Background. The problem of antiepileptic therapy in children remains highly relevant due to the insufficient efficacy of standard drugs, adverse events, and limitations of clinical guidelines.Aim. To assess the efficacy, tolerability, and continuation of zonisamide (Zonegran) therapy in children with epilepsy.Materials and methods. This retrospective multicenter study was conducted in epileptology centers in various regions of the Russian Federation, including Moscow, Novosibirsk, Krasnodar, Tyumen, Krasnoyarsk, Voronezh, Ryazan). We included 340 patients under the age of 18 (202 boys and 138 girls) with various epileptic syndromes receiving zonisamide (mean age was 10.63 years). Zonisamide was administered to patients with the following epileptic syndromes: age-dependent self-limited focal epilepsy of childhood (n = 49; 14 %) structural focal epilepsy (n = 102; 30 %), focal epilepsy of childhood with structural brain changes and benign epileptiform discharges of childhood visualized at electroencephalography (n = 38; 11.2 %), idiopathic generalized epilepsy (n = 23; 6.7 %), developmental and epileptic encephalopathies (n = 44; 12.9 %) (including developmental and epileptic encephalopathies with spike-and-wave activation during sleep (n = 23; 6.7 %)), Lennox–Gastaut syndrome and infantile epileptic spasms syndrome (n = 32; 9.4 %), genetic epilepsy with generalized and focal seizures (n = 81; 23.8 %). The type of the seizures was distributed as follows: focal motor (n = 205), bilateral tonic-clonic (n = 192), generalized (n = 197), including generalized convulsive (n = 44), tonic (n = 70), atonic (n = 2), myoclonic (n = 26), epileptic spasms (n = 36), absence seizures (n = 19). One patient could have more than one type of seizures. Magnetic resonance imaging demonstrated some changes in 185 patients, whereas 117 patients had no magnetic resonance imaging changes. Thirty-eight patients did not undergo magnetic resonance imaging as they had no indications to it. The most common structural epileptogenic changes were the consequences of perinatal lesions manifesting as cystic-gliotic transformation, atrophy (125 cases in total); less common changes included focal cortical dysplasia, developmental abnormalities (such as polymicrogyria, lissencephaly, holoprosencephaly), mesial temporal sclerosis, and tumors. Zonegran (zonisamide) as an additional therapy was administered at a dose of 3–8 mg/kg/day (mean dose 5 mg/kg/day) to 321 patients.Results. Zonegran (zonisamide) therapy was effective in 257 (75.6 %) of patients; remission was achieved in 174 patients (67.7 %), while reduced seizure frequency (50 % and greater) was registered in 83 patients (32.3 %). A total of 72 patients (21.2 %) reported no adverse events. Twenty participants (5.8 %) had some adverse events; in 4 cases, they were resolved after dosage decrease; in 16 cases, treatment with zonisamide was discontinued.Conclusion. Zonegran (zonisamide) is effective for comprehensive treatment of both focal and generalized epilepsy in children*.

Objectives. To assess published data and a series of clinical cases in relation to the clinical features of epilepsy, electroencephalographic changes, and other phenotypic features in X-linked intellectual disability (ID) caused by mutations in the KIAA2022 gene. Materials and methods. Retrospective analysis of medical records from various medical institutions of the Russian Federation was conducted, addressing disease and genealogical histories, , and clinical, genetic, electroencephalographic (EEG), and neuroimaging (brain MRI) investigations. The study included seven clinical cases (five girls and two boys, 5–13 years old) with confirmed diagnoses of X-linked ID due to mutations in KIAA2022 in whom the clinical picture of the underlying disease was combined with epilepsy. Results. The main general phenotypic characteristics of patients with X-linked ID due to KIAA2022 mutations were mental retardation, speech impairment, motor developmental delay, and dysmorphism. The most frequently encountered epileptic seizures were myoclonic and atonic, with nodding, propulsion, atypical absences, and EEG changes showing diffuse “spike– multispike–slow wave” complexes. No pathognomonic brain changes were found on MRI. Antiepileptic therapy was ineffective in many cases. Conclusions. The cases of X-linked ID combined with epilepsy described here indicate that this disease can occur both in males and females and that epilepsy is more often apparent as generalized seizures and in many cases is drug-resistant. More information is needed about this rare genetic syndrome.

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.

