Comparison of individuals with radiologically isolated syndrome, early multiple sclerosis patients, and healthy controls using a digital neurological examination

Background: The revised McDonald criteria shifted toward the recognition of the radiologically isolated syndrome (RIS) as the first phase of the multiple sclerosis (MS) spectrum. Objectives: To characterize differences between RIS individuals, early MS patients, and healthy controls (HCs) using a high-precision clinical assessment tool based on digital technology. Methods: We performed a multicentric, cross-sectional study involving RIS, early MS patients, and HC. Subjects were assessed using Neuraccure, an iPad application capable of detecting subtle abnormalities in four neurological functions: hand coordination, low-contrast vision, reaction time, and eye movements. Results: In total, 565 individuals were included (MS: 255, RIS: 146, HC: 164). HC performed better than RIS and MS across all digital measures ( p < 0.0001 to 0.03). There was no statistical difference between RIS and MS patients, except for the coordination test, which was slightly worse in MS patients ( p = 0.03). The receiver operating characteristic (ROC) analysis indicated that the presence of at least two impaired functions could detect RIS and MS from HC with 83.2% sensitivity and 84.3% specificity. A higher number of impaired functions were associated with lower brain magnetic resonance imaging (MRI) volumes. Conclusion: High-precision neurological evaluation can distinguish HC from RIS and MS at an individual scale with a good performance.