Skip to main content

Advertisement

SpringerLink
Log in

Localization of grey matter atrophy in early RRMS

A longitudinal study

  • ORIGINAL COMMUNICATION
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Previous MR studies have established that grey matter (GM) atrophy occurs in multiple sclerosis (MS) from clinical onset. However, it is uncertain whether early GM atrophy is global or has certain local predilections: using Voxel-Based Morphometry this study aimed to address this question.

Twenty-one patients with early RRMS (mean age 36 years, mean disease duration from symptom onset 25.8 months) and 10 healthy control subjects (mean age 37 years) were studied. T1-weighted three-dimensional MRI images were acquired at baseline and two year follow-up, and analysed with statistical parametric mapping software (SPM2). Two-sample t-tests (p < 0.05 corrected for multiple comparisons at cluster level) were used to compare GM maps from all patients and controls on a voxel-by-voxel basis. At baseline, no GM region appears significantly atrophic in MS subjects compared with controls. However, during the follow-up period significantly greater atrophy occurred in both thalami and the right lateral prefrontal cortex of MS patients when compared with controls. By year two, cross-sectional group comparison revealed GM atrophy in the thalami of MS patients relative to controls. The rate of thalamic atrophy in MS subjects was correlated with changes in EDSS during the follow-up period.

This study suggests that early in the clinical course of RRMS, the thalamic atrophy is more consistently apparent than regional cortical atrophy.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2

Similar content being viewed by others

References

  1. Alexander G, Crutcher M (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 13:166–171

    Article  Google Scholar 

  2. Amato MP, Bartolozzi ML, Zipoli V, Portaccio E, Mortilla M, Guidi L, Siracusa G, Sorbi S, Federico A, De Stefano N (2004) Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment. Neurology 63:89–93

    CAS  PubMed  Google Scholar 

  3. Ashburner J, Friston KJ (2000) Voxel-based morphometry–the methods. Neuroimage 11:805–821

    Article  CAS  PubMed  Google Scholar 

  4. Audoin B, Ranjeva JP, My Van AD, Ibarrola D, Malikova I, Confort-Gouny S, Soulier E, Viout P, Ali-Cherif A, Pelletier J, Cozzone PJ (2004) Voxel-based analysis of MTR images: a method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis. J Magn Reson Imaging 20:765–771

    Article  PubMed  Google Scholar 

  5. Bakshi R, Benedict RH, Bermel RA, Caruthers SD, Puli SR, Tjoa CW, Fabiano AJ, Jacobs L (2002) T2 hypointensity in the deep gray matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study. Arch Neurol 59:62–68

    Article  PubMed  Google Scholar 

  6. Benedict RH, Weinstock-Guttman B, Fishman I, Sharma J, Tjoa CW, Bakshi R (2004) Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden. Arch Neurol 61:226–230

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  8. Brex PA, Jenkins R, Fox NC, Crum WR, O’Riordan JI, Plant GT, Miller DH (2000) Detection of ventricular enlargement in patients at the earliest clinical stage of MS. Neurology 54:1689–1691

    CAS  PubMed  Google Scholar 

  9. Brownell B, JT 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 

  10. Chard DT, Brex PA, Ciccarelli O, Griffin CM, Parker GJ, Dalton C, Altmann DR, Thompson AJ, Miller DH (2003) The longitudinal relation between brain lesion load and atrophy in multiple sclerosis: a 14 year follow up study. J Neurol Neurosurg Psychiatry 74:1551–1554

    Article  CAS  PubMed  Google Scholar 

  11. Chard DT, Griffin CM, Parker GJ, Kapoor R, Thompson AJ, Miller DH (2002) Brain atrophy in clinically early relapsing-remitting multiple sclerosis. Brain 125:327–337

    Article  CAS  PubMed  Google Scholar 

  12. Chard DT, Griffin CM, Rashid W, Davies GR, Altmann DR, Kapoor R, Barker GJ, Thompson AJ, Miller DH (2004) Progressive grey matter atrophy in clinically early relapsing-remitting multiple sclerosis. Mult Scler 10:387–391

