Dataset Information

Evoked potentials as a biomarker of remyelination.

ABSTRACT: Multiple sclerosis (MS) is a common cause of neurologic disease in young adults that is primarily treated with disease-modifying therapies which target the immune and inflammatory responses. Promotion of remyelination has opened a new therapeutic avenue, but how best to determine efficacy of remyelinating drugs remains unresolved. Although prolongation and then shortening of visual evoked potential (VEP) latencies in optic neuritis in MS may identify demyelination and remyelination, this has not been directly confirmed. We recorded VEPs in a model in which there is complete demyelination of the optic nerve, with subsequent remyelination. We examined the optic nerves microscopically during active disease and recovery, and quantitated both demyelination and remyelination along the length of the nerves. Latencies of the main positive component of the control VEP demonstrated around 2-fold prolongation during active disease. VEP waveforms were nonrecordable in a few subjects or exhibited a broadened profile which precluded peak identification. As animals recovered neurologically, the VEP latencies decreased in association with complete remyelination of the optic nerve but remained prolonged relative to controls. Thus, it has been directly confirmed that VEP latencies reflect the myelin status of the optic nerve and will provide a surrogate marker in future remyelination clinical trials.

SUBMITTER: Heidari M

PROVIDER: S-EPMC6936696 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Evoked potentials as a biomarker of remyelination.

Heidari Moones M Radcliff Abigail B AB McLellan Gillian J GJ Ver Hoeve James N JN Chan Kore K Kiland Julie A JA Keuler Nicholas S NS August Benjamin K BK Sebo Dylan D Field Aaron S AS Duncan Ian D ID

Proceedings of the National Academy of Sciences of the United States of America 20191216 52

Multiple sclerosis (MS) is a common cause of neurologic disease in young adults that is primarily treated with disease-modifying therapies which target the immune and inflammatory responses. Promotion of remyelination has opened a new therapeutic avenue, but how best to determine efficacy of remyelinating drugs remains unresolved. Although prolongation and then shortening of visual evoked potential (VEP) latencies in optic neuritis in MS may identify demyelination and remyelination, this has not ...[more]

PMID: 31843913

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Project description:Motor Evoked Potentials (MEPs) are used to monitor disability progression in multiple sclerosis (MS). Their morphology plays an important role in this process. Currently, however, there is no clear definition of what constitutes a normal or abnormal morphology. To address this, five experts independently labeled the morphology (normal or abnormal) of the same set of 1,000 MEPs. The intra- and inter-rater agreement between the experts indicates they agree on the concept of morphology, but differ in their choice of threshold between normal and abnormal morphology. We subsequently performed an automated extraction of 5,943 time series features from the MEPs to identify a valid proxy for morphology, based on the provided labels. To do this, we compared the cross-validation performances of one-dimensional logistic regression models fitted to each of the features individually. We find that the approximate entropy (ApEn) feature can accurately reproduce the majority-vote labels. The performance of this feature is evaluated on an independent test set by comparing to the majority vote of the neurologists, obtaining an AUC score of 0.92. The model slightly outperforms the average neurologist at reproducing the neurologists consensus-vote labels. We can conclude that MEP morphology can be consistently defined by pooling the interpretations from multiple neurologists and that ApEn is a valid continuous score for this. Having an objective and reproducible MEP morphological abnormality score will allow researchers to include this feature in their models, without manual annotation becoming a bottleneck. This is crucial for large-scale, multi-center datasets. An exploratory analysis on a large single-center dataset shows that ApEn is potentially clinically useful. Introducing an automated, objective, and reproducible definition of morphology could help overcome some of the barriers that are currently obstructing broad adoption of evoked potentials in daily care and patient follow-up, such as standardization of measurements between different centers, and formulating guidelines for clinical use.

Dataset Information

Evoked potentials as a biomarker of remyelination.

Publications

Evoked potentials as a biomarker of remyelination.

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