Latency of Multifocal Visual Evoked Potential in Multiple Sclerosis: A Visual Pathway Biomarker for Clinical Trials of Remyelinating Therapies.


Journal

Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society
ISSN: 1537-1603
Titre abrégé: J Clin Neurophysiol
Pays: United States
ID NLM: 8506708

Informations de publication

Date de publication:
01 May 2021
Historique:
pubmed: 26 11 2020
medline: 23 6 2021
entrez: 25 11 2020
Statut: ppublish

Résumé

Acute focal demyelination is the characteristic feature of multiple sclerosis, with the majority of damaged axons undergoing limited remyelination and forming chronic lesions. Potential remyelinating agents are currently under development and there is therefore an urgent need for reliable in vivo biomarkers of remyelination. This study aimed to investigate potential changes in multifocal visual evoked potentials' (mfVEPs) latency in a cohort of relapsing-remitting multiple sclerosis (RRMS) patients. The potential sample size required for a remyelination-based clinical trial using different treatment effect sizes and the mfVEP latency as an outcome measure was also estimated. A total of 50 RRMS consecutive patients with no previous history of optic neuritis in at least one eye and 15 normal controls of similar age and gender composition were prospectively enrolled. Fifteen patients had a history of unilateral ON more than 12 months earlier, whereas 41 patients demonstrated optic radiations lesions on MRI at baseline. Most patients were on disease modifying therapy. A mfVEP was recorded at baseline and 12 months later. At baseline, the mfVEP latency in RRMS patients was delayed compared with normal controls in both optic neuritis and nonoptic neuritis eyes. Latency delay was significantly correlated to optic radiation lesion volume (R2 = 0.38, P < 0.001). There was no significant latency change in multiple sclerosis patients' eyes or optic neuritis and nonoptic neuritis eyes over the follow-up period with latency remaining remarkably constant. This was despite the fact that 46 of 50 patients were on disease-modifying therapies, implying current treatments do not affect myelination in chronic RRMS cases. Sample size calculations to evaluate an additional or alternative remyelinating agent, based on a 40% treatment effect, revealed that a relatively small sample size (78 patients) would be required to demonstrate efficacy in future trials of remyelination therapies. Given its known sensitivity for latency changes and the stability found in this RRMS population, the mfVEP represents an ideal biomarker to assess the degree of latency recovery that may be achieved by remyelination in multiple sclerosis.

Identifiants

pubmed: 33235179
pii: 00004691-202105000-00006
doi: 10.1097/WNP.0000000000000757
doi:

Substances chimiques

Antirheumatic Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

186-191

Informations de copyright

Copyright © 2020 by the American Clinical Neurophysiology Society.

Déclaration de conflit d'intérêts

The authors have no conflicts of interest to disclose.

