Imaging Cerebral Grey Matter Volume in Multiple Sclerosis

  • N. De Stefano
Part of the Topics in Neuroscience book series (TOPNEURO)


Axonal and neuronal pathology have recently been increasingly regaining attention in multiple sclerosis (MS). There has been a shift in focus from considering functional impairment as primarily resulting from changes in the electrical conduction properties of axons after demyelination, towards an appreciation of the apparently primary role of neurodegeneration in the pathogenesis of this disease. Brain atrophy, which constantly occurs and progressively increases in MS patients, has greatly contributed to the development of this concept. As an expression of general tissue loss, brain atrophy is generally considered a global marker of adverse disease outcome. This seems to include, even in a primarily demyelinating disease such as MS, grey matter (GM) tissue abnormality. Accordingly, selective pathology in the cerebral GM has been shown in recent post-mortem [1–3] and in vivo [4–9] MS studies suggesting that neocortical pathology is more relevant in MS than previously thought.


Multiple Sclerosis White Matter Lesion Brain Atrophy Grey Matter Atrophy Brain Volume Loss 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kidd D, Barkhof F, McConnell R et al (1999) Cortical lesions in multiple sclerosis. Brain 122:17–26PubMedCrossRefGoogle Scholar
  2. 2.
    Peterson JW, Bö L, Mork S, Chang A, Trapp BD (2001) Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 50:389–400PubMedCrossRefGoogle Scholar
  3. 3.
    Cifelli A, Arridge M, Jezzard P et al (2002) Thalamic neurodegeneration in multiple sclerosis. Ann Neurol 52:650–653PubMedCrossRefGoogle Scholar
  4. 4.
    Sharma R, Narayana PA, Wolinsky JS (2001) Grey matter abnormalities in multiple sclerosis: proton magnetic resonance spectroscopic imaging. Mult Scler 7:221–226PubMedGoogle Scholar
  5. 5.
    Rovaris M, Bozzali M, Iannucci G et al (2002) Assessment of normal-appearing white and grey matter in patients with primary progressive multiple sclerosis: a diffusiontensor magnetic resonance imaging study. Arch Neurol 59:1406–1412PubMedCrossRefGoogle Scholar
  6. 6.
    Chard DT, Griffin CM, Parker GJ et al (2002) Brain atrophy in clinically early relapsing-remitting multiple sclerosis. Brain 125:327–337PubMedCrossRefGoogle Scholar
  7. 7.
    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 60:1157–1162PubMedCrossRefGoogle Scholar
  8. 8.
    Wylezinska M, Cifelli A, Jezzard P et al (2003) Thalamic neurodegeneration in relapsing-remitting multiple sclerosis. Neurology 60:1949–1954PubMedCrossRefGoogle Scholar
  9. 9.
    Cercignani M, Bozzali M, Iannucci G et al (2001) Magnetisation transfer ratio and mean diffusivity of normal appearing white and grey matter from patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 70:311–317PubMedCrossRefGoogle Scholar
  10. 10.
    Fox NC, Crum WR, Scahill RI et al (2001) Imaging of onset and progression of Alzheimer’s disease with voxel-compression mapping of serial magnetic resonance images. Lancet 358:201–205PubMedCrossRefGoogle Scholar
  11. 11.
    O’Brien JT, Paling S, Barber R et al (2001) Progressive brain atrophy on serial MRI in dementia with Lewy bodies, AD, and vascular dementia. Neurology 56:1386–1388PubMedCrossRefGoogle Scholar
  12. 12.
    De Stefano N, Iannucci G, Sormani MP et al (2002) MR correlates of cerebral atrophy in patients with multiple sclerosis. J Neurol 249:1072–1077PubMedCrossRefGoogle Scholar
  13. 13.
    Miller DH, Barkhof F, Frank JA et al (2002) Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance. Brain 125:1676–1695PubMedCrossRefGoogle Scholar
  14. 14.
    Losseff NA, Wang L, Lai HM et al (1996) Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. Brain 119:2009–2019PubMedCrossRefGoogle Scholar
  15. 15.
    Simon JH, Jacobs LD, Campion MK et al (1999) A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Neurology 53:139–148PubMedCrossRefGoogle Scholar
  16. 16.
