Which is more deleterious to cognitive performance? Interictal epileptiform discharges vs. anti-seizure medication.

Children with epilepsy commonly suffer from comorbid neurocognitive impairments that severely impact their psychosocial wellbeing, education, and future career prospects. While the provenance of these deficits is multifactorial, the effects of interictal discharges (IEDs) and anti-seizure medications (ASMs) are thought to be particularly severe. Therefore, although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition. To examine this question, 25 children undergoing invasive monitoring for refractory focal epilepsy performed one or more sessions of a cognitive flexibility task. Electrophysiological data were recorded to detect IEDs. Between repeated sessions, prescribed ASMs were either continued or titrated to <50% of the baseline dosage. Hierarchical mixed-effects modelling assessed the relationship between task reaction time (RT), IED occurrence, ASM type, and dose while controlling for seizure frequency Both presence (β±SE=49.91±16.55ms, p=0.003) and number of interictal discharges (β±SE=49.84±12.51ms, p<0.001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p=0.009) and improved task performance (β±SE=-107.43±39.54ms, p=0.007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of these potentials is associated with improved neurocognitive function following treatment with select ASMs.