Background. Real world data help to provide more information on the effects and tolerability of therapy. However, data on the use of perampanel in Russian population of children remain limited.Aim. To conduct a retrospective analysis of perampanel efficacy and tolerability in children and adolescents with epilepsy in real clinical practice.Materials and methods. A total of 106 children aged 4–18 years receiving perampanel as part of combination therapy for epilepsy were observed at 18 centers. Seizure frequency at 1–3, after 6 and 12 months of treatment, presence and type of adverse events (AEs) were analyzed. The main assessed efficacy parameters were seizure control, significant (≥50 %) decrease in seizure frequency. All other outcomes (<50 % decrease, no change or increased seizure frequency) were considered to be no effect. The assessed safety parameters were the percentage of patients with or without AEs and the percentage of perampanel withdrawals due to AEs.Results. We defined 3 age groups for comparison: children 4–6, 7–11 and 12–17 years old. Perampanel efficacy was 69 % (seizure control – 23.6 %, ≥50 % decrease in seizure frequency – 45.3 %). The mean duration of the effect was 7.3 ± 4.1 months. No significant difference in efficacy between age groups was found. However, some greater efficacy of perampanel was noted in adolescents: absence of effect in the form of remission or significant decrease in seizures frequency was noted only in 25.5 %, with 40 % in children 4–11 years old. Among those with inefficacy, 3.8 % reported seizure aggravation. AEs occurred in only 23 % of patients, with the least frequent occurrence in adolescents (11.8 %) and the most frequent in children aged 7–11 years (40 %). The most frequent AEs was sluggishness and/or drowsiness. Discontinuation of perampanel due to AEs was required in 7.6 %.Conclusion. Perampanel has demonstrated high efficacy and good tolerability in real clinical practice among children from 4 years of age and adolescents with partial (focal) and secondary generalized seizures. The AEs that developed were not serious and very rarely led to withdrawal of the therapy. The results are comparable to those of phase III studies and previous real-world data. The usage of perampanel in children with primary generalized seizures should be further investigated.

OBJECTIVE:To describe the spectrum of being detected gene mutations in patients with epilepsy in clinical practice of neurologists specializing in epilepsy with an analysis of diagnosed epileptic syndromes, the characteristics of seizures, the timing of a genetic diagnosis, options and treatment effectiveness.PATIENTS AND METHODS:The study included 100 patients (40 boys, 60 girls) with epilepsy and/or epileptic encephalopathy and a gene mutation identified. The average age was 6.9±5.1 years. Through remote access, epilepsy specialists filled out a specially designed unified table containing information from outpatient case history.RESULTS AND DISCUSSION:There are patients with a wide range of gene mutations, the leading of which is a mutation in the SCN1A gene (15%). The main method (85%) of detection remains the sequencing of the last generation in the «Hereditary Epilepsy» panel. Years pass from the onset of the disease to the genetic diagnosis (Me - 3 years). In most cases, patients with severe (52% have epileptic encephalopathy, 88% have developmental disorders) and pharmacoresistant (mean amount of anti-epileptic drugs - 3.8±2.2, multitherapy - 70%) syndromes have undergone genetic testing. In the treatment of these patients epileptologists are increasingly (52%) use alternative methods: steroids, ketogenic diet and others. The absence of seizures was observed only in 46% of patients.CONCLUSION:Thus, in the outpatient practice of epileptologists, patients with a wide range of gene mutations are found. As a rule, these are patients with severe, therapy-resistant epileptic syndromes.

Juvenile myoclonic epilepsy (JME) is a common disease. However, some aspects of etiology and pathogenesis are not yet fully clarified. This publication describes the development of ideas about JME, the types of seizures that occur in JME, provides a list of triggering factors and a prognosis severity scale that depending on these triggering factors. The section on JME diagnostics discusses methods of neuroimaging, electroencephalography, and approaches to assessing the mental status of JME patients. The data of meta-analysis of prevalence and risk factors of refractory JME in the context of assessment of the disease state and prognosis are presented. The data on advantages and disadvantages of various Antiepileptic Drugs (AEDs) for the control of the disease are considered. The results of the own study of AED spectrum and effectiveness in gender-sensitive and ILAE-recommended therapy in adults, as well as the GENERAL study of perampanel efficacy and safety in patients with idiopathic generalized epilepsy, are presented. It confirmed the high efficacy of the perampanel primarily for myoclonic seizures and generalized tonic-clonic seizures. A case study of a female patient with JME was also described, in which refractory to therapy was noted, including due to low compliance to the prescribed therapy.

