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Journal of Neurology
Published in: Journal of Neurology 8/2023

17-04-2023 | Multiple Sclerosis | Original Communication

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

Authors: Ranjani Ganapathy Subramanian, Robert Zivadinov, Niels Bergsland, Michael G. Dwyer, Bianca Weinstock-Guttman, Dejan Jakimovski

Published in: Journal of Neurology | Issue 8/2023

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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.
Appendix
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Literature
1.
Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O (2018) Multiple sclerosis. Lancet 391:1622–1636PubMedCrossRef
2.
Benedict RHB, Amato MP, DeLuca J, Geurts JJG (2020) Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues. Lancet Neurol 19:860–871PubMedPubMedCentralCrossRef
3.
4.
Sanchez-Dalmau B, Martinez-Lapiscina EH, Torres-Torres R et al (2018) Early retinal atrophy predicts long-term visual impairment after acute optic neuritis. Mult Scler 24:1196–1204PubMedCrossRef
5.
Balcer LJ, Miller DH, Reingold SC, Cohen JA (2015) Vision and vision-related outcome measures in multiple sclerosis. Brain 138:11–27PubMedCrossRef
6.
Henderson AP, Altmann DR, Trip AS et al (2010) A serial study of retinal changes following optic neuritis with sample size estimates for acute neuroprotection trials. Brain 133:2592–2602PubMedCrossRef
7.
University of California SFMSET, Cree BAC, Hollenbach JA, et al. Silent progression in disease activity-free relapsing multiple sclerosis. Ann Neurol 2019;85:653–666.
8.
Hemond CC, Bakshi R. Magnetic Resonance Imaging in Multiple Sclerosis. Cold Spring Harb Perspect Med 2018;8.
9.
Petzold A, Balcer LJ, Calabresi PA et al (2017) Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol 16:797–812PubMedCrossRef
10.
Petzold A, de Boer JF, Schippling S et al (2010) Optical coherence tomography in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol 9:921–932PubMedCrossRef
11.
Gabilondo I, Martinez-Lapiscina EH, Fraga-Pumar E et al (2015) Dynamics of retinal injury after acute optic neuritis. Ann Neurol 77:517–528PubMedCrossRef
12.
Wicki CA, Hanson JVM, Schippling S (2018) Optical coherence tomography as a means to characterize visual pathway involvement in multiple sclerosis. Curr Opin Neurol 31:662–668PubMedCrossRef
13.
Paul F, Calabresi PA, Barkhof F et al (2021) Optical coherence tomography in multiple sclerosis: a 3-year prospective multicenter study. Ann Clin Transl Neurol 8:2235–2251PubMedPubMedCentralCrossRef
14.
15.
Gordon-Lipkin E, Chodkowski B, Reich DS et al (2007) Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis. Neurology 69:1603–1609PubMedCrossRef
16.
Abalo-Lojo JM, Limeres CC, Gomez MA et al (2014) Retinal nerve fiber layer thickness, brain atrophy, and disability in multiple sclerosis patients. J Neuroophthalmol 34:23–28PubMedCrossRef
17.
Saidha S, Al-Louzi O, Ratchford JN et al (2015) Optical coherence tomography reflects brain atrophy in multiple sclerosis: A four-year study. Ann Neurol 78:801–813PubMedPubMedCentralCrossRef
18.
Zivadinov R, Bergsland N, Cappellani R et al (2014) Retinal nerve fiber layer thickness and thalamus pathology in multiple sclerosis patients. Eur J Neurol 21:1137-e1161PubMedCrossRef
19.
Jakimovski D, Zivadinov R, Vaughn CB, Ozel O, Weinstock-Guttman B (2021) Clinical effects associated with five-year retinal nerve fiber layer thinning in multiple sclerosis. J Neurol Sci 427:117552PubMedCrossRef
20.
Talman LS, Bisker ER, Sackel DJ et al (2010) Longitudinal study of vision and retinal nerve fiber layer thickness in multiple sclerosis. Ann Neurol 67:749–760PubMedPubMedCentral
21.
22.
Vanburen JM (1963) Trans-synaptic retrograde degeneration in the visual system of primates. J Neurol Neurosurg Psychiatry 26:402–409PubMedCrossRef
23.
Coleman M (2005) Axon degeneration mechanisms: commonality amid diversity. Nat Rev Neurosci 6:889–898PubMedCrossRef
24.
25.
Kolbe S, Bajraszewski C, Chapman C et al (2012) Diffusion tensor imaging of the optic radiations after optic neuritis. Hum Brain Mapp 33:2047–2061PubMedCrossRef
26.
Reich DS, Smith SA, Gordon-Lipkin EM et al (2009) Damage to the optic radiation in multiple sclerosis is associated with retinal injury and visual disability. Arch Neurol 66:998–1006PubMedPubMedCentralCrossRef
27.
Rocca MA, Mesaros S, Preziosa P et al (2013) Wallerian and trans-synaptic degeneration contribute to optic radiation damage in multiple sclerosis: a diffusion tensor MRI study. Mult Scler 19:1610–1617PubMedCrossRef
28.
Audoin B, Fernando KT, Swanton JK, Thompson AJ, Plant GT, Miller DH (2006) Selective magnetization transfer ratio decrease in the visual cortex following optic neuritis. Brain 129:1031–1039PubMedCrossRef
29.
Balk LJ, Steenwijk MD, Tewarie P et al (2015) Bidirectional trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis. J Neurol Neurosurg Psychiatry 86:419–424PubMedCrossRef
30.
Ciccarelli O, Toosy AT, Hickman SJ et al (2005) Optic radiation changes after optic neuritis detected by tractography-based group mapping. Hum Brain Mapp 25:308–316PubMedPubMedCentralCrossRef
31.
Gabilondo I, Martinez-Lapiscina EH, Martinez-Heras E et al (2014) Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis. Ann Neurol 75:98–107PubMedCrossRef
32.
Sinnecker T, Oberwahrenbrock T, Metz I et al (2015) Optic radiation damage in multiple sclerosis is associated with visual dysfunction and retinal thinning–an ultrahigh-field MR pilot study. Eur Radiol 25:122–131PubMedCrossRef
33.
Klistorner A, Sriram P, Vootakuru N et al (2014) Axonal loss of retinal neurons in multiple sclerosis associated with optic radiation lesions. Neurology 82:2165–2172PubMedPubMedCentralCrossRef
34.
Al-Louzi O, Button J, Newsome SD, Calabresi PA, Saidha S (2017) Retrograde trans-synaptic visual pathway degeneration in multiple sclerosis: a case series. Mult Scler 23:1035–1039PubMedPubMedCentralCrossRef
35.
Pawlitzki M, Horbrugger M, Loewe K, et al. MS optic neuritis-induced long-term structural changes within the visual pathway. Neurol Neuroimmunol Neuroinflamm 2020;7.
36.
Jakimovski D, Kuhle J, Ramanathan M et al (2019) Serum neurofilament light chain levels associations with gray matter pathology: a 5-year longitudinal study. Ann Clin Transl Neurol 6:1757–1770PubMedPubMedCentralCrossRef
37.
Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452PubMedCrossRef
38.
Jakimovski D, Gandhi S, Paunkoski I et al (2019) Hypertension and heart disease are associated with development of brain atrophy in multiple sclerosis: a 5-year longitudinal study. Eur J Neurol 26:87-e88PubMedCrossRef
39.
Smith SM, Zhang Y, Jenkinson M et al (2002) Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. Neuroimage 17:479–489PubMedCrossRef
40.
Patenaude B, Smith SM, Kennedy DN, Jenkinson M (2011) A Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage 56:907–922PubMedCrossRef
41.
Fischl B, Dale AM (2000) Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci U S A 97:11050–11055PubMedPubMedCentralCrossRef
42.
Zivadinov R, Tavazzi E, Hagemeier J et al (2018) The effect of glatiramer acetate on retinal nerve fiber layer thickness in patients with relapsing-remitting multiple sclerosis: a longitudinal optical coherence tomography study. CNS Drugs 32:763–770PubMedCrossRef
43.
Cruz-Herranz A, Balk LJ, Oberwahrenbrock T et al (2016) The APOSTEL recommendations for reporting quantitative optical coherence tomography studies. Neurology 86:2303–2309PubMedPubMedCentralCrossRef
44.
Schippling S, Balk LJ, Costello F et al (2015) Quality control for retinal OCT in multiple sclerosis: validation of the OSCAR-IB criteria. Mult Scler 21:163–170PubMedCrossRef
45.
Murphy OC, Sotirchos ES, Kalaitzidis G, et al. Trans-Synaptic Degeneration Following Acute Optic Neuritis in Multiple Sclerosis. Ann Neurol 2022.
46.
Kleerekooper I, Del Porto L, Dell’Arti L et al (2022) Pattern ERGs suggest a possible retinal contribution to the visual acuity loss in acute optic neuritis. Doc Ophthalmol 145:185–195PubMedCrossRef
47.
Sharma S, Chitranshi N, Wall RV et al (2022) Trans-synaptic degeneration in the visual pathway: Neural connectivity, pathophysiology, and clinical implications in neurodegenerative disorders. Surv Ophthalmol 67:411–426PubMedCrossRef
48.
Jindahra P, Petrie A, Plant GT (2012) The time course of retrograde trans-synaptic degeneration following occipital lobe damage in humans. Brain 135:534–541PubMedCrossRef
49.
Keller J, Sanchez-Dalmau BF, Villoslada P (2014) Lesions in the posterior visual pathway promote trans-synaptic degeneration of retinal ganglion cells. PLoS ONE 9:e97444PubMedPubMedCentralCrossRef
50.
51.
Schneider CL, Prentiss EK, Busza A et al (2019) Survival of retinal ganglion cells after damage to the occipital lobe in humans is activity dependent. Proc Biol Sci 286:20182733PubMedPubMedCentral
52.
Meier PG, Maeder P, Kardon RH, Borruat FX (2015) Homonymous ganglion cell layer thinning after isolated occipital lesion: macular OCT demonstrates transsynaptic retrograde retinal degeneration. J Neuroophthalmol 35:112–116PubMedCrossRef
53.
Yamashita T, Miki A, Goto K et al (2016) Retinal ganglion cell atrophy in homonymous hemianopia due to acquired occipital lesions observed using cirrus high-definition-OCT. J Ophthalmol 2016:2394957PubMedPubMedCentralCrossRef
54.
Ye C, Kwapong WR, Tao W et al (2022) Alterations of optic tract and retinal structure in patients after thalamic stroke. Front Aging Neurosci 14:942438PubMedPubMedCentralCrossRef
55.
Ye C, Kwapong WR, Tao W, et al. Characterization of Macular Structural and Microvascular Changes in Thalamic Infarction Patients: A Swept-Source Optical Coherence Tomography-Angiography Study. Brain Sci 2022;12.
56.
Button J, Al-Louzi O, Lang A et al (2017) Disease-modifying therapies modulate retinal atrophy in multiple sclerosis: a retrospective study. Neurology 88:525–532PubMedPubMedCentralCrossRef
57.
Schuff N, Tosun D, Insel PS et al (2012) Nonlinear time course of brain volume loss in cognitively normal and impaired elders. Neurobiol Aging 33:845–855PubMedCrossRef
Metadata
Title
Multiple sclerosis optic neuritis and trans-synaptic pathology on cortical thinning in people with multiple sclerosis
Authors
Ranjani Ganapathy Subramanian
Robert Zivadinov
Niels Bergsland
Michael G. Dwyer
Bianca Weinstock-Guttman
Dejan Jakimovski
Publication date
17-04-2023
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology / Issue 8/2023
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-023-11709-y

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