Abstract: his paper presents the results of therapeutic drug monitoring (TDM) of anticonvulsants (valproats and carbamazepins) in 614 patients with epilepsy in clinical practices. 295 patients were treated with different drugs of valproats and 314 patients were treated with different drugs of carbamazepine. The frequency of achievement the therapeutic concentrations on valproat treatment was 66,4%, the average daily dose was 1325,1 mg. The frequency of achievement the therapeutic concentrations on treatment with drug forms with prolong release (Depakin chrono, Convulex retard) was higher, than on drug forms with immediate release. The frequency of subtherapeutic concentrations on valproat treatment was 16,3% and overtherapeutic concentrations – 1%. In doses of valproats less then 500 mg there was no patients with therapeutic concentrations, in doses 1001-1500 mg/day the therapeutic concentrations have 75% patients, in doses higher than 2000 mg/day – there was a risk of overdose. The frequency of achievement the therapeutic concentrations on carbamazepine treatment was 78,6%, the average daily dose was 922,2 mg. The frequency of achievement the therapeutic concentrations on treatment with drug forms with prolong release (Tedretol CR, Finlepsin retard) was higher, than on drug forms with immediate release. The frequency of subtherapeutic concentrations on carbamazepine treatment was 6,3% and overtherapeutic concentrations – 1,25%. When used initial daily doses (less then 600 mg) 64,3% patients have therapeutic concentrations , when used highly doses (high than 600 mg) 87% patients have therapeutic concentrations. In daily doses of carbamazepine higher then 600 mg and 1200 mg the frequency of the overtherapeutic concentrations were 1,3% and 4,1% both by Cmin and Cmax, only by overtherapeutic Cmax – 8,8% and 18,4%.

Abstract: study of genetic polymorphism of the P450 CYP2C9 and CYP2C19 detoxifying enzyme genes in epileptic children. Study objective: to justify the effectiveness of therapy in children with severe forms of epilepsy by performing the genetic polymorphism analysis of the CYP2C9 and CYP2C19 detoxifying enzymes of the cytochrome P450 family. Materials and methods: a group of children with severe forms of epilepsy comprising 46 (53.49%) boys and 40 (46.51%) girls has been examined. Children were aged between 3 months and 17 years. Their epilepsy forms were diagnosed, the analysis of complications due to administration of anti-epileptic drugs (AED) was carried out and children with rare genotypes present in groups with both treatment resistant and non-resistant forms of epilepsy have been revealed. Results: the disease appeared to be treatment resistant in 56 (65.12%) of all children examined of whom 28 (50%) were boys and 28 (50%) were girls. Treatment resistant form of epilepsy was found in all (100%) children with epileptic encephalopathies and in 63.83% of children with symptomatic and cryptogenic focal epilepsy (with and without secondary generalization). 67 (77.91%) children received valproate monotherapy, 10 (11.63%) children received polytherapy that included valproates and 9 (10.47%) children received other AED. The non-resistant patients with idiopathic epilepsy more often developed complications during treatment with the AED. Gene polymorphism was found in 43 (50%) epileptic children, and in 36 (83.72%) cases rare genotypes were found in children with treatment resistant form of epilepsy and in 7 (16.28) cases in children with treatment non-resistant form of epilepsy. In children with polymorphic CYP2C9 and CYP2C19 genes the conventional average daily dose of valproates (30.56 mg/kg) exceeded the average daily dose of valproates (27.91 mg/kg) in children lacking the polymorphisms located in the same genes. Conclusion: we have revealed polymorphism in the CYP2C9 and CYP2C19 genes of the cytochrome P450 family in 50% of children with severe form of epilepsy, and in 41.86% of cases children with treatment resistant form of epilepsy had rare genotypes at that. Therefore, the results of genetic polymorphism analysis aiming to determine the presence or absence of polymorphic CYP2C9 and CYP2C19 genes should be taken into account before instigating treatment in children with epilepsy.

