Evoked potentials as a biomarker of remyelination.

Gillian McLellan // James Verhoeve // Publications // Dec 16 2019

PubMed ID: 31843913

Author(s): Heidari M, Radcliff AB, McLellan GJ, Ver Hoeve JN, Chan K, Kiland JA, Keuler NS, August BK, Sebo D, Field AS, Duncan ID. Evoked potentials as a biomarker of remyelination. Proc Natl Acad Sci U S A. 2019 Dec 16. pii: 201906358. doi: 10.1073/pnas.1906358116. [Epub ahead of print] PMID 31843913

Journal: Proceedings Of The National Academy Of Sciences Of The United States Of America, Dec 2019

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.