Treatment adequacy outweighs treatment sequence in non‐convulsive status epilepticus

OBJECTIVE: Treatment strategies for non-convulsive status epilepticus (NCSE) are largely extrapolated from convulsive SE, despite biological and clinical differences. NCSE arises from heterogeneous etiological substrates that may influence treatment response and prognosis. We examined the association between treatment sequence, anti-seizure medication (ASM) adequacy, etiological context, and clinical outcomes in NCSE. METHODS: We analyzed 189 adult non-anoxic NCSE patients from a 6-year ambispective registry. Treatment variables included first-line benzodiazepine (BDZ) use, ASM underdosing, and escalation to continuous intravenous anesthetic drugs (CIVADs). Etiology was classified according to International League Against Epilepsy (ILAE) categories and further stratified as potentially fatal v non-fatal and as primary vs secondary central nervous system (CNS) pathology. Outcomes were failure of NCSE cessation, in-hospital mortality, and functional worsening at discharge. Associations between treatment patterns and outcomes were evaluated using univariate and multivariable logistic regression analyses, with exploratory pre-specified subgroup analyses across etiological categories. RESULTS: ASM underdosing occurred in 73 of 189 episodes (38.6%) and was independently associated with failure of NCSE cessation (odds ratio [OR] 6.56, 95% confidence interval [CI] 1.98-21.78) and in-hospital mortality (OR 4.38, 95% CI 2.01-9.54). Lack of first-line BDZs (93/189, 49.2%) and escalation to CIVADs (41/189, 21.7%) were not independently associated with outcome. In subgroup analyses, the association between ASM underdosing and adverse outcomes was observed more consistently in acute primary CNS pathology and non-fatal etiologies. SIGNIFICANCE: In NCSE, outcome appears more closely associated with ASM dosing adequacy than strict adherence to a pre-defined treatment sequence, particularly in clinical contexts where epileptic activity is likely to contribute substantially to prognosis. Pending future prospective, ideally randomized, investigations, optimal therapeutic strategies across heterogeneous NCSE subtypes remain to be clearly established.