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

Author:

Longoni Giulia1,Martinez Chavez Edgar2,Young Kimberly3,Brown Robert A4,Bells Sonya2ORCID,Fetco Dumitru5ORCID,Kim Laura2,Grover Stephanie A3,Costello Fiona6ORCID,Reginald Arun7,Bar-Or Amit8,Marrie Ruth Ann9ORCID,Arnold Douglas L10ORCID,Narayanan Sridar5,Branson Helen M11,Banwell Brenda L.12,Sled John G13,Mabbott Donald J.2,Yeh E Ann1ORCID

Affiliation:

1. Division of Neurology, Department of Pediatrics, University of Toronto, Toronto, ON, Canada/Department of Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada

2. Department of Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada

3. Division of Neurology, Department of Pediatrics, University of Toronto, Toronto, ON, Canada

4. ShadowLab Research Inc., Toronto, ON, Canada

5. McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada

6. Departments of Clinical Neurosciences and Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

7. Department of Ophthalmology and Visual Sciences, The University of Toronto, Toronto, ON, Canada

8. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

9. Departments of Internal Medicine and Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada

10. McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada/Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada

11. Department of Diagnostic Imaging, University of Toronto, Toronto, ON, Canada

12. Division of Neurology, The Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

13. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

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.

Funder

Multiple Sclerosis Scientific Research Foundation

National Multiple Sclerosis Society

Ontario Institute for Regenerative Medicine

Stem Cell Network

Publisher

SAGE Publications

Subject

Neurology (clinical),Neurology

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