For more than half a century, valproic acid (VA) has been a first-line drug to control seizures in various forms of epilepsy and status epilepticus; VA is also used in bipolar disorders. However, the accumulated clinical evidence indicates negative outcomes of pregnancies in women receiving valproate. Thus, babies born to mothers receiving VA for their epilepsy or bipolar disorder had an increased risk of serious congenital malformations. In addition, VA was found to affect the development of the CNS in a fetus that may result in attention-deficit hyperactivity syndrome (ADHD), autism spectrum disorder (ASD), childhood autism, and other diseases. The data on teratogenic effects of VA have led the regulatory authorities and the manufacturer to adopt restrictive recommendations regarding the use of VA in female patients of reproductive age. The Russian League Against Epilepsy (RLAE) presents this article to inform the medical community about the consequences of using valproic acid in pregnancy and also recommends a number of preventive measures. The article elaborates on the evidence of teratogenic risks associated with VA and reviews documents from the regulatory authorities (EMA, MHRA, Roszdravnadzor of the Russian Federation), which specify the measures needed to prevent the adverse effects of VA during pregnancy. According to these documents, medications containing VA should no longer be used in female patients of childbearing potential, except in cases where other treatments for epilepsy are ineffective or contraindicated. The changes made by the manufacturer in the official instructions for using the reference drug, and the unified instructions of the RF regulatory bodies on the reproduced (generic) drugs containing VA are also presented. The Pregnancy Prevention Program is proposed to minimize individual risks for women using VA. The article also addresses the international clinical practice on the prevention of VA-associated adverse effects during pregnancy and the recommendations of RLAE on alternative anti-epileptic therapy using minimally teratogenic drugs: lamotrigine, levetiracetam, and oxcarbazepine.

Melatonin - the most well studied factor of the circadian rhythm - attracts much intereset in regard to a disease-modifying therapy for epilepsy. In some forms of epilepsy, circadian dysrhythmias and sleep disorders can trigger the development of epileptic seizures, while in others - seizures develop from the REM-phase of sleep.

The aim is to review and analyze studies on the efficacy and safety of exogenous melatonin as an additional medication for disease-modifying therapy in pediatric and adult patients with epilepsy.

Materials and methods. The search was conducted for Russian and English articles reflecting the results of studies on the efficacy and safety of exogenous melatonin in patients with epilepsy. We used the following databases: ELibrary.ru, Web of Science, Scopus, Clinical Case, PubMed, Cochrane Database of Systematic Reviews. The search was carried out using the keywords: melatonin, epilepsy, epileptic syndrome, disease-modifying therapy, children, adolescents, adults, safety, efficacy, reduction of seizures, adverse drug reactions, quality of life. The following materials were included in the search: full-text articles in Russian and English; original research papers; Cochrane reviews; clinical observations; publication dates - from 2003 to 2018. We did not reviwed: abstracts; theses; monographs; handbooks; textbooks; materials published before 2003. In total we found 986 publications; of those, 114 met the inclusion criteria.

Results. Clinical studies on the efficacy and safety of exogenous melatonin in a disease-modifying therapy for epilepsy in children and adults are rare, conducted in small groups of patients, and differ in their design. These findings do not allow recommending melatonin, at the present time, for widespread use in the routine clinical treatment of epilepsia. Notably, determining the optimal daily dose of exogenous melatonin is rather difficult because this drug has both proconvulsive and anticonvulsant effects. Therefore, such a disease-modifying therapy requires a personalized approach to achieve a balance between these two actions of melatonin.

Conclusion. The role of exogenous melatonin as a treatment modality in epilepsy remains unclear, although this approach is considered possible for disease-modifying therapy. Large-scale clinical studies on the efficacy and safety of exogenous melatonin in epilepsy are needed. Currently, the use of exogenous melatonin in epilepsy is not regulated by law.

Aim. This study was aimed to test the instrumental complex called «Bioscope» for its ability to determine the optimal dose of the anticonvulsant drugs lamotrigine and topiramate in the treatment of epileptiform states.

