Progressive Injury in Chronic Multiple Sclerosis Lesions Is Gender-Specific: A DTI Study

Alexander Klistorner; Chenyu Wang; Con Yiannikas; Stuart L Graham; John Parratt; Michael H Barnett

doi:10.1371/journal.pone.0149245

Progressive Injury in Chronic Multiple Sclerosis Lesions Is Gender-Specific: A DTI Study

PLoS One. 2016 Feb 22;11(2):e0149245. doi: 10.1371/journal.pone.0149245. eCollection 2016.

Authors

Alexander Klistorner^{1

2

3}, Chenyu Wang^{3

4}, Con Yiannikas⁵, Stuart L Graham², John Parratt⁵, Michael H Barnett^{3

4}

Affiliations

¹ Department of Ophthalmology, Save Sight Institute, University of Sydney, Sydney, Australia.
² Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia.
³ Sydney Neuroimaging Analysis Centre, Sydney, NSW, Australia.
⁴ Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.
⁵ North Shore Hospital, Sydney, NSW, Australia.

Abstract

Objective: To evaluate the longitudinal integrity of white matter tracts in patients with relapsing remitting multiple sclerosis (RRMS) as determined by changes in diffusivity indices of lesional and non-lesional white matter in the optic radiation over 12 months.

Methods: The optic radiation (OR) was identified in sixty RRMS patients using probabilistic tractography. MS lesions were segmented on FLAIR T2 images and a lesion mask was intersected with the co-registered OR. Lesions within the OR were identified in 39 patients. Voxel-based analysis of axial diffusivity (AD) and radial diffusivity (RD) within OR lesions and non-lesional normal appearing white matter (NAWM) was performed at baseline and 12 months in 34 patients (five patients excluded due to new OR lesions).

Results: Both RD and AD demonstrated much higher values within the lesions compared with non-lesional NAWM. There was a significant (p<0.001) increase of lesional AD and RD during the follow-up period. This increase, however, was driven almost entirely by the male cohort, in which a significantly greater change in both AD (M-2.7%, F-0.9%) and RD (M-4.6%, F-0.7%) was observed during the follow-up period. Non-lesional NAWM also demonstrated an increase in both AD and RD, albeit on a much lesser scale (1.0% and 0.6% respectively). In contradistinction to lesions, the diffusivity change in non-lesional NAWM was similar between sexes.

Conclusions: The evolution of AD and RD in chronic MS lesions over 12 months suggests ongoing inflammatory demyelinating activity accompanied by axonal loss. In addition, our findings are consistent with the recently observed trend of more rapid clinical progression in males and establish a potential in vivo biomarker of gender dichotomy by demonstrating a significantly faster rate of microstructural change in the chronic lesions of male patients with MS.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Follow-Up Studies
Humans
Middle Aged
Multiple Sclerosis
Sex Characteristics*
White Matter / pathology*
White Matter / physiopathology*

Grants and funding

The work was supported by Save Neuron grant (Novartis), grants from National MS Society (US) and Sydney Eye Hospital. MRI acquisition for this study was partially funded by Novartis Farma. However, this does not alter the authors adherence to PLOS ONE policies on sharing data and materials. None of the authors employed by or receive consultancy from or involved in product development or holding patents with Novartis Farma. AK takes full responsibility for the data, the analysis, the interpretation and the conduct of the research. AK has full access to all of the data and has right to publish any data and all data separate and apart from any sponsor. All authors report no conflicts of interest. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.