Elisabetta Pagani1, Raffaello Bonacchi1,2, Alessandro Meani1, Laura Cacciaguerra1,2, Ermelinda De Meo1,2, Paolo Preziosa1,2, Maria A. Rocca1,2, and Massimo Filippi1,2,3
1Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy, 2Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy, 3Vita-Salute San Raffaele University, Milan, Italy
Synopsis
Cervical spinal cord involvement is common in multiple sclerosis (MS).
We performed a comprehensive multiparametric MRI study to explore
pathophysiological substrates of damage and to identify the most accurate
imaging predictors of disability and disease course. We found that the
processes contributing to disability differ according to the stage of the
disease. In relapsing-remitting MS patients, lesions and microstructural damage
to cervical spinal cord tracts have a prominent role, whereas in progressive MS
patients, cervical cord grey matter atrophy becomes clinically meaningful.
Introduction
Cervical spinal cord (cSC) involvement is common in multiple
sclerosis (MS). However, partly due to technical issues, no comprehensive
multiparametric MRI study has been performed yet.Objective
To explore pathophysiological substrates of cSC
damage in MS patients and to identify the most accurate imaging predictors of
disability and disease course, using a multiparametric MRI approach.Methods
One-hundred and eleven MS patients, 57 with
relapsing-remitting (RR) and 54 with progressive MS (PMS), and 32 age- and
sex-matched healthy controls (HC) underwent brain and cSC 3 Tesla MRI with
pulse sequences for assessing lesions and atrophy, and a diffusion-weighted
scan for microstructural damage. Neurological assessment included Expanded
Disability Status Scale
(EDSS) scoring, and Nine-Hole
Peg Test and 25-Foot Walking Test for limb function.
Brain T2-hyperintense lesion volume (LV) were measured using
Jim software.1 Whole brain, grey matter (GM) and white matter (WM)
atrophy were assessed using SIENAX.2 For the cSC analysis, T2-hyperintense LV and
diffusion tensor derived metrics were calculated between the C1 and C5
vertebral levels for the whole SC, the GM, WM, dorsal columns and lateral
funiculi, applying a probabilistic regional atlas available in the Spinal Cord
Toolbox,3 previously registered to the T2-weighted image space (Figure 1). Total SC
cross-sectional area was calculated on 2D phase-sensitive inversion recovery
sequences, using the active surface method,4 whereas GM was manually
segmented. Between group differences and associations of MRI variables with
these metrics were explored by age-, sex- and phenotype-adjusted linear models.Results
MS patients had cSC
lesions, higher brain T2-LV,
brain and cSC atrophy and microstructural damage,
compared to HC. In MS
patients, multivariable analysis identified brain GM volume, cSC lateral
funiculi fractional anisotropy (FA) and lateral funiculi T2-LV as independent predictors of
EDSS score. The independent predictors of EDSS score were cSC lateral funiculi
FA, brain T2-LV and cSC lateral funiculi T2-LV in RRMS (R2=0.48); and cSC
lateral funiculi FA and cSC GM atrophy in PMS (R2=0.52). Similar results were
confirmed for limb function tests. Logistic regression analysis identified cSC
GM atrophy and cSC T2-LV as independent predictors of phenotype (AUC=0.964).Conclusions
cSC involvement has a central role in
explaining disability in MS. The processes contributing to disability differ
according to the stage of the disease. In RRMS, lesions and microstructural
damage to cSC tracts have a prominent role, whereas in PMS, cSC GM atrophy
becomes clinically meaningful.Acknowledgements
No acknowledgement found.References
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Levy S, Benhamou M, Naaman
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Horsfield MA, Sala
S, Neema M, et al. Rapid semi-automatic segmentation of the spinal cord from
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