Skip to main content
Log in

Cortical atrophy is relevant in multiple sclerosis at clinical onset

Journal of Neurology Aims and scope Submit manuscript

Abstract

Introduction

Increasing evidence suggests relevant cortical gray matter pathology in patients with Multiple Sclerosis (MS), but how early this pathology begins; its impact on clinical disability and which cortical areas are primarily affected needs to be further elucidated.

Methods

115 consecutive patients (10 Clinically Isolated Syndrome (CIS), 32 possible MS (p-MS), 42 Relapsing Remitting MS (RR-MS), 31 Secondary Progressive MS (SP-MS)), and 40 age/gender-matched healthy volunteers (HV) underwent a neurological examination and a 1.5 T MRI. Global and regional Cortical Thickness (CTh) measurements, brain parenchyma fraction and T2 lesion load were analyzed.

Results

We found a significant global cortical thinning in p-MS (2.22 ± 0.09 mm), RR-MS (2.16 ± 0.10 mm) and SP-MS (1.98 ± 0.11 mm) compared to CIS (2.51 ± 0.11 mm) and HV (2.48 ± 0.08 mm). The correlations between mean CTh and white matter (WM) lesion load was only moderate in MS (r = )0.393, p = 0.03) and absent in p-MS (r = )0.147, p = 0.422). Analysis of regional CTh revealed that the majority of cortical areas were involved not only in MS, but also in p-MS. The type of clinical picture at onset (in particular, pyramidal signs/symptoms and optic neuritis) correlated with atrophy in the corresponding cortical areas.

Discussion

Cortical thinning is a diffuse and early phenomenon in MS already detectable at clinical onset. It correlates with clinical disability and is partially independent from WM inflammatory pathology.

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

Similar content being viewed by others

References

  1. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG (2000) Multiple sclerosis. N Engl J Med 343(13):938–952. Review

    Article  CAS  PubMed  Google Scholar 

  2. Patwardhan MB, Matchar DB, Gpe S et al. (2005) Cost of multiple sclerosis by level of disability: a review of literature. Mult Scler 11(2):232–239

    Article  CAS  PubMed  Google Scholar 

  3. Pozzilli C, Romano S, Cannoni S (2002) Epidemiology and current treatment of multiple sclerosis in Europe today. J Rehabil Res 39:175–185

    Google Scholar 

  4. Sospedra M, Martin R (2005) Immunology of multiple sclerosis. Annu Rev Immunol 23:683–647

    Article  CAS  PubMed  Google Scholar 

  5. Bo L, Vedeler CA, Nyland HI et al. (2003) Subpial demyelination in the cerebral cortex of multiple sclerosis patients. J Neuropathol Exp Neurol 62(7):723–732

    PubMed  Google Scholar 

  6. Brownell B, Hughes JT (1962) The distribution of plaques in the cerebrum in multiple sclerosis. J Neurol Neurosurg Psychiatry 25:315–320

    Article  CAS  PubMed  Google Scholar 

  7. Dawson JW (1916) The histology of multiple sclerosis. Trans R Soc, Edinburgh 50:517–540

    Google Scholar 

  8. Lumsden CE (1970) The neuropathology of multiple sclerosis. In: Vinken PJ, Bruin GW (eds) Handbook of clinical neurology. Elsevier Science Publishers, Amsterdam, pp 217–309

  9. Peterson JW, Bo L, Mork S et al. (2001) Transected neurites, apoptotic neurons and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 50:389–400

    Article  CAS  PubMed  Google Scholar 

  10. Geurts JJ, Bo L, Pouwels PJ et al. (2005) Cortical lesions in multiple sclerosis: combined postmortem MR imaging and histopathology. AJNR Am J Neuroradiol 26(3):572–577

    PubMed  Google Scholar 

  11. Kapeller P, McLean MA, Griffin CM et al. (2001) Preliminary evidence for neuronal damage in cortical grey matter and normal appearing white matter in short duration relapsing-remitting multiple sclerosis: a quantitative MR spectroscopic imaging study. J Neurol 248(2):131–138

    Article  CAS  PubMed  Google Scholar 

  12. Kidd D, Barkhof F, McConnel R et al. (1999) Cortical lesions in multiple sclerosis. Brain 122:17–26

    Article  PubMed  Google Scholar 

  13. Chard DT, Griffin CM, McLean MA et al. (2002) Brain metabolite changes in cortical grey and normal-appearing white matter in clinically early relapsing- remitting multiple sclerosis. Brain 125(Pt 10):2342–2352

    Article  CAS  PubMed  Google Scholar 

  14. Sastre-Garriga J, Ingle GT, Chard DT et al. (2005) Grey and white matter volume changes in early primary progressive multiple sclerosis: a longitudinal study. Brain 128(Pt 6):1454–1460

