Stage 1 Plus: A phenotype‐based framework for rational polytherapy in status epilepticus

Current guidelines for status epilepticus (SE) prioritize treatment with a benzodiazepine (BDZ), followed, if seizures continue, by sequential stepwise therapy. Yet this pragmatic framework does not fully capture the biological heterogeneity apparent at first clinical evaluation. Some patients are treatment-naive but may already be at increased risk of early BDZ failure, because duration, semiology, etiology, or delayed recognition have moved the disorder into a less responsive state, in the context of time-dependent receptor trafficking and evolving pharmacoresistance. These presentations can be classified as Stage 1 Plus: a semiology- and etiology-based framework for a likely BDZ-resistant, high-risk phase of SE in which early polytherapy may be warranted. It includes prolonged SE (defined by semiology-adapted thresholds), nonconvulsive SE with coma, and acute symptomatic SE due to primary central nervous system disorders. Stage 1 Plus is proposed as a framework for prospective testing of biologically grounded polytherapy in selected SE phenotypes.