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Which is more deleterious to cognitive performance? Interictal epileptiform discharges vs anti-seizure medication
Nebras M Warsi1,2, Simeon M Wong2,3, Carolina Gorodetsky1,4
1Division of Neurosurgery, Hospital for Sick Children, Toronto, Ontario, Canada.
Insights
Interictal epileptiform discharges (IEDs) in children with epilepsy slow cognitive processing. Reducing IEDs with anti-seizure medications (ASMs) like oxcarbazepine improved cognitive flexibility, showing IEDs, not just medications, impact cognition.
Area of Science:
- Pediatric Neurology
- Neuropsychology
- Epileptology
Background:
- Children with epilepsy often experience neurocognitive impairments affecting daily life.
- Interictal epileptiform discharges (IEDs) and anti-seizure medications (ASMs) are suspected contributors to these cognitive deficits.
- The relative impact of IEDs versus ASMs on cognition remains unclear.
Purpose of the Study:
- To investigate whether IEDs or ASMs are more detrimental to cognitive function in children with epilepsy.
- To assess the relationship between IEDs, ASM dosage, and cognitive flexibility.
- To determine if reducing IEDs through ASMs improves cognitive performance.
Main Methods:
- 25 children with refractory focal epilepsy performed a cognitive flexibility task during invasive monitoring.
- Electrophysiological data were collected to detect IEDs.
- ASMs were continued or titrated down, and hierarchical mixed-effects modeling analyzed task reaction time (RT) in relation to IEDs and ASMs.
Main Results:
- Both the presence and number of IEDs were significantly associated with slower task RT.
- Higher doses of oxcarbazepine reduced IED frequency and improved task performance.
- Cognitive flexibility improved when IEDs were inhibited by ASMs.
Conclusions:
- IEDs have a significant negative impact on neurocognitive function in children with epilepsy, independent of seizure frequency.
- Reducing IEDs through ASM treatment, such as with oxcarbazepine, can lead to improved cognitive flexibility.
- These findings highlight the importance of managing IEDs for enhancing cognitive outcomes in pediatric epilepsy.
Abstract:
Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well-being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti-seizure medications (ASMs) are thought to be particularly severe. 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 dose. Hierarchical mixed-effects modeling 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 ± 16.55 ms, p = .003) and number of IEDs (β ± SE = 49.84 ± 12.51 ms, p < .001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p = .009) and improved task performance (β ± SE = -107.43 ± 39.54 ms, p = .007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of IEDs following treatment with select ASMs is associated with improved neurocognitive function.
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