Skip to main content
Log in

Optic radiation damage in multiple sclerosis is associated with visual dysfunction and retinal thinning – an ultrahigh-field MR pilot study

  • Magnetic Resonance
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objective

To investigate posterior visual pathway damage in multiple sclerosis using ultrahigh-field magnetic resonance imaging (MRI) at 7 Tesla (7 T), and to determine its correlation with visual disability and retinal fibre layer (RNFL) damage detectable by optic coherence tomography (OCT).

Methods

We studied 7 T MRI, OCT, functional acuity contrast testing (FACT), and visually evoked potentials (VEP, n = 16) in 30 patients (including 26 relapsing-remitting MS and four clinically isolated syndrome patients) and 12 healthy controls to quantify RNFL thickness, optic radiation lesion volume, and optic radiation thickness.

Results

Optic radiation lesion volume was associated with thinning of the optic radiation (p < 0.001), delayed VEP (p = 0.031), and visual disability indicated by FACT (p = 0.020). Furthermore, we observed an inverse correlation between optic radiation lesion volume and RNFL thickness (p < 0.001), including patients without previous optic neuritis (p < 0.001).

Conclusions

Anterior visual pathway damage, but also (subclinical) optic radiation integrity loss detectable by 7 T MRI are common findings in MS that are mutually affected. Given the association between optic radiation damage, visual impairment, and increased VEP latency in this exploratory study of a limited sample size, clinicians should be aware of acute lesions within the optic radiation in patients with (bilateral) visual disturbances.

Key Points

Focal destruction of the optic radiation is detectable by 7 T MRI.

Focal optic radiation damage is common in MS.

Optic radiation damage is associated with RNFL thinning, detectable by OCT.

Optic radiation damage is associated with delayed VEP and visual dysfunction.

RNFL thickness in non-optic neuritis eyes correlates with optic radiation demyelination.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302

    Article  PubMed Central  PubMed  Google Scholar 

  2. Filippi M, Bozzali M, Rovaris M et al (2003) Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain 126:433–437

    Article  CAS  PubMed  Google Scholar 

  3. Oberwahrenbrock T, Ringelstein M, Jentschke S et al (2013) Retinal ganglion cell and inner plexiform layer thinning in clinically isolated syndrome. Mult Scler 19:1887–1895

    Article  PubMed  Google Scholar 

  4. Kitajima M, Korogi Y, Takahashi M, Eto K (1996) MR signal intensity of the optic radiation. AJNR Am J Neuroradiol 17:1379–1383

    CAS  PubMed  Google Scholar 

  5. Bürgel U, Mecklenburg I, Blohm U, Zilles K (1997) Histological visualization of long fiber tracts in the white matter of adult human brains. J Hirnforsch 38:397–404

    PubMed  Google Scholar 

  6. Sinnecker T, Mittelstaedt P, Dörr J et al (2012) Multiple sclerosis lesions and irreversible brain tissue damage: a comparative ultrahigh-field strength magnetic resonance imaging study. Arch Neurol 69:739–745

    PubMed  Google Scholar 

  7. Kollia K, Maderwald S, Putzki N et al (2009) First clinical study on ultra-high-field MR imaging in patients with multiple sclerosis: comparison of 1.5T and 7T. AJNR Am J Neuroradiol 30:699–702

    Article  CAS  PubMed  Google Scholar 

  8. Kilsdonk ID, Wattjes MP, Lopez-Soriano A et al (2014) Improved differentiation between MS and vascular brain lesions using FLAIR* at 7 Tesla. Eur Radiol 24:841–849

    Article  PubMed  Google Scholar 

  9. Kilsdonk ID, de Graaf WL, Barkhof F, Wattjes MP (2012) Inflammation high-field magnetic resonance imaging. Neuroimaging Clin N Am 22:135–157

    Article  PubMed  Google Scholar 

  10. Tallantyre EC, Dixon JE, Donaldson I et al (2011) Ultra-high-field imaging distinguishes MS lesions from asymptomatic white matter lesions. Neurology 76:534–539

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Wuerfel J, Sinnecker T, Ringelstein EB et al (2012) Lesion morphology at 7 Tesla MRI differentiates Susac syndrome from multiple sclerosis. Mult Scler 18:1592–1599

    Article  PubMed  Google Scholar 

  12. Dörr J, Krautwald S, Wildemann B et al (2013) Characteristics of Susac syndrome: a review of all reported cases. Nat Rev Neurol 9:307–316

    Article  PubMed  Google Scholar 

  13. Sinnecker T, Dörr J, Pfueller CF et al (2012) Distinct lesion morphology at 7-T MRI differentiates neuromyelitis optica from multiple sclerosis. Neurology 79:708–714

    Article  PubMed  Google Scholar 

  14. 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 

  15. Oberwahrenbrock T, Schippling S, Ringelstein M et al (2012) Retinal damage in multiple sclerosis disease subtypes measured by high-resolution optical coherence tomography. Mult Scler Int 2012:530305

