ORIGINAL ARTICLE Fractional anisotropy of white matter, disability and blood iron parameters in multiple sclerosis Estelle Herbert 1 & Penelope Engel-Hills 1 & Coenraad Hattingh 2 & Jean-Paul Fouche 3,4 & Martin Kidd 5 & Christine Lochner 3 & Maritha J. Kotze 2 & Susan J. van Rensburg 2 Received: 24 April 2017 /Accepted: 18 December 2017 # Springer Science+Business Media, LLC, part of Springer Nature 2018 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. Keywords DTI . Fractional anisotropy . Multiple sclerosis . Disability . EDSS . Iron parameters Introduction Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). One of the diagnostic features of MS is the presence of white matter (WM) lesions in the brain and spinal cord, detected with magnetic resonance imaging (MRI), reflecting a variable extent of myelin and/or neuronal damage (Lassmann 1998; Trapp et al. 1999; Bjartmar et al. 2003). Concurrent with the lesions are a range of clinical symp- toms that can vary considerably between patients. For some, these clinical manifestations are aBlifelong occasional nuisance^, while others experience severe incapacity (DeLuca et al. 2007). This disparity in disability outcome appears to be unrelated to the use of disease modifying therapies (Tremlett et al. 2012; Karim et al. 2014; Shirani et al. 2012; Zhang et al. 2015; Pittock and Rodriguez 2008; Curtiss 2007). What is apparent is that disability in MS involves a failure of functional connectivity in the CNS (Faivre et al. 2016; Lyksborg et al. 2014). One of the most studied mechanisms Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11011-017-0171-5) contains supplementary material, which is available to authorized users. * Estelle Herbert herberte@cput.ac.za 1 Department of Medical Imaging and Therapeutic Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa 2 Division of Chemical Pathology, Department of Pathology, National Health Laboratory Service (NHLS) and Stellenbosch University, Cape Town, South Africa 3 MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Cape Town, South Africa 4 Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa 5 Centre for Statistical Consultation, Stellenbosch University, Cape Town, South Africa Metabolic Brain Disease https://doi.org/10.1007/s11011-017-0171-5