Contributions
Abstract: P541
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Fatigue is one of the most common and disabling symptoms in people with multiple sclerosis (pwMS), but its pathophysiological basis is still not fully understood. Modern, tractography-driven approaches are now capable of quantifying specific disruptions caused by white matter (WM) lesions. Coupled with connectome-style analysis, they may be able to better elucidate the causes of fatigue.
Objective: To identify structural brain networks whose disruption relates most significantly with fatigue among pwMS.
Methods: The Fatigue Severity Scale (FSS) was employed to assess fatigue in 141 pwMS and CIS. Severity of lesion-based WM tract disruption between pairwise gray matter 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 gray matter regions. Next, network-level analysis, controlling for disease group, age, sex, and depression, was carried out with the Network-Based-Statistics (NBS) tool. Results were considered significant at p< 0.05, corrected for multiple comparisons. Post-hoc hierarchical regressions were employed to determine the direction of the relationship between significantly associated networks and fatigue. Corticospinal tract disruption was also included in these models in order to discriminate between primary vs. secondary fatigue.
Results: Disruption in three networks were found to be significantly associated with fatigue (all p ≤ 0.001) after adjustment for age, gender and depression. These three networks consisted of a total of 6 region pairs (average test-statistic = 4.44). Two of these networks consisted of amygdala to ipsilateral temporal pole and amygdala to other surrounding ipsilateral structures. The third network included a single connection, banks of the superior temporal sulcus to inferior parietal. Post-hoc analysis revealed that the amygdala-based network disruption was negatively associated with fatigue, such that increased amygdala network disruption was associated with decreased fatigue. In contrast, disruption of corticospinal tracts was positively associated with fatigue.
Conclusions: Corticospinal tract disruption is associated with increased fatigue, but damage to WM connections between the amygdala and surrounding ipsilateral structures is associated with a paradoxical reduction in fatigue in pwMS.
Disclosure:
Tom Fuchs, Caila Vaughn, Sanjeevani Choudhery, Keith Carolus, Niels Bergsland, 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.
Ralph 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
R 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.
Michael G. Dwyer has received consultant fees from Claret Medical and EMD Serono and research grant support from Novartis.
Abstract: P541
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Fatigue is one of the most common and disabling symptoms in people with multiple sclerosis (pwMS), but its pathophysiological basis is still not fully understood. Modern, tractography-driven approaches are now capable of quantifying specific disruptions caused by white matter (WM) lesions. Coupled with connectome-style analysis, they may be able to better elucidate the causes of fatigue.
Objective: To identify structural brain networks whose disruption relates most significantly with fatigue among pwMS.
Methods: The Fatigue Severity Scale (FSS) was employed to assess fatigue in 141 pwMS and CIS. Severity of lesion-based WM tract disruption between pairwise gray matter 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 gray matter regions. Next, network-level analysis, controlling for disease group, age, sex, and depression, was carried out with the Network-Based-Statistics (NBS) tool. Results were considered significant at p< 0.05, corrected for multiple comparisons. Post-hoc hierarchical regressions were employed to determine the direction of the relationship between significantly associated networks and fatigue. Corticospinal tract disruption was also included in these models in order to discriminate between primary vs. secondary fatigue.
Results: Disruption in three networks were found to be significantly associated with fatigue (all p ≤ 0.001) after adjustment for age, gender and depression. These three networks consisted of a total of 6 region pairs (average test-statistic = 4.44). Two of these networks consisted of amygdala to ipsilateral temporal pole and amygdala to other surrounding ipsilateral structures. The third network included a single connection, banks of the superior temporal sulcus to inferior parietal. Post-hoc analysis revealed that the amygdala-based network disruption was negatively associated with fatigue, such that increased amygdala network disruption was associated with decreased fatigue. In contrast, disruption of corticospinal tracts was positively associated with fatigue.
Conclusions: Corticospinal tract disruption is associated with increased fatigue, but damage to WM connections between the amygdala and surrounding ipsilateral structures is associated with a paradoxical reduction in fatigue in pwMS.
Disclosure:
Tom Fuchs, Caila Vaughn, Sanjeevani Choudhery, Keith Carolus, Niels Bergsland, 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.
Ralph 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
R 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.
Michael G. Dwyer has received consultant fees from Claret Medical and EMD Serono and research grant support from Novartis.