Valproate is generally the drug of choice in genetic generalized epilepsy (GGE). But its therapy was changed after the appearance of the 2015 International League against Epilepsy (ILAE) recommendations to limit the dose of valproates in women.Objective: to assess the spectrum of antiepileptic drugs (AEDs) and to evaluate the efficiency of therapy in adults with GGE, in terms of the gender characteristics of the latter and the ILAE recommendations.Patients and methods. A retrospective open-label observational study was conducted. A cohort of patients was formed according to their visits to physicians in 2013 to 2017. Two patient groups were identified. Group 1 included 80 patients (35 males, 45 females); their mean age was 27.1±3.6 years; they were followed in 2013–2014. Group 2 consisted of 137 patients (53 males, 84 females); their mean age was 29.4±4.6 years; they visited their physicians in 2015–2017. The spectrum of AEDs that were used in monotherapy or polytherapy was assessed. The efficiency of therapy was determined by the onset of remission.Results and discussion. The patients of the two groups were matched for the spectrum of GGE syndromes. Most patients received valproates; more than 35% took levetiracetam; lamotrigine was used slightly less often. In Group 2, females used polytherapy more frequently than males (p=0.03). The percentage of achievement of clinical and encephalographic remission (CER) was higher in Group 2 (p=0.05); there was no significant difference in this indicator between men and women in the two groups. In Group 2, among those achieving CER, the percentage ofpatients receiving monotherapy decreased and that of those having polytherapy increased (p=0.02). The spectrum of AEDs used to achieve CEPremained unchanged in both groups; however, there was a significant difference in the drug dosing regimens.Conclusion. Current therapy for GGE is successful and leads to remission in most patients. After 2015, dual therapy for GGE is used significantlymore often in women than in men (p<0.05). The combination of valproate with levetiracetam or lamotrigine predominates.

Fejerman syndrome, a benign nonepileptic myoclonus of infancy (BNMI), is a rare type of paroxysmal events, which mimics epileptic spasms. It is difficult to determine the nature of myoclonus without video electroencephalography (VEEG) monitoring.Objective: to present the clinical and electroencephalographic characteristics of new cases of benign nonepileptic myoclonus of infancy and early childhood.Patients and methods. The data of 33 children (19 boys and 14 girls) aged 5 months to 3 years with BNMI, who had been followed in 2011 to 2017, were analyzed.Results and discussion. The age at onset of paroxysms ranged from 4 to 24 months and that was 5–8 months in most cases. The most common movements were extensor muscle jerks (30.3%), head titubation with rotation (27.3%), axial spasms (27.3%), and nods (24.2%). The same child may have different types of paroxysms. Motor paroxysms were sporadic in all the patients and formed into clusters in 33.3% of cases. The frequency of clusters was up to 10 times daily. There were 2 to 50 paroxysms in the cluster. There was delayed psychomotor development in 5 of the 33 children and hyperexcitability was present in 10. VEEG monitoring indicated that the brain bioelectrical activity conformed to the age in 97% of cases; none of the children showed abnormal movements accompanied by EEG pathological activity. The duration of the disease was 2 to 19 months, averaging 7 months. In all cases paroxysms were stopped without using antiepileptic drugs.Conclusion. It is extremely important to timely recognize BNMI, since anti-epileptic therapy can be unreasonably prescribed in cases of an erroneous diagnosis. VEEG monitoring plays a crucial role in diagnosing nonepileptic and epileptic myoclonus.

Objective: to generalize the Russian experience with perampanel (PER) in routine clinical practice; to do this, the results of its use as an adjuvant partial epilepsy medication were retrospectively assessed. The study is still in progress now; therefore, the paper gives its preliminary results. Patients and methods. The investigation included 52 patients with drug-resistant partial epilepsy. Their mean age was 28.92±14.02 years (asmall number of the patients had not attained the age of 12 years); the proportion of men was 56%; the disease duration was over 10 years (69.2%); symptomatic epilepsy was in 76.9% with an epileptic focus being in the frontal (46.2%) and temporal (44.2%) regions. PER was prescribed to the majority (71.2%) of patients after three previous therapy lines. The baseline monthly rates of all types of seizures were 127.29±82.29; those of generalized seizures were 6.72±1.90.Results and discussion. After addition of PER to therapy just within the first month, there was a significant reduction in the frequency of all types of seizures to 52.06±29.26 per month (Sign test; p = 0.00001) and in that of secondary generalized seizures to 3.71±1.71 (Sign test; p=0.00001). The duration of PER administration was more than 6 months in the overwhelming majority of cases. In 58% of the patients, the frequency of seizures decreased by more than 50% (respondents). The lack of all types of seizures was noted in 8%; that of only secondary generalized seizures was in 31%. Adverse events were observed in 30.1% of the patients (aggression in 11.5% and somnolence in 9.6%; others were seen more rarely). The dose of PER was decreased because of side effects in 7 (13.5%) patients; the drug was discontinued in 4 (7.7%). The mean dose of PER for adults was as high as 6 mg.

