Advertisement

Atrophy

  • W. Rashid
  • D.T. Chard
  • D.H. Miller
Part of the Topics in Neuroscience book series (TOPNEURO)

Abstract

In this chapter we provide a brief overview of atrophy measurements in people with multiple sclerosis (MS). In particular we highlight the main findings from previous MRI studies, the main methodologies used to measure atrophy including their pros and cons, and the clinical relevance of such measures.

Keywords

Multiple Sclerosis Expand Disability Status Scale Brain Atrophy Primary Progressive Multiple Sclerosis Spinal Cord Atrophy 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Peterson JW, Bö L, Monk S et al (2001) Transected neuritis, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 50:389–400PubMedCrossRefGoogle Scholar
  2. 2.
    Bo L, Vedeler CA, Nyland H et al (2003) Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration. Mult Scler 9:323–331PubMedCrossRefGoogle Scholar
  3. 3.
    Brink BP, Veerhuis R, Breij EC et al (2005) The pathology of multiple sclerosis is location-dependent: no significant complement activation is detected in purely cortical lesions. J Neuropathol Exp Neurol 64:147–155PubMedGoogle Scholar
  4. 4.
    Brex PA, Jenkins R, Fox NC et al (2000) Detection of ventricular enlargement in patients at the earliest clinical stage of MS. Neurology 54:1689–1691PubMedGoogle Scholar
  5. 5.
    Dalton CM, Brex PA, Jenkins R et al (2002) Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis. J Neurol Neurosurg Psychiat 73:141–147PubMedCrossRefGoogle Scholar
  6. 6.
    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 127:1101–1107PubMedCrossRefGoogle Scholar
  7. 7.
    Ge Y, Grossman RI, Udupa JK et al (2000) Brain atrophy in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis: longitudinal quantitative analysis. Radiology 214:665–670PubMedGoogle Scholar
  8. 8.
    Bakshi R, Benedict RH, Bermel RA, Jacobs L (2001) Regional brain atrophy is associated with physical disability in multiple sclerosis: semiquantitative magnetic resonance imaging and relationship to clinical findings. J Neuroimaging 11:129–136PubMedCrossRefGoogle Scholar
  9. 9.
    Lin X, Blumhardt LD (2001) Inflammation and atrophy in multiple sclerosis: MRI associations with disease course. J Neurol Sci 189:99–104PubMedCrossRefGoogle Scholar
  10. 10.
    Kalkers NF, Ameziane N, Bot JC et al (2002) Longitudinal brain volume measurement in multiple sclerosis: rate of brain atrophy is independent of the disease subtype. Arch Neurol 59:1572–1576PubMedCrossRefGoogle Scholar
  11. 11.
    Turner B, Lin X, Calmon G et al (2003) Cerebral atrophy and disability in relapsingremitting and secondary progressive multiple sclerosis over four years. Mult Scler 9:21–27PubMedCrossRefGoogle Scholar
  12. 12.
    Pagani E, Rocca MA, Gallo A et al (2005) Regional brain atrophy evolves differently in patients with multiple sclerosis according to clinical phenotype. Am J Neuroradiol 26:341–346PubMedGoogle Scholar
  13. 13.
    Tedeschi G, Lavorgna L, Russo P et al (2005) Brain atrophy and lesion load in a large population of patients with multiple sclerosis. Neurology 65:280–285PubMedCrossRefGoogle Scholar
  14. 14.
    Chard DT, Griffin CM, Parker GJM et al (2002) Brain atrophy in clinically early relapsing-remitting multiple sclerosis. Brain 125:327–337PubMedCrossRefGoogle Scholar
  15. 15.
    Chard DT, Griffin CM, Rashid W et al (2004) Progressive grey matter atrophy in clinically early relapsing-remitting multiple sclerosis. Mult Scler 10:387–391PubMedGoogle Scholar
  16. 16.
    Tiberio M, Chard DT, Altmann DR et al (2005) Grey and white matter volume changes in early RRMS: a two-year longitudinal study. Neurology 65:1001–1007Google Scholar
  17. 17.
