Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Spinal cord MRI in multiple sclerosis—diagnostic, prognostic and clinical value

Nature Reviews Neurology volume 11, pages 327–338 (2015)Cite this article

Subjects

Key Points

  • Spinal cord MRI in multiple sclerosis (MS) has both diagnostic and prognostic value

  • Spinal cord MRI should be performed in patients with suspected demyelination who present with a partial myelitis and/or whose brain scan(s) do not fulfil the criteria for dissemination in space and time

  • A combination of both sagittal and axial MRI sequences should be performed to improve identification of focal lesions and diffuse abnormalities

  • Longitudinal studies of quantitative spinal cord MRI are required to further elucidate the pathological processes underlying disease progression in MS

  • Future trials of experimental disease-modifying treatments in MS should include both brain and spinal cord imaging

  • Spinal cord atrophy, reflecting axonal loss, could now be considered to be a potential endpoint to MS clinical trials

Abstract

Multiple sclerosis (MS) is an inflammatory disorder of the CNS that affects both the brain and the spinal cord. MRI studies in MS focus more often on the brain than on the spinal cord, owing to the technical challenges in imaging this smaller, mobile structure. However, spinal cord abnormalities at disease onset have important implications for diagnosis and prognosis. Furthermore, later in the disease course, in progressive MS, myelopathy becomes the primary characteristic of the clinical presentation, and extensive spinal cord pathology—including atrophy, diffuse abnormalities and numerous focal lesions—is common. Recent spinal cord imaging studies have employed increasingly sophisticated techniques to improve detection and quantification of spinal cord lesions, and to elucidate their relationship with physical disability. Quantitative MRI measures of cord size and tissue integrity could be more sensitive to the axonal loss and other pathological processes in the spinal cord than is conventional MRI, putting quantitative MRI in a key role to elucidate the association between disability and spinal cord abnormalities seen in people with MS. In this Review, we summarize the most recent MS spinal cord imaging studies and discuss the new insights they have provided into the mechanisms of neurological impairment. Finally, we suggest directions for further and future research.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Spinal cord lesions in progressive multiple sclerosis.
Figure 2: Axial images of the upper cervical cord lesions.
Figure 3: Sagittal images of the cervical spinal cord lesions.
Figure 4: Quantification of spinal cord area.
Figure 5: An overview of spinal cord atrophy in MS.

Similar content being viewed by others

References

  1. Kidd, D. et al. Spinal cord MRI using multi-array coils and fast spin echo. II. Findings in multiple sclerosis. Neurology 43, 2632–2637 (1993).

    Article  CAS  PubMed  Google Scholar 

  2. McDonald, I. & Compston, A. McAlpine's Multiple Sclerosis 287–342 (Elsevier, 2006).

    Book  Google Scholar 

  3. Bot, J. C. et al. Spinal cord abnormalities in recently diagnosed MS patients. Added value of spinal MRI examination. Neurology 62, 226–233 (2004).

    Article  CAS  PubMed  Google Scholar 

  4. Lycklama à Nijeholt, G. J. et al. Brain and spinal cord abnormalities in multiple sclerosis: correlation between MRI parameters, clinical subtypes and symptoms. Brain 121, 687–697 (1998).

    Article  Google Scholar 

  5. Barkhof, F. The clinico–radiological paradox in multiple sclerosis revisited. Curr. Opin. Neurol. 15, 239–245 (2002).

    Article  PubMed  Google Scholar 

  6. Bergers, E. et al. Axonal damage in the spinal cord of MS patients occurs largely independent of T2 MRI lesions. Neurology 59, 1766–1771 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Bergers, E. et al. Diffuse signal abnormalities in the spinal cord in multiple sclerosis: direct postmortem in situ magnetic resonance imaging correlated with in vitro high-resolution magnetic resonance imaging and histopathology. Ann. Neurol. 51, 652–656 (2002).