    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 53:1698–1704PubMedCrossRefGoogle Scholar
  17. 17.
    Liu C, Edwards S, Gong Q et al (1999) Three dimensional MRI estimates of brain and spinal cord atrophy in multiple sclerosis. J Neurol Neurosurg Psychiatry 66:323–330PubMedCrossRefGoogle Scholar
  18. 18.
    Luks TL, Goodkin DE, Nelson SJ et al (2000) A longitudinal study of ventricular volume in early relapsing-remitting multiple sclerosis. Mult Scler 6:332–337PubMedGoogle Scholar
  19. 19.
    Fox NC, Jenkins R, Leary SM et al (2000) Progressive cerebral atrophy in MS: a serial study using registered, volumetric MRI. Neurology 54:807–812PubMedCrossRefGoogle Scholar
  20. 20.
    Brex PA, Jenkins R, Fox NC et al (2000) Detection of ventricular enlargement in patients at the earliest clinical stage of MS. Neurology 54:1689–1691PubMedCrossRefGoogle Scholar
  21. 21.
    Smith SM, De Stefano N, Jenkinson M, Matthews PM (2001) Normalized accurate measurement of longitudinal brain change. J Comput Assist Tomogr 25:466–475PubMedCrossRefGoogle Scholar
  22. 22.
    Freeborough PA, Fox NC (1997) The boundary shift integral: an accurate and robust measure of cerebral volume changes from registered repeat MRI. IEEE Trans Med Imaging 16:623–629PubMedCrossRefGoogle Scholar
  23. 23.
    Quarantelli M, Ciarmiello A, Morra VB et al (2003) Brain tissue volume changes in relapsing-remitting multiple sclerosis: correlation with lesion load. Neuroimage 18:360–366PubMedCrossRefGoogle Scholar
  24. 24.
    Smith SM, Zhang Y, Jenkinson M et al (2002) Accurate, robust and automated longitudinal and cross-sectional brain change analysis. Neuroimage 17:479–489PubMedCrossRefGoogle Scholar
  25. 25.
    Ge Y, Grossman RI, Udupa JK et al (2001) Brain atrophy in relapsing-remitting multiple sclerosis: fractional volumetric analysis of grey matter and white matter. Radiology 220:606–610PubMedCrossRefGoogle Scholar
  26. 26.
    Sailer M, Fischl B, Salat D et al (2003) Focal thinning of the cerebral cortex in multiple sclerosis. Brain 126:1734–1744PubMedCrossRefGoogle Scholar
  27. 27.
    Bakshi R, Dmochowski J, Shaikh ZA, Jacobs L (2001) Grey matter T2 hypointensity is related to plaques and atrophy in the brains of multiple sclerosis patients. J Neurol Sci 185:19–26PubMedCrossRefGoogle Scholar
  28. 28.
    Bakshi R, Benedict RH, Bermel RA et al (2002) T2 hypointensity in the deep grey matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study. Arch Neurol 59:62–68PubMedCrossRefGoogle Scholar
  29. 29.
    McDonald WI (1994) Rachelle Fishman-Matthew Moore Lecture. The pathological and clinical dynamics of multiple sclerosis. [Review.] J Neuropathol Exp Neurol 53:338–343PubMedCrossRefGoogle Scholar
  30. 30.
    Trapp BD, Ransohoff RM, Fisher E, Rudick RA (1999) Neurodegeneration in multiple sclerosis: relationship to neurological disability. Neuroscientist 5:48–57CrossRefGoogle Scholar
  31. 31.
    Rao SM, Leo GJ, Bernardin L, Unverzagt F (1991) Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 41:685–691PubMedCrossRefGoogle Scholar
  32. 32.
    Feinstein A, Youl B, Ron M (1992) Acute optic neuritis. A cognitive and magnetic resonance imaging study. Brain 115:1403–1415PubMedCrossRefGoogle Scholar
  33. 33.
    Thompson AJ, Polman CH, Miller DH et al (1997) Primary progressive multiple sclerosis. Brain 120:1085–1096PubMedCrossRefGoogle Scholar
  34. 34.
    Bruck W, Lucchinetti C, Lassmann H (2002) The pathology of primary progressive multiple sclerosis. Mult Scler 8:93–97PubMedCrossRefGoogle Scholar
  35. 35.
    Revesz T, Kidd D, Thompson AJ, Barnard RO, McDonald WI (1994) A comparison of the pathology of primary and secondary progressive multiple sclerosis. Brain 117:759–765PubMedCrossRefGoogle Scholar
  36. 36.
    Rovaris M, Bozzali M, Santuccio G et al (2001) In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis. Brain 124:2540–2549PubMedCrossRefGoogle Scholar
  37. 37.
