Nationwide Study of Pediatric Drug-Resistant Epilepsy in Estonia: Lower Incidence and Insights into Etiology

Background/Objectives: Drug-resistant epilepsy (DRE) is a significant health problem leading to cognitive impairment and reduced quality of life. This study aimed to in-vestigate the incidence and etiology of DRE in children in Estonia. Methods: A retrospective, population-based study of childhood DRE was conducted in Estonia from January 1, 2013, to December 31, 2017. All cases were identified through the only two pediatric neurology departments in the country, both located at tertiary care hospitals (Tartu University Hospital and Tallinn Children’s Hospital), ensuring complete nationwide coverage. Epidemiological, magnetic resonance imaging (MRI), and genetic data (chromosomal microarray, single-gene tests, gene panels, and exome/genome se-quencing) were collected. Results: The incidence rate of childhood epilepsy was 84.1 per 100,000. DRE developed in 10% of children with new-onset epilepsy, corresponding to an incidence rate of 8.5 per 100,000. Etiologically relevant MRI abnormalities were identified in 43% of patients with DRE, most commonly congenital brain malformations (19%). Pathogenic single-gene sequence variants were detected in 27% of patients who underwent genetic testing. Copy number variants were identified in 4% of tested patients, and chromosomal aberrations in 1%. Four patients carried novel candidate disease genes, although their pathogenicity remains uncertain. The most frequent etiology of DRE was structural (29%), followed by genetic (19%), with combined etiologies (13%) also contributing significantly. Conclusions: Our study is the first epidemiological study of DRE in children in Estonia and the Baltic region. The relatively low incidence observed may reflect the comprehensive national ascertainment and centralized management of pediatric epilepsy in tertiary care centers.