Relationship of Neonatal Seizure Burden Before Treatment and Response to Initial Antiseizure Medication
Adam L. Numis, Hannah C. Glass, Bryan A. Comstock, Fernando F. Gonzalez, Nathalie L. Maitre, Shavonne L. Massey, Dennis E. Mayock, Ulrike Mietzsch, Niranjana Natarajan, Gregory M. Sokol, Sonia L. Bonifacio, Krisa P. Van Meurs, Cameron Thomas, Kaashif A. Ahmad, Patrick J. Heagerty, Sandra E. Juul, Yvonne W. Wu, Courtney J. Wusthoff
Abstract
OBJECTIVE: To assess among a cohort of neonates with hypoxic-ischemic encephalopathy (HIE) the association of pretreatment maximal hourly seizure burden and total seizure duration with successful response to initial antiseizure medication (ASM). STUDY DESIGN: This was a retrospective review of data collected from infants enrolled in the HEAL Trial (NCT02811263) between January 25, 2017, and October 9, 2019. We evaluated a cohort of neonates born at ≥36 weeks of gestation with moderate-to-severe HIE who underwent continuous electroencephalogram monitoring and had acute symptomatic seizures. Poisson regression analyzed associations between (1) pretreatment maximal hourly seizure burden, (2) pretreatment total seizure duration, (3) time from first seizure to initial ASM, and (4) successful response to initial ASM. RESULTS: Among 39 neonates meeting inclusion criteria, greater pretreatment maximal hourly seizure burden was associated with lower chance of successful response to initial ASM (adjusted relative risk for each 5-minute increase in seizure burden 0.83, 95% CI 0.69-0.99). There was no association between pretreatment total seizure duration and chance of successful response. Shorter time-to-treatment was paradoxically associated with lower chance of successful response to treatment, although this difference was small in magnitude (relative risk 1.007, 95% CI 1.003-1.010). CONCLUSIONS: Maximal seizure burden may be more important than other, more commonly used measures in predicting response to acute seizure treatments.