    Amato MP, Ponziani G, Pracucci G et al (1995) Cognitive impairment in early-onset multiple sclerosis. Pattern, predictors, and impact on everyday life in a 4-year followup. Arch Neurol 52:168–172PubMedCrossRefGoogle Scholar
  38. 38.
    Rao SM, Leo GJ, Haughton VM et al (1989) Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis. Neurology 39:161–166PubMedCrossRefGoogle Scholar
  39. 39.
    Rovaris M, Filippi M, Falautano M et al (1998) Relation between MR abnormalities and patterns of cognitive impairment in multiple sclerosis. Neurology 50:1601–1608PubMedCrossRefGoogle Scholar
  40. 40.
    Lazeron RH, Langdon DW, Filippi M et al (2000) Neuropsychological impairment in multiple sclerosis patients: the role of (juxta)cortical lesion on FLAIR. Mult Scler 6:280–285.PubMedGoogle Scholar
  41. 41.
    Filippi M, Tortorella C, Rovaris M et al (2000) Changes in the normal appearing brain tissue and cognitive impairment in multiple sclerosis. J Neurol Neurosurg Psychiatry 68:157–161PubMedCrossRefGoogle Scholar
  42. 42.
    Trapp BD, Bö L, Mork S, Chang A (1999) Pathogenesis of tissue injury in MS lesions. J Neuroimmunol 98:49–56PubMedCrossRefGoogle Scholar
  43. 43.
    Rao SM, Bernardin L, Leo GJ et al (1989) Cerebral disconnection in multiple sclerosis. Relationship to atrophy of the corpus callosum. Arch Neurol 46:918–920PubMedCrossRefGoogle Scholar
  44. 44.
    Amato MP, Bartolozzi ML, Zipoli V et al (2004) Neocortical volume decrease in relapsing-remitting ms patients with mild cognitive impairment. Neurology (in press)Google Scholar
  45. 45.
    Ge Y, Grossman RI, Udupa JK et al (2001) Magnetization transfer ratio histogram analysis of grey matter in relapsing-remitting multiple sclerosis. AJNR Am J Neuroradiol 22:470–475PubMedGoogle Scholar
  46. 46.
    Bozzali M, Cercignani M, Sormani MP et al (2002) Quantification of brain grey matter damage in different MS phenotypes by use of diffusion tensor MR imaging. AJNR Am J Neuroradiol 23:985–988PubMedGoogle Scholar
  47. 47.
    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 248:131–138PubMedCrossRefGoogle Scholar
  48. 48.
    Sarchielli P, Presciutti O, Tarducci R et al (2002) Localized (1)H magnetic resonance spectroscopy in mainly cortical grey matter of patients with multiple sclerosis. J Neurol 249:902–910PubMedCrossRefGoogle Scholar
  49. 49.
    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 124:1813–1820PubMedCrossRefGoogle Scholar
  50. 50.
    Bjartmar C, Trapp BD (2001) Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences. Curr Opin Neurol 14:271–278PubMedCrossRefGoogle Scholar
  51. 51.
    Evangelou N, Esiri MM, Smith S, Palace J, Matthews PM (2000) Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis. Ann Neurol 47:391–395PubMedCrossRefGoogle Scholar
  52. 52.
    Garbern JY, Yool DA, Moore GJ et al (2002) Patients lacking the major CNS myelin protein, proteolipid protein 1, develop length-dependent axonal degeneration in the absence of demyelination and inflammation. Brain 125:551–561PubMedCrossRefGoogle Scholar
  53. 53.
    Meyer R, Weissert R, Diem R et al (2001) Acute neuronal apoptosis in a rat model of multiple sclerosis. J Neurosci 21:6214–6220PubMedGoogle Scholar
  54. 54.
    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 248:131–138PubMedCrossRefGoogle Scholar
  55. 55.
    Lumsden CE (1970) The neuropathology of multiple sclerosis. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology. North Holland and American Elsevier, Amsterdam and New York, pp 296–298Google Scholar
  56. 56.
    Rocca MA, Falini A, Colombo B et al (2002) Adaptive functional changes in the cerebral cortex of patients with nondisabling multiple sclerosis correlate with the extent of brain structural damage. Ann Neurol 51:330–339PubMedCrossRefGoogle Scholar
  57. 57.
    Cifelli A, Matthews PM (2002) Cerebral plasticity in multiple sclerosis: insights from fMRI. Mult Scler 8:193–199PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2004

Authors and Affiliations

  • N. De Stefano

There are no affiliations available

Personalised recommendations