Structural brain MRI abnormalities in SCN1A-, SCN2A-, SCN3A-, and SCN8A-related epilepsies: a cohort study

To characterize the prevalence and patterns of structural brain magnetic resonance imaging (MRI) abnormalities in children with genetically confirmed SCN1A-, SCN2A-, SCN3A-, or SCN8A-related epilepsy and to identify genotype-specific imaging features.

We retrospectively analyzed brain MRI findings from a single-center cohort of 139 pediatric patients with pathogenic variants of SCN1A (n = 114), SCN2A (n = 17), SCN3A (n = 1), or SCN8A (n = 7), evaluated between 2010 and 2023. MRI abnormalities were categorized using a standardized classification framework and compared across the genotypes.

MRI abnormalities were identified in 52 of the 139 patients (37.4%). The most common findings were atrophy (21.6%), hippocampal abnormalities (6.5%), white matter signal abnormalities (5.0%) and hypoxic-ischemic encephalopathy (3.6%). Abnormalities were most frequent in the SCN2A (70.6%) group, followed by the SCN8A (42.9%) and SCN1A (31.6%) groups; one patient with SCN3A-related epilepsy also exhibited abnormal findings. In SCN1A-related epilepsies, the most common abnormalities were cerebral atrophy (15.8%) and hippocampal abnormalities (6.1%). In SCN2A-related epilepsies, common abnormalities included atrophy (58.8%), white matter signal abnormalities (17.6%), hypoxic-ischemic encephalopathy (11.8%) and malformations of cortical development (11.8%). In SCN8A-related epilepsies, common findings included atrophy (28.6%), hippocampal abnormalities (14.3%), and white matter signal abnormalities (14.3%). One patient with SCN3A-related epilepsy exhibited vascular abnormalities.

Contrary to earlier assumptions, structural MRI abnormalities are common in SCN-related epilepsies, particularly in SCN2A-and SCN8A-related epilepsies. MRI may aid in the diagnosis, phenotypic stratification, and prognostication of genetic epilepsy involving voltage-gated sodium channels.