    Article  PubMed  Google Scholar 

  8. Weier, K. et al. Biplanar MRI for the assessment of the spinal cord in multiple sclerosis. Mult. Scler. 18, 1560–1569 (2012).

    Article  PubMed  Google Scholar 

  9. Stroman, P. W. et al. The current state-of-the-art of spinal cord imaging: methods. Neuroimage 84, 1070–1081 (2014).

    Article  CAS  PubMed  Google Scholar 

  10. Losseff, N. A. et al. Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression. Brain 119, 701–708 (1996).

    Article  PubMed  Google Scholar 

  11. Kremenchutzky, M., Rice, G. P., Baskerville, J., Wingerchuck, D. M. & Ebers, G. C. The natural history of multiple sclerosis: a geographically based study 9: observations on the progressive phase of the disease. Brain 129, 584–594 (2006).

    Article  CAS  PubMed  Google Scholar 

  12. Kalkers, N. F., Barkhof, F., Bergers E, van Schijndel, R. & Polman, C. H. The effect of the neuroprotective agent riluzole on MRI parameters in primary progressive multiple sclerosis: a pilot study. Mult. Scler. 8, 532–533 (2002).

    Article  CAS  PubMed  Google Scholar 

  13. Wheeler-Kingshott, C. A. et al. The current state-of-the-art of spinal cord imaging: applications. Neuroimage 84, 1082–1093 (2014).

    Article  CAS  PubMed  Google Scholar 

  14. Oh, J. et al. Multiparametric MRI correlates of sensorimotor function in the spinal cord in multiple sclerosis. Mult. Scler. 19, 427–435 (2013).

    Article  PubMed  Google Scholar 

  15. Zackowski, K. M. et al. Sensorimotor dysfunction in multiple sclerosis and column-specific magnetisation transfer-imaging abnormalities in the spinal cord. Brain 132, 1200–1209 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Polman, C. H. et al. Diagnostic criteria for multiple sclerosis: revisions to the McDonald criteria. Ann. Neurol. 69, 292–302 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Thorpe, J. W. et al. Serial gadolinium-enhanced MRI of the brain and spinal cord in early relapsing remitting multiple sclerosis. Neurology 46, 373–378 (1996).

    Article  CAS  PubMed  Google Scholar 

  18. O'Riordan, J. I. et al. Asymptomatic spinal cord lesions in clinically isolated optic nerve, brain stem and spinal cord syndromes suggestive of demyelination. J. Neurol. Neurosurg. Psychiatry 64, 353–357 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Miller, D. H. et al. Differential diagnosis of suspected multiple sclerosis: a consensus approach. Mult. Scler. 14, 1157–1174 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bot, J. C. et al. Differentiation of multiple sclerosis from other inflammatory disorders and cerebrovascular disease: value of spinal MR imaging. Radiology 223, 46–56 (2002).

    Article  PubMed  Google Scholar 

  21. Barkhof, F. Spinal cord MRI should always be performed in clinically isolated syndrome patients: yes. Mult. Scler. 20, 1688–1689 (2014).

    Article  PubMed  Google Scholar 

  22. Rovira, A. & Tintoré, M. Spinal cord MRI should always be performed in clinically isolated syndrome patients: no. Mult. Scler. 20, 1686–1687 (2014).

    Article  PubMed  Google Scholar 

  23. Theodoridou, A. & Settas, L. Demyelination in rheumatic diseases. J. Neurol. Neurosurg. Psychiatry 77, 290–295 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Lycklama à Nijeholt, G. J. et al. Post-mortem high resolution MRI of the spinal cord in multiple sclerosis: a correlative study with conventional MRI, histopathology and clinical phenotype. Brain 124, 154–166 (2001).

    Article  Google Scholar 

  25. Seewann, A. et al. Diffusely abnormal white matter in chronic multiple sclerosis: imaging and histopathologic analysis. Arch. Neurol. 66, 601–609 (2009).