    PubMed Central  PubMed  Google Scholar 

  16. Trip SA, Schlottmann PG, Jones SJ et al (2005) Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis. Ann Neurol 58:383–391

    Article  PubMed  Google Scholar 

  17. Pueyo V, Martin J, Fernandez J et al (2008) Axonal loss in the retinal nerve fiber layer in patients with multiple sclerosis. Mult Scler 14:609–614

    Article  CAS  PubMed  Google Scholar 

  18. Wu GF, Schwartz ED, Lei T et al (2007) Relation of vision to global and regional brain MRI in multiple sclerosis. Neurology 69:2128–2135

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  20. Bermel RA, Bakshi R, Tjoa C et al (2002) Bicaudate ratio as a magnetic resonance imaging marker of brain atrophy in multiple sclerosis. Arch Neurol 59:275–280

    Article  PubMed  Google Scholar 

  21. Benedict RHB, Bruce JM, Dwyer MG et al (2006) Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis. Arch Neurol 63:1301–1306

    Article  PubMed  Google Scholar 

  22. Tewarie P, Balk L, Costello F et al (2012) The OSCAR-IB consensus criteria for retinal OCT quality assessment. PLoS One 7:e34823

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Bock M, Brandt AU, Kuchenbecker J et al (2012) Impairment of contrast visual acuity as a functional correlate of retinal nerve fibre layer thinning and total macular volume reduction in multiple sclerosis. Br J Ophthalmol 96:62–67

    Article  PubMed  Google Scholar 

  24. Ferreras A, Pablo LE, Garway-Heath DF et al (2008) Mapping standard automated perimetry to the peripapillary retinal nerve fiber layer in glaucoma. Invest Ophthalmol Vis Sci 49:3018–3025

    Article  PubMed  Google Scholar 

  25. Tallantyre EC, Brookes MJ, Dixon JE et al (2008) Demonstrating the perivascular distribution of MS lesions in vivo with 7-Tesla MRI. Neurology 70:2076–2078

    Article  CAS  PubMed  Google Scholar 

  26. Ide S, Kakeda S, Korogi Y et al (2012) Delineation of optic radiation and stria of Gennari on high-resolution phase difference enhanced imaging. Acad Radiol 19:1283–1289

    Article  PubMed  Google Scholar 

  27. Sukstanskii AL, Yablonskiy DA (2014) On the role of neuronal magnetic susceptibility and structure symmetry on gradient echo MR signal formation. Magn Reson Med 71:345–353

    Article  PubMed  Google Scholar 

  28. Trapp BD, Peterson J, Ransohoff RM et al (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338:278–285

    Article  CAS  PubMed  Google Scholar 

  29. Saidha S, Syc SB, Ibrahim MA et al (2011) Primary retinal pathology in multiple sclerosis as detected by optical coherence tomography. Brain 134:518–533

    Article  PubMed  Google Scholar 

  30. Brandt AU, Oberwahrenbrock T, Ringelstein M et al (2011) Primary retinal pathology in multiple sclerosis as detected by optical coherence tomography. Brain 134:e193

    Article  CAS  PubMed  Google Scholar 

  31. Cowey A, Alexander I, Stoerig P (2011) Transneuronal retrograde degeneration of retinal ganglion cells and optic tract in hemianopic monkeys and humans. Brain 134:2149–2157

    Article  PubMed  Google Scholar 

  32. Dasenbrock HH, Smith SA, Ozturk A et al (2011) Diffusion tensor imaging of the optic tracts in multiple sclerosis: association with retinal thinning and visual disability. J Neuroimaging 21:e41–e49

    Article  PubMed Central  PubMed  Google Scholar 

  33. Jindahra P, Petrie A, Plant GT (2009) Retrograde trans-synaptic retinal ganglion cell loss identified by optical coherence tomography. Brain 132:628–634

    Article  PubMed  Google Scholar 

  34. Evangelou N, Konz D, Esiri MM et al (2001) Size-selective neuronal changes in the anterior optic pathways suggest a differential susceptibility to injury in multiple sclerosis. Brain 124:1813–1820

    Article  CAS  PubMed  Google Scholar 

  35. Matthews MR, Cowan WM, Powell TP (1960) Transneuronal cell degeneration in the lateral geniculate nucleus of the macaque monkey. J Anat 94:145–169

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Bridge H, Jindahra P, Barbur J, Plant GT (2011) Imaging reveals optic tract degeneration in hemianopia. Invest Ophthalmol Vis Sci 52:382–388

    Article  PubMed  Google Scholar 

  37. Sepulcre J, Goñi J, Masdeu JC et al (2009) Contribution of white matter lesions to gray matter atrophy in multiple sclerosis: evidence from voxel-based analysis of T1 lesions in the visual pathway. Arch Neurol 66:173–179

    PubMed  Google Scholar 

  38. Pfueller CF, Brandt AU, Schubert F et al (2011) Metabolic changes in the visual cortex are linked to retinal nerve fiber layer thinning in multiple sclerosis. PLoS One 6:e18019

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Gabilondo I, Martínez-Lapiscina EH, Martínez-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 

