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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].

References

  1. Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O (2018) Multiple sclerosis. Lancet 391:1622–1636

    Article  PubMed  Google Scholar 

  2. Benedict RHB, Amato MP, DeLuca J, Geurts JJG (2020) Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues. Lancet Neurol 19:860–871

    Article  PubMed  PubMed Central  Google Scholar 

  3. Balcer LJ (2006) Clinical practice. Optic neuritis N Engl J Med 354:1273–1280

    Article  CAS  PubMed  Google Scholar 

  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 24:1196–1204

    Article  PubMed  Google Scholar 

  5. Balcer LJ, Miller DH, Reingold SC, Cohen JA (2015) Vision and vision-related outcome measures in multiple sclerosis. Brain 138:11–27

    Article  PubMed  Google Scholar 

  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 133:2592–2602

    Article  PubMed  Google Scholar 

  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 16:797–812

    Article  PubMed  Google Scholar 

  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 9:921–932

    Article  PubMed  Google Scholar 

  11. Gabilondo I, Martinez-Lapiscina EH, Fraga-Pumar E et al (2015) Dynamics of retinal injury after acute optic neuritis. Ann Neurol 77:517–528

    Article  PubMed  Google Scholar 

  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 31:662–668

    Article  PubMed  Google Scholar 

  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 8:2235–2251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dorr J, Wernecke KD, Bock M et al (2011) Association of retinal and macular damage with brain atrophy in multiple sclerosis. PLoS ONE 6:e18132

    Article  PubMed  PubMed Central  Google Scholar 

  15. Gordon-Lipkin E, Chodkowski B, Reich DS et al (2007) Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis. Neurology 69:1603–1609

    Article  CAS  PubMed  Google Scholar 

  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 34:23–28

    Article  PubMed  Google Scholar 

  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 78:801–813

    Article  PubMed  PubMed Central  Google Scholar 

  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-e1161

    Article  CAS  PubMed  Google Scholar 

  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 427:117552

    Article  PubMed  Google Scholar 

  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 67:749–760

    PubMed  PubMed Central  Google Scholar 

  21. Herro AM, Lam BL (2015) Retrograde degeneration of retinal ganglion cells in homonymous hemianopsia. Clin Ophthalmol 9:1057–1064

    Article  PubMed  PubMed Central  Google Scholar 

  22. Vanburen JM (1963) Trans-synaptic retrograde degeneration in the visual system of primates. J Neurol Neurosurg Psychiatry 26:402–409

    Article  CAS  PubMed  Google Scholar 

  23. Coleman M (2005) Axon degeneration mechanisms: commonality amid diversity. Nat Rev Neurosci 6:889–898

    Article  CAS  PubMed  Google Scholar 

  24. Tur C, Goodkin O, Altmann DR et al (2016) Longitudinal evidence for anterograde trans-synaptic degeneration after optic neuritis. Brain 139:816–828

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kolbe S, Bajraszewski C, Chapman C et al (2012) Diffusion tensor imaging of the optic radiations after optic neuritis. Hum Brain Mapp 33:2047–2061

    Article  PubMed  Google Scholar 

  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 66:998–1006

    Article  PubMed  PubMed Central  Google Scholar 

  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 19:1610–1617

    Article  PubMed  Google Scholar 

  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 129:1031–1039

    Article  PubMed  Google Scholar 

  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 86:419–424

    Article  CAS  PubMed  Google Scholar 

  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 25:308–316

    Article  PubMed  PubMed Central  Google Scholar 

  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 75:98–107

    Article  CAS  PubMed  Google Scholar 

  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 25:122–131

    Article  PubMed  Google Scholar 

  33. Klistorner A, Sriram P, Vootakuru N et al (2014) Axonal loss of retinal neurons in multiple sclerosis associated with optic radiation lesions. Neurology 82:2165–2172

    Article  PubMed  PubMed Central  Google Scholar 

  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 23:1035–1039

    Article  PubMed  PubMed Central  Google Scholar 

  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 6:1757–1770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452

    Article  CAS  PubMed  Google Scholar 

  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-e88

    Article  CAS  PubMed  Google Scholar 

  39. Smith SM, Zhang Y, Jenkinson M et al (2002) Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. Neuroimage 17:479–489

    Article  PubMed  Google Scholar 

  40. Patenaude B, Smith SM, Kennedy DN, Jenkinson M (2011) A Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage 56:907–922

    Article  PubMed  Google Scholar 

  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 97:11050–11055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 32:763–770

    Article  CAS  PubMed  Google Scholar 

  43. Cruz-Herranz A, Balk LJ, Oberwahrenbrock T et al (2016) The APOSTEL recommendations for reporting quantitative optical coherence tomography studies. Neurology 86:2303–2309

    Article  PubMed  PubMed Central  Google Scholar 

  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 21:163–170

    Article  CAS  PubMed  Google Scholar 

  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 145:185–195

    Article  CAS  PubMed  Google Scholar 

  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 67:411–426

    Article  PubMed  Google Scholar 

  48. Jindahra P, Petrie A, Plant GT (2012) The time course of retrograde trans-synaptic degeneration following occipital lobe damage in humans. Brain 135:534–541

    Article  PubMed  Google Scholar 

  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:e97444

    Article  PubMed  PubMed Central  Google Scholar 

  50. Handley SE, Panteli VS, Liasis A (2017) Trans-synaptic retrograde degeneration following hemispherectomy in childhood. Neuroophthalmology 41:103–107

    Article  PubMed  PubMed Central  Google Scholar 

  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 286:20182733

    PubMed  PubMed Central  Google Scholar 

  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 35:112–116

    Article  PubMed  Google Scholar 

  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 2016:2394957

    Article  PubMed  PubMed Central  Google Scholar 

  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 14:942438

    Article  PubMed  PubMed Central  Google Scholar 

  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 88:525–532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 33:845–855

    Article  PubMed  Google Scholar 

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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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