CNS lesions due to perinatal pathology and hereditary predisposition is described. Outcomes of dysphasia in children reached school-age are discussed. A screening method of the identification of speech delay in early childhood is presented. Early diagnosis and treatment of speech disorders in children are of great importance. Timely treatment with nootropics facilitates the correction of speech disorders.В статье рассматриваются причины, клинические варианты, принципы диагностики развития речи у детей. Представлены данные о роли нейробиологических факторов в генезе расстройств развития речи и дисфазий развития (алалия), в том числе раннего органического повреждения ЦНС в связи с перинатальной патологией и наследственной предрасположенностью. Обсуждаются исходы дисфазии развития к школьному возрасту. Представлен скрининговый метод выявления отставания в развитии речи у детей раннего возраста. Важное значение имеют ранние диагностика и терапия нарушений развития речи у детей. Коррекции нарушений развития речи способствует своевременное применение препаратов ноотропного ряда.В статье рассматриваются причины, клинические варианты, принципы диагностики развития речи у детей. Представлены данные о роли нейробиологических факторов в генезе расстройств развития речи и дисфазий развития (алалия), в том числе раннего органического повреждения ЦНС в связи с перинатальной патологией и наследственной предрасположенностью. Обсуждаются исходы дисфазии развития к школьному возрасту. Представлен скрининговый метод выявления отставания в развитии речи у детей раннего возраста. Важное значение имеют ранние диагностика и терапия нарушений развития речи у детей. Коррекции нарушений развития речи способствует своевременное применение препаратов ноотропного ряда.

To study clinical characteristics mechanisms and pathogenesis of the tension-type headache (TTH) in children and adolescents treated with nooclerin.The blind randomized placebo-controlled study of the efficacy of nooclerin (deanol aceglumate) indicated during 2 months as a preventive treatment of TTH was performed. Forty patients (15 male and 25 female), aged 9-16 years, were randomized into two equal groups to receive either nooclerin or placebo.Nooclerin significantly reduced the frequency, duration and intensity of TTH. The treatment resulted in positive dynamics in daily activities, regression of fatigue symptoms and normalization of the sleep-wake cycle.Цель исследования. Оценка эффективности препарата нооклерин в профилактической терапии головной боли напряжения (ГБН) у детей и подростков. Материал и методы. Проведено слепое рандомизированное плацебо-контролируемое исследование эффективности нооклерина (деанола ацеглумат), назначавшегося в течение 2 мес с целью профилактической терапии ГБН. Лечили 40 пациентов, 15 мужского и 25 женского пола в возрасте 9-16 лет, распределенных на две группы по 20 человек (препарат и плацебо). Результаты и заключение. Применение нооклерина привело к существенному уменьшению частоты, продолжительности и интенсивности ГБН, положительной динамике в повседневной активности пациентов, регрессу проявлений астении и нормализации цикла сон-бодрствование.

To assess the efficacy and safety of children tenoten in the treatment of children and adolescents with anxiety disorders.It was conducted a multicenter, double-blind, placebo-controlled trial of the drug tenoten children at a dose of 1 tablet 3 times a day for 12 weeks. The study included 98 patients (boys and girls from 5 to 15 years with a confirmed diagnosis of anxiety disorder), randomized into two groups: the first included 48 patients treated tenotenom children, in the second - 50 patients receiving placebo.Tenoten children has a strong anti-anxiety effect both on the results of self-assessment of patients, and on the reports of parents. This anxiolytic activity of the drug manifested most significantly in children aged 5 to 7 years. In addition, in patients 8-15 years of treatment spent tenotenom children to regress the symptoms of anxiety disorders by anxiety subscales SCAS «Separation anxiety», «panic attacks and agoraphobia» and «social phobia». Throughout the course of treatment tenoten children have been no adverse events.Цель исследования - оценка эффективности и безопасности применения тенотена детского у детей и подростков с тревожными расстройствами. Материал и методы. Было проведено многоцентровое двойное слепое плацебо-контролируемое исследование препарата тенотен детский в дозе по 1 таблетке 3 раза в день в течение 12 нед. В исследование были включены 98 пациентов (девочки и мальчики от 5 до 15 лет с подтвержденным диагнозом тревожного расстройства), рандомизированные в две группы: в 1-ю вошли 48 больных, лечившихся тенотеном детским, во 2-ю - 50 пациентов, получавшие плацебо. Результаты и заключение. Тенотен детский обладает выраженным противотревожным эффектом как по результатам самооценки пациентов, так и по отчетам родителей. При этом анксиолитическая активность препарата наиболее значимо проявилась у детей в возрасте от 5 до 7 лет. Кроме того, у пациентов 8-15 лет лечение тенотеном детским приводило к регрессу симптомов тревожных расстройств по подшкалам тревожности SCAS 'Сепарационная тревожность', 'Панические атаки и агорафобия' и 'Социальная фобия'. На протяжении всего курса лечения тенотеном детским не было зафиксировано нежелательных явлений.