    Article  PubMed  Google Scholar 

  26. Wingerchuk, D. M. et al. The spectrum of neuromyelitis optica. Lancet Neurol. 6, 805–815 (2007).

    Article  CAS  PubMed  Google Scholar 

  27. Wingerchuk, D. M. et al. Revised diagnostic criteria for neuromyelitis optica. Neurology 66, 1485–1489 (2006).

    Article  CAS  PubMed  Google Scholar 

  28. Flanagan, E. P. et al. Short myelitis lesions in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders. JAMA Neurol. 72, 81–87 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Lennon, V. A. et al. A serum antibody marker of neuromyelitis optica. Lancet 364, 2106–2112 (2004).

    Article  CAS  PubMed  Google Scholar 

  30. Kim, H. J. et al. MRI characteristics of neuromyelitis optica spectrum disorder: an international update. Neurology 84, 1165–1173 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Liu, Y. et al. Differential patterns of spinal cord and brain atrophy in NMO and MS. Neurology 84, 1465–1472 (2015).

    Article  PubMed  Google Scholar 

  32. Yonezu, T. et al. “Bright spotty lesions” on spinal magnetic resonance imaging differentiate neuromyelitis optica from multiple sclerosis. Mult. Scler. 20, 331–337 (2014).

    Article  PubMed  Google Scholar 

  33. Kearney, H., Miszkiel, K. A., Yiannakas, M. C., Ciccarelli, O. & Miller, D. H. A pilot study of white and grey matter involvement by multiple sclerosis spinal cord lesions. Mult. Scler. Relat. Disord. 2, 103–108 (2013).

    Article  CAS  PubMed  Google Scholar 

  34. Sombekke, M. H. et al. Spinal cord lesions in patients with clinically isolated syndrome: a powerful tool in diagnosis and prognosis. Neurology 80, 69–75 (2013).

    Article  PubMed  Google Scholar 

  35. Swanton, J. K. et al. Early MRI in optic neuritis: the risk for disability. Neurology 72, 542–550 (2009).

    Article  CAS  PubMed  Google Scholar 

  36. Perumal, J. et al. Acute transverse myelitis with normal brain MRI: long-term risk of MS. J. Neurol. 255, 89–93 (2008).

    Article  PubMed  Google Scholar 

  37. Cordonnier, C. et al. Prospective study of patients presenting with acute partial transverse myelopathy. J. Neurol. 250, 1447–1452 (2003).

    Article  CAS  PubMed  Google Scholar 

  38. Sastre-Garriga, J. et al. Long-term clinical outcome of primary progressive MS: predictive value of clinical and MRI data. Neurology 65, 633–635 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Fog, T. Topographical distribution of plaques in the spinal cord of multiple sclerosis. Arch. Neurol. Psychiatry 63, 382–414 (1950).

    Article  Google Scholar 

  40. Oppenheimer, D. R. The cervical cord in multiple sclerosis. Neuropathol. Appl. Neurobiol. 4, 151–162 (1978).

    Article  CAS  PubMed  Google Scholar 

  41. White, M. L., Zhang, Y. & Healey, K. Cervical spinal cord multiple sclerosis: evaluation with 2D multi-echo recombined gradient echo MR imaging. J. Spinal Cord Med. 34, 93–98 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Ozturk, A. et al. Axial 3D gradient-echo imagingfor improved multiple sclerosis lesion detection in the cervical spinal cord at 3 T. Neuroradiology 55, 431–439 (2013).

    Article  PubMed  Google Scholar 

  43. Nair, G., Absinta, M. & Reich, D. S. Optimized T1-MPRAGE sequence for better visualization of spinal cord multiple sclerosis lesions at 3 T. AJNR Am. J. Neuroradiol. 34, 2215–2222 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Poonawalla, A. H., Hou, P., Nelson, F., Wolinski, J. S. & Narayana, P. A. Cervical spinal cord lesions in multiple sclerosis: T1-weighted inversion-recovery MR imaging with phase-sensitive reconstruction. Radiology 246, 258–264 (2008).

