[Efficacy and tolerability of perampanel as adjunctive treatment of focal and generalized tonic-clonic epileptic seizures in children over 4 years of age]. / Effektivnost' i perenosimost' perampanela kak dopolnitel'nogo preparata v lechenii fokal'nykh i generalizovannykh toniko-klonicheskikh epilepticheskikh pristupov u detei v vozraste ot 4 do 12 let.

The article is a short review of an observational study that proves the good efficacy and tolerability of perampanel suspension in the adjunctive treatment of epilepsy in children over 4 years of age. The study demonstrated a high level of 50% responders: 47% with focal seizures, 65% with transition of focal seizures to bilateral tonic-clonic seizures, 65% with primary generalized tonic-clonic seizures. Cessation of seizures was achieved in 12%, 19% and 55% of patients, respectively. The most common side-effects were fatigue (26%), nasopharyngitis (19%), lightheadedness, irritability, fever (13% each), and vomiting (11%). There were no significant clinical negative changes in cognitive functions according to the assessment on the Aldenkamp-Baker scale, both on the total score and subscales. Also, there were no significant changes in laboratory data, vital functions and ECG parameters.

[The problem of comorbidity of epilepsy and psychogenic paroxysms]. / Problema komorbidnosti epilepsii i psikhogennykh paroksizmov.

A review of publications over the last two decades is presented. Psychogenic paroxysms develop in approximately 12% of patients with epilepsy. The analysis of social and demographic data, history details, semiological features and results of electrophysiological and neuroimaging studies does not unequivocally support the comorbidity of epilepsy and psychogenic paroxysms. The pathogenetic mechanisms of the development of comorbidity are various and depend on the presence of pharmacoresistance, psychological traumas in the past, intellectual disability etc. Video-EEG-monitoring is the gold standard in the diagnosis of comorbidity of epilepsy and psychogenic paroxysms. Treatment of such cases includes anticonvulsants and cognitive-behavioral therapy.

[Difficulties in the diagnosis, prognosis and treatment of genetic epileptic encephalopathies: the view of a neurologist]. / Trudnosti v diagnostike, prognoze i lechenii geneticheskikh épilepticheskikh éntsefalopatii: vzgliad nevrologa.

Genetic epileptic encephalopathies are a rather wide spectrum of childhood epilepsies with onset of epilepsy in the first 1.5-2 years of life, regression or delayed psychomotor and speech development and 'massive' epileptiform activity on electroencephalogram (EEG). The review discusses the difficulties of choosing the optimal method of genetic examination, problems with the interpretation of the results obtained, the formulation of the diagnosis, the determination of the prognosis of the course and targeted therapy. It is emphasized that the interpretation of the identified genetic variants is not an easy task, requiring close interaction between specialists in molecular genetics, bioinformatics, neurology and clinical genetics. The possibilities of targeted treatment of genetic epileptic encephalopathies are still limited, but knowledge of the genetic cause of epilepsy allows making a more informed choice of the treatment.

[Why the diagnosis of Lennox-Gastaut syndrome is a rare one?] / Pochemu tak redko stavitsia diagnoz sindroma Lennoksa-Gasto?

The review addresses the problem of the diagnosis of Lennox-Gastaut syndrome, a severe epileptic encephalopathy. Despite the presence of a vivid clinical and encephalographic picture, classical Lennox-Gastaut syndrome, which meets all of its diagnostic criteria, is quite rare. Many authors believe that the diagnosis of the syndrome is possible if the patient has tonic seizures and typical ictal and interictal patterns on the electroencephalogram (EEG). The diagnosis of the syndrome is considered probable if there are typical EEG patterns of wakefulness and sleep, but no tonic seizures are recorded. Diagnosis of the syndrome is complicated by its polyetiology (clinical and EEG manifestations can vary significantly), the evolution of seizure types and EEG characteristics as the patient matures, the presence of other epileptic syndromes similar to Lennox-Gastaut syndrome.

[Epilepsy and autism spectrum disorders in children]. / Épilepsiia i rasstroistva autisticheskogo spektra u detei.

