Sage Journals: Discover world-class research

Abstract

Background:

Little is known on longer term changes of spinal cord volume (SCV) in primary progressive multiple sclerosis (PPMS).

Objective:

Longitudinal evaluation of SCV loss in PPMS and its correlation to clinical outcomes, compared to relapse-onset multiple sclerosis (MS) subtypes.

Methods:

A total of 60 MS age-, sex- and disease duration-matched patients (12 PPMS, each 24 relapsing-remitting (RRMS) and secondary progressive MS (SPMS)) were analysed annually over 6 years of follow-up. The upper cervical SCV was measured on 3D T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images using a semi-automatic software (CORDIAL), along with the total brain volume (TBV), brain T2 lesion volume (T2LV) and Expanded Disability Status Scale (EDSS).

Results:

PPMS showed faster SCV loss over time than RRMS (p < 0.01) and by trend (p = 0.066) compared with SPMS. In contrast to relapse-onset MS, in PPMS SCV loss progressed independent of TBV and T2LV changes. Moreover, in PPMS, SCV was the only magnetic resonance imaging (MRI) measurement associated with EDSS increase over time (p < 0.01), as opposed to RRMS and SPMS.

Conclusion:

SCV loss is a strong predictor of clinical outcomes in PPMS and has shown to be faster and independent of brain MRI metrics compared to relapse-onset MS.

Keywords

Multiple sclerosis MRI atrophy biomarkers

Get full access to this article

View all access options for this article.

References

McDonald

Compston

Edan

et al . Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol 2001; 50(1): 121–127.

Thompson

Polman

Miller

et al . Primary progressive multiple sclerosis. Brain 1997; 120(6): 1085–1096.

Nijeholt

Walderveen

van Castelijns

et al . Brain and spinal cord abnormalities in multiple sclerosis. Correlation between MRI parameters, clinical subtypes and symptoms. Brain 1998; 121(4): 687–697.

Kantarci

Lebrun

Siva

et al . Primary progressive multiple sclerosis evolving from radiologically isolated syndrome. Ann Neurol 2016; 79(2): 288–294.

Ingle

Stevenson

Miller

et al . Primary progressive multiple sclerosis: A 5-year clinical and MR study. Brain 2003; 126(11): 2528–2536.

Galego

Gouveia

Batista

et al . Brain atrophy and physical disability in primary progressive multiple sclerosis: A volumetric study. Neuroradiol J 2015; 28(3): 354–358.

Ruggieri

Petracca

Miller

et al . Association of deep gray matter damage with cortical and spinal cord degeneration in primary progressive multiple sclerosis. JAMA Neurol 2015; 72(12): 1466–1474.

Aymerich

Auger

Alonso

et al . Cervical cord atrophy and long-term disease progression in patients with primary-progressive multiple sclerosis. Am J Neuroradiol, http://www.ajnr.org/content/early/2017/12/28/ajnr.a5495 (2018, accessed 8 January 2018).

Lukas

Knol

Sombekke

et al . Cervical spinal cord volume loss is related to clinical disability progression in multiple sclerosis. J Neurol Neurosurg Psychiatry 2015; 86(4): 410–418.

10.

Lukas

Sombekke

Bellenberg

et al . Relevance of spinal cord abnormalities to clinical disability in multiple sclerosis: MR imaging findings in a large cohort of patients. Radiology 2013; 269(2): 542–552.

11.

Kearney

Miller

Ciccarelli

Spinal cord MRI in multiple sclerosis – Diagnostic, prognostic and clinical value. Nat Rev Neurol 2015; 11(6): 327–338.

12.

Brownlee

Altmann

Mota

PAD

et al . Association of asymptomatic spinal cord lesions and atrophy with disability 5 years after a clinically isolated syndrome. Mult Scler 2017; 23(5): 665–674.

13.

Bieniek

Altmann

Davies

et al . Cord atrophy separates early primary progressive and relapsing remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 2006; 77(9): 1036–1039.

14.