To evaluate the efficacy and safety of hopantenic acid (Pantogam) in the complex treatment of prematurely born infants, aged 6-12 months, with psychomotor developmental delay due to hypoxic-ischemic encephalopathy.Eighty-seven patients were randomized into two groups: 44 received standardized treatment and pantogam for two months, 43 standardized treatment and placebo. Pantogam (syrup 100 mg/ml) or placebo were prescribed orally 15-30 minutes after feeding, twice a day, in a daily dosage of 30-50 mg/kg body weight. The assessment of psychomotor development from birth to two years was performed with the Griffiths Mental Development Scales (GMDS-ER) twice (before and after completion of therapy).The response to two month therapy determined as the reduction of developmental delay for more than 6% of the initial GMDS-ER general quotient (GQ) score was significantly better in the group I after pantogam treatment (63.6% of patients) compared to group II (36.4%, p=0.021). Group I demonstrated the significant decrease of the developmental delay in two domains ('Personal-Social' and 'Performance') and a trend to overcome the delay in three other domains: 'Locomotor', 'Hearing and Speech', 'Eye and Hand Coordination'. The improvement after pantogam treatment was more obvious in the subgroup of infants born late preterm (gestational age 34-36 weeks) compared to infants born moderate preterm (gestational age 32-33 weeks). The favorable safety profile of pantogam was confirmed, comparable to that of placebo.Pantogam is efficient and safe medication in the complex treatment of psychomotor developmental delay in preterm infants, aged 6-12 months.Цель исследования. Изучение эффективности и безопасности лекарственного препарата (ЛП) гопантеновой кислоты Пантогам в комплексном лечении рожденных недоношенными детей в возрасте 6-12 мес с задержкой психомоторного развития вследствие перенесенного гипоксически-ишемического поражения центральной нервной системы. Материал и методы. Обследовали 87 пациентов, рандомизированных на две группы. Пациентам 1-й группы (44 ребенка) в течение 2 мес назначена стандартная терапия и дополнительно ЛП Пантогам, пациентам 2-й группы (43 ребенка) - стандартная терапия плюс плацебо. Пантогам (сироп 100 мг/мл) или плацебо применяли внутрь через 15-30 мин после кормления 2 раза в день в суточной дозе 30-50 мг на 1 кг массы тела. Продолжительность терапии составила 67 дней. Всех пациентов дважды (до и по окончании курса лечения) обследовали с помощью шкал Гриффитс для оценки психомоторного развития детей от рождения до 2 лет (использовали дополненную и пересмотренную версию - GMDS-ER). Результаты. В 1-й группе после лечения отмечено улучшение психомоторного развития более чем на 6% (от исходной величины общего показателя по шкалам Гриффитс) у 63,6% пациентов, что значимо превысило аналогичный показатель во 2-й группе - 39,5% (p=0,021). В 1-й группе наблюдали значимое сокращение отставания в развитии по сферам 'Личностно-социальная' и 'Манипуляции с предметами', а также тенденцию к уменьшению отставания по трем остальным сферам: 'Двигательная активность', 'Слух и речь', 'Зрительно-моторная координация'. Более выраженная положительная динамика после лечения ЛП Пантогам определена в подгруппе пациентов с поздней недоношенностью (34-36 нед) по сравнению с детьми с умеренной недоношенностью (32-33 нед). Подтвержден благоприятный профиль безопасности ЛП Пантогам, сопоставимый с плацебо. Заключение. Пантогам является эффективным и безопасным средством в комплексном лечении задержки психомоторного развития у детей первого года жизни.