Abstracts

Rationale: Status epilepticus (SE) is a life-threatening medical and neurologic emergency that requires prompt diagnosis and treatment (Riviello. Neurology, 2006. 67(9): p. 1542-50). In a minority of cases, previously healthy individuals develop a rare and challenging entity characterized by prolonged period of refractory seizures with no readily identifiable etiology. This clinical entity has been given multiple names and acronyms in the literature which has complicated multicenter investigations and created confusion among physicians and families. Recently a consensus definition was proposed by a group of international experts clearly defining new onset refractory status epilepticus (NORSE) and other related disorders (Hirsch. Epilepsia. 2018;59:739–744). The etiology of most cases of NORSE remains cryptogenic so far. There is currently no specific therapy for NORSE, various modalities including immunotherapy have been tried with variable success (Gaspard. Epilepsia. 2018;59:745–752) . In this study, we aim to characterize children presenting with NORSE to a tertiary children’s hospital, to elucidate etiologies, investigations, treatment including immunotherapy and outcome of this rare entity. Methods: This is a single-center retrospective observational study. We identified all patients between ages 1 month and 21 years old who were admitted to Children’s Medical Center with new onset refractory status epilepticus between January 2004 and July 2017. Electronic medical records and the neurophysiology database were reviewed. Exclusion criteria include: prior history of epilepsy, developmental delay, known neurological disorder, focal status epilepticus without alteration of awareness (i.e. epilepsia partialis continua), psychogenic non-epileptic spells and neonates. Those patients with a clear acute structural, toxic or metabolic etiology of their SE were excluded as well. Results: A total of 674 unique patients presented with status epilepticus, 40 of them with NORSE. The etiologies, demographics and baseline characteristics are shown in table 1. 17 patients (44%) had cerebrospinal fluid pleocytosis (>5 cells/mm³). CSF protein was elevated in 16 patients (41%) as well. 36 patients (90%) had abnormal EEG while 27 patients (67%) had abnormal brain MRI. Average number of anti-seizure medication was 4.3 ±  1.5 with a range from 3 – 8. 23 patients (58%) received intravenous anesthetic agents. Half of the patients received immunotherapy, time from onset of SE to administration of immunotherapy (TTI) was collected. 4 patients (10%) died during their hospitalization, 1 patient (2.5%) was discharged to hospice and died six months later. Upon discharge, 12 patients (30%) had a poor outcome based on modified Rankin Score (4-6). Median years of follow up was 3.8, 20 (64%) developed epilepsy, 12 (38%) had intractable epilepsy. Only 3 patients (9%) had recurrence of SE. About 40% (13 patients) had mild and 16% (5 patients) had severe neurocognitive impairment. Shorter TTI was associated with shorter ICU stay (P <0.01) and length of hospitalization (P 0.04). Earlier use of immunotherapy was associated with marginally better neurocognitive outcomes (P 0.05). Conclusions: Earlier use of immunotherapy is associated with shorter hospital and ICU stay and better neurocognitive outcomes in pediatric NORSE. Pediatric NORSE is associated with significant mortality and morbidity, two third of patients having residual neurocognitive impairment and one third developing intractable epilepsy. The etiology of most of children presenting with NORSE remains cryptogenic. Funding: Service Package Grant Award from Children’s Health? - Children Medical Center.