Objective: to generalize the Russian experience with perampanel (PER) in routine clinical practice; to do this, the results of its use as an adjuvant partial epilepsy medication were retrospectively assessed. The study is still in progress now; therefore, the paper gives its preliminary results. Patients and methods. The investigation included 52 patients with drug-resistant partial epilepsy. Their mean age was 28.92±14.02 years (a small number of the patients had not attained the age of 12 years); the proportion of men was 56%; the disease duration was over 10 years (69.2%); symptomatic epilepsy was in 76.9% with an epileptic focus being in the frontal (46.2%) and temporal (44.2%) regions. PER was prescribed to the majority (71.2%) of patients after three previous therapy lines. The baseline monthly rates of all types of seizures were 127.29±82.29; those of generalized seizures were 6.72±1.90. Results and discussion. After addition of PER to therapy just within the first month, there was a significant reduction in the frequency of all types of seizures to 52.06±29.26 per month (Sign test; p = 0.00001) and in that of secondary generalized seizures to 3.71±1.71 (Sign test; p=0.00001). The duration of PER administration was more than 6 months in the overwhelming majority of cases. In 58% of the patients, the frequency of seizures decreased by more than 50% (respondents). The lack of all types of seizures was noted in 8%; that of only secondary generalized seizures was in 31%. Adverse  events were observed in 30.1% of the patients (aggression in 11.5% and somnolence in 9.6%; others were seen more rarely). The dose of PER was decreased because of side effects in 7 (13.5%) patients; the drug was discontinued in 4 (7.7%). The mean dose of PER for adults was as high as 6 mg.

Abstract: rolandic Epilepsy is one of the most common forms of idiopathic epilepsy. Its clinical profile and intercritical EEG are well-defined and widely described in medical literature. However, ictal EEG patterns in benign focal epilepsy with centrotemporal spikes are rarely recorded due to low frequency of seizures, mostly occurring during sleep. Only a small number of publications on the subject are available globally. This article provides a description of an ictal EEG during a roladic epileptic seizure.

Idiopathic occipital epilepsy is a rare epileptic syndrome. Its incidence in a Novosibirsk cohort of patients with idiopathic focal epilepsy is 0.9%. Objective: to present a clinical description of new cases of Gastaut syndrome, the types of its course, and treatment options in these patients. Patients and methods. The study covers 17 cases of Gastaut type idiopathic occipital epilepsy in 13 women and 4 men aged 11–53 years. Results. Among 17 cases we present 4 family cases with the disease. Three generations in 2 families were observed to have epilepsy, including Gastaut syndrome concurrent with childhood absence epilepsy. The adolescent onset of the disease was seen in most cases. Its main symptoms were focal visual seizures (100%), focal sensory seizures (58.9%), cephalalgia (47.1%), speech disorders (41.2%), and secondarily generalized convulsive seizures (35.3%). According to the frequency of seizures, the investigators identified 5 types of the course: single focal seizures, rare focal seizures with or without convulsions, frequent focal seizures with or without convulsions. The identity of the course of epilepsy was found in familial cases. 76.5% of the patients had a good quality of life: 41.2% of them were untreated while 35.3% were treated; no seizures were noted.

An objective of this paper was to study treatment outcomes in patients with infantile spasms (IS) in the evolutionary aspects and from the point of view of drug resistance. We have treated 124 children with IS. Standard therapy included hormones synacthen depot (0.03-0.05 mg/kg) or dexasone (0.3-0.5 mg.kg). The drug regimen was as follows: 10 injections daily initially, following with 5 injections every other day, then 5 injections every two days, plus a valproate in dose 30-40 mg/kg/day. Seventy-three patients were followed up: 21 patients continued to manifest spasms despite the use of several adequate and well-tolerated antiepileptic drugs (AEDs) as a monotherapy, as well as a combination therapy. The patients were divided into 2 groups. In Group 1 (n=12) the remission period was from 0 to 4 months, while in Group 2 (n=9) remission lasted from 7 months up to 4 years. The patients demonstrated all types of IS and modified hypsarrhythmia. In Group 1, the patients were relieved of IS in 66% of the cases and the EEGs showed no epileptic activity in 58%. 83% of the patients then experienced a return of IS and 50% of the patients had hypsarrhythmia. Adding 2 and 3 AEDs to the treatment did not bring any change. A transformation of hypsarrhythmia was observed as the patients grew older. All patients in Group 2 had a cessation of IS, and 77% of the patients had no hypsarrhythmia. In one third of the cases, the IS returned while the other two thirds had focal seizures. EEGs predominantly demonstrated the focal epileptic activity. Adding 2 AEDs had positive effect on seizures in 66% of the cases and EEGs improved in 88% of the cases. Adding 3 AEDs had no effect on the course of the condition in one third of the cases, and in most cases the EEGs did not change. In Group 1, the condition was of drug-resistant nature, and in Group 2 we saw a remission in the condition. After the hormone regimen was completed, a relief of the epileptic activity was achieved for most patients in Group 2. In Group 1, the recurrence of IS was in correlation with the persistence of hypsarrhythmia. We have not found any obvious benefit from the use of any one AED or a combination of AEDs. 78% of the patients in Group 1 demonstrated further persistence of IS for several years. In Group 2, the return of seizures and the EEGs were age-dependent and the treatment had a more positive outcome.