The association of environmental exposure with multiple sclerosis severity score: A study based on sequential data modeling

Introduction Multiple Sclerosis (MS) is a chronic neuroinflammatory disease influenced by clinical, demographic, and environmental factors. Predicting MS progression is challenging due to the disease's heterogeneity. This study aimed to apply Artificial Intelligence (AI) methods to investigate the association between the MS Severity Score (MSSS), which is a measure that integrates disability level and disease duration, and patients' longitudinal clinical data and environmental exposures. Methods We integrated long-term clinical records from the Mondino MS Center (Pavia, Italy) with environmental data, including air pollution and weather conditions, based on patients' residential locations. To address missing data, we applied a hybrid imputation strategy combining exponentially weighted moving average and linear mixed-effect models. Automated Machine Learning (AutoML) was used for feature selection. We evaluated multiple Deep Learning (DL) architectures, including recurrent neural network, long short-term memory, and Gated Recurrent Unit (GRU), using varying historical window lengths to predict the MSSS class at the next follow-up. Results The final retrospective dataset comprised 4022 visits from 535 MS patients. AutoML identified both clinical and environmental variables as important features for prediction. Models incorporating environmental data performed comparably to or better than those using only clinical variables. The GRU model achieved the most stable performance, with an average Area Under the Curve of 0.814 when environmental data were included with four prior visits. Moreover, SHAP-based feature importance ranked environmental variables like PM₁₀, PM_2.5, nitrogen dioxide, precipitation, and humidity among the top predictors. Conclusion Incorporating environmental exposures into DL models can improve MSSS prediction, highlighting the value of diverse real-world data for MS monitoring. Prediction performance across different historical window lengths was comparable, suggesting that using data from two prior follow-ups (approximately one year of monitoring) may be sufficient to provide clinically meaningful predictions of MS progression.