Data-driven explainable machine learning for personalized risk classification of myasthenic crisis

Objective: Myasthenic crisis (MC) is a critical progression of Myasthenia gravis (MG), requiring intensive care treatment and invasive therapies. Classifying patients at high-risk for MC facilitates treatment decisions such as changes in medication or the need for mechanical ventilation and helps prevent disease progression by decreasing treatment-induced stress on the patient. Here, we investigated whether it is possible to reliably classify MG patients into groups at low or high risk of MC based entirely on routine medical data using explainable machine learning (ML). Methods: In this single-center pseudo-prospective cohort study, we investigated the precision of ML models trained with real-world routine clinical data to identify MG patients at risk for MC, and identified explainable distinctive features for the groups. 51 MG patients, including 13 MC, were used for model training based on realworld clinical data available from the hospital management system. Patients were classified to high or low risk for MC using Lasso regression or random forest ML models. Results: The mean cross-validated AUC classifying MG patients as high or low risk for MC based on simple or compound features derived from real-world clinical data showed a predictive accuracy of 68.8% for a regularized Lasso regression and 76.5% for a random forest model. Studying feature importance across 5100 model runs identified explainable features to distinguish MG patients at high or low risk for MC. Feature importance scores suggested that multimorbidity may play a role in risk classification. Conclusion: This study establishes feasibility and proof-of-concept for risk classification of MC based on realworld routine clinical data using ML with explainable features and variance control at the point of care. Future research on ML-based prediction of MC should include multi-center, multinational data collection, more in-depth data per patient, more patients, and an attention-based ML model to include free-text.