The problem of epilepsy comorbidity with autism spectrum disorders in children is discussed. The incidence data of autism spectrum disorders in epilepsy, epileptiform discharges on the EEG in autism spectrum disorders and epilepsy in autism spectrum disorders are reviewed. The following types of epilepsy and autism co-occurrence are discussed: both conditions are independent, have different causes and may co-occur by chance; epilepsy and autism are associated, both being independent consequences of the same genetic disorder or early cerebral damage; autism is caused by the epileptic process which interferes with the function of specific brain networks involved in the development of communication and social behavior; autism is a result of the withdrawal reaction in the epileptic child. The known genetic causes of epilepsy and autism spectrum disorders comorbidity are provided. The practical issues are discussed, in particular the rational indication of antiepileptic drugs to the children suffering autism spectrum disorders.

[Vaccination, febrile seizures and epilepsy]. / Vaktsinatsiia u detei, febril'nye sudorogi i épilepsiia.

This literature review addresses the risk of vaccination complications including neurological ones. Some vaccines associated with vaccine-induced febrile seizures (FS), e.g. vaccines against pertussis, diphtheria and tetanus, can provoke FS but they are not their cause. Therefore, delaying a vaccination to an older age does not reduce the risk of FS. The author also considers international and Russian recommendations on vaccination in children with epilepsy, West syndrome and Drave's syndrome.

[New classifications of epilepsies and seizure types created by the International League against Epilepsy (2017)]. / Novye mezhdunarodnye klassifikatsii épilepsii i épilepticheskikh pristupov Mezhdunarodnoi ligi po bor'be s épilepsiei (2017).

This review presents the recently published revised classifications of epilepsies and seizure types developed by the International League Against Epilepsy (ILAE). The Classification of Epilepsies includes several diagnostic levels (steps): 1) from seizure type to epilepsy type (generalized/focal/combined generalized and focal/unknown), 2) diagnosis of epilepsy syndrome 3) etiology (genetic/ structural/ infectious/ metabolic/ immune/unknown). A clinician can use any level of the classification. Operational classification of seizure types is replaced by the previous classification that was grounded on the anatomical basis. Seizures are classified by the onset (focal, generalized or unknown). All types of seizures can be motor or non-motor. Focal seizure may evolve to bilateral tonic-clonic (previously called secondary-generalized). Atonic, clonic, tonic, myoclonic seizures and epileptic spasms can be either of focal or generalized onset. Unclassified type of seizure was introduced. New types of seizures (absence with eyelid myoclonia, myoclonic absence, myoclonic atonic and clonic-tonic-clonic seizures) were added. New terminology, definitions and some concepts developed by ILAE are presented.

[The decreased level of plasma carnitine in patients with epilepsy]. / Snizhenie kontsentratsii karnitina u patsientov s épilepsiei.

Antiepileptic drugs (AEDs) have long been known to affect carnitine metabolism, dropping the plasma free carnitine. Valproate (VPA) was considered to be the strongest carnitine-reducing agent. VPA-induced hyperammonemic encephalopathy and hepatotoxicity are well known, and pre-existing carnitine deficiency can be a predisposing factor, especially in congenital metabolic disorders. Several studies have shown that carnitine supplementation in patients receiving VPA to result in subjective and objective improvements and to prevent VPA-induced hepatotoxicity and encephalopathy, in parallel with increases in carnitine serum concentrations. Level of free plasma carnitine <20 micromol/l (syn. carnitine deficiency) in patients with epilepsy (in 15-30% of cases) may occur not only with administration of VPA but with administration of other AEDs (phenobarbital, phenytoin, carbamazepine) and low nutritional intake of carnitine. Some findings indicate that the number of AEDs used is a risk factor for carnitine deficiency. It was established that body weight, height and multidrug therapy are significantly associated with low level of free plasma in epileptic patients. Carnitine deficiency can have severe consequences; but most epileptic patients suffering from it are asymptomatic. Although carnitine deficiency is not uncommon among patients receiving AEDs, it seems not necessary to routinely monitor carnitine levels in epileptic ambulatory patients, this is reasonable only in groups of risk. L-carnitine supplementation is clearly indicated in case of VPA-induced hepatotoxicity (i.v. administration) VPA overdose (i.v. administration), primary carnitine-transporter defect and is strongly recommended in specific secondary carnitine deficiency syndromes, symptomatic VPA-associated hyperammonemia, infants and young children receiving VPA, especially those younger than 2 years, patients with a complex neurologic disorder, who are receiving multiple AEDs, patients who have risk factors for hepatotoxicity and carnitine insufficiency. In the absence of double blind trials, clinical practice is based on empiric observation, clinical experience, and theory. Well-designed studies of specific and general uses of L-carnitine replacement therapy in patients with epilepsy are needed.

[Hormonal treatment in West syndrome]. / Gormonal'naya terapiya sindroma Vesta.

West syndrome is one of the most well-known epileptic encephalopathies, a catastrophic epilepsy syndrome with onset in the first year of life. Prognosis of this condition depends on the etiology and adequate treatment. The authors review the hormonal treatment of West syndrome. Adrenocorticotrophic hormone (ACTH) is used in USA and its synthetic analogue tetracosactide is used in Europe. Both of the drugs are not registered in the Russian Federation. The data on the efficacy of corticosteroids, including prednisolone, are contradictory. Recent results have demonstrated the high efficacy of prednisolone in the treatment of West syndrome. The authors discuss different aspects of hormonal treatment of West syndrome: possible mechanisms, choice of medication, hormone doses, its duration, efficacy ant tolerability.

[Genetics and treatment of early infantile epileptic encephalopathies]. / Genetika i differentsirovannoe lechenie rannikh epilepticheskikh entsefalopatii.

Epileptic encephalopathies (EE) are the group of progressive conditions with various etiologies that can produce neurocognitive deficit both per se and due to constant epileptiform discharges. Epileptic encephalopathies constitute about 15% of epilepsy in childhood and 40% of all seizures occurring in the first 3 years of life. Ten syndrome forms of EE are identified. Genetic factors contribute to 70-80% of all epileptic diseases and approximately 40% of idiopathic epilepsies have a monogenic mode of inheritance. Thirty-five genes of EE have been identified and the search is still continuing. The marked genetic heterogeneity of early EE, including 16 with autosomal-dominant-, 13 with autosomal-recessive-, 4 with X-linked recessive- and 2 with X-linked autosomal inheritance, was shown. The article describes differentiated approaches to the treatment of certain EE syndromes. Recent publications record the effectiveness of targeted therapy for certain forms of monogenic early EE (stiripentol in SCN1A mutations, diphenine in SCN8A mutations, levetiracetam in STXBP1 mutations). These results indicate the necessity for accurate diagnosis of genetic variants in early infantile EE for preventive actions in burdened families and for increasing the effectiveness of treatment.

[Diagnosis of tuberous sclerosis complex].

Tuberous sclerosis complex is a autosomal dominant instantly progressing disease, causing the development of benign tumors in all organs and tissues of human body. According to International Consensus Conference (2012), definite or possible TSC diagnosis can be made. For the definite diagnosis of TSC, two major criteria or one major criterion and ≥2 minor criteria have to be present. For a possible diagnosis, 1 major criterion or ≥2 minor criteria should be found. A pathogenic mutation in the TSC1 or TSC2 gene is by itself sufficient for a definite diagnosis. There are following major diagnostic criteria: angiofibromas (≥3) or forehead plaque; hypomelanotic macules (≥3); ungual fibromas (≥2); chagrin patch; multiple retinal hamartomas; cortical dysplasias (≥3, include tubers and cerebral white matter radial migration lines; subependymal nodules; subependymal giant cell astrocytoma; cardiac rhabdomyoma; lymphagioleiomatosis and renal angiomyolipomas (≥2). The minor criteria are the following ones: dental enamel pits (≥3); intraoral fibromas (≥2); non-renal hamartomas; retinal achromatic patch; confetti skin lesions; multiple renal cysts. Diagnosis of TSC is not difficult if a physician is familiar with clinical presentation of the disease.

[Perampanel in treatment of refractory partial epilepsy in adolescents and adults: results of international multicenter randomized, double-blind, placebo-controlled phase III studies].