Abstract: myoclonic-atonic seizures (MAS) – short epileptic generalized seizures in the form of sudden falling spells (or drop attacks). Inour study were vealed MAS in 1.3% of all cases of epilepsy with onset of seizures before 18 years old (n=1261). Predominance of man among the patients was revealed (76.5% men versus 23.5% woman). The most often in the patients with MAS myoclonic-astatic epilepsy (MAE) was diagnosed – 41,2% of cases. Symptomatic and cryptogenic forms of focal epilepsy were diagnosed in 35.2% of the patients. Lennox-Gastaut syndrome was revealed in 23.6% of cases. Onset of epilepsy with MAS varied widely – from 9 month to 6 year soflife; middle age of onset was 3.4 years±1.28 years. In all the cases MAS occurred in combination with other types of seizures: there can be any of 9 differenttypes of seizures. The most often myoclonic seizures (70.6% of cases), generalized convulsive seizures (47.1%) and absences (47.1%) were registered. Remission was achieved in 64.7% cases of epilepsy, associated with MAS. Reduction of seizure frequency ≥50% on antiepileptic treatment was achieved in 29.4% of the patients. Only in one patient (5.9%) the therapy was not effective. Our study demonstrated different efficacyof antiepileptic drugs in the treatment of different epileptic syndromes, associated with MAS.

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

Abstract: the experience of the authors and critical analysis of existing results of the various studies showed unambiguous conclusions about the prospects of the use of modern medicines, in particular the efficiency and safety of Depakine® Chronosphere™. The inclusion of valproatеs in the form of microgranules to standards of treatment of children and adult patients with epilepsy seems justified with clinical and economic perspectives.

Abstract: paraneoplastic limbic encephalitis (PLE) is clinical form of paraneoplastic neurological syndrome, an autoimmune disorder of the central nevrous system. The incidence of PLE is about 3 cases per 1,000 patients with cancer. PLE is characterized by acute or subacute development of memory disorders, symptomatic epilepsy, psychiatric disorders. The authors present the current data on the pathogenesis, clinical presentation, diagnosis, and treatment of PLE, a clinical case of symptomatic epilepsy in the 38-year-old man with PLE associated with testicular cancer.

Abstract: major issues of differentiating epileptic and non-epileptic paroxysmal phenomena of sleep are presented in this article. Quality differentiation is possible in case of good knowledge of semiology of sleep-related epileptic seizure types and epileptic syndromes. Difficulties in identification can lead to further diagnostic mistakes. Parasomnias are the most frequently encountered non-epileptic paroxysmal events in sleep, which are related to both non-rapid-eye movement (NREM) sleep and rapid-eye movement (REM) sleep. NREM-sleep parasomnias are otherwise referred to as arousal disorders. They could be mistaken for frontal lobe epilepsy seizures, which predominantly occur at night and are not readily accompanied by epileptiformabnormalities on EEG. Other sleep phenomena also should be considered in differentiating nocturnal epilepsies. Obstructive sleep apnea, periodic leg movements in sleep and some sleep episodes sometimes are expressed with a pattern hardly distinguishable from epileptic seizures. Complex approach and appropriate diagnostic algorithm would further help clinicians in this field to better assess any given situation.

Abstract: A number of pathophysiologic manifestations can be distinguished that are characteristic of both epilepsy and other common vascular, demyelinating and degenerative central neural system (CNS) diseases. This is a consequence of neural system's endogenizing capacity that determines the possibility of its response with non-specific typical pathologic processes to various pathologies and at different levels of structural and functional organization. The current concept of the blood-brain barrier (BBB) structural and functional organization fundamentally differs from those previously suggested: by early 1980s it became recognized that the BBB represents a dynamic morphofunctional entity, formed by brain capillary endothelial cells and periendothelial structures. This reflects the accumulation of knowledge on this subject that received close attention of scientific and academic communities resulting in an increased number of fundamental and applied BBB studies. In order to realize the role of the BBB in CNS functioning in normal and pathologic settings, it is necessary to clearly understand its development during the ontogeny, as well as exogenous and endogenous factors that can lead to BBB damage ('disrupture'). This will help to verify the number of markers that allow adequate evaluation of the BBB and neural tissue condition, and also to chose a strategy for the management of patients with CNS disorders.

Abstract: he review presents an analysis of the formation of the views of scientists on the pathogenesis and treatment of epilepsy in the XIX century. The authors analyze the main works of scholars Department of Nervous and Mental Diseases of the Imperial Medical-Surgical Academy, devoted to issues of experimental studies of changes in cerebral blood flow during seizures, the improvement of the treatment of patients with epilepsy. The paper also highlighted the prerequisites for the development and nature of the hypothesis of «convulsive center», and the role of V.M. Bekhterev and his students in establishing the role of the cerebral cortex in the pathogenesis of epileptic seizures.