Regina Gamirova

Introduction. Juvenile myoclonic epilepsy is the most common form of genetic generalized epilepsy, which is included in the group of idiopathic generalized epilepsies. The etiology of drug-resistant forms of juvenile myoclonic epilepsy, which represent a serious clinical problem, is currently a controversial issue. Aim. To reveal the most significant risk factors of resistance in juvenile myoclonic epilepsy. Materials and Methods. The observational retrospective study included 56 patients, 46 (82%) women and 10 (18%) men. Inclusion criteria: patients diagnosed with juvenile myoclonic epilepsy based on the criteria of the International League Against Epilepsy, treatment for at least 2 years. The type and frequency of epileptic seizures, the onset and course of the disease, concomitant diseases, family history, all available results of 1-2 hours video electroencephalographic monitoring with sleep, and magnetic resonance imaging results were analyzed. Depending on the treatment effect, all patients were divided into two groups: 1 – without seizures, 2 – with seizures. Lack of complete seizure control for at least 2 years was considered intractable epilepsy. Risk ratios as outcomes for dichotomous variables in two compared groups for various characteristics and their confidence intervals were calculated using the Review Manager program (v5.3). Differences were considered significant at P<0.05. Results and Discussion. As a result, there were obtained data on the resistance of juvenile myoclonic epilepsy depending on the age of disease onset, the type of epileptic seizures, changes in the electroencephalogram, and the type of antiepileptic treatment. Conclusions. The most significant risk factors of resistance in juvenile myoclonic epilepsy have been identified: frequent generalized tonic-clonic seizures (more than 5 times a year) accompanying the basic disease, depression, anxiety, and lack of response to the treatment with valproic acid. At the same time, non-compliance, sleep disturbances, consumption of alcohol and energy drinks during therapy are factors that can be controlled during the physician’s individual work with the patient aimed at the explanation and prevention of risks in treatment.

Many questions remain regarding the genetics of idiopathic generalized epilepsy (IGE), a subset of genetic generalized epilepsy (GGE). We aimed to identify the candidate coding variants of epilepsy panel genes in a cohort of affected individuals, using variant frequency information from a control cohort of the same region. We performed whole-exome sequencing analysis of 121 individuals and 10 affected relatives, focusing on variants of 950 candidate genes associated with epilepsy according to the Genes4Epilepsy curated panel. We identified 168 candidate variants (CVs) in 137 of 950 candidate genes in 88 of 121 affected individuals with IGE, of which 61 were novel variants. Notably, we identified five CVs in known GGE-associated genes (CHD2, GABRA1, RORB, SCN1A, and SCN1B) in five individuals and CVs shared by affected individuals in each of four family cases for other epilepsy candidate genes. The results of this study demonstrate that IGE is a disease with high heterogeneity and provide IGE-associated CVs whose pathogenicity should be proven by future studies, including advanced functional analysis. The low detection rate of CVs in the GGE-associated genes (4.1%) in this study suggests the current incompleteness of the Genes4Epilepsy panel for the diagnosis of IGE in clinical practice.