Brain, Vol. 119, No. 3, 701-708, 1996
© 1996 Guarantors of Brain
research-article |
Spinal cord atrophy and disability in multiple sclerosis
A new reproducible and sensitive MRI method with potential to monitor disease progression
NMR Research Unit, Institute of Neurology London
Correspondence to:
Correspondence to: Dr A. J. Thompson, NMR Research Unit, Institute of Neurology, Queen Square, London WC1N 3BG, UK
Recent MRI studies in multiple sclerosis have highlighted the potential importance of spinal cord atrophy (implicating axonal loss) in the development of disability. However, the techniques applied in these initial studies have poor reproducibility which limits their application in the serial monitoring of patients. The aim of this study was to develop a highly reproducible and accurate method for the quantification of atrophy. The technique we describe demonstrates an intra-observer coefficient of variation (scan-rescan) of only 0.8%. When applied to 60 patients with clinically definite multiple sclerosis there was a strong correlation between spinal cord area and disability measured by Kurtzke's Expanded Disability Status Scale(EDSS) (r = –0.7, P<<0.001). The correlation was graded providing evidence for a causal connection. At levels 3 and 8 of the EDSS we observed a reduction in average cord area of 12 and 35%,respectively. Given its reproducibility, the magnitude of the change detected and the strong correlation with disability, this new technique should prove to be a sensitive measure of progressive neurological deterioration and could be readily incorporated into imaging protocols aimed at monitoring therapy.
multiple sclerosis; MRI; disability; spinal cord atrophy; clinical measurement
Received December 12, 1995. Revised January 16, 1996. Accepted February 16, 1996.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Z. Liptak, A.M. Berger, M.P. Sampat, A. Charil, O. Felsovalyi, B.C. Healy, P. Hildenbrand, S.J. Khoury, H.L. Weiner, R. Bakshi, et al. Medulla Oblongata Volume: A Biomarker of Spinal Cord Damage and Disability in Multiple Sclerosis AJNR Am. J. Neuroradiol., September 1, 2008; 29(8): 1465 - 1470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Furby, T Hayton, V Anderson, D Altmann, R Brenner, J Chataway, R. Hughes, K. Smith, D. Miller, and R Kapoor Magnetic resonance imaging measures of brain and spinal cord atrophy correlate with clinical impairment in secondary progressive multiple sclerosis Multiple Sclerosis, September 1, 2008; 14(8): 1068 - 1075. [Abstract] [PDF]
|
|
|
|
 |
|
 R. Diem, I. Demmer, S. Boretius, D. Merkler, B. Schmelting, S. K. Williams, M. B. Sattler, M. Bahr, T. Michaelis, J. Frahm, et al. Autoimmune Optic Neuritis in the Common Marmoset Monkey: Comparison of Visual Evoked Potentials with MRI and Histopathology Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3707 - 3714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rovaris, E. Judica, J. Sastre-Garriga, A. Rovira, M. Pia Sormani, B. Benedetti, T. Korteweg, N. De Stefano, Z. Khaleeli, X. Montalban, et al. Large-scale, multicentre, quantitative MRI study of brain and cord damage in primary progressive multiple sclerosis Multiple Sclerosis, May 1, 2008; 14(4): 455 - 464. [Abstract] [PDF]
|
|
|
|
|
|
R. Zivadinov, A.C. Banas, V. Yella, N. Abdelrahman, B. Weinstock-Guttman, and M.G. Dwyer Comparison of Three Different Methods for Measurement of Cervical Cord Atrophy in Multiple Sclerosis AJNR Am. J. Neuroradiol., February 1, 2008; 29(2): 319 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Manconi, M.A. Rocca, L. Ferini-Strambi, P. Tortorella, F. Agosta, G. Comi, and M. Filippi Restless legs syndrome is a common finding in multiple sclerosis and correlates with cervical cord damage Multiple Sclerosis, January 1, 2008; 14(1): 86 - 93. [Abstract] [PDF]
|
|
|
|
 |
|
 A. H. Poonawalla, P. Hou, F. A. Nelson, J. S. Wolinsky, and P. A. Narayana Cervical Spinal Cord Lesions in Multiple Sclerosis: T1-weighted Inversion-Recovery MR Imaging with Phase-Sensitive Reconstruction Radiology, December 1, 2007; 246(1): 258 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Agosta, E. Pagani, D. Caputo, and M. Filippi Associations Between Cervical Cord Gray Matter Damage and Disability in Patients With Multiple Sclerosis Arch Neurol, September 1, 2007; 64(9): 1302 - 1305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Ciccarelli, C.A. Wheeler-Kingshott, M.A. McLean, M. Cercignani, K. Wimpey, D.H. Miller, and A.J. Thompson Spinal cord spectroscopy and diffusion-based tractography to assess acute disability in multiple sclerosis Brain, August 1, 2007; 130(8): 2220 - 2231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Benedetti, M. Rovaris, E. Judica, G. Donadoni, G. Ciboddo, and M. Filippi Assessing "occult" cervical cord damage in patients with neuropsychiatric systemic lupus erythematosus using diffusion tensor MRI J. Neurol. Neurosurg. Psychiatry, August 1, 2007; 78(8): 893 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Agosta, M. Absinta, M. P. Sormani, A. Ghezzi, A. Bertolotto, E. Montanari, G. Comi, and M. Filippi In vivo assessment of cervical cord damage in MS patients: a longitudinal diffusion tensor MRI study Brain, August 1, 2007; 130(8): 2211 - 2219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P Valsasina, F Agosta, B Benedetti, D Caputo, M Perini, F Salvi, A Prelle, and M Filippi Diffusion anisotropy of the cervical cord is strictly associated with disability in amyotrophic lateral sclerosis J. Neurol. Neurosurg. Psychiatry, May 1, 2007; 78(5): 480 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Selvarajah, I. D. Wilkinson, C. J. Emery, N. D. Harris, P. J. Shaw, D. R. Witte, P. D. Griffiths, and S. Tesfaye Early Involvement of the Spinal Cord in Diabetic Peripheral Neuropathy Diabetes Care, December 1, 2006; 29(12): 2664 - 2669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kolln, H.-M. Ren, R.-R. Da, Y. Zhang, E. Spillner, M. Olek, N. Hermanowicz, L. G. Hilgenberg, M. A. Smith, S. van den Noort, et al. Triosephosphate Isomerase- and Glyceraldehyde-3-Phosphate Dehydrogenase-Reactive Autoantibodies in the Cerebrospinal Fluid of Patients with Multiple Sclerosis J. Immunol., October 15, 2006; 177(8): 5652 - 5658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rovaris, E. Judica, A. Gallo, B. Benedetti, M. P. Sormani, D. Caputo, A. Ghezzi, E. Montanari, A. Bertolotto, G. Mancardi, et al. Grey matter damage predicts the evolution of primary progressive multiple sclerosis at 5 years Brain, October 1, 2006; 129(10): 2628 - 2634. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Benedetti, P. Valsasina, E. Judica, V. Martinelli, A. Ghezzi, R. Capra, R. Bergamaschi, G. Comi, and M. Filippi Grading cervical cord damage in neuromyelitis optica and MS by diffusion tensor MRI. Neurology, July 11, 2006; 67(1): 161 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ge Multiple Sclerosis: The Role of MR Imaging AJNR Am. J. Neuroradiol., June 1, 2006; 27(6): 1165 - 1176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.M. Hesseltine, M. Law, J. Babb, M. Rad, S. Lopez, Y. Ge, G. Johnson, and R.I. Grossman Diffusion Tensor Imaging in Multiple Sclerosis: Assessment of Regional Differences in the Axial Plane within Normal-Appearing Cervical Spinal Cord AJNR Am. J. Neuroradiol., June 1, 2006; 27(6): 1189 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. DeLuca, K. Williams, N. Evangelou, G. C. Ebers, and M. M. Esiri The contribution of demyelination to axonal loss in multiple sclerosis Brain, June 1, 2006; 129(6): 1507 - 1516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Brettschneider, A Petzold, A Junker, and H Tumani Axonal damage markers in the cerebrospinal fluid of patients with clinically isolated syndrome improve predicting conversion to definite multiple sclerosis Multiple Sclerosis, April 1, 2006; 12(2): 143 - 148. [Abstract] [PDF]
|
|
|
|
|
|
C. Confavreux and S. Vukusic Natural history of multiple sclerosis: a unifying concept Brain, March 1, 2006; 129(3): 606 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W Rashid, G R Davies, D T Chard, C M Griffin, D R Altmann, R Gordon, A J Thompson, and D H Miller Increasing cord atrophy in early relapsing-remitting multiple sclerosis: a 3 year study J. Neurol. Neurosurg. Psychiatry, January 1, 2006; 77(1): 51 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Iwasaki, O. Igarashi, J. Aoyagi, K. Iwamoto, K. Ikeda, M. M. Reilly, and M. Laura Chronic inflammatory demyelinating polyradiculoneuropathy: MRI study of brain and spinal cord Neurology, October 25, 2005; 65(8): 1340 - 1340. [Full Text] [PDF]
|
|
|
|
|
|
G T Ingle, J Sastre-Garriga, D H Miller, and A J Thompson Is inflammation important in early PPMS? a longitudinal MRI study J. Neurol. Neurosurg. Psychiatry, September 1, 2005; 76(9): 1255 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Brettschneider, M Maier, S Arda, A Claus, S D Sussmuth, J Kassubek, and H Tumani Tau protein level in cerebrospinal fluid is increased in patients with early multiple sclerosis Multiple Sclerosis, June 1, 2005; 11(3): 261 - 265. [Abstract] [PDF]
|
|
|
|
|
|
M. Laura, W. Leong, N. M.F. Murray, G. Ingle, K. A. Miszkiel, D. R. Altmann, D. H. Miller, and M. M. Reilly Chronic inflammatory demyelinating polyradiculoneuropathy: MRI study of brain and spinal cord Neurology, March 8, 2005; 64(5): 914 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Agosta, B. Benedetti, M. A. Rocca, P. Valsasina, M. Rovaris, G. Comi, and M. Filippi Quantification of cervical cord pathology in primary progressive MS using diffusion tensor MRI Neurology, February 22, 2005; 64(4): 631 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Petzold, M J Eikelenboom, G Keir, D Grant, R H C Lazeron, C H Polman, B M J Uitdehaag, E J Thompson, and G Giovannoni Axonal damage accumulates in the progressive phase of multiple sclerosis: three year follow up study J. Neurol. Neurosurg. Psychiatry, February 1, 2005; 76(2): 206 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Evangelou, G. C. DeLuca, T. Owens, and M. M. Esiri Pathological study of spinal cord atrophy in multiple sclerosis suggests limited role of local lesions Brain, January 1, 2005; 128(1): 29 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bakshi, G. J. Hutton, J. R. Miller, and E.-W. Radue The use of magnetic resonance imaging in the diagnosis and long-term management of multiple sclerosis Neurology, December 14, 2004; 63(11_suppl_5): S3 - S11. [Abstract] [Full Text]
|
|
|
|
|
|
J. C. J. Bot, E. L. A. Blezer, W. Kamphorst, G. J. Lycklama a Nijeholt, H. J. Ader, J. A. Castelijns, K. N. Ig, E. Bergers, R. Ravid, C. Polman, et al. The Spinal Cord in Multiple Sclerosis: Relationship of High-Spatial-Resolution Quantitative MR Imaging Findings to Histopathologic Results Radiology, November 1, 2004; 233(2): 531 - 540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Petzold, K Rejdak, and G T Plant Axonal degeneration and inflammation in acute optic neuritis J. Neurol. Neurosurg. Psychiatry, August 1, 2004; 75(8): 1178 - 1180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lucchinetti and W. Bruck The pathology of primary progressive multiple sclerosis Multiple Sclerosis, June 1, 2004; 10(1_suppl): S23 - S30. [Abstract] [PDF]
|
|
|
|
|
|
C. M. Dalton, D. T. Chard, G. R. Davies, K. A. Miszkiel, D. R. Altmann, K. Fernando, G. T. Plant, A. J. Thompson, and D. H. Miller Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes Brain, May 1, 2004; 127(5): 1101 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. DeLuca, G. C. Ebers, and M. M. Esiri Axonal loss in multiple sclerosis: a pathological survey of the corticospinal and sensory tracts Brain, May 1, 2004; 127(5): 1009 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lucchinetti and W. Bruck The pathology of primary progressive multiple sclerosis Multiple Sclerosis, May 1, 2004; 10(3_suppl): S23 - S30. [Abstract] [PDF]
|
|
|
|
|
|
N. Kumar and D. H. Davis Absence of Lower-Limb Deficits Despite Severe Spinal Cord Atrophy Arch Neurol, March 1, 2004; 61(3): 428 - 428. [Full Text] [PDF]
|
|
|
|
|
|
A. Minneboo, F. Barkhof, C. H. Polman, B. M. J. Uitdehaag, D. L. Knol, and J. A. Castelijns Infratentorial Lesions Predict Long-term Disability in Patients With Initial Findings Suggestive of Multiple Sclerosis Arch Neurol, February 1, 2004; 61(2): 217 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Lo, C. Y. Saab, J. A. Black, and S. G. Waxman Phenytoin Protects Spinal Cord Axons and Preserves Axonal Conduction and Neurological Function in a Model of Neuroinflammation In Vivo J Neurophysiol, November 1, 2003; 90(5): 3566 - 3571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Ingle, V. L. Stevenson, D. H. Miller, and A. J. Thompson Primary progressive multiple sclerosis: a 5-year clinical and MR study Brain, November 1, 2003; 126(11): 2528 - 2536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X Lin, C R Tench, B Turner, L D Blumhardt, and C S Constantinescu 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 {beta}-1a (Rebif) treatment trial J. Neurol. Neurosurg. Psychiatry, August 1, 2003; 74(8): 1090 - 1094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Castriota-Scanderbeg, F. Fasano, G. Hagberg, U. Nocentini, M. Filippi, and C. Caltagirone Coefficient Dav Is More Sensitive Than Fractional Anisotropy in Monitoring Progression of Irreversible Tissue Damage in Focal Nonactive Multiple Sclerosis Lesions AJNR Am. J. Neuroradiol., April 1, 2003; 24(4): 663 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.J. Eikelenboom, A. Petzold, R.H.C. Lazeron, E. Silber, M. Sharief, E.J. Thompson, F. Barkhof, G. Giovannoni, C.H. Polman, and B.M.J. Uitdehaag Multiple sclerosis: Neurofilament light chain antibodies are correlated to cerebral atrophy Neurology, January 28, 2003; 60(2): 219 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.M. Leary, D.H. Miller, V.L. Stevenson, P.A. Brex, D.T. Chard, and A.J. Thompson Interferon {beta}-1a in primary progressive MS: An exploratory, randomized, controlled trial Neurology, January 14, 2003; 60(1): 44 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Reddy, S. Narayanan, M. Woolrich, T. Mitsumori, Y. Lapierre, D. L. Arnold, and P. M. Matthews Functional brain reorganization for hand movement in patients with multiple sclerosis: defining distinct effects of injury and disability Brain, December 1, 2002; 125(12): 2646 - 2657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Fisher, R. A. Rudick, J. H. Simon, G. Cutter, M. Baier, J. -C. Lee, D. Miller, B. Weinstock-Guttman, M. K. Mass, D. S. Dougherty, et al. Eight-year follow-up study of brain atrophy in patients with MS Neurology, November 12, 2002; 59(9): 1412 - 1420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Schmierer, K. Irlbacher, P. Grosse, S. Roricht, and B.-U. Meyer Correlates of disability in multiple sclerosis detected by transcranial magnetic stimulation Neurology, October 22, 2002; 59(8): 1218 - 1224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E L. Hoogervorst, C H Polman, and F Barkhof Cerebral volume changes in multiple sclerosis patients treated with high-dose intravenous methylprednisolone Multiple Sclerosis, October 1, 2002; 8(5): 415 - 419. [Abstract] [PDF]
|
|
|
|
|
|
R Leigh, J Ostuni, D Pham, A Goldszal, B K Lewis, T Howard, N Richert, H McFarland, and J A Frank Estimating cerebral atrophy in multiple sclerosis patients from various MR pulse sequences Multiple Sclerosis, October 1, 2002; 8(5): 420 - 429. [Abstract] [PDF]
|
|
|
|
|
|
P. Coyle and H-P. Hartung Use of interferon beta in multiple sclerosis: rationale for early treatment and evidence for dose- and frequency-dependent effects on clinical response Multiple Sclerosis, September 1, 2002; 8(1_suppl): 2 - 9. [Abstract] [PDF]
|
|
|
|
|
|
H. McFarland, F. Barkhof, J. Antel, and D. Miller The role of MRI as a surrogate outcome measure in multiple sclerosis Multiple Sclerosis, September 1, 2002; 8(1_suppl): 40 - 51. [Abstract] [PDF]
|
|
|
|
|
|
C M Dalton, P A Brex, R Jenkins, N C Fox, K A Miszkiel, W R Crum, J I O'Riordan, G T Plant, A J Thompson, and D H Miller Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis J. Neurol. Neurosurg. Psychiatry, August 1, 2002; 73(2): 141 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Miller, F. Barkhof, J. A. Frank, G. J. M. Parker, and A. J. Thompson Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance Brain, August 1, 2002; 125(8): 1676 - 1695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I McDonald Multiple sclerosis in its European matrix Multiple Sclerosis, June 1, 2002; 8(3): 181 - 191. [PDF]
|
|
|
|
|
|
M. Filippi and R. I. Grossman MRI techniques to monitor MS evolution: The present and the future Neurology, April 23, 2002; 58(8): 1147 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Arnold and P.M. Matthews MRI in the diagnosis and management of multiple sclerosis Neurology, April 23, 2002; 58(90084): S23 - 31. [Abstract] [Full Text]
|
|
|
|
|
|
M E Morris, C Cantwell, L Vowels, and K Dodd Changes in gait and fatigue from morning to afternoon in people with multiple sclerosis J. Neurol. Neurosurg. Psychiatry, March 1, 2002; 72(3): 361 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P K Coyle and H-P Hartung Use of interferon beta in multiple sclerosis: rationale for early treatment and evidence for dose- and frequency-dependent effects on clinical response Multiple Sclerosis, February 1, 2002; 8(1): 2 - 9. [Abstract] [PDF]
|
|
|
|
|
|
H F McFarland, F Barkhof, J Antel, and D H Miller The role |