[The course and development of epilepsy in patients with typical variant of Rett syndrome and mutations]. / Osobennosti épilepsii u detei s tipichnym variantom sindroma Retta, vyzvannym mutatsiei.

AIM: To study the anamnesis, clinical state, electro-encephalographic and brain MRI characteristics in patients with Rett syndrome (МЕСР2) and epilepsy. MATERIAL AND METHODS: Eleven female patients, aged from 3 to 23 years, with Rett syndrome and MeCP2 mutations were studied. The study continued for 10 years (2006-2015). Assessment of neurological and mental status, night sleep video-EEG monitoring, MRI were performed. RESULTS AND CONCLUSION: Epilepsy was diagnosed in six cases (54.5%). Mean age at onset of epileptic seizures was 3 years 9 month. The following types of seizures were described: generalized, myoclonic, myotonic, tonic, versive, focal motor, atypical absences. Status epilepticus developed in one patient. Generalized seizures were identified in 56.25%, focal seizures in 43.75%. EEG changes were found in 9 patients (81.8%): slowing of the activity, episodes of periodic regional slowing, regional epileptiform activity and diffuse epileptiform activity, benign focal epileptiform discharges (BFED) of childhood, multiregional epileptiform activity. Five patients were treated with antiepileptic drugs. All of them had improved during treatment: a reduction of frequency of seizures was up to 50% in 4 cases (80%). One patient with resistant epilepsy was treated with the combination of drugs (levetiracetam, topiramate, zonisamide, benzodiazepine) that led to stopping of seizures during night sleep and decrease in the frequency of daytime seizures by 50%. Further research of epilepsy and efficacy of antiepileptic drugs in Rett syndrome is required.

[The course and the development of epilepsy in patients with typical variant of Rett syndrome and mutations]. / Osobennosti techeniia i razvitiia épilepsii u detei s tipichnym variantom sindroma Retta, vyzvannogo mutatsiei.

AIM: Studying data of anamnesis, clinical state, electro-encephalographic, brain MRI in patients with Rett syndrome (МЕСР2). MATERIAL AND METHODS: We studied 11 patients (female) from three to 23 years old with Rett syndrome and MeCP2 mutations. Observation continued 10 years (2006-2015). We analyzed the results of the neurological status, night sleep video-EEG monitoring, MRI. RESULTS AND CONCLUSION: Epilepsy diagnosed in six cases (54, 5%). The overage age of debut of epileptic seizures was 3 years 9 months. There are some types of seizures: generalized, myoclonic, myotonic, tonic, versive, focal motor, atypical absences. Status epilepticus evolved in one patient. Generalized seizures were 56, 25%, focal seizures - 43, 75%. EEG changing marked in nine patients (81, 8%): slowdown back activity, episodes of periodic regional slowdown, regional epileptiform activity, and diffuse epileptiform activity like benign focal epileptiform discharges (BFED). five patients took antiepileptic drugs. All of them had improved during treatment. There were reducing of frequency of the seizures up 50% - 4 cases (80%). one patients with resistant epilepsy was taken combination of drugs (levetirecetam, topiromat, zonisamide, benzodiazepine) with stopping of seizures in the night sleep and decreasing of frequency of daytime seizures to 50%. We believe there is very important of study epilepsy in patients with Rett syndrome and improvement of its treatment.

[Russian experience of lacosamide (vimpat) usage in treatment of uncontrolled focal epilepsy]. / Rossiiskii opyt primeneniya lakosamida (vimpat) pri lechenii patsientov s nekontroliruemoi fokal'noi epilepsiei.

Many patients with epilepsy receive treatment in polytherapy. Selection of antiepileptic drugs (AEDs) for the combination should be carried out in accordance with the principles of rational polytherapy, taking into account the mechanism of action, pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs. Along with levetiracetam, gabapentin, vigabatrin and pregabalin, lacosamide (LCM) shows superior PK profile in rating of all AED and can be combined with any of them. The goal of this study was to evaluate efficacy and tolerability of LCM in patients with uncontrolled partial onset seizures (POS) in routine clinical practice. METHODS: 181 patient's charts from 14 sites in Russia have been analyzed in retrospective manner. Patients 16 years old and older with POS with or without secondary generalization were included. Documented observation period of up to 12 months after initiation or until discontinuation of LCM therapy. Primary effectiveness variables was retention at Observational Point 3 (approximately 12 months). Other variables were: percentage change from historical baseline in seizure frequency, 50% and 75% treatment response and seizure-free status at the Observational Points 1, 2 and 3 (approximately 3, 6 and 12 months) and incidence and reason of treatment discontinuation. RESULTS: retention rate was high with 89.5% after 12-month observation. The development of seizure frequency showed a continuous decrease in terms of 50%, 75% treatment respond rates and seizure free status. A total of 5 adverse drug reactions leading to discontinuation of LCM therapy were recorded in 5 of 181 patients (2.8%) during the observation period. The high retention rate observed in this retrospective chart review is assumed to indicate a good tolerability and effectiveness of an adjunctive LCM treatment in patients with uncontrolled partial epilepsy in Russia.

[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.

[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.

[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 of topiramate (Topamax) in epileptic patients of different ages.

The aim of the present work was to assess the efficacy and tolerance of topiramate (Topamax) in patients of different ages with different types of epilepsy. This agent was used as monotherapy and combined therapy in 114 patients (53 male, 61 female) of the following age groups: early childhood (16), preschool and school age (20), pubertal (16), young (23), adult (38), and elderly (1). Treatment produced complete clinical remission in 48% of patients and decreases in fit frequency by more than 50% in 44% of patients. In terms of remission, Topamax was more effective in adolescents, youths and adults than in younger children, and this pattern was also seen in the treatment of symptomatic epilepsy. Tolerance was good in patients of all groups, and cases of side effects (weight loss, irritability, allergic skin reactions, paresthesia) were occasional.

