Analysis of Clinical Characteristics, Background, and Paroxysmal Activity in EEG of Patients with Juvenile Myoclonic Epilepsy

Juvenile myoclonic epilepsy (JME) appears in adolescence with myoclonic, absence, and generalized tonic clonic (GTC) seizures with paroxysmal activity of polyspike and slow wave (PSW), or spike and wave (SW) complexes in EEG. Our aim was to analyze the clinical characteristics, background EEG activity, and paroxysmal events in 41 patients with JME. Background EEG activity was analyzed with visual, quantitative (QEEG), and neurometric parameters. Our JME patients started with absence seizures at 11.4 ± 1.5 years old, myoclonic seizures at 13.6 ± 2.5 years, and GTC seizures at 15.1 ± 0.8 years. The seizures presented in awakening at 7:39 h with sleep deprivation, alcoholic beverage intake, and stress as the most frequent precipitant factors. Paroxysmal activity was of PSW and fast SW complexes with 40.5 ± 62.6 events/hour and a duration of 1.7 s. Right asymmetric paroxysmal activity was present in 68.3% of patients. Background EEG activity was abnormal in 31.7% of patients with visual analysis. With QEEG beta AP (absolute power) increase and AP delta decrease were the most frequent abnormalities found. Spectral analysis showed that 48.7% of patients had normal results, and 26.83% and 24.4% had higher and lower frequencies than 10.156 Hz, respectively. We concluded that, with visual analysis, background EEG activity was abnormal in a few patients and the abnormalities increased when QEEG was used.

Juvenile myoclonic epilepsy: current state of the problem

Due to the high prevalence of the disease, its genetic and clinical heterogeneity, the need for lifelong therapy and the emergence of new views on the pathogenesis and course of JME, it is necessary to provide primary care physicians (general practitioners, district therapists, neurologists) with up-to-date systematized information about the most common form of genetic generalized epilepsy (Herpin-Janz syndrome). JME is a genetically determined disease of the brain, accompanied by a triad of seizures (absences, myoclonia, generalized tonic-clonic seizures), and developing mainly in adolescence and young age. In recent years, monogenic and multifactorial forms of JME have been identified, but questions about the genetics of JME are far from being resolved. JME is characterized by the preservation of intelligence, life expectancy with adequate therapy does not differ from the average population, but the frequency of failures of pharmaco-induced remission is high when taking anticonvulsants is canceled. This explains the need for lifelong pharmacotherapy, individual selection of anticonvulsants. About 30% of patients with JME have non-psychotic mental disorders, disorders of the sleep and wake cycle, which in turn leads to an aggravation of epileptic seizures mainly in the first half of the day. This review presents an analysis of full-text publications in Russian and English over the past five years in the databases eLibrary, PubMed, Web of Science, OxfordPress, Springer, and Clinicalkeys. In addition, the review includes earlier publications of historical significance.

Clinical and genetic characteristics of juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is reported as a clinically and genetically heterogeneous disease with a high risk of inheritance. The aim of the study was to establish phenotype features and genetic risk factors for juvenile myoclonic epilepsy to advance existing approaches of prevention, treatment, and observation of patients with JME. Methods: anamnestic; clinical; neurophysiological (EEG); neuroradiological (MRI), neuropsychological; laboratory (DNA-diagnostics). JME starts with absences more frequently in females as compared to males (32.0% vs. 15.4%), and with GTCS and myoclonic in males as compared to females (46.2% and 36.5% vs. 36.0% and 31.2%, respectively). The 1st phenotype of JME was more frequently encountered in male individuals in comparison with female ones (55.8% vs. 34.7%), and the 2nd phenotype was more frequently encountered in female individuals in comparison with male ones (16.9% vs. 5.8%). Homozygous carriage of the T allele of the GJD2 gene (rs3743123) was associated with the development of JME in the study population, OR = 2.66 (95% CI 1.24 to 5.74). 41.5% of patients with JME have a slow metabolizer pharmacogenetic status, which is a risk factor for pseudo-pharmacoresistance and the development of adverse drug reactions.

Zebrafish Paralogs brd2a and brd2b Are Needed for Proper Circulatory, Excretory and Central Nervous System Formation and Act as Genetic Antagonists during Development

Brd2 belongs to the BET family of epigenetic transcriptional co-regulators that act as adaptor-scaffolds for the assembly of chromatin-modifying complexes and other factors at target gene promoters. Brd2 is a protooncogene and candidate gene for juvenile myoclonic epilepsy in humans, a homeobox gene regulator in Drosophila, and a maternal-zygotic factor and cell death modulator that is necessary for normal development of the vertebrate central nervous system (CNS). As two copies of Brd2 exist in zebrafish, we use antisense morpholino knockdown to probe the role of paralog Brd2b, as a comparative study to Brd2a, the ortholog of human Brd2. A deficiency in either paralog results in excess cell death and dysmorphology of the CNS, whereas only Brd2b deficiency leads to loss of circulation and occlusion of the pronephric duct. Co-knockdown of both paralogs suppresses single morphant defects, while co-injection of morpholinos with paralogous RNA enhances them, suggesting novel genetic interaction with functional antagonism. Brd2 diversification includes paralog-specific RNA variants, a distinct localization of maternal factors, and shared and unique spatiotemporal expression, providing unique insight into the evolution and potential functions of this gene.