Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Feb;29(2):212-220.
doi: 10.1177/13524585221137500. Epub 2022 Dec 22.

Magnetization transfer saturation reveals subclinical optic nerve injury in pediatric-onset multiple sclerosis

Giulia Longoni  1 , Edgar Martinez Chavez  2 , Kimberly Young  3 , Robert A Brown  4 , Sonya Bells  2 , Dumitru Fetco  5 , Laura Kim  2 , Stephanie A Grover  3 , Fiona Costello  6 , Arun Reginald  7 , Amit Bar-Or  8 , Ruth Ann Marrie  9 , Douglas L Arnold  10 , Sridar Narayanan  5 , Helen M Branson  11 , Brenda L Banwell  12 , John G Sled  13 , Donald J Mabbott  2 , E Ann Yeh  1
Affiliations

Magnetization transfer saturation reveals subclinical optic nerve injury in pediatric-onset multiple sclerosis

Giulia Longoni et al. Mult Scler. 2023 Feb.

Abstract

Background: The presence of subclinical optic nerve (ON) injury in youth living with pediatric-onset MS has not been fully elucidated. Magnetization transfer saturation (MTsat) is an advanced magnetic resonance imaging (MRI) parameter sensitive to myelin density and microstructural integrity, which can be applied to the study of the ON.

Objective: The objective of this study was to investigate the presence of subclinical ON abnormalities in pediatric-onset MS by means of magnetization transfer saturation and evaluate their association with other structural and functional parameters of visual pathway integrity.

Methods: Eleven youth living with pediatric-onset MS (ylPOMS) and no previous history of optic neuritis and 18 controls underwent standardized brain MRI, optical coherence tomography (OCT), Magnetoencephalography (MEG)-Visual Evoked Potentials (VEPs), and visual battery. Data were analyzed with mixed effect models.

Results: While ON volume, OCT parameters, occipital MEG-VEPs outcomes, and visual function did not differ significantly between ylPOMS and controls, ylPOMS had lower MTsat in the supratentorial normal appearing white matter (-0.26 nU, p = 0.0023), and in both in the ON (-0.62 nU, p < 0.001) and in the normal appearing white matter of the optic radiation (-0.56 nU, p = 0.00071), with these being positively correlated (+0.57 nU, p = 0.00037).

Conclusions: Subclinical microstructural injury affects the ON of ylPOMS. This may appear as MTsat changes before being detectable by other currently available testing.

Keywords: Pediatric MS; magnetization transfer; optic nerve; optical coherence tomography; quantitative MRI; visual functions.

PubMed Disclaimer

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Giulia Longoni, Edgar Martinez Chavez, Kimberly Young, Robert A. Brown, Sonya Bells, Dumitru Fetco, Laura Kim, Stephanie A. Grover, Helen M. Branson, Arun Reginald, John G. Sled, and Donald J. Mabbott have nothing to disclose. Fiona Costello has received speaker honoraria for Accure Therapeutics, Novartis, Alexion; and consultant honoraria for Frequency Therapeutics and Alexion. Amit Bar-Or participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from Janssen/Actelion; Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Roche/Genentech, MAPI, Medimmune, Merck/EMD Serono, Novartis, Sanofi-Genzyme. Ruth Ann Marrie receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, US Department of Defense and the Arthritis Society. She is supported by the Waugh Family Chair in Multiple Sclerosis. She is a co-investigator on a study funded in part by Biogen Idec and Roche (no funds to her/her institution). Douglas L. Arnold has received personal compensation for serving as a Consultant for Alexion, Biogen, Celgene, Eli Lilly, EMD Serono, Frequency Therapeutics, Genentech, Merck, Novartis, Roche, Sanofi, and Shionogi, and holds an equity interest in NeuroRx. Sridar Narayanan has received speaker’s honoraria from Novartis Canada and Roche and is a part-time employee of NeuroRx Research. Brenda L. Banwell serves as a consultant to Novartis, Roche, UCB, Sanofi-Genzyme, Biogen, and UTSW regarding design and safe conduce of clinical trials and as a central reviewer for Novartis and Roche. E. Ann Yeh has received research funding from NMSS, CMSC, CIHR, NIH, OIRM, SCN, CBMH Chase an Idea, SickKids Foundation, Rare Diseases Foundation, MS Scientific Foundation (Canada), McLaughlin Center, Mario Battaglia Foundation. Investigator initiated research funding from Biogen. Scientific advisory: Biogen, Hoffman-LaRoche, Vielabio. Speaker honoraria: Saudi Epilepsy Society, NYU, MS-ATL; ACRS, PRIME.

Figures

Figure 1.
Figure 1.
Example of segmentation. Axial (a), sagittal (b), and coronal (c) views from the manual segmentation of the optic nerves of a ylPOMS. The left optic nerve, shown in yellow, and the right optic nerve, in red, are visualized on the MTsat map of the subject. The panel in (d) shows, in yellow, the three-dimensional rendering of the segmented left intraorbital optic nerve (www.itksnap.org).
Figure 2.
Figure 2.
MTsat of the ON in ylPOMS and HC according to age. The two lines of best fit represent the intraorbital ON MTsat values predicted by the model for each study group according to age. The points connected by vertical lines are values from the two eyes of individual participants. Shaded areas are 95% confidence intervals. Average intraorbital ON MTsat is expressed in normalized MT units [nU]. After accounting for sex (not shown) and age, ylPOMS show higher ON MTsat compared with HC.
See this image and copyright information in PMC

References

    1. Halliday AM, McDonald WI, Mushin J. Visual evoked response in diagnosis of multiple sclerosis. Br Med J 1973; 4: 661–664. - PMC - PubMed
    1. Trip SA, Schlottmann PG, Jones SJ, et al.. Optic nerve magnetization transfer imaging and measures of axonal loss and demyelination in optic neuritis. Mult Scler 2007; 13(7): 875–879. - PubMed
    1. Henderson AP, Trip SA, Schlottmann PG, et al.. An investigation of the retinal nerve fibre layer in progressive multiple sclerosis using optical coherence tomography. Brain 2008; 131(Pt. 1): 277–287. - PubMed
    1. Pulicken M, Gordon-Lipkin E, Balcer LJ, et al.. Optical coherence tomography and disease subtype in multiple sclerosis. Neurology 2007; 69: 2085–2092. - PubMed
    1. Johnson G, Miller DH, MacManus D, et al.. STIR sequences in NMR imaging of the optic nerve. Neuroradiology 1987; 29(3): 238–245. - PubMed

Publication types