    Article  PubMed  Google Scholar 

  45. Philpott, C. & Brotchie, P. Comparison of MRI sequences for evaluation of multiple sclerosis of the cervical spinal cord at 3 T. Eur. J. Radiol. 80, 780–785 (2011).

    Article  PubMed  Google Scholar 

  46. Calabrese, M. et al. Detection of cortical inflammatory lesions by double inversion recovery magnetic resonance imaging in patients with multiple sclerosis. Arch. Neurol. 64, 1416–1422 (2007).

    Article  PubMed  Google Scholar 

  47. Riederer, I. et al. Double inversion recovery sequence of the cervical spinal cord in multiple sclerosis and related inflammatory diseases. AJNR Am. J. Neuroradiol. 36, 219–225 (2014).

    Article  PubMed  Google Scholar 

  48. Bot, J. C. et al. Comparison of a conventional cardiac-triggered dual spin-echo and a fast STIR sequence in detection of spinal cord lesions in multiple sclerosis. Eur. Radiol. 10, 753–758 (2000).

    Article  CAS  PubMed  Google Scholar 

  49. Sethi, V. et al. Improved detection of cortical MS lesions with phase-sensitive inversion recovery MRI. J. Neurol. Neurosurg. Psychiatry 83, 877–882 (2012).

    Article  PubMed  Google Scholar 

  50. Kearney, H. et al. Cervical cord lesion load is associated with disability independently from atrophy in MS. Neurology 84, 367–373 (2015).

    Article  PubMed  Google Scholar 

  51. Gilmore, C. P. et al. Spinal cord grey matter lesions in multiple sclerosis detected by post-mortem high field MR imaging. Mult. Scler. 15, 180–188 (2009).

    Article  CAS  PubMed  Google Scholar 

  52. Gilmore, C. P. et al. Spinal cord gray matter demyelination in multiple sclerosis: a novel pattern of residual plaque morphology. Brain Pathol. 16, 202–208 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Lovas, G., Szilágyi, N., Majtényi, K., Palkovits, M. & Komoly, S. Axonal changes in chronic demyelinated cervical spinal cord plaques. Brain 123, 308–317 (2000).

    Article  PubMed  Google Scholar 

  54. Ganter, P., Prince, C. & Esiri, M. M. Spinal cord axonal loss in multiple sclerosis: a post-mortem study. Neuropathol. Appl. Neurobiol. 25, 459–467 (1999).

    Article  CAS  PubMed  Google Scholar 

  55. Evangelou, N., DeLuca, G. C., Owens, T. & Esiri, M. M. Pathological study of spinal cord atrophy in multiple sclerosis suggests limited role of local lesions. Brain 128, 29–34 (2005).

    Article  CAS  PubMed  Google Scholar 

  56. Bot, J. C. et al. The spinal cord in multiple sclerosis: relationship of high-spatial-resolution quantitative MR imaging findings to histopathologic results. Radiology 233, 531–540 (2004).

    Article  PubMed  Google Scholar 

  57. Daams, M. et al. Mean upper cervical cord area (MUCCA) measurement in long standing multiple sclerosis: relation to brain findings and clinical disability. Mult. Scler. 20, 1860–1865 (2014).

    Article  PubMed  Google Scholar 

  58. Kearney, H. et al. Magnetic resonance imaging correlates of physical disability in relapse onset multiple sclerosis of long disease duration. Mult. Scler. 20, 72–80 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Oh, J. et al. Spinal cord normalization in multiple sclerosis. J. Neuroimaging 24, 577–584 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Healy, B. C. et al. Approaches to normalization of spinal cord volume: application to multiple sclerosis. J. Neuroimaging 22, e12–e19 (2012).

