Utility of the Weighted APE2SM Score for Diagnosing Autoimmune Encephalitis: Comparison with APE2 and Graus Criteria

Objective To evaluate the diagnostic performance of an exploratory modified score (APE2SM) incorporating seizure and movement disorder weighting for autoimmune encephalitis (AE), and to compare its performance with the APE 2 score and Graus criteria. Background Diagnosis of AE, particularly in antibody-negative cases, remains challenging and relies on clinical criteria and supportive investigations. The APE 2 score provides a quantitative framework for risk stratification but may underweight key clinical features such as seizures and movement presentations. We developed and assessed the APE2SM score to address this limitation. Design/Methods We conducted a retrospective study of consecutive patients referred for suspected AE (January 2017–May 2023). Final diagnosis was determined by expert consensus based on clinical features, exclusion of alternative diagnoses, and response to immunotherapy. APE 2 , Graus criteria, and APE2SM scores were assigned retrospectively. The APE2SM score weights movement disorders and seizure presentations more heavily compared to the APE 2 score. Diagnostic performance was assessed using receiver operating characteristic analysis, contingency tables, and logistic regression to model probability of AE across score thresholds. Results Eighty-five patients were included (56.5% female; mean age 53.8 years), of whom 59 (69.4%) had AE, including 34 antibody-positive cases. In exploratory analyses, APE2SM demonstrated the strongest overall diagnostic performance, with comparable discrimination to APE 2 but improved sensitivity and negative predictive value, particularly at clinically relevant thresholds and in antibody-negative patients. APE 2 outperformed Graus criteria in the full cohort (AUC 0.894 vs 0.804) and in antibody-negative patients (AUC 0.905 vs 0.850). An APE 2 cutoff ≥4 achieved balanced sensitivity and specificity near or above 80%, whereas no Graus threshold achieved similar balance. Conclusions The exploratory APE2SM score improves sensitivity while maintaining acceptable specificity and may enhance early recognition of AE, particularly in antibody-negative cases. These findings support further prospective validation. APE 2 remains a robust and practical screening tool with a clinically useful cutoff of ≥4.