    Article  CAS  PubMed  Google Scholar 

  13. Cifelli A, Arridge M, Jezzard P, Esiri MM, Palace J, Matthews PM (2002) Thalamic neurodegeneration in multiple sclerosis. Ann Neurol 52:650–653

    Article  PubMed  Google Scholar 

  14. Dalton CM, Brex PA, Jenkins R, Fox NC, Miszkiel KA, Crum WR, O’Riordan JI, Plant GT, Thompson AJ, Miller DH (2002) Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis. J Neurol Neurosurg Psychiatry 73:141–147

    Article  CAS  PubMed  Google Scholar 

  15. Dalton CM, Chard DT, Davies GR, Miszkiel KA, Altmann DR, Fernando K, Plant GT, Thompson AJ, Miller DH (2004) Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. Brain 127:1101–1107

    Article  PubMed  Google Scholar 

  16. Davies GR, Altmann DR, Rashid W, Chard DT, Griffin CM, Barker GJ, Kapoor R, Thompson AJ, Miller DH (2005) Emergence of thalamic magnetization transfer ratio abnormality in early relapsing-remitting multiple sclerosis. Mult Scler 11:276–281

    Article  CAS  PubMed  Google Scholar 

  17. De Stefano N, Matthews PM, Filippi M, Agosta F, De Luca M, Bartolozzi ML, Guidi L, Ghezzi A, Montanari E, Cifelli A, Federico A, Smith SM (2003) Evidence of early cortical atrophy in MS: relevance to white matter changes and disability. Neurology 60:1157–1162

    PubMed  Google Scholar 

  18. Fabiano AJ, Sharma J, Weinstock-Guttman B, Munschauer FE, 3rd, Benedict RH, Zivadinov R, Bakshi R (2003) Thalamic involvement in multiple sclerosis: a diffusion-weighted magnetic resonance imaging study. J Neuroimaging 13:307–314

    Article  PubMed  Google Scholar 

  19. Fischer JS, Rudick RA, Cutter GR, Reingold SC (1999) The Multiple Sclerosis Functional Composite Measure (MSFC): an integrated approach to MS clinical outcome assessment. National MS Society Clinical Outcomes Assessment Task Force. Mult Scler 5:244–250

    Article  CAS  PubMed  Google Scholar 

  20. Fisher E, Rudick RA, Simon JH, Cutter G, Baier M, Lee JC, Miller D, Weinstock-Guttman B, Mass MK, Dougherty DS, Simonian NA (2002) Eight-year follow-up study of brain atrophy in patients with MS. Neurology 59:1412–1420

    CAS  PubMed  Google Scholar 

  21. Friston KJ, Holmes AP, Price CJ, Buchel C, Worsley KJ (1999) Multisubject fMRI studies and conjunction analyses. Neuroimage 10:385–396

    Article  CAS  PubMed  Google Scholar 

  22. Grimaud J, Lai M, Thorpe J, Adeleine P, Wang L, Barker GJ, Plummer DL, Tofts PS, McDonald WI, Miller DH (1996) Quantification of MRI lesion load in multiple sclerosis: a comparison of three computer-assisted techniques. Magn Reson Imaging 14:495–505

    Article  CAS  PubMed  Google Scholar 

  23. Kidd D, Barkhof F, McConnell R, Algra PR, Allen IV, Revesz T (1999) Cortical lesions in multiple sclerosis. Brain 122(Pt 1):17–26

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  25. Losseff NA, Wang L, Lai HM, Yoo DS, Gawne-Cain ML, McDonald WI, Miller DH, Thompson AJ (1996) Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. Brain 119(Pt 6):2009–2019

    PubMed  Google Scholar 

  26. Luks TL, Goodkin DE, Nelson SJ, Majumdar S, Bacchetti P, Portnoy D, Sloan R (2000) A longitudinal study of ventricular volume in early relapsing-remitting multiple sclerosis. Mult Scler 6:332–337

    Article  CAS  PubMed  Google Scholar 

  27. Lumsden CE (1970) The neuropathology of multiple sclerosis. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, Volume 9. Amsterdam, pp 217–309

  28. Pagani E, Rocca MA, Gallo A, Rovaris M, Martinelli V, Comi G, Filippi M (2005) Regional brain atrophy evolves differently in patients with multiple sclerosis according to clinical phenotype. AJNR Am J Neuroradiol 26:341–346