    Article  PubMed  Google Scholar 

  61. Biberacher, V. et al. Atrophy and structural variability of the upper cervical cord in early multiple sclerosis. Mult. Scler. http://dx.doi.org/10.1177/1352458514546514.

  62. Lukas, C. et al. Cervical spinal cord volume loss is related to clinical disability progression in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 86, 410–418 (2015).

    Article  PubMed  Google Scholar 

  63. De Stefano, N. et al. Assessing brain atrophy rates in a large population of untreated multiple sclerosis subtypes. Neurology 74, 1868–1876 (2010).

    Article  CAS  PubMed  Google Scholar 

  64. Kapoor, R. et al. Lamotrigine for neuroprotection in secondary progressive multiple sclerosis: a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Neurol. 9, 681–688 (2010).

    Article  CAS  PubMed  Google Scholar 

  65. Chataway, J. et al. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet 383, 2213–2221 (2014).

    Article  CAS  PubMed  Google Scholar 

  66. Lin, X., Tench, C. R., Turner, B., Blumhardt, L. D. & Constantinescu, C. S. 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 β-1a (Rebif) treatment trial. J. Neurol. Neurosurg. Psychiatry 74, 1090–1094 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gilmore, C. P. et al. Spinal cord neuronal pathology in multiple sclerosis. Brain Pathol. 19, 642–649 (2009).

    Article  PubMed  Google Scholar 

  68. Schlaeger, R. et al. Spinal cord gray matter atrophy correlates with multiple sclerosis disability. Ann. Neurol. 76, 568–580 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Tench, C. R., Morgan, P. S. & Constantinescu, C. S. Measurement of cervical spinal cord cross-sectional area by MRI using edge detection and partial volume correction. J. Magn. Reson. Imaging 18, 368–371 (2003).

    Article  Google Scholar 

  70. Horsfield, M. A. et al. Rapid semi-automatic segmentation of the spinal cord from the magnetic resonance images: application in multiple sclerosis. Neuroimage 50, 446–455 (2010).

    Article  PubMed  Google Scholar 

  71. Kearney, H. et al. Improved MRI quantification of spinal cord atrophy in multiple sclerosis. J. Magn. Reson. Imaging. 39, 617–623 (2014).

    Article  PubMed  Google Scholar 

  72. Rocca, M. A. et al. A multicenter assessment of cervical cord atrophy among MS clinical phenotypes. Neurology 76, 2096–2102 (2011).

    Article  CAS  PubMed  Google Scholar 

  73. Liptak, Z. et al. Medulla oblongata volume: a biomarker of spinal cord damage and disability in multiple sclerosis. AJNR Am. J. Neuroradiol. 29, 1465–1470 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Zheng, L. et al. Cervical cord area measurement using volumetric brain magnetic resonance imaging in multiple sclerosis. Mult. Scler. Relat. Disord. 4, 52–57 (2015).

    Article  Google Scholar 

  75. Valsasina, P. et al. Regional cervical cord atrophy and disability in multiple sclerosis: a voxel-based analysis. Radiology 266, 853–861 (2013).

    Article  PubMed  Google Scholar 

  76. Liu, W. et al. In vivo imaging of spinal cord atrophy in neuroinflammatory diseases. Ann. Neurol. 76, 370–378 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Rocca, M. A. et al. Voxel-wise mapping of cervical cord damage in multiple sclerosis patients with different clinical phenotypes. J. Neurol. Neurosurg. Psychiatry 84, 35–41 (2013).

    Article  PubMed  Google Scholar 

  78. Evangelou, N., DeLuca, G. C., Owens, T. & Esiri, M. M. Pathological study of spinal cord atrophy in multiple sclerosis suggests limited role of local lesions. Brain 128, 29–34 (2005).

    Article  CAS  PubMed  Google Scholar 

  79. Androdias, G. et al. Meningeal T cells associate with diffuse axonal loss in multiple sclerosis spinal cords. Ann. Neurol. 68, 465–476 (2010).

