Abstracts

Rationale: We evaluated whether the onset of pediatric refractory status epilepticus (rSE) follows a 24-hour distribution throughout the day. Methods: This multi-center, prospective observational study was performed on pediatric convulsive rSE patients (1 month to 21 years) from June 2011 to January 2018. If a patient had more than one rSE episode during the study, only the first episode was included. rSE was defined as the failure of at least two antiseizure medications (ASM) classes, one benzodiazepine and one non-benzodiazepine ASM; or the use of a continuous infusion for seizure cessation. The time of rSE onset was analyzed utilizing a cosinor analysis with a 12-hour cycle based on the distribution of the data. A cosinor analysis evaluates whether the temporal distribution of pediatric rSE onset followed a time of day pattern.  The midline estimating statistic of rhythm (MESOR) estimates the mean number of rSE episodes per hour if they were evenly distributed and the amplitude is the difference in episodes per hour between the MESOR and the peak or the MESOR and the trough. Results: We included 300 episodes, one episode per patient, (55% males) with a median (p25 – p75) age of 4.2 (1.3 – 9.9) years (Table 1). The MESOR was 12.5 (95% CI: 10.9 – 14.1) with an amplitude of 2.4 (95% CI: -0.1 – 4.7), p = 0.04, demonstrating that the distribution was not even over 24 hours. The rSE episodes peaked in the late morning (10am – 11am) and reached a trough during the early night (10pm – 11pm) (Figure 1). The time from rSE onset to administration of the first non-benzodiazepine antiseizure medication peaked during the night (3am – 4am), with a minimum during the afternoon (3pm – 4pm) (p = 0.03). Conclusions: Pediatric rSE onset exhibits a 24-hour distribution pattern. Although fewer rSE episodes occurred at night, the time to ASM administration was the longest; thus nighttime rSE episodes may be at higher risk for delayed treatment. Findings may inform additional preventative monitoring strategies and chronotherapeutic, as well as, rescue regimens at times of greatest rSE susceptibility in patients at risk. Funding: Funded by the Pediatric Epilepsy Research Foundation & the Epilepsy Research Fund