[The role of the phenosanic acid in the combined treatment of patients with epilepsy]. / Rol' fenozanovoi kisloty v lechenii patsientov s epilepsiei.

Epilepsy is one of the most studied chronic neurological disorders in the world. Despite significant progress in epilepsy research, some patients continue to experience recurrent seizures. It has been proven that oxidative stress plays an important role in epilepsy. Targeting oxidative stress may provide a novel therapeutic intervention to attenuate epileptogenesis as well as cognitive and psychiatric impairment in patients with epilepsy. One of the promising directions in the search for new strategies for the treatment of epilepsy is the combined use of antiepileptic drugs with antioxidants that affect the pathogenetic links of this disease. The new Russian antiepileptic drug fenosanoic acid (Dibufelon) has an anticonvulsant effect due to the inhibition of lipid peroxidation of brain cells and the reconstruction of cell membranes. This mechanism of action also paves the way for an increase in the effectiveness of co-administered drugs with phenosanoic acid. The effect of the drug on the cognitive and mental functions of patients, the regression of asthenia phenomena is also observed. The clinical efficacy and safety of the combination of this drug with other antiepileptic drugs in epilepsy has been demonstrated in experimental and clinical studies.

[Encephalopathy GNAO1]. / Entsefalopatiya GNAO1.

OBJECTIVE: To study the clinical picture of all patients with GNAO1 encephalopathy detected in the Russian Federation. This publication is a multicenter study combining data from epileptological centers in Moscow, Novosibirsk, St. Petersburg, Nizhny Novgorod, Tyumen. MATERIAL AND METHODS: Nine patients were included, aged 2 to 19 years, with 4 mutations. Male to female sex ratio = 5:4. RESULTS: 8 patients (5 with mutation c.607G>A (p.Gly203Arg), 1 - c.155A>G (Gln52Arg), 1 - c.485G>A (p.Arg162Gln)) had a variant of epileptic encephalopathy, developmental encephalopathy, 1 patient had torsion dystonia without epilepsy (mutation c.713A>G (p.Asp238Gly)). Epileptic seizures in 8 children with epileptic encephalopathy GNAO1 in 100% debuted at 1 month of life, becoming the earliest symptom of the disease. Motor development delayed in 100% of cases. Mental development was not affected only in the case of the dystonic variant. Hyperkinesis (dystonia, choreoathetosis, ballism) followed later, from 2 to 8 months. They were more severe than epilepsy. 4 patients with the c.607G>A (p.Gly203Arg) mutation developed repeated dystonic storms that were resistant to most drugs. CONCLUSION: Epilepsy in GNAO1 is difficult to treat, but temporary or complete remission is possible. Effective drug strategies for the treatment of hyperkinesis have not yet been developed. Expansion of indications for surgical therapy (DBS) of hyperkinesis in this syndrome is desirable.

[Differential diagnosis of paroxysms of tonic muscle tension in children of early age with delay of psychomotor development and abnormal neurologic status]. / Differentsial'naia diagnostika paroksizmov tonicheskogo napriazheniia myshts épilepticheskoi i neépilepticheskoi prirody u detei rannego vozrasta s zaderzhkoi psikhomotornogo razvitiia i ochagovymi nevrologicheskimi simptomami.

AIM: To study neurologic status, results of video-EEG monitoring and magnetic resonance imaging in children under 3 years old with paroxysms of tonic muscle tension. MATERIAL AND METHODS: One hundred and forty-six infants and young children with motor disturbances and different variants of clinically similar epileptic seizures, hyperkinesis and stereotypes were examined. RESULTS AND CONCLUSION: Cerebral palsy (91%), genetic and chromosomal abnormalities (6%), brain malformations (2%) were identified. Neurological status was characterized by pseudobulbar syndrome (100% of cases), hemiparesis (1%), tetraparesis (81%), diffuse muscular hypotonia (18%), intellectual and speech development delay (76%), autistic behavior (16%). During the prolong video-EEG monitoring, paroxysmal tonic muscle tensions were recorded in all patients: epileptic seizures were observed in 113 patients (77.40%), non-epileptic paroxysms in 51 (34.93%). The combination of epileptic and non-epileptic paroxysms was observed in 18 patients (12.33%). In 4 patients (2.75%), it was not possible to determine the genesis of paroxysms even during the prolong video-EEG-monitoring because of myographic artefacts. Five clinical and electroencephalographic combinations of dystonic attacks, epileptic seizures and epileptiform activity were identified. These data allow improving the diagnosis of epilepsy and avoiding unnecessary treatment with antiepileptic drugs. Our study has shown a high diagnostic value of video-EEG monitoring with the inclusion of sleep in patients with paroxysmal conditions in infancy and early childhood.

