Continuous seizure emergency evoked in mice with pharmacological, electrographic, and pathological features distinct from status epilepticus

Summary Objectives Benzodiazepines are the standard of care for the management of sustained seizure emergencies, including status epilepticus (SE) and seizure clusters. Seizure clusters are a variably defined seizure emergency wherein a patient has multiple seizures above a baseline rate, with intervening periods of recovery, distinguishing clusters from SE. Although these seizure emergencies are phenotypically distinct, the precise pathophysiological and mechanistic differences between SE and seizure clusters are understudied. Emergency‐specific preclinical models may differentiate the behavioral and pathological mechanisms that are acutely associated with seizure emergencies and seizure termination to better manage these events. Methods Herein we characterize a novel model of sustained seizure emergency induced in CF‐1 mice through the combined administration of high‐dose phenytoin (PHT; 50 mg/kg, i.p.) and pentylenetetrazol (PTZ; 100 mg/kg, s.c.). Results We presently describe a mouse model of sustained seizure emergency that is pathologically, pharmacologically, and behaviorally distinct from SE. Acute administration of PHT 1 h prior to PTZ led to significantly more mice with unremitting continuous seizure activity (CSA; 73.4%) vs vehicle‐pretreated mice (13.8%; p