Background: Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting about 2.8 million people worldwide. Disease course after the most common diagnoses of relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) is highly variable and cannot be reliably predicted. This impairs early personalized treatment decisions. Objectives: The main objective of this study was to algorithmically support clinical decision-making regarding the options of early platform medication or no immediate treatment of patients with early RRMS and CIS. Design: Retrospective monocentric cohort study within the Data Integration for Future Medicine (DIFUTURE) Consortium. Methods: Multiple data sources of routine clinical, imaging and laboratory data derived from a large and deeply characterized cohort of patients with MS were integrated to conduct a retrospective study to create and internally validate a treatment decision score [Multiple Sclerosis Treatment Decision Score (MS-TDS)] through model-based random forests (RFs). The MS-TDS predicts the probability of no new or enlarging lesions in cerebral magnetic resonance images (cMRIs) between 6 and 24 months after the first cMRI. Results: Data from 65 predictors collected for 475 patients between 2008 and 2017 were included. No medication and platform medication were administered to 277 (58.3%) and 198 (41.7%) patients. The MS-TDS predicted individual outcomes with a cross-validated area under the receiver operating characteristics curve (AUROC) of 0.624. The respective RF prediction model provides patient-specific MS-TDS and probabilities of treatment success. The latter may increase by 5–20% for half of the patients if the treatment considered superior by the MS-TDS is used. Conclusion: Routine clinical data from multiple sources can be successfully integrated to build prediction models to support treatment decision-making. In this study, the resulting MS-TDS estimates individualized treatment success probabilities that can identify patients who benefit from early platform medication. External validation of the MS-TDS is required, and a prospective study is currently being conducted. In addition, the clinical relevance of the MS-TDS needs to be established.

Background Somatosensory evoked potentials (SSEP) are still broadly used, although not explicitly recommended, for the diagnostic work-up of suspected multiple sclerosis (MS). Objective To relate disability, SSEP, and lesions on T2-weighted magnetic resonance imaging (MRI) in patients with early MS. Methods In this monocentric retrospective study, we analyzed a cohort of patients with relapsing–remitting MS or clinically isolated syndrome, with a maximum disease duration of two years, as well as with available data on the score at the expanded disability status scale (EDSS), on SSEP, on whole spinal cord (SC) MRI, and on brain MRI. Results Complete data of 161 patients were available. Tibial nerve SSEP (tSSEP) were less frequently abnormal than SC MRI (22% vs. 68%, p < 0.001). However, higher EDSS scores were significantly associated with abnormal tSSEP (median, 2.0 vs. 1.0; p = 0.001) but not with abnormal SC MRI (i.e., at least one lesion; median, 1.5 vs. 1.5; p = 0.7). Of the 35 patients with abnormal tSSEP, 32 had lesions on SC MRI, and 2 had corresponding lesions on brain MRI. Conclusion Compared to tSSEP, SC MRI is the more sensitive diagnostic biomarker regarding SC involvement. In early MS, lesions as detectable by T2-weighted MRI are the main driver of abnormal tSSEP. However, tSSEP were more closely associated with disability, which is compatible with a potential role of tSSEP as prognostic biomarker in complementation of MRI.

Background: CSF protein concentrations vary greatly among individuals. Accounting for brain volume may lower the variance and increase the diagnostic value of CSF protein concentrations. Objective: To determine the relation between CSF protein concentrations and brain volume. Methods: Brain volumes (total intracranial, gray matter, white matter volumes) derived from brain MRI and CSF protein concentrations (total protein, albumin, albumin CSF/serum ratio) of 29 control patients and 497 patients with clinically isolated syndrome or multiple sclerosis were studied. Finding: We found significant positive correlations of CSF protein concentrations with intracranial, gray matter, and white matter volumes. None of the correlations remained significant after correction for age and sex. Conclusion: Accounting for brain volume derived from brain MRI is unlikely to improve the diagnostic value of protein concentrations in CSF.