[Algorithms of mono- and polytherapy in clinical epileptology. Part 1. General principles of drug choice]. / Algoritmy mono- i politerapii v klinicheskoi épileptologii. Chast' 1. Obshchie printsipy vybora farmakoterapii.

The large number of antiepileptic drugs (AEDs) at the physician's disposal provides not only a broad therapeutic potential in the treatment of epilepsy (EP), but creates difficulties in the adequate choice of AED. The sufficient experience in the management of patients with epilepsy has been gained so far in the world, based on which the International League Against Epilepsy (ILAE), updated classification, adopted the basic definition of efficiency, remission, resistance, evidence of research on the effectiveness of AED therapy, and introduced the concept of "resolved" epilepsy. In this article, a group of Russian experts suggest recommendations on the main steps in the choice of therapy in epilepsy. Possible drug interactions between different AEDs and other drugs as well as main characteristics of mono- and polytherapy of epilepsy are described. Some features of the use of AEDs in the elderly, characteristics of the "female" epilepsy related to the reproductive function and basic requirements for the therapy of epilepsy in children are presented.

[Algorithms of mono- and polytherapy in clinical epileptology]. / Algoritmy mono- i politerapii v klinicheskoi épileptologii. Chast' 2. Osobennosti lecheniia otdel'nykh grupp patsientov.

The large number of antiepileptic drugs (AEDs) at the physician's disposal provides not only a broad therapeutic potential in the treatment of epilepsy (EP), but creates difficulties in the adequate choice of AED. The sufficient experience in the management of patients with epilepsy has been gained so far in the world, based on which the International League Against Epilepsy (ILAE), updated classification, adopted the basic definition of efficiency, remission, resistance, evidence of research on the effectiveness of AED therapy, and introduced the concept of "resolved" epilepsy. In this article, a group of Russian experts suggest recommendations on the main steps in the choice of therapy in epilepsy. Possible drug interactions between different AEDs and other drugs as well as main characteristics of mono- and polytherapy of epilepsy are described. Some features of the use of AEDs in the elderly, characteristics of the "female" epilepsy related to the reproductive function and basic requirements for the therapy of epilepsy in children are presented.

[Etiology of stroke in children]. / Étiologiia insul'ta u detei.

The lecture contains information on terminology, etiology and pathogenesis of stroke in children. The current statistics on the incidence of stroke in the pediatric population, prognosis and principles of early diagnosis are presented. Different states, complicating stroke in children are described.

[Cerebrolysin in pediatric neurology practice].

Мany aspects of сerebrolysin treatment in a wide range of nervous system disorders in children are described. High efficacy and well tolerated therapy are revealed. These findings expand the perspectives of using сerebrolysin in pediatric neurology.

[Eye movement disorders in children].

The article includes review of literature on anatomy, physiology, symptoms of ocular movement and their disturbance in children. Differential diagnosis between early developmental disturbances of vision in the normal child and during the diseases of central nervous system is very hard. There is data on such pediatric neuro-ophthalmology complex disorders as nystagmus, paroxysmal tonic upgaze, opsoclonus, spasmus nutans, seizures (eyelid myoclonia, absences).

[Lacosamide in the treatment of epilepsy].

The new antiepileptic drug (AED) lacosamide (vimpat, "UCB Pharma") with a new mechanism of action was registered in Russia in 2010. The drug should be used as add-on treatment in patients over 16 years and older with non-controlled focal seizures with- or without secondary localization. The authors review the data of literature and the results of trials on efficacy and safety of lacosamide for peroral and intravenous introduction. Randomized clinical trials of the peroral form of this drug provide evidence that lacosamide is a prospective preparation for complex treatment of drug-resistant epilepsy in the view of its safety and tolerability. The availability of the infusion form is advantageous compared to other AED making it possible to continue treatment in cases when the peroral intake of AED is temporary impossible.

