Brain Advance Access originally published online on May 29, 2007
Brain 2007 130(8):2211-2219; doi:10.1093/brain/awm110
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In vivo assessment of cervical cord damage in MS patients: a longitudinal diffusion tensor MRI study
1Neuroimaging Research Unit, 2Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, 3Unit of Biostatistics, DISSAL, University of Genoa, Genoa, 4Multiple Sclerosis Center, Gallarate Hospital, Gallarate, 5Department of Neurology, Orbassano Hospital, Orbassano and 6Multiple Sclerosis Center, Fidenza Hospital, Fidenza, Italy
Correspondence to: Dr Massimo Filippi, Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Via Olgettina, 60, 20132 Milan, Italy E-mail: filippi.massimo{at}hsr.it
Cervical cord damage is likely to contribute to the accumulation of disability in multiple sclerosis (MS) and can be quantified in vivo using MRI. We used conventional and diffusion tensor (DT) MRI to: (a) define the temporal evolution of intrinsic tissue injury and atrophy in the cervical cord from MS patients, (b) investigate how these two aspects of cord damage are interrelated and (c) assess the correlation of cord MRI metrics with concomitant brain damage and disability. Conventional and DT MRI of the brain and cervical cord were obtained from 42 MS patients and 9 healthy controls at baseline and after a mean follow-up of 2.4 years. At each time-point, we measured: cervical cord lesion number, cross-sectional area, mean diffusivity (MD) and fractional anisotropy (FA). Brain T2 lesion volume, grey matter MD, normal appearing white matter (NAWM) MD and FA, as well as longitudinal normalized percentage brain volume changes were also measured.
In MS patients, cervical cord cross-sectional area (P < 0.001) and FA (P = 0.01) decreased, and cervical cord MD increased (P < 0.001) during follow-up. Cord FA decrease, but not cord cross-sectional area and MD, was significantly higher (P = 0.05) in primary progressive MS patients than in those with either relapsing–remitting or secondary progressive MS. At baseline and follow-up, moderate correlations were found between intrinsic cord diffusivity abnormalities and cord cross-sectional area (r values ranging from 0.34 to 0.58), but not between their changes over time. No cross-sectional and longitudinal correlations were found between these MRI metrics and the number of cord T2-visible lesions. Brain NAWM MD (P = 0.03) and brain volume (P < 0.001) also changed in patients. There was no significant correlation between cord and brain MRI metrics at both time-points, as well as between their changes occurred over the follow-up. Baseline cord cross-sectional area (r = –0.40, P = 0.01) and FA (r = –0.40, P = 0.03) correlated with increase in disability at follow-up.
This study shows that both progressive tissue loss and injury to the remaining tissue occur in the cervical cord of MS patients, and that these two components of cord damage are not strictly interrelated, thus suggesting that a multiparametric MRI approach is needed to achieve more accurate estimates of such a damage. MS cord pathology also seems to be independent of concomitant brain changes, to develop at different rates according to disease phenotype, and to be associated to medium-term disability accrual.
Key Words: multiple sclerosis; cervical cord; magnetic resonance imaging; diffusion tensor; disability
Abbreviations: DE, dual-echo; DT, diffusion tensor; DW, diffusion-weighted; EDSS, Expanded Disability Status Scale; EP, echo planar; ETL, echo train length; FA, fractional anisotropy; Fast-STIR, fast-short-tau inversion recovery; FOV, field of view; FU, follow up; GM, grey matter; LV, lesion volume; MD, mean diffusivity; MP-RAGE, magnetization-prepared rapid acquisition gradient echo; MR, magnetic resonance; MRI, magnetic resonance imaging; MS, multiple sclerosis; NA, normal appearing; NAWM, normal appearing white matter; PBVC, percentage brain volume change; PPMS, primary progressive multiple sclerosis; RRMS, relapsing–remitting multiple sclerosis; SD, standard deviation; SE, spin echo; SENSE, sensitivity encoded; SIENA, Structural Imaging Evaluation of Normalised Atrophy; SPMS, secondary progressive multiple sclerosis; TE, echo time; TR, repetition time; WM, white matter
Received November 29, 2006. Revised April 11, 2007. Accepted April 16, 2007.
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