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Multiple sclerosis optic neuritis and trans-synaptic pathology on cortical thinning in people with multiple sclerosis

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Abstract

Background

The multi-order visual system represents an excellent testing site regarding the process of trans-synaptic degeneration. The presence and extent of global versus trans-synaptic neurodegeneration in people with multiple sclerosis (pwMS) is not clear.

Objective

To explore cross-sectional and longitudinal relationships between retinal, thalamic and cortical changes in pwMS with and without MS-related optic neuritis (pwMSON and pwoMSON) using MRI and optical coherence tomography (OCT).

Methods

162 pwMS and 47 healthy controls (HCs) underwent OCT and brain MRI at baseline and 5.5-years follow-up. Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell inner plexiform layer (mGCIPL) thicknesses were determined. Global volume measures of brain parenchymal volume (BPV)/percent brain volume change (PBVC), thalamic volume and T2-lesion volume (LV) were derived using standard analysis protocols. Regional cortical thickness was determined using FreeSurfer. Cross-sectional and longitudinal relationship between the retinal measures, thalamic volume and cortical thickness were assessed using age, BPV/PBVC and T2-LV adjusted correlations and regressions.

Results

After age, BPV and T2-LV adjustment, the thalamic volume explained additional variance in the thickness of pericalcarine (R2 increase of 0.066, standardized β = 0.299, p = 0.039) and lateral occipital (R2 increase of 0.024, standardized β = 0.299, p = 0.039) gyrii in pwMSON. In pwoMSON, the thalamic volume was a significant predictor only of control (frontal) regions of pars opercularis. There was no relationship between thalamic atrophy and cortical thinning over the follow-up in both pwMS with and without MSON. While numerically lower in the pwMSON group, the inter-eye difference was not able to predict the presence of MSON.

Conclusions

MSON can induce a measurable amount of trans-synaptic pathology on second-order cortical regions.

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Data availability

The data that support the findings of this study are available on request from the corresponding author, [DJ].

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Authors and Affiliations

  1. Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, 100 High Street, Buffalo, NY, 14203, USA

    Ranjani Ganapathy Subramanian, Robert Zivadinov, Niels Bergsland, Michael G. Dwyer & Dejan Jakimovski

  2. Center for Biomedical Imaging at the Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, USA

    Robert Zivadinov

  3. IRCCS, Fondazione Don Carlo Gnocchi, Milan, Italy

    Niels Bergsland

  4. Department of Neurology, Jacobs Comprehensive MS Treatment and Research Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

    Bianca Weinstock-Guttman

Authors
  1. Ranjani Ganapathy Subramanian
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Corresponding author

Correspondence to Dejan Jakimovski.

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Conflict of interst

Ranjani Ganapathy and Niels Bergsland have nothing to disclose. Michael G. Dwyer received personal compensation from Keystone Heart for speaking and consultant fees. He received financial support for research activities from Bristol Myers Squibb, Novartis and Keystone Heart. Bianca Weinstock-Guttman has participated in speaker’s bureaus and/or served as a consultant for Biogen, Novartis, Genzyme & Sanofi, Genentech, Abbvie, Bayer AG, and Celgene/ BMS. Dr. Weinstock-Guttman also has received grant/research support from the agencies listed in the previous sentence as well as Mallinckrodt Pharmaceuticals, Inc. She serves in the editorial board for BMJ Neurology, Journal of International MS and CNS Drugs. Robert Zivadinov received personal compensation from Bristol Myers Squibb, EMD Serono, Sanofi, Novartis and Keystone Heart for speaking and consultant fees. He received financial support for research activities from Bristol Myers Squibb, Sanofi, Novartis, Keystone Heart, V-WAVE Medical, Mapi Pharma and Protembis. Dejan Jakimovski serves as Associate Editor of Clinical Neurology and Neurosurgery and compensated by Elsevier B.V. The study has been approved by the appropriate ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The specific national laws have been observed.

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Ganapathy Subramanian, R., Zivadinov, R., Bergsland, N. et al. Multiple sclerosis optic neuritis and trans-synaptic pathology on cortical thinning in people with multiple sclerosis. J Neurol 270, 3758–3769 (2023). https://doi.org/10.1007/s00415-023-11709-y

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  • DOI: https://doi.org/10.1007/s00415-023-11709-y

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