Epilepsia partialis continua in tick-borne Russian spring-summer encephalitis.

OBJECTIVES: Epilepsia partialis continua (EPC) is characterized by localized continuous jerks, from time to time with spreading Jacksonian seizures and, more rarely, secondarily generalized tonic-clonic seizures. EPC has numerous possible etiologies. In this paper we describe EPC in the tick-borne Russian spring-summer encephalitis (TBRSSE) and compare it with Rasmussen syndrome. METHODS AND METHODS: We included patients with EPC in TBRSSE (between 2003 and 2010). The diagnosis was verified by immunology (antibodies against TBRSSE virus). The patients were followed 1-7 (mean 3.4) years. RESULTS: We studied 10 patients (eight males, age 10-21 years) with MRI and video-EEG. Nine developed EPC after acute TBRSSE (meningoencephalitic form), and one had a tick bite without clinical symptoms of encephalitis, but with subsequent EPC. All patients came from Ural and Siberia. The onset was at age 4-14 (mean 8.6 years). The interval from onset of TBRSSE or the tick bite to seizure onset was 1 day-4 years. We identified three phases of clinical course EPC in TBRSSE: (i) acute (meningoencephalitic/encephalitic); (ii) development of EPC; and (iii) chronic EPC. The effect of antiepileptic drugs differed according to seizure types. CONCLUSION: EPC caused by TBRSSE is relatively frequent in the Eastern parts of the Russian Federation but not west of the Ural. Unlike Rasmussen encephalitis, EPC with TBRSSE does not progress even in the long term. It appears as disabling but not fatal condition with a time course where three phases can be distinguished.

[Side-effects of antiepileptic treatment: the current state of the problem].

The current treatment of epilepsy is directed not only at the control of seizures and comorbid states but at the improvement of quality of life and destigmatization that is the key strategic direction. The basis of treatment of epilepsy is a long-term regular taking of antiepileptic drugs (AED). However, it has been shown that quality of life of patients depends not only on clinical presentations of the disease, including seizures and higher mental functions, but on the tolerability of AED. The safety of these drugs becomes the most important component of the treatment even compared to the control of seizures. Therefore, tolerability and compliance (a patient's adherence to a recommended course of treatment, common understanding between a doctor and a patient as well as his/her relatives) receive special attention. The timed detection and correction of side-effects is an integral component of treatment of epilepsy. In some cases, the presence of rare seizures with minimal clinical presentations and even more frequent seizures that are not danger for a patient seems to be more appropriate than the increase in the number and doses of AED reducing quality of life. The balance between therapeutic and toxic effects of AED is a key issue of treatment of epilepsy.

[Modern principles of epilepsy therapy].

Long regular use of antiepileptic drugs (AED) aimed at reducing frequency of seizures or stopping them completely without any significant side-effects is a main principle of epilepsy treatment. The main attention is drawn to the issues of tolerability of antiepileptic therapy and compliancy, mutual understanding between a physician and a patient as well as relatives and other significant persons. The timely detection and correction of side-effects is integral part of epilepsy treatment. Currently, the attention is focused on quality of life of patients with epilepsy including physical and mental health, education, social and psychological functioning. In some cases, the occurrence of rare seizures with minimal clinical presentation or even more frequent seizures which are not dangerous to a patient is less harmful than decreasing of quality of life due to the effect of larger AED number or dose. The balance between AED therapeutic and toxic effects is a main question in epilepsy therapy. Pharmacotherapy of epilepsy requires deep knowledge of AED: spectrum of therapeutic efficacy and extent of drug effect; safety, tolerability and side-effects, in particular severe and life-threatening ones, specifics of pharmacokinetics, pharmacodynamics, between-drug interactions and mechanisms of action; titration rate, necessity in laboratory tests during treatment, peculiarities of application of pharmacoeconomics. The present review addresses modern aspects of epilepsy therapy.

[Efficacy and safety of the monotherapy with trileptal (oxcarbazepine) in children and adolescents].