    Article  CAS  PubMed  Google Scholar 

  80. DeLuca, G. C. et al. Casting a light on multiple sclerosis heterogeneity: the role of HLA-DRB1 on spinal cord pathology. Brain 136, 1025–1034 (2013).

    Article  PubMed  Google Scholar 

  81. Dousset, V. et al. Experimental allergic encephalomyelitis and multiple sclerosis: lesion characterization with magnetization transfer imaging. Radiology 182, 483–491 (1992).

    Article  CAS  PubMed  Google Scholar 

  82. Mottershead, J. P. et al. High field MRI correlates of myelin content and axonal density in multiple sclerosis—a post-mortem study of the spinal cord. J. Neurol. 250, 1293–1301 (2003).

    Article  CAS  PubMed  Google Scholar 

  83. Bozzali, M. et al. Magnetization-transfer histogram analysis of the cervical cord in patients with multiple sclerosis. AJNR Am. J. Neuroradiol. 20, 1803–1808 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Filippi, M. et al. A conventional and magnetization transfer MRI study of the cervical cord in patients with MS. Neurology 54, 207–213 (2000).

    Article  CAS  PubMed  Google Scholar 

  85. Charil, A. et al. Cervical cord magnetization transfer ratio and clinical changes over 18 months in patients with relapsing-remitting multiple sclerosis: a preliminary study. Mult. Scler. 12, 662–665 (2006).

    Article  CAS  PubMed  Google Scholar 

  86. Rovaris, M. et al. Relative contributions of brain and cervical cord pathology to multiple sclerosis disability: a study with magnetisation transfer ratio histogram analysis. J. Neurol. Neurosurg. Psychiatry 69, 723–727 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Rovaris, M. et al. In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis. Brain 124, 2540–2549 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. Agosta, F., Pagani, E., Caputo, D. & Filippi, M. Associations between cervical cord gray matter damage and disability in patients with multiple sclerosis. Arch. Neurol. 64, 1302–1305 (2007).

    Article  PubMed  Google Scholar 

  89. Kearney, H. et al. Investigation of magnetization transfer ratio-derived pial and subpial abnormalities in the multiple sclerosis spinal cord. Brain 137, 2456–2468 (2014).

    Article  PubMed  Google Scholar 

  90. Le Bihan, D., Turner, R., Pekar, J. & Moonen, C. T. Diffusion and perfusion imaging by gradient sensitisation: design, strategy and significance. J. Magn. Reson. Imaging 1, 7–28 (1991).

    Article  CAS  PubMed  Google Scholar 

  91. Wilm, B. J. et al. Reduced field-of-view MRI using outer volume suppression for spinal cord diffusion imaging. Magn. Reson. Med. 57, 625–630 (2007).

    Article  CAS  PubMed  Google Scholar 

  92. Zollinger, L. V. et al. Using diffusion tensor imaging and immunofluorescent assay to evaluate the pathology of multiple sclerosis. J. Magn. Reson. Imaging 33, 557–564 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Klawiter, E. C. et al. Radial diffusivity predicts demyelination in ex vivo multiple sclerosis spinal cords. Neuroimage. 55, 1454–1460 (2011).

    Article  PubMed  Google Scholar 

  94. Oh, J. et al. Spinal cord quantitative MRI discriminates between disability levels in multiple sclerosis. Neurology 80, 540–547 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Valsasina, P. et al. Mean diffusivity and fractional anisotropy histogram analysis of the cervical cord in MS patients. Neuroimage 26, 822–828 (2005).

    Article  PubMed  Google Scholar 

  96. Benedetti, B. et al. A diffusion tensor MRI study of cervical cord damage in benign and secondary progressive multiple sclerosis patients. J. Neurol. Neurosurg. Psychiatry 81, 26–30 (2010).

