Utility of the APE2 Score as a Diagnostic Tool for Autoimmune Encephalitis.

OBJECTIVE: To retrospectively evaluate the diagnostic performance of the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score relative to clinician-adjudicated autoimmune encephalitis (AE) and the Graus criteria in a tertiary neuroimmunology referral cohort, including antibody-negative AE. METHODS: We conducted a retrospective single-center study of consecutive referrals to a tertiary neuroimmunology clinic (January 2017-May 2023). AE diagnosis was determined by expert consensus based on clinical features, investigations, exclusion of alternative diagnoses, and immunotherapy response. APE2 scores and Graus categories, were assigned retrospectively; APE2SM [APE2 seizure/movement] was examined as a post hoc exploratory secondary analysis. Diagnostic performance was assessed using ROC analysis and contingency tables, and logistic regression modeled the probability of AE across scores within this study cohort. RESULTS: Eighty-five patients were included (56.5% female; mean age 53.8 years). Fifty-nine (69.4%) had AE (34 antibody-positive). APE2 demonstrated higher discriminative performance than Graus categories in this cohort (AUC 0.894 vs. 0.804) and in antibody-negative patients (AUC 0.905 vs. 0.850). In both models, an APE2 cutoff ≥ 4 balanced sensitivity and specificity near or above 80%, whereas in the full patient cohort no Graus criteria threshold achieved a similar balance. Probability modeling showed APE2 ≥ 4 crossed 80% in all patients and 60% in antibody-negative patients within this cohort. Exploratory analysis showed that APE2SM had overall discrimination comparable to the original APE2 score, with a slightly lower AUC in the full cohort (0.888 vs. 0.894). INTERPRETATION: APE2 score demonstrated good diagnostic discrimination and may represent a useful adjunctive tool for early AE evaluation, including antibody-negative cases. The exploratory APE2SM model may further enhance sensitivity; however, prospective multicenter validation is needed before routine clinical implementation.