Abstract
Multiple sclerosis (MS) is a disorder related to myelin damage, which can be investigated by neuroimaging techniques such as fractional anisotropy (FA), a measure of microstructural white matter properties. The objectives of this study were to investigate (1) the relationship between FA and disability using an extremes of outcome approach, and (2) whether blood iron parameters were associated with FA and/or disability. Patients diagnosed with MS (n = 107; 14 males and 93 females) had iron parameter tests and disability determinations using the Expanded Disability Status Scale (EDSS). FA was recorded in 48 white matter tracts in 11 of the female patients with MS and 12 female controls. Results: In patients with high disability scores the mean FA was significantly lower (0.34 ± 0.067) than in the control group (0.45 ± 0.036; p = 0.04), while patients with low disability had mean FA values (0.44 ± 0.014) similar to controls (p = 0.5). Positive associations were found between FA and the iron parameters serum iron, ferritin and percentage transferrin saturation (%Tfsat) in all the white matter tracts. For % Tfsat, the associations were highly significant in 14 tracts (p < 0.01; r-values 0.74–0.84) and p < 0.001 (r = 0.83) in the superior fronto occipital fasciculus (LH). In the whole patient group a trend was found towards an inverse association between the EDSS and the %Tfsat (r = −0.26, p = 0.05) after excluding male gender and smoking as confounders, suggesting reduced disability in the presence of higher blood iron parameters. Additionally, significant inverse associations between disease duration and haemoglobin (p = 0.04) as well as %Tfsat (p = 0.02) suggested that patients with MS may experience a decrease in blood iron concentrations over time.
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Acknowledgements
We wish to thank Dr. Heloise Avenant for the EDSS measurements. We also thank Mr. Shafick Hassan for his involvement with the project. We gratefully acknowledge the financial support given by the National Research Foundation (NRF), Winetech, and the National Health Laboratory Service.
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This study was funded by the National Research Foundation Award Number 2011 and Award Number CPR20110726000022168; Winetech Award Number N07/09/203 and the National Health Laboratory Service Award Number 94139.
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Performed the DTI and Collected the data: EH, CL. Analyzed the data: JPF, MK, CH. Wrote the paper: EH, SJVR. Interpreted the data: JPF, CH, SJVR, EH, MK, MJK. Revised the manuscript: PEH, MJK, MK, CH, CL.
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Professors SJ van Rensburg and MJ Kotze are listed as inventors on patent number 2010/00058. Prof Kotze is also a director and shareholder of Gknowmix (Pty) Ltd. that has developed a database tool for research translation under the auspices of the Innovation Centre of the South African Medical Research Council. Prof SJ van Rensburg applied the Gknowmix database tool and open innovation genetic testing service delivery model for development of the Demyelinating Diseases GeneScreenTM. A treatment regimen was developed for application with this genomic solution (patent number 2012/07347). The remaining authors declared no conflict of interest. No writing assistance was utilised in the preparation of this manuscript.
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Herbert, E., Engel-Hills, P., Hattingh, C. et al. Fractional anisotropy of white matter, disability and blood iron parameters in multiple sclerosis. Metab Brain Dis 33, 545–557 (2018). https://doi.org/10.1007/s11011-017-0171-5
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DOI: https://doi.org/10.1007/s11011-017-0171-5