    Article  CAS  PubMed  Google Scholar 

  97. Agosta, F. et al. Quantification of cervical cord pathology in primary progressive MS using diffusion tensor MRI. Neurology 64, 631–635 (2005).

    Article  CAS  PubMed  Google Scholar 

  98. Agosta, F. et al. In vivo assessment of cervical cord damage in MS patients: a longitudinal diffusion tensor MRI study. Brain 130, 2211–2219 (2007).

    Article  CAS  PubMed  Google Scholar 

  99. Théaudin, M. et al. Short-term evolution of spinal cord damage in multiple sclerosis: a diffusion tensor MRI study. Neuroradiology 54, 1171–1178 (2012).

    Article  PubMed  Google Scholar 

  100. Freund, P. et al. Recovery after spinal cord relapse in multiple sclerosis is predicted by radial diffusivity. Mult. Scler. 16, 1193–1202 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  101. Hesseltine, S. M. et al. Diffusion tensor imaging in multiple sclerosis: assessment of regional differences in the axial plane within normal-appearing cervical spinal cord. AJNR Am. J. Neuroradiol. 27, 1189–1193 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Naismith, R. T. et al. Spinal cord tract diffusion tensor imaging reveals disability substrate in demyelinating disease. Neurology 80, 2201–2209 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Kearney, H. et al. Spinal cord grey matter abnormalities are associated with secondary progression and physical disability in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry http://dx.doi.org/10.1136/jnnp-2014-308241.

  104. Toosy, A. T. et al. Voxel-based cervical spinal cord mapping of diffusion abnormalities in MS-related myelitis. Neurology 83, 1321–1325 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  105. Kendi, A. T., Tan, F. U., Kendi, M., Huvaj, S. & Tellioglu, S. MR spectroscopy of cervical spinal cord in patients with multiple sclerosis. Neuroradiology 46, 764–769 (2004).

    Article  PubMed  Google Scholar 

  106. Bjartmar, C., Kidd, G., Mörk, S., Rudick, R. & Trapp, B. D. Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann. Neurol. 48, 893–901 (2000).

    Article  CAS  PubMed  Google Scholar 

  107. Blamire, A. M., Cader, S., Lee, M., Palace, J. & Matthews, P. M. Axonal damage in the spinal cord of multiple sclerosis patients detected by magnetic resonance spectroscopy. Magn. Reson. Med. 58, 880–885 (2007).

    Article  CAS  PubMed  Google Scholar 

  108. Ciccarelli, O. et al. Spinal cord spectroscopy and diffusion-based tractography to assess acute disability in multiple sclerosis. Brain 130, 2220–2231 (2007).

    Article  CAS  PubMed  Google Scholar 

  109. Ciccarelli, O. et al. Spinal cord repair in MS: does mitochondrial metabolism play a role? Neurology 74, 721–727 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Bellenberg, B. et al. 1H-magnetic resonance spectroscopy in diffuse and focal cervical cord lesions in multiple sclerosis. Eur. Radiol. 23, 3379–3392 (2013).

    Article  PubMed  Google Scholar 

  111. Ciccarelli, O. et al. Low myo-inositol indicating astrocytic damage in case series of neuromyelitis optica. Ann. Neurol. 74, 301–305 (2013).

    CAS  PubMed  Google Scholar 

  112. Bates, S. E. et al. Inhibition of N-acetylaspartate production: implications for 1H MRS studies in vivo. Neuroreport 7, 1397–1400 (1996).

    Article  CAS  PubMed  Google Scholar 

  113. Solanky, B. S. et al. In vivo magnetic resonance spectroscopy detection of combined glutamate-glutamine in healthy upper cervical cord at 3 T. NMR Biomed. 26, 357–366 (2013).

    Article  CAS  PubMed  Google Scholar 

  114. Abdel-Aziz, K. et al. Age related changes in metabolite concentrations in the normal spinal cord. PLoS ONE 9, e105774 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Abdel-Aziz, K. et al. Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis. Brain http://dx.doi.org/10.1093/brain/awv086.

