Contributions
Abstract: P1016
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 19 Neurodegeneration
Background: Subcortical gray matter (SGM) atrophy in multiple sclerosis (MS) is a key component of the disease, but it is not clear to what extent this is a primary process as opposed to a secondary result of focal white matter (WM) damage. Although there is evidence of a moderate relationship between SGM volume and lesions in connected tracts, this phenomenon is poorly characterized longitudinally.
Objective: To determine the impact of lesion-based changes in WM tract disruption on gray matter atrophy over 5 years.
Methods: 184 people with MS underwent MRI at baseline and 5-year follow-up. SGM volumes were measured for right and left thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, and accumbens using FIRST. Lesion-based disruption of tracts connecting to SGM regions was assessed using the Network Modification tool. Each lesion was used as a seed region in a high resolution reference cohort, and diffusion streamlines were followed to individual atlas-based SGM regions. Hierarchical regressions were then used to determine the relationship between change in WM tract disruption over 5 years and change in individual SGM volumes, controlling for age, sex, and whole brain atrophy.
Results: Change in connected WM tract disruption explained significant (p< 0.05) unique, additive variance in regression models predicting regional SGM atrophy for four of the fourteen SGM regions included in our analysis. These included the left hippocampus (R2 change = 0.058), right putamen (R2 change = 0.064), right globus pallidus (R2 change = 0.028), and right amygdala (R2 change = 0.043). Weak trends were also seen for the left putamen (R2 change =0.012, p=0.066) and left globus pallidus (R2 change = 0.01, p=0.083).
Conclusions: Change in lesion-based disconnection and change in SGM volume are associated for some SGM regions, but the associations are weaker than previously reported for cross-sectional analyses. This may indicate either an increased role for primary SGM damage or a longer time window than 5 years for lesions to substantially impact atrophy.
Disclosure:
Tom Fuchs, Keith Carolus, Xian Li, Niels P. Bergsland, Deepa Ramasamy, and Dejan Jakimovki have nothing to disclose.
Bianca Weinstock-Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme, Sanofi, Novartis and Acorda. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono,Genzyme, Sanofi, Novartis, Acorda.
Robert Zivadinov received personal compensation from EMD Serono, Genzyme-Sanofi, Novartis, Claret-Medical, Celgene for speaking and consultant fees. He received financial support for research activities from Claret Medical, Genzyme-Sanofi, QuintilesIMS Health, Intekrin-Coherus, Novartis and Intekrin-Coherus.
Ralph H.B. Benedict has acted as a consultant or scientific advisory board member for Bayer, Biogen Idec, Actelion, and Novartis. He receives royalties from Psychological Assessment Resources, Inc. He has received financial support for research activities from Shire Pharmaceuticals, Accorda and Biogen Idec
Michael G. Dwyer has received consultant fees from Claret Medical and EMD Serono and research grant support from Novartis.
Abstract: P1016
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 19 Neurodegeneration
Background: Subcortical gray matter (SGM) atrophy in multiple sclerosis (MS) is a key component of the disease, but it is not clear to what extent this is a primary process as opposed to a secondary result of focal white matter (WM) damage. Although there is evidence of a moderate relationship between SGM volume and lesions in connected tracts, this phenomenon is poorly characterized longitudinally.
Objective: To determine the impact of lesion-based changes in WM tract disruption on gray matter atrophy over 5 years.
Methods: 184 people with MS underwent MRI at baseline and 5-year follow-up. SGM volumes were measured for right and left thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, and accumbens using FIRST. Lesion-based disruption of tracts connecting to SGM regions was assessed using the Network Modification tool. Each lesion was used as a seed region in a high resolution reference cohort, and diffusion streamlines were followed to individual atlas-based SGM regions. Hierarchical regressions were then used to determine the relationship between change in WM tract disruption over 5 years and change in individual SGM volumes, controlling for age, sex, and whole brain atrophy.
Results: Change in connected WM tract disruption explained significant (p< 0.05) unique, additive variance in regression models predicting regional SGM atrophy for four of the fourteen SGM regions included in our analysis. These included the left hippocampus (R2 change = 0.058), right putamen (R2 change = 0.064), right globus pallidus (R2 change = 0.028), and right amygdala (R2 change = 0.043). Weak trends were also seen for the left putamen (R2 change =0.012, p=0.066) and left globus pallidus (R2 change = 0.01, p=0.083).
Conclusions: Change in lesion-based disconnection and change in SGM volume are associated for some SGM regions, but the associations are weaker than previously reported for cross-sectional analyses. This may indicate either an increased role for primary SGM damage or a longer time window than 5 years for lesions to substantially impact atrophy.
Disclosure:
Tom Fuchs, Keith Carolus, Xian Li, Niels P. Bergsland, Deepa Ramasamy, and Dejan Jakimovki have nothing to disclose.
Bianca Weinstock-Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme, Sanofi, Novartis and Acorda. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono,Genzyme, Sanofi, Novartis, Acorda.
Robert Zivadinov received personal compensation from EMD Serono, Genzyme-Sanofi, Novartis, Claret-Medical, Celgene for speaking and consultant fees. He received financial support for research activities from Claret Medical, Genzyme-Sanofi, QuintilesIMS Health, Intekrin-Coherus, Novartis and Intekrin-Coherus.
Ralph H.B. Benedict has acted as a consultant or scientific advisory board member for Bayer, Biogen Idec, Actelion, and Novartis. He receives royalties from Psychological Assessment Resources, Inc. He has received financial support for research activities from Shire Pharmaceuticals, Accorda and Biogen Idec
Michael G. Dwyer has received consultant fees from Claret Medical and EMD Serono and research grant support from Novartis.