Schlaeger

Papinutto

Panara

et al . Spinal cord gray matter atrophy correlates with multiple sclerosis disability. Ann Neurol 2014; 76(4): 568–580.

15.

Antel

Caramanos

et al . Primary progressive multiple sclerosis: Part of the MS disease spectrum or separate disease entity? Acta Neuropathol 2012; 123(5): 627–638.

16.

Agosta

Benedetti

Rocca

et al . Quantification of cervical cord pathology in primary progressive MS using diffusion tensor MRI. Neurology 2005; 64(4): 631–635.

17.

Abdel-Aziz

Schneider

Solanky

et al . Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis. Brain 2015; 138(Pt 6): 1568–1582.

18.

Cawley

Tur

Prados

et al . Spinal cord atrophy as a primary outcome measure in phase II trials of progressive multiple sclerosis. Mult Scler 2018; 24(7): 932–941.

19.

Zeydan

Atkinson

et al . Cervical spinal cord atrophy: An early marker of progressive MS onset. Neurol Neuroimmunol Neuroinflamm 2018; 5(2), http://nn.neurology.org/content/5/2/e435.abstract

20.

Weier

Mazraeh

Naegelin

et al . Biplanar MRI for the assessment of the spinal cord in multiple sclerosis. Mult Scler 2012; 18(11): 1560–1569.

21.

Pezold

Fundana

Amann

et al . Automatic segmentation of the spinal cord using continuous max flow with cross-sectional similarity prior and tubularity features. In: Yao

Glocker

Klinder

et al . (eds) Recent advances in computational methods and clinical applications for spine imaging. Lecture Notes in Computational Vision and Biomechanics. Springer International Publishing, 2015, pp. 107–118, http://link.springer.com/chapter/10.1007/978-3-319-14148-0_10 (accessed 18 July 2016).

22.

Amann

Pezold

Naegelin

et al . Reliable volumetry of the cervical spinal cord in MS patient follow-up data with cord image analyzer (Cordial). J Neurol 2016; 263(7): 1364–1374.

23.

Smith

Jenkinson

Woolrich

et al . Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage 2004; 23(Supplement 1): S208–S219.

24.

Magon

Chakravarty

Amann

et al . Label-fusion-segmentation and deformation-based shape analysis of deep gray matter in multiple sclerosis: The impact of thalamic subnuclei on disability. Hum Brain Mapp 2014; 35(8): 4193–4203.

25.

Maarouf

Audoin

Konstandin

et al . Topography of brain sodium accumulation in progressive multiple sclerosis. Magn Reson Mater Phy 2013; 27(1): 53–62.

26.

Stevenson

Miller

Rovaris

et al . Primary and transitional progressive MS: A clinical and MRI cross-sectional study. Neurology 1999; 52(4): 839–839.

27.

Narayana

Wolinsky

Rao

et al . Multicentre proton magnetic resonance spectroscopy imaging of primary progressive multiple sclerosis. Mult Scler 2004; 10(3 suppl): S73–S78.

28.

Montalban

Hauser

Kappos

et al . Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med 2017; 376(3): 209–220.

29.

Ontaneda

Fox

Chataway

Clinical trials in progressive multiple sclerosis: Lessons learned and future perspectives. Lancet Neurol 2015; 14(2): 208–223.

30.

Papinutto

Schlaeger

Panara

et al . Age, gender and normalization covariates for spinal cord gray matter and total cross-sectional areas at cervical and thoracic levels: A 2D phase sensitive inversion recovery imaging study. PLoS ONE 2015; 10(3): e0118576.

31.

Liu

Yaldizli

Pardini

et al . Cervical cord area measurement using volumetric brain magnetic resonance imaging in multiple sclerosis. Mult Scler Relat Disord 2015; 4(1): 52–57.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.47 MB

Preferential spinal cord volume loss in primary progressive multiple sclerosis

Abstract

Background:

Objective:

Methods:

Results:

Conclusion:

Keywords

Get full access to this article

References

Supplementary Material