[Epilepsy with electrical status epilepticus during slow sleep: diagnostic criteria and approaches to therapy].

Fourteen patients, aged from 5 to 14 years, with syndrome of electrical status epilepticus during slow sleep (ESESS) have been studied. The absence of epileptic attacks was observed in 21.5% of patients and diagnosis was established by a combination of continuous diffuse epileptiform activity with marked cognitive disturbances. In 78.5% patients, epileptic attacks presented as follows: pharyngeal and oral, hemicephalgia (100% patients with attacks), hemiclonic (18%), atypical absences (27%), negative myoclonus (18%), automotor (18%), focal adverse with vomiting (18%), secondary generalized (36%). Drugs of choice were valproate (depakine) and topamax in patients with attacks; suxilep and frisium in the absence of attacks and in case of continuous diffuse epileptiform activity on the sleep EEG. Two variants have been singled out by the character of ESESS syndrome. The first one, a "symptom variant", was featured by mostly hemiclonic, secondary generalized and automotor epileptic attacks, presence of continuous regional or lateral, less frequent diffuse epileptiform activity, detected by the local structural lesions in MRI, marked cognitive disturbances persisting after stopping of the attacks. The second ("idiopathic") variant is characterized by normal development of children before attack manifestation, appearance of mostly "rolandic" attacks, atypical absences and negative myoclonus, presence of exclusively continuous diffuse epileptiform activity in the phase of slow sleep, standard MRI results (moderate cortical subatrophy in single cases), cessation or substantial decrease of cognitive disturbances after attack stopping. It is emphasized that prognosis of ESESS syndrome should be considered separately with regard to attacks and cognitive disturbances. A prognosis for attacks is always favorable. Cognitive disturbances despite the therapy can persist for a long time.

[Use of reminyl (galantamine) in the treatment of dementia].

Clinical efficacy and safety of reminyl monotherapy has been studied in patients with dementia of Alzheimer's and mixed vascular-degenerative types. The reminyl treatment has been conducted in dosage of 16 mg/kg daily during 6 months in 30 patients (20 female, 10 male) aged from 59 to 86 years. The results of the study revealed high efficacy of reminyl in the treatment of patients with mild and moderate dementia and good tolerability of the medication.

[Efficacy and safety of antiepileptic therapy in children (a comparative analysis of valproates and barbiturates)]. / Effektivnost' i bezopasnost' antiépilepticheskoi terapii u detei (sravnitel'naia otsenka preparatov val'proevoi kisloty i barbituratov).

The study aimed at a comparative analysis of safety and efficacy of valproic acid (valproate) and barbiturates in the treatment of epilepsy in children. Two hundred and forty children were treated with valproate, 94% being assigned to depakine and depakine chrono, and 210 children received barbiturates. Therapeutic effect (a decrease of seizures frequency by 2 and more times or remission) was detected in 82 of 127 (65 +/- 8.53%) patients for valproate monotherapy and only in 26 of 89 (30 +/- 9.45%) for barbiturates monotherapy. An efficacy of antiepileptic therapy in children was significantly higher (p<0.05) for valproates as compared to barbiturates. A drug withdrawal due to poor tolerability was recorded in 6 of 127 (5 +/- 3.7%) patients treated with valproate in monotherapy and in 14 of 210 (7 +/- 3.45%)--in polytherapy; in 53 of 89 (59 +/- 10.2%) patients treated with barbiturates in monotherapy and in 78 of 121 (65 +/- 8.53%) patients treated with barbiturates in polytherapy. Therefore, adverse effects occurred more often in barbiturates than in valproate treatment both for mono- and polytherapy (p<0.05). The results of the study confirmed the high efficacy and safety of valproates, specifically depakine chrono, in the treatment of epilepsy in children. depakine chrono in-take is associated with lower frequency of adverse effects; side-effects are mostly of dose-dependent character and do not result in the drug withdrawal. The authors do not recommend using barbiturates in the first-line treatment in children, because of the lower efficacy, high frequency of medical complications that might result in the drug withdrawal and reducing of the efficacy of other antiepileptic medications.

[Benign myoclonic epilepsy in infancy]. / Dobrokachestvennaia mioklonicheskaia épilepsiia mladenchestva.

Benign myoclonic epilepsy in infancy (NMEI) is one of rare epileptic syndromes. 5 patients (all female sex) aged 4-16 years were observed. NMEI debuted at the age from 7 months till 2.5 years (mean age 1.3 years). Pathology of pregnancy and labor, disorders in both psychomotor development and genetic predisposition were not found. In all the cases the disease began with typical transitory repeated myoclonic paroxysms of different intensity and frequency, without loss of consciousness and with primary involvement of the muscles of the neck and the upper extremities. Most patients had muscular hypotension, mild coordinatory disorders, delayed psycho-speech development, mental retardation, EEG signs of generalized epileptic activity. Valproates, suxilep, clonazepam and lamotrigin (lamiktal) were used for treatment. The most pronounced effect was achieved using either monotherapy with valproates (depakin) or a combination depakin + lamiktal. A stable clinical-encephalographic remission was achieved in all the patients, but during puberty in 2 patients (15 and 16 years old) rare generalized convulsive fits debuted. High frequency of intellectual-mnestic disorders were found even after a complete remission. So benign definition concerns only a course of the fits, but not NMEI prognosis.