RT Journal Article SR Electronic T1 Impact of Focal White Matter Damage on Localized Subcortical Gray Matter Atrophy in Multiple Sclerosis: A 5-Year Study JF American Journal of Neuroradiology JO Am. J. Neuroradiol. FD American Society of Neuroradiology DO 10.3174/ajnr.A5720 A1 T.A. Fuchs A1 K. Carolus A1 R.H.B. Benedict A1 N. Bergsland A1 D. Ramasamy A1 D. Jakimovski A1 B. Weinstock-Guttman A1 A. Kuceyeski A1 R. Zivadinov A1 M.G. Dwyer YR 2018 UL http://www.ajnr.org/content/early/2018/07/05/ajnr.A5720.abstract AB BACKGROUND AND PURPOSE: It is unclear to what extent subcortical gray matter atrophy is a primary process as opposed to a result of focal white matter damage. Correlations between WM damage and atrophy of subcortical gray matter have been observed but may be partly attributable to indirect relationships between co-occurring processes arising from a common cause. Our aim was to cross-sectionally and longitudinally characterize the unique impact of focal WM damage on the atrophy of connected subcortical gray matter regions, beyond what is explainable by global disease progression.MATERIALS AND METHODS: One hundred seventy-six individuals with MS and 47 healthy controls underwent MR imaging at baseline and 5 years later. Atrophy and lesion-based disruption of connected WM tracts were evaluated for 14 subcortical gray matter regions. Hierarchic regressions were applied, predicting regional atrophy from focal WM disruption, controlling for age, sex, disease duration, whole-brain volume, and T2-lesion volume.RESULTS: When we controlled for whole-brain volume and T2-lesion volume, WM tract disruption explained little additional variance of subcortical gray matter atrophy and was a significant predictor for only 3 of 14 regions cross-sectionally (ΔR2 = 0.004) and 5 regions longitudinally (ΔR2 = 0.016). WM tract disruption was a significant predictor for even fewer regions when correcting for multiple comparisons.CONCLUSIONS: WM tract disruption accounts for a small percentage of atrophy in connected subcortical gray matter when controlling for overall disease burden and is not the primary driver in most cases.HChealthy controlsNeMoNetwork ModificationSGMsubcortical gray matterT2LVT2-lesion volumeWBVwhole-brain volume