    Sailer M, Fischl B, Salat D et al (2003) Focal thinning of the cerebral cortex in multiple sclerosis. Brain 126:1734–1744PubMedCrossRefGoogle Scholar
  18. 18.
    Audoin B, Davies GR, Fishniku L et al (2006) Localization of grey matter atrophy in early RRMS: a longitudinal study. J Neurol 253:1495–1501PubMedCrossRefGoogle Scholar
  19. 19.
    Carone DA, Benedict RH, Dwyer MG et al (2006) Semi-automatic brain region extraction (SABRE) reveals superior cortical and deep gray matter atrophy in MS. NeuroImage 29:505–514PubMedCrossRefGoogle Scholar
  20. 20.
    Prinster A, Quarantelli M, Orefice G et al (2006) Grey matter loss in relapsing-remitting multiple sclerosis: a voxel-based morphometry study. NeuroImage 29:859–867PubMedCrossRefGoogle Scholar
  21. 21.
    Cifelli A, Arridge M, Jezzard P et al (2002) Thalamic neurodegeneration in multiple sclerosis. Ann Neurol 52:650–653PubMedCrossRefGoogle Scholar
  22. 22.
    Redmond IT, Barbosa S, Blumhardt LD, Roberts N (2000) Short-term ventricular volume changes on serial MRI in multiple sclerosis. Acta Neurol Scand 102:99–105PubMedCrossRefGoogle Scholar
  23. 23.
    Fox NC, Jenkins R, Leary SM et al (2000) Progressive cerebral atrophy in MS: a serial study using registered, volumetric MRI. Neurology 54:807–812PubMedGoogle Scholar
  24. 24.
    Dalton CM, Miszkiel KA, O’Connor PW et al (2006) Ventricular enlargement in MS: one-year change at various stages of disease. Neurology 66:693–698PubMedCrossRefGoogle Scholar
  25. 25.
    Benedict RH, Bruce JM, Dwyer MG et al (2006) Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis. Arch Neurol 63:1301–1306PubMedCrossRefGoogle Scholar
  26. 26.
    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 Psychiat 66:323–330PubMedGoogle Scholar
  27. 27.
    Rudick RA, Fisher E, Lee JC et al (2000) Brain atrophy in relapsing multiple sclerosis: relationship to relapses, EDSS and treatment with interferon beta-1a. Mult Scler 6:365–372PubMedGoogle Scholar
  28. 28.
    Zivadinov R, Locatelli L, Stival B et al (2003) Normalized regional brain atrophy measurements in multiple sclerosis. Neuroradiology 45:793–798PubMedCrossRefGoogle Scholar
  29. 29.
    Quarantelli M, Ciarmiello A, Morra VB et al (2003) Brain tissue volume changes in relaps-ing-remitting multiple sclerosis: correlation with lesion load. NeuroImage 18:360–366PubMedCrossRefGoogle Scholar
  30. 30.
    Sastre-Garriga J, Ingle GT, Chard DT et al (2004) Grey and white matter atrophy in early clinical stages of primary progressive multiple sclerosis. NeuroImage 22:353–359PubMedCrossRefGoogle Scholar
  31. 31.
    Filippi M, Rovaris M, Iannucci G et al (2000) Whole brain volume changes in patients with progressive MS treated with cladribine. Neurology 55:1714–1718PubMedGoogle Scholar
  32. 32.
    Paolillo A, Pozzilli C, Gasperini C et al (2000) Brain atrophy in relapsing-remitting multiple sclerosis: relationship with ‘black holes’, disease duration and clinical disability. J Neurol Sci 174:85–91PubMedCrossRefGoogle Scholar
  33. 33.
    Kalkers NF, Vrenken H, Uitdehaag BM et al (2002) Brain atrophy in multiple sclerosis: impact of lesions and of damage of whole brain tissue. Mult Scler 8:410–414PubMedCrossRefGoogle Scholar
  34. 34.
    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
  35. 35.
    Kassubek J, Tumani H, Ecker D et al (2003) Age-related brain parenchymal fraction is significantly decreased in young multiple sclerosis patients: quantitative MRI study. Neuroreport 14:427–430PubMedCrossRefGoogle Scholar
  36. 36.
