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

## TL;DR

This study reports on the incidence and causes of drug-resistant epilepsy in Estonian children, finding lower rates and highlighting structural and genetic factors.

## Contribution

This is the first nationwide epidemiological study of pediatric drug-resistant epilepsy in Estonia and the Baltic region.

## Key findings

- The incidence of childhood epilepsy in Estonia is 84.1 per 100,000.
- Drug-resistant epilepsy occurs in 10% of children with new-onset epilepsy.
- Structural abnormalities and genetic factors are the most common causes of DRE.

## Abstract

Background/Objectives: Drug-resistant epilepsy (DRE) is a significant health problem leading to cognitive impairment and reduced quality of life. This study aimed to investigate the incidence and etiology of DRE in children in Estonia. Methods: A retrospective, population-based study of childhood DRE was conducted in Estonia from 1 January 2013, to 31 December 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 sequencing) 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 25 of 110 patients (23%), copy number variants in four patients (4%), and chromosomal aberrations in one patient (1%). Novel candidate disease genes of uncertain pathogenicity were identified in four patients (4%). 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.