  40. Sriram P, Graham SL, Wang C et al (2012) Transsynaptic retinal degeneration in optic neuropathies: optical coherence tomography study. Invest Ophthalmol Vis Sci 53:1271–1275

    Article  PubMed  Google Scholar 

  41. Klistorner A, Garrick R, Barnett MH et al (2013) Axonal loss in non-optic neuritis eyes of patients with multiple sclerosis linked to delayed visual evoked potential. Neurology 80:242–245

    Article  PubMed  Google Scholar 

  42. Zimmermann H, Freing A, Kaufhold F et al (2013) Optic neuritis interferes with optical coherence tomography and magnetic resonance imaging correlations. Mult Scler 19:443–450

    Article  PubMed  Google Scholar 

  43. 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 

  44. Dörr 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 Central  PubMed  Google Scholar 

  45. 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

    PubMed Central  PubMed  Google Scholar 

  46. Kolbe SC, Marriott M, van der Walt A et al (2012) Diffusion tensor imaging correlates of visual impairment in multiple sclerosis and chronic optic neuritis. Invest Ophthalmol Vis Sci 53:825–832

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the German Research Foundation (DFG Exc 257). Our technicians and study nurses Antje Els, Susan Pikol, Cynthia Kraut, and Gritt Stoffels gave invaluable support.

The scientific guarantor of this publication is Jens Wuerfel.

The authors of this manuscript declare relationships with the following companies: TS received a travel grant from Bayer and Genzyme as well as speaker honoraria from Novartis. TO has nothing to disclose. IM received payments for lectures from Teva, Biogen Idec, and Sanofi as well as travel/accommodation/meeting expenses from Biogen Idec and Bayer. HZ has nothing to disclose. CFP has received travel grants from Teva. LH has received speaker honoraria from Biogen Idec, Bayer, Novartis, Merck-Serono, and Talecris. He serves on the advisory board for Biomarin and has received research support from Biogen and Bayer. KR has received travel grants and speaker honoraria from Merck-Serono, Biogen Idec, Bayer, and Novartis, and receives research support from Novartis. KH has nothing to disclose. WB received grants from Teva, Biogen Idec, Novartis, and Bayer. He also received honoraria for talks from Bayer, Biogen Idec, Merck-Serono, Teva, Genzyme, and Novartis and is member of the company advisory boards of Teva/Sanofi, Novartis, and Biogen Idec. TN is founder of MRI.TOOLS GmbH, Berlin, Germany and received speaker honoraria from Siemens Healthcare, Erlangen, Germany. AUB is cofounder and director of Motognosis UG (haftungsbeschränkt) and has received speaker honoraria, research grants and travel support from Bayer, Biogen Idec, Novartis Pharma, and Heidelberg Engineering. FP has received speaker honoraria, travel grants and research grants from Teva/Sanofi, Bayer, Merck-Serono, Biogen Idec, and Novartis. FP is supported by the German Research Foundation (Exc 257) and has received travel reimbursement from the Guthy Jackson Charitable Foundation. JD receives research grants from Novartis and Bayer, and has received travel support from Novartis, Teva, Bayer, and Merck-Serono, honoraria for consultancy from Bayer, Genzyme, and Teva, and speaker honoraria from Bayer, Teva, Genzyme, and Novartis. JW serves for a Novartis advisory board, received a Novartis research grant, and speaker honoraria from Novartis, Bayer, and Biogen Idec. He is supported by the German ministry for science and research (BMBF/KKNMS).

This study has received funding by the German Research Foundation (DFG Exc 257) and by a restricted research grant from TEVA Pharma, Germany.

One of the authors (Alexander U. Brandt) has significant statistical expertise.

Institutional review board approval was obtained.

Written informed consent was obtained from all subjects (patients) in this study.

Methodology: prospective cross sectional study performed at one institution.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Friedemann Paul.

Additional information

Jan Dörr and Jens Wuerfel are equally contributing senior authors

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplemental Fig. 1

Degeneration of the optic radiation. Patient A (male, 42 years, disease duration 14.6 years, EDSS 4.5) had extensive bilateral focal damage (white arrows) and atrophy of the optic radiation (black arrows). When looking at all patient data (B) including CIS (nON), RRMS (nON/ON), and early MS (nON/ON) patients, an association between the OR thickness and OR lesion volume was detectable. C shows seven consecutive T2*w FLASH MRI slices of patient C (female, 37 years old, disease duration 18.0 years, EDSS 2.5; this patient was excluded for technical reasons). A large lesion (white arrows) within the optic radiation (black arrows) is shown. The visibility of the optic radiation is dramatically diminished in the occipital part, indicative of anterograde degeneration. Sequence parameters: 7 T T2*w FLASH, TE = 25 ms, TR = 1,820 ms, spatial resolution = (0.5 × 0.5) mm2 (GIF 131 kb)

High Resolution Image (TIFF 1736 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sinnecker, T., Oberwahrenbrock, T., Metz, I. et al. 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 (2015). https://doi.org/10.1007/s00330-014-3358-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-014-3358-8

Keywords

Navigation