    Article  PubMed  Google Scholar 

  15. Chard DT, Griffin CM, Rashid W et al. (2004) Progressive grey matter atrophy in clinically early relapsing-remitting multiple sclerosis. Mult Scler 10(4):387–391

    Article  CAS  PubMed  Google Scholar 

  16. Dalton CM, Chard DT, Davies GR et al. (2004) Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. Brain 127(Pt 5):1101–1107

    Article  PubMed  Google Scholar 

  17. De Stefano N, Matthews PM, Filippi M et al. (2003) Evidence of early cortical atrophy in MS: relevance to white matter changes and disability. Neurology 60(7):1157–1162

    CAS  PubMed  Google Scholar 

  18. Tiberio M, Chard DT, Altmann DR et al. (2005) Grey and white matter volume changes in early RRMS: a 2-year longitudinal study. Neurology 64(6):1001–1007

    CAS  PubMed  Google Scholar 

  19. Amato MP, Bartolozzi ML, Zipoli V et al. (2004) Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment. Neurology 63:89–93

    CAS  PubMed  Google Scholar 

  20. Pagani E, Rocca MA, Gallo A et al. (2005) Regional brain atrophy evolves differently in patients with multiple sclerosis according to clinical phenotype. AJNR Am J Neuroradiol 26(2):341–346

    PubMed  Google Scholar 

  21. Sailer M, Fischl B, Salat D et al. (2003) Focal Thinning of the cerebral cortex in multipe sclerosis. Brain 126:1734–1744

    Article  PubMed  Google Scholar 

  22. Chen JT, Narayanan S, Collins DL et al. (2004) Relating neocortical pathology to disability progression in multiple sclerosis using MRI. Neuroimage 23(3):1168–1175

    Article  CAS  PubMed  Google Scholar 

  23. McDonald WI, Compston A, Edan G et al. (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50(1):121–127

    Article  CAS  PubMed  Google Scholar 

  24. Polman CH, Reingold SC, Edan G et al. (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria” Ann Neurol 58(6):840–846

    Article  PubMed  Google Scholar 

  25. Barkhof F, Filippi M, Miller DH et al. (1997) Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 120(Pt 11):2059–2069. Review

    Article  PubMed  Google Scholar 

  26. Tintore M, Rovira A, Rio J et al. (2003) New diagnostic criteria for multiple sclerosis: application in first demyelinating episode. Neurology 60(1):27–30

    CAS  PubMed  Google Scholar 

  27. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33(11):1444–1452

    CAS  PubMed  Google Scholar 

  28. Pham DL, Xu C, Prince JL (2001) A survey of current methods in medical image segmentation. Technical Report JHU/ECE 99-01. Department of Electrical and Computer Engineering, The Johns Hopkins University, Baltimore

  29. Pelletier D, Garrison K, Henry R (2004) Measurement of whole-brain atrophy in multiple sclerosis. J Neuroimaging 14(3 Suppl):11S–19S

    Article  PubMed  Google Scholar 

  30. Rudick RA, Fisher E, Lee JC et al. (1999) Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple sclerosis collaborative research group. Neurology 53:1698–1704

    CAS  PubMed  Google Scholar 

  31. Smith SM (2002) Fast robust automated brain extraction. Hum Brain Mapp 17(3):143–155. Review

    Article  PubMed  Google Scholar 

  32. Dale AM, Fischl B, Sereno MI (1999) Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage 9:179–194

    Article  CAS  PubMed  Google Scholar 

  33. Fischl B, Sereno M, Dale AM (1999) Cortical surface-based analysis. II. Inflation, flattening and a surface-based coordinate system. Neuroimage 9:272–284

    Article  Google Scholar 

  34. Fischl B, Liu A, Dale AM (2001) Automated manifold surgery: constructing geometrically accurate and topologically correct models of the human cerebral cortex. IEEE Trans Med Imaging 20(1):70–80

    Article  CAS  PubMed  Google Scholar 

  35. Yandell BS (1997) Practical data analysis for designed experiments. Chapman & Hall, London

  36. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338(5):278–285

    Article  CAS  PubMed  Google Scholar 

  37. Barkhof F (1999) MRI in multiple sclerosis: correlation with expanded disability status scale (EDSS). Mult Scler 5(4):283–286. Review

    CAS  PubMed  Google Scholar 

  38. Filippi M, Paty DW, Kappos L et al. (1995) Correlations between changes in disability and T2-weighted brain MRI activity in multiple sclerosis: a followup study. Neurology 45(2):255–260

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Massimiliano Calabrese MD.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Calabrese, M., Atzori, M., Bernardi, V. et al. Cortical atrophy is relevant in multiple sclerosis at clinical onset. J Neurol 254, 1212–1220 (2007). https://doi.org/10.1007/s00415-006-0503-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-006-0503-6

Key words

Navigation