[Improvement of the efficacy and safety of treatment of epilepsy using new forms of controlled release antiepileptic drugs]. / Povyshenie éffektivnosti i bezopasnosti terapii épilepsii s ispol'zovaniem novykh form protivoépilepticheskikh preparatov s kontroliruemym vysvobozhdeniem.

The paper summarizes the results of the studies on the efficacy and safety of a new form of controlled release levetiracetam XR (Lev XR) compared to standard tablet immediate release form in treatment of resistant partial seizures. The authors present the data on the bioequivalence and absorption of LevXR related to the meal and therapeutic doses in the range between 1000 to 3000 mg/day. It has been concluded that LevXR has high efficacy and safety due to its stable plasma concentration during the day. The results meet FDA bioequivalence criteria and, in authors opinion, can be recommended as drug of choice in additional treatment of partial seizures in patients above 12 years of age.

[Exalief as a newer antiepileptic drug for adjunctive therapy of refractory partial-onset seizures].

Results of a multicenter international study on the efficacy of exalief (eslicarbazepine acetate (ESL)), a newer blocker of voltage-gated sodium channels and T-type voltage gated calcium channels, for adjunctive therapy of refractory partial-onset seizures are presented. A clinical program included phase II (BIA-2093-201) followed by three phase Ill studies (BIA-2093-301, -302 and-303), each of which was accompanied by an additional open one-year study (301 E, 302E, 303E). In three parallel phase Ill studies patients were randomized to receive ESL in single doses 400, 800, 1200 mg or placebo together with 1 - 3 antiepileptic drugs used in stable doses, with the exception of felbamate and oxcarbazepine. The design of the study included 8-week initial period, double-blind phase (2-week titration period, 12-week maintenance period), 4-week dose reduction period. The results of clinical phase II trials demonstrated the high efficacy and best tolerability profile for single dose titration regimen. Median changes in the frequency of partial-onset seizures were greater (p<0,0001) in patients receiving 800 and 1200 mg ESL (35 and 39%)compared to placebo (15%). The proportion of treatment responders was significantly higher in the groups treated with ESL indoses 800 mg (36%) and 1200 mg (44%) compared to the placebo group (22%). The aversive effects of the drug were of mild or moderate severity. Treatment retention was higher in patients receiving ESL (84,9% of patients completed the 6-month treatment period and 76,6% completed the one-year period). The use of ESL leads to the reduction in partial seizure frequency and the increase in the proportion of treatment responders. The drug has a good tolerability profile.

[Focal features of idiopathic generalized epilepsy].

Idiopathic generalized epilepsies (IGE), in some cases, have focal features in the kinematic of seizures and in the EEG. The aim of the paper was to study these clinical phenomena using video-EEG monitoring. We studied 180 patients (80 men and 100 women) with different forms of IGE with epileptic seizures recorded with this method. The effect of the "superposition" of focal electro-clinical features on the kinematic matrix and EEG pattern of the generalized myo- (clonic)-tonic-clonic seizures was noted. The authors suggest to discuss the definition of the "phenomenon of secondary focalization". This is the clinical/electroencephalographic phenomenon developed in IGE and presented by the appearance of secondary focal features (clinical and electroencephalographic) in the structure of the generalized epileptic seizure. The evidence for the secondary generalization of the seizure with the presence of the regional cortical ictogenic source as well as the diagnosis of focal epilepsy are the exclusion criteria for the phenomenon of secondary focalization.

[Focal characteristics in the clinical examination and EEG in children with idiopathic generalized epilepsy].

The aim of the study was to determine the prevalence of focal characteristics in the clinical symptoms of seizures and in EEG in children with different clinical variants of generalized idiopathic epilepsy. We studied 71 patients, 29 boys and 42 girls, aged from 2 to 18 years. Video-EEG-monitoring and MRI were performed in all cases. The results provided further evidence fort the continuum between focal and generalized epilepsy supported by the presence of focal characteristics in the semiology of seizures and in EEG as well.

[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.

[Transitory cognitive dysfunction in rolandic epilepsy].

Forty-four patients with rolandic epilepsy (32 boys, 12 girls), aged from 5 to 14 years, were examined in the prospective study during 5 years. Before the antiepileptic treatment, most of patients had transitory cognitive disturbances. There were the impairment of verbal functions, especially verbal intellect, while non-verbal intellect remained intact; dyspraxia, impairment of auditory-speech memory, disturbances of arbitrary regulation and optical-motor coordination. The cognitive impairment was not severe and did not impact on learning of school program. No significant correlations were found between the lateralization of regional EEG changes and the character of cognitive dysfunction though the age-related lateralization of the focal epileptiform activity was shown: the right-side localization of central-temporal EEG spikes predominated in children at the age of 6.29 +/- 0.9 years, the left-side localization - in children at the age of 8.4 +/- 1.4 years. The clinical remission was achieved 4-5 years earlier than the recovery of cognitive functions. Valproates used as monotherapy or in the combination with ethosuximidum and levetiracetam were drugs of choice.

[Epilepsies with electric status epilepticus in sleep: peculiarities of clinical course and rational approaches to treatment].

We studied 52 patients with electric status epilepticus in slow sleep (EESSS) during 3-5 years. Age-dependent peculiarities of clinical course of the disease, risk factors for EESSS and rational approaches to antiepileptic treatment for these cases were singled out. Symptomatic and idiopathic EESSS variants were revealed. Combinations of valproates, levetiracetam and ethosuximidum were the most effective antiepileptic drugs in the treatment of EESSS.

[Idiopathic focal epilepsies of infancy and childhood].

We studied 1036 children with epileptic seizures, aged from 1 to 18 years, during 2004-2008. One hundred and six patients were diagnosed with idiopathic focal epilepsy (IFE). The following forms of IFE were singled out: benign seizures of infancy (familial and non-familial) - Watanabe--Vigevano syndrome - 5,7%, occipital epilepsy of childhood with early manifestation (Panayiotopoulos syndrome) -26,4%, occipital epilepsy of childhood with late manifestation (Gastaut syndrome) - 12,3%, benign epilepsy of childhood with central-temporal spikes (rolandic epilepsy) - 51%, benign focal epilepsy with affective symptoms - 4,7%. The efficacy of the first monotherapy was significantly worse in rolandic epilepsy compared to the other IFE forms. Prescription of valproate or the combination of valproate, ethosuximidum and levetiracetam, in case of resistant course, as a starting therapy was found optimal.

[Epilepsy with prolonged epileptiform activity during sleep in children and adolescents].

Benign epileptic discharges of childhood (BEDC) are typical age-related EEG patterns associated with idiopathic benign focal epilepsy (BFE). The study of BFE revealed the symptomatic phenocopies in patients with structural brain lesions in infantile cerebral paralysis and malformations. The authors discuss the question of "benignity" of BEDC that may lead to various disturbances of cognitive functions and behavior, i.e. to signs of epileptic encephalopathy. Based on the examination of 1862 children, including 840 patients with epileptic seizures and 1022 neurologic patients, clinical and neurophysiological features of epileptic syndromes associated with prolonged epileptiform EEG activity in children were found. The most rational antiepileptic therapy was determined.