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SeruNet-MS: A Two-Stage Interpretable Framework for Multiple Sclerosis Risk Prediction with SHAP-Based

Serra Aksoy¹, Pinar Demircioglu², Ismail Bogrekci²

¹Institute of Computer Science, Ludwig Maximilian University of Munich (LMU), Oettingenstrasse 67, 80538 Munich, Germany.

Neurology International

|September 26, 2025

Summary

A new two-stage machine learning model accurately predicts multiple sclerosis (MS) conversion from clinically isolated syndrome (CIS). Explainable AI (SHAP) provides transparent, patient-specific risk factors, enhancing clinical trust and adoption for MS diagnosis.

Keywords:

SHAP analysis SeruNet-MS clinical decision support clinically isolated syndrome (CIS)demographic bias disease progression explainable AI multiple sclerosis (MS)neurological biomarkers predictive modeling two-stage machine learning

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Area of Science:

Neurology
Artificial Intelligence
Biostatistics

Background:

Multiple sclerosis (MS) diagnosis requires early identification of clinically isolated syndrome (CIS) to clinically definite MS.
Current machine learning (ML) models for MS prediction lack interpretability, hindering clinical trust.
A need exists for explainable AI (XAI) to address demographic bias and improve MS risk stratification.

Purpose of the Study:

Develop and validate a novel, interpretable two-stage ML framework (SeruNet-MS) for predicting CIS-to-MS conversion.
Mitigate demographic bias in MS risk prediction.
Enhance clinical adoption through transparent, patient-specific risk factor explanations.

Main Methods:

Analyzed 177 CIS patients using a two-stage ML framework (SeruNet-MS).
Stage 1: Logistic regression on demographic features. Stage 2: Incorporated 25 clinical/symptom features (MRI, CSF biomarkers, etc.).
Utilized SHAP (SHapley Additive exPlanations) for patient-level interpretability and risk factor attribution.

Main Results:

The two-stage model achieved high performance: ROC-AUC 0.909, accuracy 0.806, precision 0.842, recall 0.800.
Cross-validation confirmed stable performance (AUC 0.838 ± 0.095).
SHAP analysis identified periventricular lesions, oligoclonal bands, and symptom complexity as key predictors.

Conclusions:

The two-stage approach effectively separates demographic bias from clinical risk factors.
SHAP explanations provide clinicians with actionable, individualized insights for MS risk assessment.
This interpretable framework advances AI adoption in MS clinical practice.