Materials and methods. The experiments were conducted with 40 mongrel white male rats weighing 180-220g. In total, there were 5 series of experiments where different doses of lamotrigine and topiramate were used. The integrative state of the animals (as determined with the Bioscope) was monitored, first at the baseline and then after the anti-epileptic drug administration and subsequently after the administration of corazol.

Results. The Bioscope signals changed with changing doses of the anticonvulsant drugs. Low doses did not affect the integrative indicators, while the increasing doses caused these indicators to change. In dependence on the anticonvulsant drug dose, the administration of corasol either brought the integrative indicators back to the baseline or did not change them at all.

Conclusion. The Bioscope instrumental complex can be used for the non-invasive evaluation of the effective dose of anticonvulsant drugs needed to suppress the epileptiform states in rats.

The aim was to study the informative value of routine EEG and nocturnal EEG-video monitoring in adult patients with epilepsy.

Materials and methods. We examined 1217 patients who were referred to a specialized epilepsy clinic; of those, 589 (48.4%) men and 628 (51.6%) women aged from 22 to 83 years. In these patients, the age of seizure onset varied from I month to 72 years. The inclusion criteria in this study were: an age over 18 years and two or more epileptic seizures in the medical history. The exclusion criteria: a history of non-epileptic seizures of any etiology and/or the inability to perform regular EEG or EEG video monitoring. The examination included medical history records, clinical and neurological examinations, routine EEG and EEG video monitoring, brain MRI, and laboratory tests. In total, 915 routine EEG and 302 nocturnal EEG video monitoring were performed.

Results. During the routine EEG procedure, no epileptiform activity was detected in 379 (41.42%) patients. Among other patients, non-epileptic changes were found in 163 (17.81%), focal epileptiform activities - in 203 (22.19%), and generalized epileptiform activities - in 170 (18.58%) patients. During the nocturnal EEG-video monitoring, no epileptiform activity was detected in 34 (11.26%) patients; among other patients, non-epileptic changes were found in 11 (3.64%), focal epileptiform activities - in 167 (55.3%), and generalized epileptiform activities - in 90 (29.8%) patients.

Conclusion. Routine EEG and nighttime EEG video monitoring do not always reveal an epileptiform activity. The probability of detecting an epileptiform activity is higher with nocturnal EEG video monitoring due to its longer record duration and an increased epileptiform activity in sleep. The probability of detecting an epileptiform activity also depends on the form of epilepsy. It is advisable to gradually replace a routine EEG procedure with a nocturnal EEG-video monitoring.

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.

This article presents the results of the clinical application of the method of transplantation of autologous bone marrow stem cells in the treatment of a patient with pharmacoresistant epilepsy, the effectiveness of combination therapy, including antiepileptic drugs and autologous bone marrow stem cells and assess the feasibility, tolerability of this kind of local treatment. The encouraging results of the effectiveness of the proposed method of treatment of pharmacoresistant epilepsy on the clinical case of one patient have been obtained, which requires further study of the clinical application of the AMSC CM transplantation method on a more significant number of clinical cases in larger clinical trials.

This article analyzes the available literature regarding the clinical manifestations, genetic determinants, prognosis and evolution of inherited generalized epilepsies. We describe the typical EEG characteristics and their correlations with negative prognostic factors. We also review studies on absence epilepsy of childhood, juvenile myoclonic epilepsy and epilepsy with generalized tonic-clonic seizures. Factors indicating a more severe course and outcome of the disease, and those indicating a more favorable development have been analyzed. Among those, age of the seizure onset, type of initial therapy, time passed before starting therapy and time before a response was seen, cognitive status, combination of seizures, abnormal discharges in EEG, and neurological deficit. The analysis shows that factors correlating with poor prognosis include the presence of more than one type of seizures, insufficient response to initial therapy, necessity of polytherapy and concomitant cognitive impairment.