A prospective non-randomized non-controlled multicenter trial has been conducted. The trial included 254 children, aged from 11 months to 18 years (mean age 9.3 +/- 4.5 years), with predominantly focal forms of epilepsy treated with trileptal (oxcarbazepine). The observation period was 31 weeks. Efficacy and safety of therapy was assessed in 3 visits: screening and assignment to therapy (visit 1), the end of titration and achievement of maintenance dose (visit 2), assessment of maintenance therapy (visit 3). The percentage of patients with a positive response to the trileptal therapy (the decrease of seizure frequency by 50% and more) was 91.1%. The complete reduction of seizures was achieved in 59.4% of patients. Most of patients (95.3%) continued to receive trileptal until the end of the trial. The significant decrease (p < 0.001) of seizure frequency from visit 1 to visit 3, the reduction of epileptiform activity (p < 0.05) on the awake EEG in visit 3 were found. The mean effective dose of trileptal was 902.4 +/- 442.7 mg/day, i.e. was less than 30 mg/kg/day, daily doses did not exceed 600 mg. Adverse effects were observed in 11.2% of patients but in 40% of cases they seemed not be related to the drug. The adverse effects were from mild to moderate extent. In conclusion, trileptal as the monotherapy is effective and well-tolerated in the treatment of focal epilepsies in the age groups studied.

[Age-related aspects of paroxysmal mental disorders in the debut of epilepsy].

Seventy-four patients with paroxysmal mental disorders in the debut of epilepsy have been examined. To study an age-related aspect of these disorders, all patients have been stratified by age at debut of epilepsy into 3 subgroups (children, adolescence and adult age). Based on a key psychopathological syndrome, three types of simple and complex partial "psychiatric" seizures have been singled out. The higher is the age of debut, the higher are the variability of clinical presentations of psychopathological disorders and more complex clinical presentations of complex partial (psychomotor) attacks in the structure of simple partial seizures. In children aged 7-14 years and people older than 18 years, the simple partial "psychiatric" seizures as well as first manifestations of disease were seen more often than in adolescents. This type of debut was not observed in children younger than 7 years. The age curve of debut of epilepsy with complex partial seizures has two distinct peaks, at the children (up to 7 years) and adult ages. In the group older than 18 years, frequencies of psychomotor seizures and first disease manifestations are inversely correlated with age.

[Clinical and molecular genetic diagnosis of leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation in children].

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a recently described disorder with autosomal recessive model of inheritance. Mutations in the DARS2 gene, which encode mitochondrial aspartyl-tRNA synthetase, have been found. We present 31 cases with characteristic clinical and neuroimaging findings of this disorder. Patients have been stratified into two groups (early and late forms) by age-at-onset and clinical symptoms. The early form was characterized clinically by progressive pyramidal dysfunction, cerebellar and intellectual problems appeared later. Patients with the late form had cerebellar and sensitive ataxia, disturbances of muscle tonus, spastic type, mostly in the low extremities, polyneuropathic and rarely - psychoorganic syndrome. The brain MRI of all patients was characterized by inhomogeneous T2W signal abnormalities in the periventricular and deep white matter and a strikingly selective involvement of certain brainstem and spinal tracts. Most of the patients were compound-heterozygous for common mutations in the DARS2. We found 4 new mutations associated with LBSL. This is the first clinical and molecular-genetic investigation of this rare leukoencephalopathy in Russia.

[West syndrome: clinico-electro-anatomical characteristics and a differential therapeutical approach].

One hundred and thirty children with West syndrome, aged 1.5 months-2 years, were studied. The symptomatic form of West syndrome was diagnosed in 95.4% of cases. The prenatal etiological factors were observed in 57% of patients. Different variants of hypsarrhythmia at EEG were revealed in 87%. The percentage of cases with typical and modified hypsarrhythmia was 13.3% and 86.7%, respectively. The choice of treatment was based on the revealed disturbances on EEG and MRI that was useful for increasing the effectiveness of treatment of West syndrome resulting not only in the reduction of seizures and improvement of EEG but also in the stabilization of intellectual disintegration and recovery of functions. The basic drugs in the treatment were valproates used both as mono- and polytherapy.