Focal and diffuse cervical spinal cord damage in patients with early relapsing–remitting MS: A multicentre magnetisation transfer ratio study

Abstract

Background:

Studies including patients with well-established multiple sclerosis (MS) have shown a significant and disability-related reduction in the cervical spinal cord (SC) magnetisation transfer ratio (MTR).

Objectives:

The objectives are to (1) assess whether MTR reduction is already measurable in the SC of patients with early relapsing–remitting multiple sclerosis (RRMS) and (2) describe its spatial distribution.

Methods:

We included 60 patients with RRMS <12 months and 34 age-matched controls at five centres. Axial T2*w, sagittal T2w, sagittal phase-sensitive inversion recovery (PSIR), 3DT1w, and axial magnetisation transfer (MT) images were acquired from C1 to C7. Lesions were manually labelled and mean MTR values computed both for the whole SC and for normal-appearing SC in different regions of interest.

Results:

Mean whole SC MTR was significantly lower in patients than controls (33.7 vs 34.9 pu, p = 0.00005), even after excluding lesions (33.9 pu, p = 0.0003). We observed a greater mean reduction in MTR for vertebral levels displaying the highest lesion loads (C2–C4). In the axial plane, we observed a greater mean MTR reduction at the SC periphery and barycentre.

Conclusion:

Cervical SC tissue damage measured using MTR is not restricted to macroscopic lesions in patients with early RRMS and is not homogeneously distributed.

Keywords

Spinal cord quantitative MRI magnetisation transfer imaging relapsing–remitting multiple sclerosis

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References

Lublin

Reingold

Cohen

et al . Defining the clinical course of multiple sclerosis: The 2013 revisions. Neurology 2014; 83(3): 278–286.

Nijeholt

van Walderveen

Castelijns

et al . Brain and spinal cord abnormalities in multiple sclerosis. Correlation between MRI parameters, clinical subtypes and symptoms. Brain 1998; 121: 687–697.

Minneboo

Jasperse

Barkhof

et al . Predicting short-term disability progression in early multiple sclerosis: Added value of MRI parameters. J Neurol Neurosurg Psychiatry 2008; 79: 917–923.

Kearney

Altmann

Samson

et al . Cervical cord lesion load is associated with disability independently from atrophy in MS. Neurology 2015; 34: 367–373.

Martin

Aleksanderek

Cohen-Adad

et al . Translating state-of-the-art spinal cord MRI techniques to clinical use: A systematic review of clinical studies utilizing DTI, MT, MWF, MRS, and fMRI. Neuroimage Clin 2016; 10: 192–238.

Bot

Blezer

Kamphorst

et al . The spinal cord in multiple sclerosis: Relationship of high-spatial-resolution quantitative MR imaging findings to histopathologic results. Radiology 2004; 233(2): 531–540.

Kearney

Yiannakas

Samson

et al . Investigation of magnetization transfer ratio-derived pial and subpial abnormalities in the multiple sclerosis spinal cord. Brain 2014; 137(9): 2456–2468.

Silver

Barker

Losseff

et al . Magnetisation transfer ratio measurement in the cervical spinal cord: A preliminary study in multiple sclerosis. Neuroradiology 1997; 39(6): 441–445.

Bozzali

Rocca

Iannucci

et al . Magnetization-transfer histogram analysis of the cervical cord in patients with multiple sclerosis. AJNR Am J Neuroradiol 1999; 20(10): 1803–1808.

10.

Agosta

Pagani

Caputo

et al . Associations between cervical cord gray matter damage and disability in patients with multiple sclerosis. Arch Neurol 2007; 64(9): 1302–1305.

11.

Rovaris

Bozzali

Santuccio

et al . In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis. Brain 2001; 124(Pt 12): 2540–2549.

12.

Filippi

Bozzali

Horsfield

et al . A conventional and magnetization transfer MRI study of the cervical cord in patients with MS. Neurology 2000; 54(1): 207–213.

13.

Filippi

Rocca

Falini

et al . Correlations between structural CNS damage and functional MRI changes in primary progressive MS. Neuroimage 2002; 15(3): 537–546.

14.

Sotirchos

Saidha

et al . Relationships between quantitative spinal cord MRI and retinal layers in multiple sclerosis. Neurology 2015; 84(7): 720–728.

15.

Zackowski

Chen

et al . Multiparametric MRI correlates of sensorimotor function in the spinal cord in multiple sclerosis. Mult Scler 2013; 19(4): 427–435.

16.

Zackowski

Smith

Reich

et al . Sensorimotor dysfunction in multiple sclerosis and column-specific magnetization transfer-imaging abnormalities in the spinal cord. Brain 2009; 132: 1200–1209.

17.

Rovaris

Judica

Ceccarelli

et al . Absence of diffuse cervical cord tissue damage in early, non-disabling relapsing-remitting MS: A preliminary study. Mult Scler 2008; 14(6): 853–856.

18.

Rovaris

Gallo

Riva

et al . An MT MRI study of the cervical cord in clinically isolated syndromes suggestive of MS. Neurology 2004; 63(3): 584–585.

19.

Brown

Pardini

Brownlee

et al . An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis. Brain 2017; 140: 387–398.

20.

Liu

Pardini

Yaldizli

et al . Magnetization transfer ratio measures in normal-appearing white matter show periventricular gradient abnormalities in multiple sclerosis. Brain 2015; 138: 1239–1246.

21.

Pardini

Sudre

Prados

et al . Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis. J Neurol Neurosurg Psychiatry 2016; 87: 1212–1217.

22.

Polman

Reingold

Banwell

et al . Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292–302.

23.

De Leener

Levy

Dupont

et al . SCT: Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data. Neuroimage 2016; 145: 24–43.

24.

Anima, https://github.com/Inria-Visages/Anima-Public/wiki/

25.

Horsfield

Sala

Neema

et al . Rapid semi-automatic segmentation of the spinal cord from magnetic resonance images: Application in multiple sclerosis. Neuroimage 2010; 50(2): 446–455.

26.

Bannier

Combès

Monteau

et al . Evaluating the reliability of cervical spine magnetization transfer imaging in the context of multicenter longitudinal studies. In: Proceedings of the ESMRMB conference, Barcelona, October 19–October 21 MAGMA.

27.

Biberacher

Boucard

Schmidt

et al . Atrophy and structural variability of the upper cervical cord in early multiple sclerosis. Mult Scler 2015; 21: 875–884.

28.

Rocca

Horsfield

Sala

et al . A multicenter assessment of cervical cord atrophy among MS clinical phenotypes. Neurology 2011; 76: 2096–2102.

29.

Brex

Leary

O’Riordan

et al . Measurement of spinal cord area in clinically isolated syndromes suggestive of multiple sclerosis. J Neurol Neurosurg Psychiatry 2011; 70: 544–547.

30.

Rashid

Davies

Chard

et al . Increasing cord atrophy in early relapsing remitting multiple sclerosis: A 3 year study. J Neurol Neurosurg Psychiatry 2006; 77: 51–55.

31.

Magliozzi

Howell

Reeves

et al . A gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol 2010; 68: 477–493.

32.

Rasoanandrianina

Grapperon

Taso

et al . Region-specific impairment of the cervical spinal cord (SC) in amyotrophic lateral sclerosis: A feasibility study using SC templates and quantitative MRI (diffusion tensor imaging/inhomogeneous magnetization transfer). NMR Biomed 2017; 30(12): e3801.

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