  116. Castillo, M., Smith, J. K. & Kwock, L. Correlation of myo-inositol levels and grading of cerebral astrocytomas. AJNR Am. J. Neuroradiol. 21, 1645–1649 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Ciccarelli, O. et al. Assessing neuronal metabolism in vivo by modeling imaging measures. J. Neurosci. 30, 15030–15033 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Agosta, F., Valsasina, P., Caputo, D., Stroman, P. W. & Filippi, M. Tactile-associated recruitment of the cervical cord is altered in patients with multiple sclerosis. Neuroimage 39, 1542–1548 (2008).

    Article  PubMed  Google Scholar 

  119. Agosta, F. et al. Evidence for enhanced functional activity of cervical cord in relapsing multiple sclerosis. Magn. Reson. Med. 59, 1035–1042 (2008).

    Article  CAS  PubMed  Google Scholar 

  120. Agosta, F. et al. Primary progressive multiple sclerosis: tactile-associated functional MR activity in the cervical spinal cord. Radiology 253, 209–215 (2009).

    Article  PubMed  Google Scholar 

  121. Valsasina, P. et al. Cervical cord functional MRI changes in relapse-onset MS patients. J. Neurol. Neurosurg. Psychiatry 81, 405–408 (2010).

    Article  CAS  PubMed  Google Scholar 

  122. Valsasina, P. et al. Cervical cord FMRI abnormalities differ between the progressive forms of multiple sclerosis. Hum. Brain Mapp. 33, 2072–2080 (2012).

    Article  PubMed  Google Scholar 

  123. Rocca, M. A. et al. Abnormal cervical cord function contributes to fatigue in multiple sclerosis. Mult. Scler. 18, 1552–1559 (2012).

    Article  CAS  PubMed  Google Scholar 

  124. Schmierer, K. et al. Diffusion tensor imaging of post mortem multiple sclerosis brain. Neuroimage. 35, 467–477 (2007).

    Article  PubMed  Google Scholar 

  125. Budde, M. D. et al. Axonal injury detected by in vivo diffusion tensor imaging correlates with neurological disability in a mouse model of multiple sclerosis. NMR Biomed. 21, 589–597 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Stroman, P. W., Tomanek, B., Krause, V., Frankenstein, U. N. & Malisza, K. L. Functional magnetic resonance imaging of the human brain based on signal enhancement by extravascular protons (SEEP fMRI). Magn. Reson. Med. 49, 433–439 (2003).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The NMR Research Unit at the Queen Square MS Centre is supported by the MS Society of Great Britain and Northern Ireland, and UCLH-UCL Biomedical Research Centre.

Author information

Authors and Affiliations

  1. NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, WC1E 6BT, London, UK

    Hugh Kearney, David H. Miller & Olga Ciccarelli

Authors
  1. Hugh Kearney
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David H. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olga Ciccarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.K. researched data for article and wrote the article. All authors provided substantial contribution to discussion of content and revieweing/editing of manuscript before submission.

Corresponding author

Correspondence to Hugh Kearney.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

A summary of studies of MS spinal cord lesion identification at 3 T MRI (DOC 49 kb)

Supplementary Table 2

A summary of the key papers on spinal cord atrophy in multiple sclerosis (DOC 33 kb)

Supplementary Table 3

A summary of studies investigating MS-associated NAA reduction in the spinal cord (DOC 45 kb)

Supplementary Table 4

A summary of fMRI studies investigating spinal cord activity in MS (DOC 47 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kearney, H., Miller, D. & Ciccarelli, O. Spinal cord MRI in multiple sclerosis—diagnostic, prognostic and clinical value. Nat Rev Neurol 11, 327–338 (2015). https://doi.org/10.1038/nrneurol.2015.80

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2015.80

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing