Brain, Vol. 124, No. 12, 2540-2549,
December 2001
© 2001 Oxford University Press
In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis
1 Neuroimaging Research Unit and 2 Clinical Trials Unit, Department of Neuroscience, Scientific Institute and University Ospedale San Raffaele, 3 Department of Neurology, Scientific Institute Don Gnocchi, University of Milan, Milan, 4 Multiple Sclerosis Center, Ospedale di Fidenza, Fidenza, 5 Department of Neurology, Ospedale di Orbassano, Orbassano, 6 Department of Neurological Sciences, Scientific Institute C. Mondino, University of Pavia, Pavia, 7 Department of Neurology, Spedali Civili, University of Brescia, Brescia, 8 Department of Neurological Sciences, University of Genoa, Genoa 9 Multiple Sclerosis Center, Ospedale di Gallarate, Gallarate, Italy
Correspondence to:
Dr Massimo Filippi, Neuroimaging Research Unit, Department of Neuroscience, Scientific Institute and University Ospedale San Raffaele, Via Olgettina 60, 20132 Milan, Italyfilippi.massimo{at}hsr.it
In patients with primary progressive (PP) multiple sclerosis, brain MRI lesion activity and burden are low, despite the presence of severe neurological impairment. On the contrary, the degree of cord atrophy and diffuse tissue damage in the brain and cervical cord have been found to be associated with clinical disability. Against this background, this study aimed at providing an in vivoindirect assessment of brain and cervical cord pathology in a large cohort of PP multiple sclerosis patients, using conventional MRI and magnetization transfer imaging (MTI). Ninety-one PP multiple sclerosis patients, 36 secondary progressive (SP) multiple sclerosis patients and 30 healthy controls underwent brain and cervical cord MRI scans, using dual echo (brain) or fast short-tau inversion recovery (cervical cord) MTI and T1-weighted sequences. For the brain, T2 hyperintense and T1 hypointense lesion volumes were calculated and the volume of the whole of the brain tissue measured. For the cervical cord, the number and burden of lesions and the cross-sectional area were assessed. MTI scans were post-processed and analysed to obtain magnetization transfer ratio (MTR) histograms from the whole of the brain and cervical cord tissue and from the normal-appearing brain tissue in isolation. In PP multiple sclerosis patients, brain, normal-appearing brain tissue and cervical cord MTR histogram-derived metrics revealed the presence of diffuse tissue damage whose characteristics did not significantly differ from those of SP multiple sclerosis patients, even though SP multiple sclerosis patients had higher MRI-visible lesion burdens. None of the correlations between MRI or MTI measures obtained from the brain and the cord were significant. PP multiple sclerosis patients' disability was significantly, albeit weakly associated with a composite MR model including measures of loss and intrinsic damage of cervical cord tissue. Our data indicate the presence of a diffuse tissue damage undetectable by conventional MRI in PP multiple sclerosis patients, whose extent seems to match that of SP multiple sclerosis patients with similar levels of disability. They also suggest that the severity of multiple sclerosis pathology in the cervical cord is one of the factors contributing to neurological impairment in PP multiple sclerosis.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M Rovaris, E Judica, A Ceccarelli, A Ghezzi, V Martinelli, G Comi, and M Filippi Absence of diffuse cervical cord tissue damage in early, non-disabling relapsing-remitting MS: a preliminary study Multiple Sclerosis, July 1, 2008; 14(6): 853 - 856. [Abstract] [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]
|
|
|
|
 |
|
 C. Di Perri, M. Battaglini, M. L. Stromillo, M. L. Bartolozzi, L. Guidi, A. Federico, and N. De Stefano Voxel-Based Assessment of Differences in Damage and Distribution of White Matter Lesions Between Patients With Primary Progressive and Relapsing-Remitting Multiple Sclerosis Arch Neurol, February 1, 2008; 65(2): 236 - 243. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M A Rocca, A Ceccarelli, A Falini, P Tortorella, B Colombo, E Pagani, G Comi, G Scotti, and M Filippi Diffusion tensor magnetic resonance imaging at 3.0 tesla shows subtle cerebral grey matter abnormalities in patients with migraine J. Neurol. Neurosurg. Psychiatry, May 1, 2006; 77(5): 686 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Frohman, E. Havrdova, F. Lublin, F. Barkhof, A. Achiron, M. K. Sharief, O. Stuve, M. K. Racke, L. Steinman, H. Weiner, et al. Most patients with multiple sclerosis or a clinically isolated demyelinating syndrome should be treated at the time of diagnosis. Arch Neurol, April 1, 2006; 63(4): 614 - 619. [Full Text] [PDF]
|
|
|
|
|
|
L Ramio-Torrenta, J Sastre-Garriga, G T Ingle, G R Davies, V Ameen, D H Miller, and A J Thompson Abnormalities in normal appearing tissues in early primary progressive multiple sclerosis and their relation to disability: a tissue specific magnetisation transfer study J. Neurol. Neurosurg. Psychiatry, January 1, 2006; 77(1): 40 - 45. [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]
|
|
|
|
|
|
A. Kutzelnigg, C. F. Lucchinetti, C. Stadelmann, W. Bruck, H. Rauschka, M. Bergmann, M. Schmidbauer, J. E. Parisi, and H. Lassmann Cortical demyelination and diffuse white matter injury in multiple sclerosis Brain, November 1, 2005; 128(11): 2705 - 2712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Frohman, M. Filippi, O. Stuve, S. G. Waxman, J. Corboy, J. T. Phillips, C. Lucchinetti, J. Wilken, N. Karandikar, B. Hemmer, et al. Characterizing the Mechanisms of Progression in Multiple Sclerosis: Evidence and New Hypotheses for Future Directions Arch Neurol, September 1, 2005; 62(9): 1345 - 1356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rovaris, A. Gallo, A. Falini, B. Benedetti, P. Rossi, M. Comola, G. Scotti, G. Comi, and M. Filippi Axonal Injury and Overall Tissue Loss Are Not Related in Primary Progressive Multiple Sclerosis Arch Neurol, June 1, 2005; 62(6): 898 - 902. [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]
|
|
|
|
 |
|
 E. Pagani, M. A. Rocca, A. Gallo, M. Rovaris, V. Martinelli, G. Comi, and M. Filippi Regional Brain Atrophy Evolves Differently in Patients with Multiple Sclerosis According to Clinical Phenotype AJNR Am. J. Neuroradiol., February 1, 2005; 26(2): 341 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. Boneschi, M. Rovaris, G. Comi, and M. Filippi The use of magnetic resonance imaging in multiple sclerosis: lessons learned from clinical trials Multiple Sclerosis, August 1, 2004; 10(4): 341 - 347. [Abstract] [PDF]
|
|
|
|
|
|
V L Stevenson, G T Ingle, D H Miller, and A J Thompson Magnetic resonance imaging predictors of disability in primary progressive multiple sclerosis: a 5-year study Multiple Sclerosis, August 1, 2004; 10(4): 398 - 401. [Abstract] [PDF]
|
|
|
|
|
|
A. Thompson Overview of primary progressive multiple sclerosis (PPMS): similarities and differences from other forms of MS, diagnostic criteria, pros and cons of progressive diagnosis Multiple Sclerosis, June 1, 2004; 10(1_suppl): S2 - S7. [Abstract] [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]
|
|
|
|
|
|
M. Filippi, M. Rovaris, and M. A Rocca Imaging primary progressive multiple sclerosis: the contribution of structural, metabolic, and functional MRI techniques Multiple Sclerosis, June 1, 2004; 10(1_suppl): S36 - S45. [Abstract] [PDF]
|
|
|
|
|
|
P. A Narayana, J. S Wolinsky, S. B Rao, Renjie He, M. Mehta, and PROMiSe Trial MRSI Group Multicentre proton magnetic resonance spectroscopy imaging of primary progressive multiple sclerosis Multiple Sclerosis, June 1, 2004; 10(1_suppl): S73 - S78. [Abstract] [PDF]
|
|
|
|
|
|
A. Thompson Overview of primary progressive multiple sclerosis (PPMS): similarities and differences from other forms of MS, diagnostic criteria, pros and cons of progressive diagnosis Multiple Sclerosis, May 1, 2004; 10(3_suppl): S2 - S7. [Abstract] [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]
|
|
|
|
|
|
M. Filippi, M. Rovaris, and M. A Rocca Imaging primary progressive multiple sclerosis: the contribution of structural, metabolic, and functional MRI techniques Multiple Sclerosis, May 1, 2004; 10(3_suppl): S36 - S45. [Abstract] [PDF]
|
|
|
|
|
|
P. A Narayana, J. S Wolinsky, S. B Rao, R. He, M. Mehta, and PROMiSe Trial MRSI Group Multicentre proton magnetic resonance spectroscopy imaging of primary progressive multiple sclerosis Multiple Sclerosis, May 1, 2004; 10(3_suppl): S73 - S78. [Abstract] [PDF]
|
|
|
|
|
|
K. Schmierer, D. R Altmann, N. Kassim, H. Kitzler, C. M Kerskens, C. A Doege, O. Aktas, J. D Lunemann, D. H Miller, F. Zipp, et al. Progressive change in primary progressive multiple sclerosis normal-appearing white matter: a serial diffusion magnetic resonance imaging study Multiple Sclerosis, April 1, 2004; 10(2): 182 - 187. [Abstract] [PDF]
|
|
|
|
|
|
M. A. Rocca, D. M. Mezzapesa, A. Ghezzi, A. Falini, F. Agosta, V. Martinelli, G. Scotti, G. Comi, and M. Filippi Cord damage elicits brain functional reorganization after a single episode of myelitis Neurology, October 28, 2003; 61(8): 1078 - 1085. [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]
|
|
|
|
|
|
M A Horsfield and M Filippi Spinal cord atrophy and disability in multiple sclerosis over four years J. Neurol. Neurosurg. Psychiatry, August 1, 2003; 74(8): 1014 - 1015. [Full Text] [PDF]
|
|
|
|
|
|
N. De Stefano, P. M. Matthews, M. Filippi, F. Agosta, M. De Luca, M. L. Bartolozzi, L. Guidi, A. Ghezzi, E. Montanari, A. Cifelli, et al. Evidence of early cortical atrophy in MS: Relevance to white matter changes and disability Neurology, April 8, 2003; 60(7): 1157 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M A Rocca, B Colombo, M Inglese, M Codella, G Comi, and M Filippi A diffusion tensor magnetic resonance imaging study of brain tissue from patients with migraine J. Neurol. Neurosurg. Psychiatry, April 1, 2003; 74(4): 501 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rovaris, M. A Rocca, and M. Filippi Magnetic resonance-based techniques for the study and management of multiple sclerosis Br. Med. Bull., March 1, 2003; 65(1): 133 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Rocca, P. M. Matthews, D. Caputo, A. Ghezzi, A. Falini, G. Scotti, G. Comi, and M. Filippi Evidence for widespread movement-associated functional MRI changes in patients with PPMS Neurology, March 26, 2002; 58(6): 866 - 872. [Abstract] [Full Text] [PDF]
|
|