T A Fuchs1,2, K Carolus1, R H B Benedict2, N Bergsland2, D Ramasamy1,2, D Jakimovski1,2, B Weinstock-Guttman2, A Kuceyeski3, R Zivadinov1,4, M G Dwyer5,2. 1. From the Department of Neurology (T.F., K.C., N.B., D.R., D.J., R.Z., M.G.D.), Buffalo Neuroimaging Analysis Center. 2. Department of Neurology (T.F., R.H.B.B., N.B., D.R., D.J., B.W.G., M.G.D.), Jacobs Multiple Sclerosis Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York. 3. Department of Radiology (A.K.), Weill Cornell Medicine, Feil Family Brain and Mind Research Institute, New York, New York. 4. MR Imaging Clinical Translational Research Center (R.Z.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York. 5. From the Department of Neurology (T.F., K.C., N.B., D.R., D.J., R.Z., M.G.D.), Buffalo Neuroimaging Analysis Center mgdwyer@buffalo.edu.
Abstract
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.
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.
Authors: Keith Carolus; Tom A Fuchs; Niels Bergsland; Deepa Ramasamy; Hoan Tran; Tomas Uher; Dana Horakova; Manuela Vaneckova; Eva Havrdova; Ralph H B Benedict; Robert Zivadinov; Michael G Dwyer Journal: J Neurol Date: 2022-04-08 Impact factor: 6.682
Authors: Dejan Jakimovski; Jens Kuhle; Murali Ramanathan; Christian Barro; Davorka Tomic; Jesper Hagemeier; Harald Kropshofer; Niels Bergsland; David Leppert; Michael G Dwyer; Zuzanna Michalak; Ralph H B Benedict; Bianca Weinstock-Guttman; Robert Zivadinov Journal: Ann Clin Transl Neurol Date: 2019-08-22 Impact factor: 4.511
Authors: Matthias Bussas; Sophia Grahl; Viola Pongratz; Achim Berthele; Christiane Gasperi; Till Andlauer; Christian Gaser; Jan S Kirschke; Benedikt Wiestler; Claus Zimmer; Bernhard Hemmer; Mark Mühlau Journal: Mult Scler Date: 2021-09-30 Impact factor: 5.855