INTRODUCTION: Despite availability of many AEDs, failure rate of first AED used in children with newly diagnosed epilepsy remains as high as 20-40%. Although likelihood of seizure freedom declines with successive AEDs, almost 1 in 5 patients become seizure free with the addition of an alternative AED after failure of 2-5 agents. New AED - perampanel (PER) was developed as a selective, non-competitive AMPA receptor antagonist to target post-synaptic glutamate transmission. METHODS: Efficacy and tolerability of PER in adolescents and adults with refractory partial seizures secondarily generalized and without generalization was assessed in international (global) randomized placebo-controlled prospective phase III trials with prolonged open follow-up phase. 1478 patients aged older than 12 years were included. All of them were unsuccessfully pretreated with 1-3 AEDs. Patients were randomized either to placebo or to 2, 4, 8, 12 mg of PER daily respectively. After completing the double blind phase they were transferred to open extension phase with titration of daily dose of PER up to 12 mg. RESULTS: PER in doses of 4, 8, and 12 mg/day provided reductions in the frequency of partial-onset seizures compared with placebo. Percentage of patients achieving ≤ 50% reduction from baseline in seizure frequency/28 days on doses 4, 8 and 12 mg daily was 29%, 35% and 35% respectively vs. 19% in placebo group (p<0,01). Median% change from baseline in seizure frequency/28 days saw also more evident in PER group. Adverse events (AEs) occurred in 65-89% of patients receiving any dose of PER vs. 67% patients receiving placebo. Most AEs were of mild or moderate intensity (dose related). Most frequently reported AEs were dizziness, somnolence and aggression. 1218 pts were enrolled in the open-label extension study. 91% of patients reached 10 or 12 mg/day of PER. Efficacy was maintained with long-term treatment with responder rates of 62.7% during Weeks 92-104. Frequency and character of AEs were consistent with that in double blind phase. CONCLUSION: The presented data indicate that PER at a daily dose of 4, 8 or 12 mg is efficacious as additional treatment of adolescents and adults with refractory partial seizures secondarily generalized and without generalization with acceptable tolerability.

[Rational polytherapy of epilepsy in children]. / Ratsional'naia politerapiia épilepsii u detei

About 30% of patients with epilepsy are resistant to pharmacological treatment. These patients benefit from combinational therapy with two or more antiepileptic drugs (AEDs). The management of resistant epileptic patients with AEDs combinations is based on the pharmacokinetic and pharmacodynamic interactions between AEDs. The article reviews the data on interactions between widely used AEDs.

[Epileptic encephalopathy with continuous spikes and waves during sleep (CSWS): a review]. / Épilepticheskaia éntsefalopatiia s prodolzhennoi spaik-vol-no-voi aktivnost'iu vo sne: obzor literatury.

Epileptic encephalopathy (EE) with continuous spikes and waves during sleep (CSWS) (epilepsy with electric epileptic status during slow sleep phase or encephalopathy with electric epileptic status during slow sleep phase) is partially reversible age-dependent epileptic encephalopathy. It is characterized by a triad of symptoms: seizures, neurocognitive regression, and an electroencephalography pattern of electrical status epilepticus during sleep. This rare condition occurs in 0,5% of children and adolescents with epilepsy. Seizures usually start when the child is 2-4 years old. Several stages in CSWS are identified: dormant stage, prodromal stage, acute stage, and residual stage. EE epileptiform activity may be focal, multifocal, unilateral, asymmetric or symmetric bilateral, and diffusive. Treatment goals of CSWS include not only improved seizure control, but also a significant reduction in EEG epileptiform activity. Benzodiazepines and steroids are most effective.

[The course and treatment of epilepsy in children with tuberose sclerosis].

Tuberous sclerosis complex is a multisystem genetic disorder. Epilepsy is very common in tuberous sclerosis and occurs in 75-92% of affected individuals during their life-time. Onset usually occurs during childhood and up to one third of children with tuberous sclerosis will develop infantile spasms. Of all the possible manifestations of this complex disorder the resistant epilepsy, the cognitive and behavioral problems represent the area of greatest concern to parents, caregivers and physicians. Treatment of epilepsy in tuberous sclerosis is similar to epilepsy resulting from other cases and includes anticonvulsant medications, the epilepsy surgery, the vagus nerve stimulation and the ketogenic diet. Vigabatrin has been shown to be particularly effective in treating infantile spasms in the setting of tuberous sclerosis.

[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.