Age-stratified interictal epileptiform discharges in SCN1A-related epilepsy: Association with early sodium channel-blocking antiseizure medication exposure.

PURPOSE: To characterize age-stratified distributions of interictal epileptiform discharges (IEDs) in SCN1A-related epilepsy, compare findings between genotype classes, and explore associations with early exposure to sodium channel-blocking antiseizure medications (SCBs). METHODS: We conducted a retrospective observational study of 57 individuals with pathogenic or likely pathogenic SCN1A variants and at least one interictal electroencephalogram (EEG). EEGs were assigned to predefined developmental age bands (0-1, 1-3, 3-6, 6-13, and 13-20 years). Within each interval, one EEG per participant was selected according to the highest degree of IED involvement. EEGs were classified as no IEDs, focal IEDs, or bilateral/multifocal IEDs. Cumulative exposure to SCBs during the first five years of life was categorized as <11 months or ≥11 months. Associations within the 6-13-year age band were examined using Firth's bias-reduced logistic regression. RESULTS: IEDs were not observed during infancy and became more frequent in later developmental stages, peaking between 6 and 13 years. No significant overall difference in the age-specific distribution of IEDs was observed between truncating and non-truncating variants. In the 6-13-year age band (n = 39), IEDs were present in 9/30 (30.0%) patients with <11 months of SCB exposure and 8/9 (88.9%) patients with ≥11 months of exposure (OR 18.67; 95% CI 2.01-173.2; p = 0.005). The association persisted after adjustment for genotype class, sex, and age at seizure onset (adjusted OR 28.74; 95% CI 3.71-497.64; p = 0.001) and was materially unchanged after additional adjustment for age at genetic diagnosis (adjusted OR 28.33; 95% CI 3.26-605.00; p = 0.001). CONCLUSION: Prolonged early exposure to SCBs was associated with the presence of IEDs in the 6-13-year age band in individuals with SCN1A-related epilepsy. These exploratory findings should be considered hypothesis-generating and require confirmation in prospective multicenter cohorts.