Machine Learning and Shapley Additive Explanations Value Integration for Predicting the Prognostic of Anti-N-Methyl-D-Aspartate Receptor Encephalitis: Model Development and Evaluation Study.

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare disease with no accurate prognostic tools to predict the prognosis of patients.

Objective: This study aims to develop an interpretable machine learning model using real-world clinical data to guide personalized therapeutic strategies.

Methods: This retrospective cohort study analyzed 140 patients with NMDAR encephalitis treated at the Third Affiliated Hospital of Sun Yat-sen University (2015-2024). Feature selection was done using recursive feature elimination. The model was constructed by 3 machine learning algorithms: decision tree, random forest (RF), and extreme gradient boosting. Mean squared error, root-mean-squared error, R² (coefficient of determination), mean absolute error, and mean absolute percentage error were used to evaluate the model performance. Finally, the optimal model was interpreted via Shapley Additive Explanations (SHAP) and deployed as a web application using the Flask framework.

Results: The median age of patients with anti-NMDAR encephalitis was 23 (IQR 18-31.8) years. The median Clinical Evaluation Scale for Autoimmune Encephalitis score at acute onset was 11 (IQR 6-16). After preprocessing, 20 features, including 4 demographic characteristics, 3 clinical characteristics, 11 laboratory parameters, and 2 neuroimaging characteristics, were selected. The RF demonstrated superior accuracy in predicting the prognosis (mean squared error=11.01; root-mean-squared error=3.32; R²=0.71; mean absolute error=2.49; mean absolute percentage error=0.48). SHAP analysis identified admission to the intensive care unit (mean |SHAP value|=1.65), initial symptoms-memory deficits (0.69), and uric acid (0.53) as the most important prognostic predictors.

Conclusions: We developed and validated an interpretable RF-based prognostic model for NMDAR encephalitis. The web-deployed tool enables real-time risk stratification, facilitating clinical decision-making and personalized therapeutic interventions for clinicians.