    Simon JH (1999) From enhancing lesions to brain atrophy in relapsing MS. J Neuroimmunol 98:7–15PubMedCrossRefGoogle Scholar
  37. 37.
    Fisher E, Rudick RA, Simon JH et al (2002) Eight-year follow-up study of brain atrophy in patients with MS. Neurology 59:1412–1420PubMedGoogle Scholar
  38. 38.
    Chard DT, Brex PA, Ciccarelli O et al (2003) The longitudinal relation between brain lesion load and atrophy in multiple sclerosis: a 14 year follow up study. J Neurol Neurosurg Psychiat 74:1551–1554PubMedCrossRefGoogle Scholar
  39. 39.
    Dastidar P, Heinonen T, Lehtimaki T et al (1999) Volumes of brain atrophy and plaques correlated with neurological disability in secondary progressive multiple sclerosis. J Neurol Sci 165:36–42PubMedCrossRefGoogle Scholar
  40. 40.
    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 53:139–148PubMedGoogle Scholar
  41. 41.
    Fisher E, Rudick RA, Cutter G et al (2000) Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients. Mult Scler 6:373–377PubMedGoogle Scholar
  42. 42.
    Zivadonov R, Sepcic J, Nasuelli D et al (2001) A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 70:773–780CrossRefGoogle Scholar
  43. 43.
    Paolillo A, Pozzilli C, Giugni E et al (2002) A 6-year clinical and MRI follow-up study of patients with relapsing-remitting multiple sclerosis treated with interferon-beta. Eur J Neurol 9:645–655PubMedCrossRefGoogle Scholar
  44. 44.
    Bermel RA, Sharma J, Tjoa CW et al (2003) A semiautomated measure of wholebrain atrophy in multiple sclerosis. J Neurol Sci 208:57–65PubMedCrossRefGoogle Scholar
  45. 45.
    Locatelli L, Zivadinov R, Grop A, Zorzon M (2004) Frontal parenchymal atrophy measures in multiple sclerosis. Mult Scler 10:562–568PubMedCrossRefGoogle Scholar
  46. 46.
    Zivadinov R, Bakshi R (2004) Central nervous system atrophy and clinical status in multiple sclerosis. J Neuroimaging 14:27S–35SPubMedCrossRefGoogle Scholar
  47. 47.
    Sanfilipo MP, Benedict RH, Sharma J et al (2005) The relationship between whole brain volume and disability in multiple sclerosis: a comparison of normalized gray vs. white matter with misclassification correction. NeuroImage 26:1068–1077PubMedCrossRefGoogle Scholar
  48. 48.
    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 128:1454–1460PubMedCrossRefGoogle Scholar
  49. 49.
    Sanfilipo MP, Benedict RH, Weinstock-Guttman B, Bakshi R (2006) Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis. Neurology 66:685–692PubMedCrossRefGoogle Scholar
  50. 50.
    Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452PubMedGoogle Scholar
  51. 51.
    Nijeholt GJ, van Walderveen MAA, Castelijns JA et al (1998) Brain and spinal cord abnormalities in multiple sclerosis: correlations between MRI parameters, clinical subtypes and symptoms. Brain 121:687–697PubMedCrossRefGoogle Scholar
  52. 52.
    Rashid W, Davies GR, Chard DT et al (2006) Increasing cord atrophy in early relapsing-remitting multiple sclerosis: a 3 year study. J Neurol Neurosurg Psychiat 77:51–55PubMedCrossRefGoogle Scholar
  53. 53.
    DeLuca GC, Williams K, Evangelou N et al (2006) The contribution of demyelination to axonal loss in multiple sclerosis. Brain 129:1507–1516PubMedCrossRefGoogle Scholar
  54. 54.
    Lin X, Tench CR, Evangelou N et al (2004) Measurement of spinal cord atrophy in multiple sclerosis. J Neuroimaging 14:20S–26SPubMedCrossRefGoogle Scholar
  55. 55.
    Bjartmar C, Kinkel RP, Kidd G et al (2001) Axonal loss in normal-appearing white matter in a patient with acute MS. Neurology 57:1248–1252PubMedGoogle Scholar
  56. 56.
    Oppenheimer DR (1978) The cervical cord in multiple sclerosis. Neuropathol Appl Neurobiol 4:151–162PubMedGoogle Scholar
  57. 57.
    Ganter P, Prince C, Esiri MM (1999) Spinal cord axonal loss in multiple sclerosis: a post-mortem study. Neuropathol Appl Neurobiol 25:459–467PubMedCrossRefGoogle Scholar
  58. 58.
    McGavern DB, Murray PD, Rivera-Quiñones C et al (2000) Axonal loss results in spinal cord atrophy, electrophysiological abnormalities and neurological deficits following demyelination in a chronic inflammatory model of multiple sclerosis. Brain 123:519–531PubMedCrossRefGoogle Scholar
  59. 59.
    Bjartmar C, Kidd G, Mörk S et al (2000) Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol 48:893–901PubMedCrossRefGoogle Scholar
  60. 60.
    Lovas G, Szilagyi N, Majtenyi K et al (2000) Axonal changes in chronic demyelinated cervical spinal cord plaques. Brain 123:308–317PubMedCrossRefGoogle Scholar
  61. 61.
    Nijeholt GJ, Bergers E, Kamphorst W et al (2001) Post-mortem high resolution MRI of the spinal cord in multiple sclerosis: a correlative study with conventional MRI, histopathology and clinical phenotype. Brain 124:154–166PubMedCrossRefGoogle Scholar
  62. 62.
    Bergers E, Bot JC, De Groot CJ et al (2002) Axonal damage in the spinal cord of MS patients occurs largely independent of T2 MRI lesions. Neurology 59:1766–1771PubMedGoogle Scholar
  63. 63.
    DeLuca GC, Ebers GC, Esiri MM (2004) Axonal loss in multiple sclerosis: a pathological survey of the corticospinal and sensory tracts. Brain 127:1009–1018PubMedCrossRefGoogle Scholar
  64. 64.
    Gilmore CP, DeLuca GC, Bö L et al (2005) Spinal cord atrophy in multiple sclerosis caused by white matter volume loss. Arch Neurol 62:1859–1862PubMedCrossRefGoogle Scholar
  65. 65.
    Gilmore CP, Bö L, Owens T et al (2006) Spinal cord gray matter demyelination in multiple sclerosis: a novel pattern of residual plaque morphology. Brain Pathol 16:202–208PubMedCrossRefGoogle Scholar
  66. 66.
    Kidd D, Thorpe JW, Thompson AJ et al (1993) Spinal cord MRI using multi-array coils and fast spin echo. II. Findings in multiple sclerosis. Neurology 43:2632–2637PubMedGoogle Scholar
  67. 67.
    Bot JC, Barkhof F, Polman CH et al (2004) Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination. Neurology 62:226–233PubMedGoogle Scholar
  68. 68.
    Lycklama à Nijeholt GJ, Barkhof F, Scheltens P et al (1997) MR of the spinal cord in multiple sclerosis: relation to clinical subtype and disability. Am J Neuroradiol 18:1041–1048PubMedGoogle Scholar
  69. 69.
    Thorpe JW, Kidd D, Moseley IF et al (1996) Serial gadolinium-enhanced MRI of the brain and spinal cord in early relapsing-remitting multiple sclerosis. Neurology 46:373–378PubMedGoogle Scholar
  70. 70.
    Losseff NA, Webb SL, O’Riordan JI et al (1996) Spinal cord atrophy and disability in multiple sclerosis: a new reproducible and sensitive MRI method with potential to monitor disease progression. Brain 119:701–708PubMedCrossRefGoogle Scholar
  71. 71.
    Filippi M, Campi A, Colombo B et al (1996) A spinal cord MRI study of benign and secondary progressive multiple sclerosis. J Neurol 243:502–505PubMedCrossRefGoogle Scholar
  72. 72.
    Filippi M, Colombo B, Rovaris M et al (1997) A longitudinal magnetic resonance imaging study of the cervical cord in multiple sclerosis. J Neuroimaging 7:78–80PubMedGoogle Scholar
  73. 73.
    Stevenson VL, Leary SM, Losseff NA et al (1998) Spinal cord atrophy and disability in MS: a longitudinal study. Neurology 51:234–238PubMedGoogle Scholar
  74. 74.
    Edwards SGM, Gong QY, Lui C et al (1999) Infratentorial atrophy on magnetic resonance imaging and disability in multiple sclerosis. Brain 122:291–301PubMedCrossRefGoogle Scholar
  75. 75.
    Rovaris M, Bozzali M, Santuccio G et al (2001) In vivo assessment of the brain and cervical cord pathology with primary progressive multiple sclerosis. Brain 124:2540–2549PubMedCrossRefGoogle Scholar
  76. 76.
    Vaithianathar L, Tench CR, Morgan PS, Constantinescu CS (2003) Magnetic resonance imaging of the cervical spinal cord in multiple sclerosis: a quantitative T1 relaxation time mapping approach. J Neurol 250:307–315PubMedCrossRefGoogle Scholar
  77. 77.
    Lin X, Tench CR, Turner B et al (2003) Spinal cord atrophy and disability in multiple sclerosis over four years: application of a reproducible automated technique in monitoring disease progression in a cohort of the interferon (*b-1a (Rebif) treatment trial. J Neurol Neurosurg Psychiatry 74:1090–1094PubMedCrossRefGoogle Scholar
  78. 78.
    Lin X, Blumhardt LD, Constantinescu CS (2003) The relationship of brain and cervical cord volume to disability in clinical subtypes of multiple sclerosis: a three-dimensional MRI study. Acta Neurol Scand 108:401–406PubMedCrossRefGoogle Scholar
  79. 79.
    Rashid W, Davies GR, Chard DT et al (2006) Upper cervical cord area in early relapsing-remitting multiple sclerosis: cross-sectional study of factors influencing cord size. J Magn Reson Imaging 23:473–476PubMedCrossRefGoogle Scholar
  80. 80.
    Beniek M, Altmann DR, Davies GR et al (2006) Cord atrophy separates early primary progressive and relapsing multiple sclerosis. J Neurol Neurosurg Psychiat 77:1036–1039CrossRefGoogle Scholar
  81. 81.
    Chard DT, Parker GJ, Griffin CM et al (2002) The reproducibility and sensitivity of brain tissue volume measurements derived from an SPM-based segmentation methodology. J Magn Reson Imaging 15:259–267PubMedCrossRefGoogle Scholar
  82. 82.
    Zivadinov R, Grop A, Sharma J et al (2005) Reproducibility and accuracy of quantitative magnetic resonance imaging techniques of whole-brain atrophy measurement in multiple sclerosis. J Neuroimaging 15:27–36PubMedCrossRefGoogle Scholar
  83. 83.
    Charil A, Dagher A, Lerch JP et al (2007) Focal cortical atrophy in multiple sclerosis: relation to lesion load and disability. NeuroImage 34:509–517PubMedCrossRefGoogle Scholar
  84. 84.
    Anderson VM, Fernando KT, Davies GR et al (2007) Cerebral atrophy measurement in clinically isolated syndromes and relapsing remitting multiple sclerosis: a comparison of registration-based methods. J Neuroimaging 17:61–68PubMedCrossRefGoogle Scholar
  85. 85.
    Lycklama G, Thompson A, Filippi M et al (2003) Spinal-cord MRI in multiple sclerosis. Lancet Neurol 2:555–562PubMedCrossRefGoogle Scholar
  86. 86.
    Coulon O, Hickman SJ, Parker GJ et al (2002) Quantification of spinal cord atrophy from magnetic resonance images via a B-spline active surface model. Magn Reson Med 47:1176–1185PubMedCrossRefGoogle Scholar
  87. 87.
    Tench CR, Morgan PS, Constantinescu CS (2005) Measurement of cervical spinal cord cross-sectional area by MRI using edge detection and partial volume correction. J Magn Reson Imaging 21:197–203PubMedCrossRefGoogle Scholar
  88. 88.
    Filippi M, Horsfield MA, Ader HJ et al (1998) Guidelines for using quantitative measures of brain magnetic resonance imaging abnormalities in monitoring the treatment of multiple sclerosis. Ann Neurol 43:499–506PubMedCrossRefGoogle Scholar
  89. 89.
    Kameyama T, Hashizume Y, Ando T, Takahashi A (1994) Morphometry of the normal cadaveric spinal cord. Spine 19:2077–2081PubMedCrossRefGoogle Scholar
  90. 90.
    Rudick RA, Fischer E, Lee J-C et al (1999) Use of brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Neurology 53:1698–1704PubMedGoogle Scholar
  91. 91.
    Hardmeier M, Freitag P, Wagenpfeil et al (2002) Short and long term brain volume changes after initiation of treatment with rIFN-beta-1A in multiple sclerosis (MS) J Neurol 249(Suppl1):20 (abstract)Google Scholar
  92. 92.
    Filippi M, Rovaris M, Inglese M et al and the ETOMS Study Group (2004) Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet 364:1489–1496PubMedCrossRefGoogle Scholar
  93. 93.
    Leary SM, Miller DH, Stevenson VL et al (2003) Interferon (*b-la in primary progressive MS: an exploratory, randomized, controlled trial. Neurology 60:44–51PubMedGoogle Scholar
  94. 94.
    Jones CK, Riddehough A, Li DKB et al (2001) MRI cerebral atrophy in relapsingremitting MS: results from the PRISMS trial. Neurology 56(Suppl3):A379Google Scholar
  95. 95.
    Gasperini C, Paolillo A, Giugni E et al (2002) MRI brain volume changes in relapsing-remitting multiple sclerosis patients treated with interferon beta-1a. Mult Scler 8:119–123PubMedCrossRefGoogle Scholar
  96. 96.
    Molyneux PD, Kappos L, Polman C et al (2000) The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. Brain 123:2256–2263PubMedCrossRefGoogle Scholar
  97. 97.
    Frank JA, Richert N, Bash C et al (2004) Interferon-(*b1b slows progression of atrophy in RRMS: three-year follow-up in NAb- and NAb+ patients. Neurology 62:719–725PubMedGoogle Scholar
  98. 98.
    Ge Y, Grossman RI, Udupa JK et al (2000) Glatiramer acetate (Copaxone) treatment in relapsing-remitting MS: quantitative MR assessment. Neurology 54:813–817PubMedGoogle Scholar
  99. 99.
    Wolinsky JS, Narayana PA, Johnson KP (2001) United States open-label glatiramer acetate extension trial for relapsing multiple sclerosis: MRI and clinical correlates. Copolymer 1 Multiple Sclerosis Study Group, MRI Analysis Center. Mult Scler 7:33–41PubMedGoogle Scholar
  100. 100.
    Sormani MP, Rovaris M, Valsasina P et al (2004) Measurement error of two different techniques for brain atrophy assessment in multiple sclerosis. Neurology 62:1432–1434PubMedGoogle Scholar
  101. 101.
    Kalkers NF, Barkhof F, Bergers E et al (2002) The effect of the neuroprotective agent riluzole on MRI parameters in primary progressive multiple sclerosis: a pilot study. Mult Scler 8:532–533PubMedCrossRefGoogle Scholar
  102. 102.
    Furby J, Hayton T, Smith KJ et al (2006) A randomised controlled trial of neuroprotection with lamotrigine in secondary progressive multiple sclerosis. Mult Scler 12 (S228):P794Google Scholar
  103. 103.
    Morgen K, Sammer G, Courtney SM et al (2006) Evidence for direct association between cortical atrophy and cognitive impairment in relapsing-remitting MS. Neuroimage 30:891–898PubMedCrossRefGoogle Scholar
  104. 104.
    Marrie RA, Fisher E, Miller DM et al (2005) Association of fatigue and brain atrophy in multiple sclerosis. J Neurol Sci 228:161–166PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2007

Authors and Affiliations

  • W. Rashid
    • 1
  • D.T. Chard
    • 1
  • D.H. Miller
    • 1
  1. 1.NMR Research Unit Department of Neuroinflammation Institute of NeurologyUniversity College LondonLondonUK

Personalised recommendations