[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.

[Experience in the management of patients with genetic epilepsies and epileptic encephalopathies in the outpatient practice]. / Opyt vedeniya patsientov s geneticheskimi epilepsiyami i epilepticheskimi entsefalopatiyami v ambulatornoi praktike.

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 Epilepsy¼ 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.

[Age-related transformation of infantile spasms into drug-resistant forms of epilepsy].

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.