Prognostic value of spinal cord lesion measures in early relapsing-remitting multiple sclerosis.

BACKGROUND: Spinal cord (SC) lesions have been associated with unfavourable clinical outcomes in multiple sclerosis (MS). However, the relation of whole SC lesion number (SCLN) and volume (SCLV) to the future occurrence and type of confirmed disability accumulation (CDA) remains largely unexplored. METHODS: In this monocentric retrospective study, SC lesions were manually delineated. Inclusion criteria were: age between 18 and 60 years, relapsing-remitting MS, disease duration under 2 years and clinical follow-up of 5 years. The first CDA event after baseline, determined by a sustained increase in the Expanded Disability Status Scale over 6 months, was classified as either progression independent of relapse activity (PIRA) or relapse-associated worsening (RAW). SCLN and SCLV were compared between different (sub)groups to assess their prospective value. RESULTS: 204 patients were included, 148 of which had at least one SC lesion and 59 experienced CDA. Patients without any SC lesions experienced significantly less CDA (OR 5.8, 95% CI 2.1 to 19.8). SCLN and SCLV were closely correlated (rs=0.91, p<0.001) and were both significantly associated with CDA on follow-up (p<0.001). Subgroup analyses confirmed this association for patients with PIRA on CDA (34 events, p<0.001 for both SC lesion measures) but not for RAW (25 events, p=0.077 and p=0.22). CONCLUSION: Patients without any SC lesions are notably less likely to experience CDA. Both the number and volume of SC lesions on MRI are associated with future accumulation of disability largely independent of relapses.

Retrospective cohort study to devise a treatment decision score predicting adverse 24-month radiological activity in early multiple sclerosis.

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.

Somatosensory evoked potentials and magnetic resonance imaging of the central nervous system in early multiple sclerosis.

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.

CSF Protein Concentration Shows No Correlation With Brain Volume Measures.

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.

Left ventricular assist device hemolysis leading to dysphagia.

A 41-year-old man with a continuous-flow left ventricular assist device presented for evaluation of dysphagia and dark urine. He was found to have a significantly elevated L-lactate dehydrogenase and an elevated plasma free hemoglobin consistent with intravascular hemolysis. After the hemolysis ceased, both the black urine and dysphagia resolved spontaneously. Transient esophageal dysfunction, as a manifestation of gastrointestinal dysmotility, is known to occur in the setting of hemolysis. Paroxysmal nocturnal hemoglobinuria is another recognized cause of massive hemolysis with gastrointestinal dysmotility occurring in 25%-35% of patients during a paroxysm. Intravascular hemolysis increases plasma free hemoglobin, which scavenges nitric oxide (NO), an important second messenger for smooth muscle cell relaxation. The decrease in NO can lead to esophageal spasm and resultant dysphagia. In our patient the resolution of hemolysis resulted in resolution of dysphagia.