SCN1A-related epilepsy with spike-wave activation in sleep: A retrospective cohort and literature review

To describe the clinical, genetic, treatment, and EEG features of patients with SCN1A-related epilepsy who showed spike-wave activation in sleep (SWAS), and to highlight the need for serial sleep EEG follow-up in this population.

We retrospectively included 19 patients with SCN1A-related epilepsy and SWAS (17 from our cohort, 2 from literature review), collecting clinical data, genotypes (categorized as loss-of-function [LOF], gain-of-function [GOF], or unclear), and EEG data (including power spectral density [PSD] and aperiodic exponent analysis) from 14 patients within our cohort.

The cohort exhibited early seizure onset (median 10 months), whereas SWAS was identified later during the disease course (median 59 months), with a high prevalence of intellectual disability (13/19, 68.42%) and developmental delay (15/19, 78.95%). Genetic analysis revealed diverse SCN1A variants, predominantly de novo, with 10/19 (52.63%) mapping to the pore loop and intracellular linker regions. Quantitative EEG analysis showed higher PSD and aperiodic exponent values in patients with SCN1A-related epilepsy and SWAS than in the comparison groups. In descriptive subgroup analyses, the LOF group showed a higher numerical burden of early seizure onset, higher seizure frequency, drug-resistant epilepsy (DRE), and motor abnormalities, whereas neurodevelopmental and behavioral abnormalities were also observed in the Unclear group. At last follow-up, 7/19 (36.84%) patients achieved seizure control, while 10/19 (52.63%) developed DRE.

SWAS may occur during the disease course of SCN1A-related epilepsy, often several years after seizure onset. These findings support serial sleep EEG follow-up and careful monitoring for developmental or behavioral changes in children with SCN1A-related epilepsy.