Références

Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998;338:278–285.
Barkhof F, Bruck W, De Groot CJA, et al. Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance. Arch Neurol 2003;60:1073–1081.
Olsen JA, Akirav EM. Remyelination in multiple sclerosis: cellular mechanisms and novel therapeutic approaches. J Neurosci Res 2015;93:687–696.
Cadavid D, Balcer L, Galetta S, et al. Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol 2017;16:189–199.
Green AJ, Gelfand JM, Cree BA, et al. Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial. Lancet 2017;390:2481–2489.
Cadavid D, Klistorner A, Ampapa R, et al. Correlation of physical, cognitive and MRI measures with multifocal visual evoked potential using baseline data from the anti-LINGO-1 SYNERGY trial in multiple sclerosis [meeting abstract]. Nerology 2016;78:P3.041.
Hood DC, Ohri N, Bo Yang E, et al. Determining abnormal latencies of multifocal visual evoked potentials: a monocular analysis. Doc Ophthalmol 2005;109:189–199.
Yang EB, Hood DC, Rodarte C, Zhang X, Odel JG, Behrens MM. Improvement in conduction velocity after optic neuritis measured with the multifocal VEP. Invest Ophthalmol Vis Sci 2007;48:692–698.
Niklas a, Sebraoui H, Hess E, Wagner a, Then Bergh F. Outcome measures for trials of remyelinating agents in multiple sclerosis: retrospective longitudinal analysis of visual evoked potential latency. Mult Scler 2009;15:68–74.
Klistorner A, Arvind H, Garrick R, Yiannikas C, Paine M, Graham SL. Remyelination of optic nerve lesions: spatial and temporal factors. Mult Scler 2010;16:786–795.
Klistorner A, Chai Y, Leocani L, Albrecht P, Aktas O, Butzkueven H. Assessment of opicinumab in acute optic neuritis using multifocal visual evoked potential. CNS Drugs 2018;32:1159–1171.
Graham SL, Klistorner A. Afferent visual pathways in multiple sclerosis: a review. Clin Exp Ophthalmol 2017;45:62–72.
Fraser C, Klistorner A, Graham SL, Garrick R, Billson F, Grigg JR. Multifocal visual evoked potential latency analysis: predicting progression to multiple sclerosis. Arch Neurol 2006;63:847–850.
Hornabrook RS, Miller D, Newton MR, et al. Frequent involvement of optic radiation in patients with acute isolated optic neuritis. Neurology 1992;42:77–79.
Klistorner A, Vootakuru N, Wang C, et al. Decoding diffusivity in multiple sclerosis: analysis of optic radiation lesional and non-lesional white matter. PLoS One 2015;10:e0122114.
Toussaint D, Perier O, Verstappen A, Bervoets S. Clinicopathological study of the visual pathways, eyes and cerebral hemispheres in 32 cases of disseminated sclerosis. J Clin Neuro Ophthalmol 1983;3:211–220.
Alshowaeir D, Yiannikas C, Garrick R, et al. Latency of multifocal visual evoked potentials in nonoptic neuritis eyes of multiple sclerosis patients associated with optic radiation lesions. Invest Ophthalmol Vis Sci 2014;55:3758–3764.
Barkhof F, van Walderveen M. Characterization of tissue damage in multiple sclerosis by nuclear magnetic resonance. Philos Trans R Soc Lond B Biol Sci 1999;354:1675–1686.
Morrissey SP, Miller DH, Kendall BE, et al. The significance of brain magnetic resonance imaging abnormalities at presentation with clinically isolated syndromes suggestive of multiple sclerosis. A 5-year follow-up study. Brain 1993;116:135–146.
Klistorner A, Graham ECEC, Yiannikas C, et al. Progression retinal ganglion cell loss in multiple sclerosis is associated with new lesions in the optic radiations. Eur J Neurol 2017;24:1392–1398.
van der Walt A, Kolbe S, Mitchell P, et al. Parallel changes in structural and functional measures of optic nerve myelination after optic neuritis. PLoS One 2015;10:e0121084.
You Y, Klistorner A, Thie J, Graham SL. Latency delay of visual evoked potential is a real measurement of demyelination in a rat model of optic neuritis. Investig Ophthalmol Vis Sci 2011;52:6911–6918.
Heidari M, Radcliff AB, McLellan GS, et al. Evoked potentials as a biomarker of remyelination. Proc Nat Acad Sci USA 2019;116:27074–27083.
Sriram P, Wang C, Yiannikas C, et al. Relationship between optical coherence tomography and electrophysiology of the visual pathway in non-optic neuritis eyes of multiple sclerosis patients. PLoS One 2014;9:e102546.
Malmqvist L, De Santiago L, Fraser C, Klistorner A, Hamann S. Exploring the methods of data analysis in multifocal visual evoked potentials. Doc Ophthalmol 2016;133:41–48.
Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3 : a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007;39:175–191.
Klistorner A, Sriram P, Vootakuru N, et al. Axonal loss of retinal neurons in multiple sclerosis associated with optic radiation lesions. Neurology 2014;82:2165–2172.
Blakemore WF, Chari DM, Gilson JM, Crang AJ. Modelling large areas of demyelination in the rat reveals the potential and possible limitations of transplanted glial cells for remyelination in the CNS. Glia 2002;38:155–168.
Bruck W. Inflammatory demyelination is not central to the pathogenesis of multiple sclerosis. J Neurol 2005;252(suppl 5):V/10–V/15.
Trapp BD, Ransohoff R, Rudick R. Axonal pathology in multiple sclerosis: relationship to neurologic disability. Curr Opin Neurol 1999;12:295–302.
Kornek B, Storch MK, Weissert R, et al. Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative study of axonal injury in active, inactive and remyelinated lesons. Am J Pathol 2000;157:267–276.
Dutta R, MsDonough J, Yin X, Peterson J, Chang A. Mitochondrial dysfunction cause of axonal degeneration in multiple sclerosis patients. Ann Neurol 2006;59:478–489.
Peterson JW, Kidd D, Trapp BD. Axonal degeneration in multiple sclerosis: the histopathological evidence. In: Waxman SG, ed. Multiple sclerosis as a neuronal disease. Amsterdam: Elsevier, 2005:165–184.
Lappe-Siefke C, Goebbels S, Gravel M. Disruption of Cnp 1 uncouples oligodendroglial functions in axonal support and myelination. Nat Genet 2003;33:366–374.
Liddelow SA, Guttenplan KA, Clarke LE, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 2017;541:481–487.
Correale J, Farez MF, Cardona AE. The role of astrocytes in multiple sclerosis progression. Front Neurol 2015;6:1–12.
Irvine KA, Blakemore WF. Remyelination protects axons from demyelination-associated axon degeneration. Brain 2008;131:1464–1477.

Auteurs

Alexander Klistorner (A)

Save Sight Institute, University of Sydney, Sydney, Australia.
Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
Sydney Neuroimaging Analysis Centre, Sydney, Australia.
Brain and Mind Centre, University of Sydney, Sydney, Australia; and.

James D Triplett (JD)

Department of Neurology, University of Sydney, Sydney, Australia.

Michael H Barnett (MH)

Sydney Neuroimaging Analysis Centre, Sydney, Australia.
Brain and Mind Centre, University of Sydney, Sydney, Australia; and.

Con Yiannikas (C)

Department of Neurology, University of Sydney, Sydney, Australia.

Joshua Barton (J)

Sydney Neuroimaging Analysis Centre, Sydney, Australia.
Brain and Mind Centre, University of Sydney, Sydney, Australia; and.

John Parratt (J)

Department of Neurology, University of Sydney, Sydney, Australia.

Yuyi You (Y)

Save Sight Institute, University of Sydney, Sydney, Australia.
Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.

Stuart L Graham (SL)

Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH