Skip to main content
SpringerLink
Log in

Clinical Relevance of Brain Volume Measures in Multiple Sclerosis

  • Review Article
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Multiple sclerosis (MS) is a chronic disease with an inflammatory and neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in the disease course and may lead to irreversible neurological impairment. Changes in brain volume, observed from the earliest stage of MS and proceeding throughout the disease course, may be an accurate measure of neurodegeneration and tissue damage. There are a number of magnetic resonance imaging-based methods for determining global or regional brain volume, including cross-sectional (e.g. brain parenchymal fraction) and longitudinal techniques (e.g. SIENA [Structural Image Evaluation using Normalization of Atrophy]). Although these methods are sensitive and reproducible, caution must be exercised when interpreting brain volume data, as numerous factors (e.g. pseudoatrophy) may have a confounding effect on measurements, especially in a disease with complex pathological substrates such as MS. Brain volume loss has been correlated with disability progression and cognitive impairment in MS, with the loss of grey matter volume more closely correlated with clinical measures than loss of white matter volume. Preventing brain volume loss may therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In clinical practice, it may therefore be important to consider the potential impact of a therapy on reducing the rate of brain volume loss. This article reviews the measurement of brain volume in clinical trials and practice, the effect of DMTs on brain volume change across trials and the clinical relevance of brain volume loss in MS.

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

Similar content being viewed by others

References

  1. Compston A, Coles A. Multiple sclerosis. Lancet. 2002;359:1221–31.

    Article  PubMed  Google Scholar 

  2. Dutta R, Trapp BD. Mechanisms of neuronal dysfunction and degeneration in multiple sclerosis. Prog Neurobiol. 2011;93:1–12.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Young CA. Factors predisposing to the development of multiple sclerosis. QJM. 2011;104:383–6.

    Article  CAS  PubMed  Google Scholar 

  4. Siffrin V, Vogt J, Radbruch H, et al. Multiple sclerosis—candidate mechanisms underlying CNS atrophy. Trends Neurosci. 2010;33:202–10.

    Article  CAS  PubMed  Google Scholar 

  5. Bar-Or A. The immunology of multiple sclerosis. Semin Neurol. 2008;28:29–45.

    Article  PubMed  Google Scholar 

  6. Barten LJ, Allington DR, Procacci KA, et al. New approaches in the management of multiple sclerosis. Drug Des Devel Ther. 2010;4:343–66.

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Filippi M, Rocca MA, Barkhof F, et al. Association between pathological and MRI findings in multiple sclerosis. Lancet Neurol. 2012;11:349–60.

    Article  PubMed  Google Scholar 

  8. Filippi M, Rocca M. Preventing brain atrophy should be the gold standard of effective theraphy in MS (after the first year of treatment): no. Mult Scler. 2013;19:1005–6.

    Article  CAS  PubMed  Google Scholar 

  9. Rudick RA, Fisher E. Preventing brain atrophy should be the gold standard of effective therapy in MS (after the first year of treatment): yes. Mult Scler. 2013;19:1003–4.

    Article  PubMed  Google Scholar 

  10. Arnold D, De Stefano N. Preventing brain atrophy should be the gold standard of effective therapy in multiple sclerosis (after the first year of treatment): commentary. Mult Scler. 2013;19:1007–8.

    Article  CAS  PubMed  Google Scholar 

  11. Barkhof F, Calabresi PA, Miller DH, et al. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol. 2009;5:256–66.

    Article  PubMed  Google Scholar 

  12. Zivadinov R, Bakshi R. Central nervous system atrophy and clinical status in multiple sclerosis. J Neuroimaging. 2004;14(3 Suppl.):27S–35S.

    Article  PubMed  Google Scholar 

  13. Bermel RA, Bakshi R. The measurement and clinical relevance of brain atrophy in multiple sclerosis. Lancet Neurol. 2006;5:158–70.

    Article  PubMed  Google Scholar 

  14. Giorgio A, Battaglini M, Smith SM, et al. Brain atrophy assessment in multiple sclerosis: importance and limitations. Neuroimaging Clin N Am. 2008;18:675–86.

    Article  PubMed  Google Scholar 

  15. Zipp F. A new window in multiple sclerosis pathology: non-conventional quantitative magnetic resonance imaging outcomes. J Neurol Sci. 2009;287(Suppl 1):S24–9.

    Article  PubMed  Google Scholar 

  16. Enzinger C, Fazekas F, Matthews PM, et al. Risk factors for progression of brain atrophy in aging: six-year follow-up of normal subjects. Neurology. 2005;64:1704–11.

    Article  CAS  PubMed  Google Scholar 

  17. Zivadinov R, Weinstock-Guttman B, Hashmi K, et al. Smoking is associated with increased lesion volumes and brain atrophy in multiple sclerosis. Neurology. 2009;73:504–10.

    Article  CAS  PubMed  Google Scholar 

  18. Durand-Dubief F, Belaroussi B, Armspach JP, et al. Reliability of longitudinal brain volume loss measurements between 2 sites in patients with multiple sclerosis: comparison of 7 quantification techniques. Am J Neuroradiol. 2012;33:1918–24.

    Article  CAS  PubMed  Google Scholar 

  19. Rudick RA, Fisher E, Lee JC, et al. Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group. Neurology. 1999;53:1698–704.

    Article  CAS  PubMed  Google Scholar 

  20. Filippi M, Rovaris M, Inglese M, et al. 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. 2004;364:1489–96.

    Article  CAS  PubMed  Google Scholar 

  21. Kappos L, Freedman MS, Polman CH, et al. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. Lancet Neurol. 2009;8:987–97.

    Article  CAS  PubMed  Google Scholar 

  22. Molyneux PD, Kappos L, Polman C, et al. The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. European Study Group on Interferon beta-1b in secondary progressive multiple sclerosis. Brain. 2000;123(Pt 11):2256–63.

    Article  PubMed  Google Scholar 

  23. Sormani MP, Rovaris M, Valsasina P, et al. Measurement error of two different techniques for brain atrophy assessment in multiple sclerosis. Neurology. 2004;62:1432–4.

    Article  CAS  PubMed  Google Scholar 

  24. Comi G, Martinelli V, Rodegher M, et al. Effects of early treatment with glatiramer acetate in patients with clinically isolated syndrome. Mult Scler. 2013;19:1074–83.

    Article  PubMed  Google Scholar 

  25. Vidal-Jordana A, Sastre-Garriga J, Pérez-Miralles F, et al. Early brain pseudoatrophy while on natalizumab therapy is due to white matter volume changes. Mult Scler. 2013;19:1175–81.

    Article  PubMed  Google Scholar 

  26. Miller DH, Soon D, Fernando KT, et al. MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS. Neurology. 2007;68:1390–401.

    Article  CAS  PubMed  Google Scholar 

  27. Barkhof F, Hulst HE, Drulovic J, et al. Ibudilast in relapsing-remitting multiple sclerosis: a neuroprotectant? Neurology. 2010;74:1033–40.

    Article  CAS  PubMed  Google Scholar 

  28. Kappos L, Radue EW, O’Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362:387–401.

    Article  CAS  PubMed  Google Scholar 

  29. O’Connor P, Wolinsky JS, Confavreux C, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011;365:1293–303.

    Article  PubMed  Google Scholar 

  30. Comi G, Jeffery D, Kappos L, et al. Placebo-controlled trial of oral laquinimod for multiple sclerosis. N Engl J Med. 2012;366:1000–9.

    Article  CAS  PubMed  Google Scholar 

  31. Filippi M, Rocca MA, Pagani E, et al. Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage. J Neurol Neurosurg Psychiatry. Epub 12 Sep 2013.

  32. Vollmer TL, Soelberg Sorensen P, Arnold DL, et al. A placebo-controlled and active comparator phase III trial (BRAVO) for relapsing–remitting multiple sclerosis. ECTRIMS 2011. Abstract P148.

  33. Arnold DL, Gold R, Kappos L, et al. Effects of BG-12 on magnetic resonance imaging outcomes in the DEFINE study. CMSC 2012. Poster DX21.

  34. Miller D, Fox RJ, Phillips JT, et al. Effects of BG-12 on magnetic resonance imaging outcomes in CONFIRM (Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis), a randomized, placebo-controlled, phase 3 study. ENS 2012. O259.

  35. O’Connor P, Filippi M, Arnason B, et al. 250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol. 2009;8:889–97.

    Article  PubMed  Google Scholar 

  36. Hardmeier M, Wagenpfeil S, Freitag P, et al. Rate of brain atrophy in relapsing MS decreases during treatment with IFN beta-1a. Neurology. 2005;64:236–40.

    Article  CAS  PubMed  Google Scholar 

  37. Borges IT, Shea CD, Ohayon J, et al. The effect of daclizumab on brain atrophy in relapsing-remitting multiple sclerosis. Mult Scler Relat Disord. 2013;2:133–40.

    Article  PubMed  Google Scholar 

  38. Bendfeldt K, Egger H, Nichols TE, et al. Effect of immunomodulatory medication on regional gray matter loss in relapsing-remitting multiple sclerosis—a longitudinal MRI study. Brain Res. 2010;1325:174–82.

    Article  CAS  PubMed  Google Scholar 

  39. Khan O, Bao F, Shah M, et al. Effect of disease-modifying therapies on brain volume in relapsing-remitting multiple sclerosis: results of a five-year brain MRI study. J Neurol Sci. 2012;312:7–12.

    Article  PubMed  Google Scholar 

  40. Portaccio E, Stromillo ML, Goretti B, et al. Natalizumab may reduce cognitive changes and brain atrophy rate in relapsing-remitting multiple sclerosis: a prospective, non-randomized pilot study. Eur J Neurol. 2013;20:986–90.

    Article  CAS  PubMed  Google Scholar 

  41. CAMMS223 Trial Investigators, Coles AJ, Compston DA, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008;359:1786–801.

  42. Coles AJ, Twyman CL, Arnold DL, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380:1829–39.

    Article  CAS  PubMed  Google Scholar 

  43. Cohen JA, Coles AJ, Arnold DL, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380:1819–28.

    Article  CAS  PubMed  Google Scholar 

  44. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362:402–15.

    Article  CAS  PubMed  Google Scholar 

  45. Takao H, Hayashi N, Ohtomo K. A longitudinal study of brain volume changes in normal aging. Eur J Radiol. 2012;81:2801–4.

    Article  PubMed  Google Scholar 

  46. Sidaros A, Skimminge A, Liptrot MG, et al. Long-term global and regional brain volume changes following severe traumatic brain injury: a longitudinal study with clinical correlates. Neuroimage. 2009;44:1–8.

    Article  PubMed  Google Scholar 

  47. Scahill RI, Frost C, Jenkins R, et al. A longitudinal study of brain volume changes in normal aging using serial registered magnetic resonance imaging. Arch Neurol. 2003;60:989–94.

    Article  PubMed  Google Scholar 

  48. Hedman AM, van Haren NE, Schnack HG, et al. Human brain changes across the life span: a review of 56 longitudinal magnetic resonance imaging studies. Hum Brain Mapp. 2012;33:1987–2002.

    Article  PubMed  Google Scholar 

  49. Giorgio A, Stromillo ML, Bartolozzi ML, et al. Ten-year brain atrophy and disability changes in multiple sclerosis. AAN 2012. Poster P065.

  50. De Stefano N, Giorgio A, Battaglini M, et al. Assessing brain atrophy rates in a large population of untreated multiple sclerosis subtypes. Neurology. 2010;74:1868–76.

    Article  PubMed  Google Scholar 

  51. Fisher E, Lee JC, Nakamura K, et al. Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol. 2008;64:255–65.

    Article  PubMed  Google Scholar 

  52. Simon JH. Brain atrophy in multiple sclerosis: what we know and would like to know. Mult Scler. 2006;12:679–87.

    Article  CAS  PubMed  Google Scholar 

  53. Minneboo A, Jasperse B, Barkhof F, et al. Predicting short-term disability progression in early multiple sclerosis: added value of MRI parameters. J Neurol Neurosurg Psychiatry. 2008;79:917–23.

    Article  CAS  PubMed  Google Scholar 

  54. Amato MP, Portaccio E, Goretti B, et al. Association of neocortical volume changes with cognitive deterioration in relapsing-remitting multiple sclerosis. Arch Neurol. 2007;64:1157–61.

    Article  PubMed  Google Scholar 

  55. Fisniku LK, Altmann DR, Cercignani M, et al. Magnetization transfer ratio abnormalities reflect clinically relevant grey matter damage in multiple sclerosis. Mult Scler. 2009;15:668–77.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Filippi M, Rocca MA. MR imaging of multiple sclerosis. Radiology. 2011;259:659–81.

    Article  PubMed  Google Scholar 

  57. Zivadinov R, Havrdová E, Bergsland N, et al. Thalamic atrophy is associated with development of clinically definite multiple sclerosis. Radiology. 2013;268:831–41.

    Article  PubMed  Google Scholar 

  58. Popescu V, Agosta F, Hulst HE, et al. Brain atrophy and lesion load predict long term disability in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013;84:1082–91.

    Article  PubMed  Google Scholar 

  59. Zivadinov R, Bergsland N, Dolezal O, et al. Evolution of cortical and thalamus atrophy and disability progression in early relapsing-remitting MS during 5 years. Am J Neuroradiol. 2013;34:1931–9.

    Article  CAS  PubMed  Google Scholar 

  60. Fisniku LK, Chard DT, Jackson JS, et al. Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol. 2008;64:247–54.

    Article  PubMed  Google Scholar 

  61. Sanfilipo MP, Benedict RH, Sharma J, et al. The relationship between whole brain volume and disability in multiple sclerosis: a comparison of normalized gray vs. white matter with misclassification correction. Neuroimage. 2005;26:1068–77.

    Article  PubMed  Google Scholar 

  62. Fisher E, Rudick RA, Cutter G, et al. Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients. Mult Scler. 2000;6:373–7.

    CAS  PubMed  Google Scholar 

  63. Shiee N, Bazin PL, Zackowski KM, et al. Revisiting brain atrophy and its relationship to disability in multiple sclerosis. PLoS One. 2012;7:e37049.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Lansley J, Mataix-Cols D, Grau M, et al. Localized grey matter atrophy in multiple sclerosis: a meta-analysis of voxel-based morphometry studies and associations with functional disability. Neurosci Biobehav Rev. 2013;37:819–30.

    Article  CAS  PubMed  Google Scholar 

  65. Zivadinov R, Tekwe C, Bergsland N, et al. Bimonthly evolution of cortical atrophy in early relapsing–remitting multiple sclerosis over 2 years: a longitudinal study. Mult Scler Int. 2013;2013:231345.

    PubMed Central  PubMed  Google Scholar 

  66. Fisher E, Rudick RA, Simon JH, et al. Eight-year follow-up study of brain atrophy in patients with MS. Neurology. 2002;59:1412–20.

    Article  CAS  PubMed  Google Scholar 

  67. Brex PA, Jenkins R, Fox NC, et al. Detection of ventricular enlargement in patients at the earliest clinical stage of MS. Neurology. 2000;54:1689–91.

    Article  CAS  PubMed  Google Scholar 

  68. Dalton CM, Brex PA, Jenkins R, et al. Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2002;73:141–7.

    Article  CAS  PubMed  Google Scholar 

  69. Pérez-Miralles F, Sastre-Garriga J, Tintoré M, et al. Clinical impact of early brain atrophy in clinically isolated syndromes. Mult Scler. 2013;19:1878–86.

    Article  PubMed  Google Scholar 

  70. Ingle GT, Stevenson VL, Miller DH, et al. Two-year follow-up study of primary and transitional progressive multiple sclerosis. Mult Scler. 2002;8:108–14.

    Article  CAS  PubMed  Google Scholar 

  71. Rudick RA, Fisher E, Lee JC, et al. Brain atrophy in relapsing multiple sclerosis: relationship to relapses, EDSS, and treatment with interferon beta-1a. Mult Scler. 2000;6:365–72.

    CAS  PubMed  Google Scholar 

  72. Lavorgna L, Bonavita S, Ippolito D, et al. Clinical and magnetic resonance imaging predictors of disease progression in multiple sclerosis: a nine-year follow-up study. Mult Scler. Epub 9 Jul 2013.

  73. Kearney H, Rocca M, Valsasina P, et al. Magnetic resonance imaging correlates of physical disability in relapse onset multiple sclerosis of long disease duration. Mult Scler. 2014;20:72–80.

    Article  CAS  PubMed  Google Scholar 

  74. Rocca MA, Valsasina P, Damjanovic D, et al. Voxel-wise mapping of cervical cord damage in multiple sclerosis patients with different clinical phenotypes. J Neurol Neurosurg Psychiatry. 2013;84:35–41.

    Article  PubMed  Google Scholar 

  75. Lukas C, Sombekke MH, Bellenberg B, et al. Relevance of spinal cord abnormalities to clinical disability in multiple sclerosis: MR imaging findings in a large cohort of patients. Radiology. 2013;269:542–52.

    Article  PubMed  Google Scholar 

  76. Valsasina P, Rocca MA, Horsfield MA, et al. Regional cervical cord atrophy and disability in multiple sclerosis: a voxel-based analysis. Radiology. 2013;266:853–61.

    Article  PubMed  Google Scholar 

  77. Lukas C, Minneboo A, de Groot V, et al. Early central atrophy rate predicts 5 year clinical outcome in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2010;81:1351–6.

    Article  PubMed  Google Scholar 

  78. Horakova D, Dwyer MG, Havrdova E, et al. Gray matter atrophy and disability progression in patients with early relapsing-remitting multiple sclerosis: a 5-year longitudinal study. J Neurol Sci. 2009;282:112–9.

    Article  PubMed  Google Scholar 

  79. Rocca MA, Mesaros S, Pagani E, et al. Thalamic damage and long-term progression of disability in multiple sclerosis. Radiology. 2010;257:463–9.

    Article  PubMed  Google Scholar 

  80. Filippi M, Preziosa P, Copetti M, et al. Gray matter damage predicts the accumulation of disability 13 years later in MS. Neurology. 2013;81:1759–67.

    Article  PubMed  Google Scholar 

  81. Covey TJ, Zivadinov R, Shucard JL, et al. Information processing speed, neural efficiency, and working memory performance in multiple sclerosis: differential relationships with structural magnetic resonance imaging. J Clin Exp Neuropsychol. 2011;33:1129–45.

    Article  PubMed  Google Scholar 

  82. Nocentini U, Bozzali M, Spanó B, et al. Exploration of the relationships between regional grey matter atrophy and cognition in multiple sclerosis. Brain Imaging Behav. Epub 15 May 2012.

  83. Benedict RH, Hulst HE, Bergsland N, et al. Clinical significance of atrophy and white matter mean diffusivity within the thalamus of multiple sclerosis patients. Mult Scler. 2013;19:1478–84.

    Article  PubMed  Google Scholar 

  84. Deloire MS, Ruet A, Hamel D, et al. MRI predictors of cognitive outcome in early multiple sclerosis. Neurology. 2011;76:1161–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Calabrese M, Rinaldi F, Grossi P, et al. Cortical pathology and cognitive impairment in multiple sclerosis. Expert Rev Neurother. 2011;11:425–32.

    Article  PubMed  Google Scholar 

  86. Sicotte NL, Kern KC, Giesser BS, et al. Regional hippocampal atrophy in multiple sclerosis. Brain. 2008;131:1134–41.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  88. Hulst HE, Steenwijk MD, Versteeg A, et al. Cognitive impairment in MS: impact of white matter integrity, gray matter volume, and lesions. Neurology. 2013;80:1025–32.

    Article  CAS  PubMed  Google Scholar 

  89. Rossi F, Giorgio A, Battaglini M, et al. Relevance of brain lesion location to cognition in relapsing multiple sclerosis. PLoS One. 2012;7:e44826.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Kapoor R, Furby J, Hayton T, et al. Lamotrigine for neuroprotection in secondary progressive multiple sclerosis: a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Neurol. 2010;9:681–8.

    Article  CAS  PubMed  Google Scholar 

  91. Zivadinov R, Reder AT, Filippi M, et al. Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis. Neurology. 2008;71:136–44.

    Article  CAS  PubMed  Google Scholar 

  92. Gauthier SA, Berger AM, Liptak Z, et al. Rate of brain atrophy in benign vs early multiple sclerosis. Arch Neurol. 2009;66:234–7.

    Article  PubMed  Google Scholar 

  93. Romero JR, Vasan RS, Beiser AS, et al. Association of matrix metalloproteinases with MRI indices of brain ischemia and aging. Neurobiol Aging. 2010;31:2128–35.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  94. Bernal F, Elias B, Hartung HP, et al. Regulation of matrix metalloproteinases and their inhibitors by interferon-beta: a longitudinal study in multiple sclerosis patients. Mult Scler. 2009;15:721–7.

    Article  CAS  PubMed  Google Scholar 

  95. Debette S, Seshadri S, Beiser A, et al. Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline. Neurology. 2011;77:461–8.

    Article  CAS  PubMed  Google Scholar 

  96. Sumowski JF, Rocca MA, Leavitt VM, et al. Brain reserve and cognitive reserve in multiple sclerosis: what you’ve got and how you use it. Neurology. 2013;80:2186–93.

    Article  CAS  PubMed  Google Scholar 

  97. Amato MP, Razzolini L, Goretti B, et al. Cognitive reserve and cortical atrophy in multiple sclerosis: a longitudinal study. Neurology. 2013;80:1728–33.

    Article  PubMed  Google Scholar 

  98. Feinstein A, Lapshin H, O’Connor P, et al. Sub-threshold cognitive impairment in multiple sclerosis: the association with cognitive reserve. J Neurol. 2013;260:2256–61.

    Article  PubMed  Google Scholar 

  99. Booth AJ, Rodgers JD, Schwartz CE, et al. Active cognitive reserve influences the regional atrophy to cognition link in multiple sclerosis. J Int Neuropsychol Soc. 2013;19:1128–33.

    Article  PubMed  Google Scholar 

  100. Zivadinov R. Steroids and brain atrophy in multiple sclerosis. J Neurol Sci. 2005;233:73–81.

    Article  CAS  PubMed  Google Scholar 

  101. Barkhof F, Simon JH, Fazekas F, et al. MRI monitoring of immunomodulation in relapse-onset multiple sclerosis trials. Nat Rev Neurol. 2011;8:13–21.

    Article  PubMed  Google Scholar 

  102. Sormani MP, Arnold DL, De Stefano N. Treatment effect on brain atrophy correlates with treatment effect on disability in multiple sclerosis. Ann Neurol. Epub 5 Sep 2013.

Download references

Acknowledgments

Editorial assistance was provided by Daniel Johnson and Katrin Schulz of Health Interactions, which included developing the outline and first draft of the manuscript under the guidance of the corresponding author and collecting and incorporating comments from all authors. This assistance was exclusively funded by Novartis Pharma AG.

Conflict of interest

Dr. De Stefano has served on scientific advisory boards and steering committees of clinical trials for Merck Serono S.A., Teva and Novartis Pharma AG, and has received support for congress participation or speaker honoraria from Biogen Idec, Novartis Pharma AG, Sanofi-Aventis and Teva. He has also received speaker honoraria from Biogen Idec, Merck Serono S.A., Bayer-Schering AG, Teva, Sanofi-Aventis and Novartis Pharma AG.

Dr. Airas has been involved in contract research through agreements between the institution and the sponsor with Novartis, Roche, GE Healthcare, Biogen Idec and Merck Serono S.A. She has received support for congress participation or speaker honoraria from Biogen Idec, Novartis Pharma AG, Sanofi-Aventis, Teva, Merck Serono S.A. and Bayer-Schering AG.

Dr. Grigoriadis has received honoraria from Novartis Pharma AG as a member of the NeuroNet advisory board and as a speaker in scientific meetings organized by Novartis Pharma AG.

Dr. Mattle, or his institution, has received speaker and consulting fees and educational and research grants from AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme-Chibret, Novartis Pharma AG, Pfizer, Sanofi-Aventis, Schering AG, Merck, Servier, St. Jude Medical, Vifor Pharma, the Swiss Society of Hypertension, the Swiss Heart Foundation and the Swiss National Science Foundation.

Dr. O’Riordan has been involved in clinical trials as principal investigator with Novartis Pharma AG, Biogen Idec, Schering AG and Teva. He has also been guest lecturer and consultant advisor in medical advisory committees for Novartis Pharma AG, Biogen Idec, Schering AG and Teva.

Dr. Oreja-Guevara has received honoraria as consultant in scientific advisory boards by Bayer-Schering AG, Merck Serono S.A., Biogen Idec, Teva and Novartis Pharma AG and has also participated in clinical trials and other research projects promoted by Biogen Idec, GlaxoSmithKline, Teva and Novartis Pharma AG.

Dr. Sellebjerg has served on scientific advisory boards for Biogen Idec, Genzyme, Merck Serono S.A., Novartis Pharma AG, Sanofi-Aventis and Teva. He has also been on the steering committee of a clinical trial sponsored by Merck Serono S.A., and served as consultant for Biogen Idec and Novo Nordisk. He has received support for congress participation from Biogen Idec, Novartis Pharma AG, Sanofi-Aventis and Teva, and he has also received speaker honoraria from Bayer-Schering AG, Biogen Idec, Genzyme, Merck Serono S.A., Novartis Pharma AG, Sanofi-Aventis and Schering-Plough.

Dr. Stankoff has received lecture fees and served as consultant and on advisory boards for Biogen Idec, Teva, Novartis Pharma AG, Genzyme, Merck Serono S.A., Bayer-Schering AG and Sanofi-Aventis.

Dr. Walczak has received a consulting fee from Novartis Pharma AG for participation in a NeuroNet advisory board.

Dr. Wiendl has received personal compensation for activities with Bayer Healthcare, Biogen Idec/Elan, Sanofi-Aventis, EMD Serono, Teva Neurosciences and Novo Nordisk as a speaker or consultant or as research support. He has received grants and contracts from Bayer Vital, Biogen Idec, Merck Serono S.A., Novartis Pharma AG, Novo Nordisk and Sanofi-Aventis.

Dr. Kieseier has received honoraria for lecturing, travel expenses for attending meetings and financial support for research from Bayer HealthCare, Biogen Idec, Genzyme/Sanofi-Aventis, Grifols, Merck Serono S.A., Mitsubishi Europe, Novartis Pharma AG, Roche, Talecris Plasma Resources and Teva.

Author information

Authors and Affiliations

  1. Department of Medicine, Surgery and Neuroscience, University of Siena, Viale Bracci 2, Siena, 53100, Italy

    Nicola De Stefano

  2. Department of Neurology, Turku University Hospital, Turku, Finland

    Laura Airas

  3. B’ Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, Aristotle University of Thessaloniki, Macedonia, Greece

    Nikolaos Grigoriadis

  4. Department of Neurology, Inselspital, University of Bern, Bern, Switzerland

    Heinrich P. Mattle

  5. Department of Neurology, Ninewells Hospital and Medical School, University of Dundee, Tayside, UK

    Jonathan O’Riordan

  6. Department of Neurology, University Hospital San Carlos, IdISCC, Madrid, Spain

    Celia Oreja-Guevara

  7. Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Finn Sellebjerg

  8. Centre d’Investigation Clinique, AP-HP, Hôpital Pitié-Salpêtrière-UPMC, Paris, France

    Bruno Stankoff

  9. Katedra i Klinika Neurologii, Uniwersytet Medyczny w Łodzi, Lodz, Poland

    Agata Walczak

  10. Department of Neurology, University of Münster Albert-Schweitzer-Campus 1, Building A10 (previously Domagkstr. 13), 48149, Münster, Germany

    Heinz Wiendl

  11. Department of Neurology, Heinrich-Heine-University, Moorenstrasse 5, 40225, Düsseldorf, Germany

    Bernd C. Kieseier

Authors
  1. Nicola De Stefano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura Airas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nikolaos Grigoriadis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Heinrich P. Mattle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jonathan O’Riordan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Celia Oreja-Guevara
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Finn Sellebjerg
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bruno Stankoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Agata Walczak
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Heinz Wiendl
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Bernd C. Kieseier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicola De Stefano.

Rights and permissions

Reprints and permissions

About this article

Cite this article

De Stefano, N., Airas, L., Grigoriadis, N. et al. Clinical Relevance of Brain Volume Measures in Multiple Sclerosis. CNS Drugs 28, 147–156 (2014). https://doi.org/10.1007/s40263-014-0140-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40263-014-0140-z

Keywords

Search

Navigation