Specific characteristics and current diagnostic and treatment modalities performance of super refractory status epilepticus in children: A comparative study

Abstract

Super-refractory status epilepticus (SRSE) is associated with significant morbidity and mortality in children. We explored the clinical spectrum, specific characteristics, and outcome in SRSE patients admitted in a pediatric intensive care unit (PICU) and investigated how well current diagnostic or treatment modalities perform compared to Status Epilepticus (SE) and Refractory SE (RSE) patients. Retrospective analysis of PICU patients admitted with convulsive SE during 2009-2019. Eighty-six patients were classified as SE, RSE, and SRSE. New-onset RSE (NORSE) and febrile infection-related epilepsy syndrome (FIRES) were also identified. Functional outcome was evaluated by the modified Rankin scale. Patients with SRSE (n=20) had longer weaning off anesthetics (p=0.014), length of stay, mechanical ventilation duration, higher illness severity scores, and poorer outcome compared to SE (n=13) or RSE (n=53) patients (all p<0.001). Diagnosis, mainly expressed by high prevalence of NORSE (n=13) and FIRES (n=9), was independently associated with SRSE (p=0.024). Abnormal MRI findings (p=0.005), and epilepsy-related pathogenic variants identified by whole-exome sequencing (WES) were mostly found in SRSE patients. Compared to intravenous immunoglobulins and steroid pulses, plasmapheresis and ketogenic diet, more often used in SRSE (p<0.01), contributed better to seizure control. Only SRSE (AUROC > 0.80, 95% CI=0.68-0.94, p<0.001) and diagnosis (AUROC > 0.70, 95% CI=0.55-0.83, p=0.02) could predict a poor outcome. The majority of SRSE patients are characterized by considerable functional decline and morbidity. WES analysis may reveal epilepsy-related pathogenic variants while early aggressive immunotherapy and/or ketogenic diet might prove beneficial. Multicenter studies for prediction models of outcome are needed.