    PubMed  Google Scholar 

  29. Peterson JW, Bo L, Mork S, Chang A, Trapp BD (2001) Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 50:389–400

    Article  CAS  PubMed  Google Scholar 

  30. Ranjeva JP, Audoin B, Duong MV, Ibarrola D, Confort-Gouny S, Malikova I, Soulier E, Viout P, Ali-Cherif A, Pelletier J, Cozzone P (2005) Local tissue damage assessed with statistical mapping analysis of brain magnetization transfer ratio: relationship with functional status of patients in the earliest stage of multiple sclerosis. AJNR Am J Neuroradiol 26:119–127

    PubMed  Google Scholar 

  31. Rudick RA, Fisher E, Lee JC, Simon J, Jacobs L (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 

  32. Sailer M, Fischl B, Salat D, Tempelmann C, Schonfeld MA, Busa E, Bodammer N, Heinze HJ, Dale A (2003) Focal thinning of the cerebral cortex in multiple sclerosis. Brain 126:1734–1744

    Article  PubMed  Google Scholar 

  33. Simon JH, Jacobs LD, Campion MK, Rudick RA, Cookfair DL, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE, Simonian N, Lajaunie M, Miller DE, Wende K, Martens-Davidson A, Kinkel RP, Munschauer FE, 3rd, Brownscheidle CM (1999) A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Neurology 53:139–148

    CAS  PubMed  Google Scholar 

  34. Talairach J, Tournoux P (1988) Co-Planar Stereotaxic Atlas of the Human Brain. Thieme Medical Publishers, Inc., New York

    Google Scholar 

  35. Tiberio M, Chard DT, Altmann DR, Davies G, Griffin CM, Rashid W, Sastre-Garriga J, Thompson AJ, Miller DH (2005) Gray and white matter volume changes in early RRMS: a 2-year longitudinal study. Neurology 64:1001–1007

    CAS  PubMed  Google Scholar 

  36. Wylezinska M, Cifelli A, Jezzard P, Palace J, Alecci M, Matthews PM (2003) Thalamic neurodegeneration in relapsing-remitting multiple sclerosis. Neurology 60:1949–1954

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The NMR Research Unit is supported by the MS Society of Great Britain and Northern Ireland. Dr B Audoin is supported by the French Association for Research on Multiple Sclerosis (A.R.S.E.P.). We thank Drs C Griffin and W Rashid for assistance with patient recruitment, Dr J P Ranjeva for methodological advice, and Dr M Tiberio for performing the volumetric analyses.

Author information

Authors and Affiliations

  1. NMR Research Group, Institute of Neurology, Queen Square, London, WC1N 3BG, UK

    Bertrand Audoin MD, PhD, Gerard R. Davies MD, PhD, Leonara Finisku MD, Declan T. Chard MD, PhD, Alan J. Thompson MD, PhD &  David H. Miller MD, PhD

  2. Dept. of Neuroinflammation, Institute of Neurology, University College London, London, UK

    Bertrand Audoin MD, PhD, Gerard R. Davies MD, PhD, Leonara Finisku MD & Declan T. Chard MD, PhD

  3. Dept. of Headache, Rehabilitation and Brain Injury, Institute of Neurology, University College London, London, UK

    Alan J. Thompson MD, PhD

  4. Centre de Résonance Magnétique, Biologique et Médicale (CRMBM) and Service de Neurologie, Hôpital de la Timone, Marseille, France

    Bertrand Audoin MD, PhD

Authors
  1. Bertrand Audoin MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gerard R. Davies MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leonara Finisku MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Declan T. Chard MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alan J. Thompson MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David H. Miller MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David H. Miller MD, PhD.

Additional information

Received in revised form: 27 March 2006

Rights and permissions

Reprints and permissions

About this article

Cite this article

Audoin, B., Davies, G., Finisku, L. et al. Localization of grey matter atrophy in early RRMS. J Neurol 253, 1495–1501 (2006). https://doi.org/10.1007/s00415-006-0264-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-006-0264-2

Keywords

Search

Navigation