Contributions
Abstract: EP1540
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: Natalizumab treatment is highly effective in limiting the formation of new white matter (WM) lesions in multiple sclerosis (MS). It is currently unknown, however, in which way natalizumab influences the functional brain network. In this study, we longitudinally examined the severity of functional network changes in MS patients treated by either interferon-β/glatiramer acetate (IFNb/GA) or natalizumab over a period of one year.
Methods: For a period of one year, we followed relapsing-remitting MS patients initiating natalizumab at baseline (N=20), continuing IFNb/GA (N=17) and healthy controls (HC; N=13). All participants underwent resting-state fMRI and structural MRI, as well as cognitive and clinical assessments. For each subject, a whole-brain functional network was constructed by calculating the functional connectivity between all pairs of brain regions in the automated anatomical labeling (AAL) atlas. For each network connection a Z-score was calculated relative to HC and the average increase or decrease in Z-scores at baseline and after one year were defined as the severity of functional network change. Progression in severity of functional network changes was related to lesion load, whole-brain WM integrity and deep grey matter volume, as well as longitudinal changes in average cognition, nine-hole peg test (9-HPT) performance and EDSS.
Results: At baseline, only significant increases in connectivity were observed in MS compared to HC (p< 0.05), without differences between the natalizumab and IFNb/GA groups. After one year, functional connectivity levels further increased, but only in patients treated with IFNb/GA (24%; p< 0.05), whereas functional connectivity levels remained stable in the natalizumab and HC group. In MS, this change in functional connectivity was associated with increasing lesion load and loss of WM integrity (resp. rho=0.408 and rho=-0.383) and a decline in performance on the 9-HPT (rho=0.419).
Conclusion: In MS patients initiating natalizumab treatment, the severity of functional network changes remained stable in the first year of treatment, while the functional connectivity of those patients treated with IFNb/GA therapy increased over a 1-year period. These findings indicate that natalizumab may stabilize the functional network in MS.
Disclosure: KA Meijer receives research support from a research grant from Biogen Idec.
O Wiebenga has nothing to disclose.
AJC Eijlers receives research support from the Dutch MS Research Foundation, grant number 14-358e.
MD Steenwijk has nothing to disclose.
JJG Geurts is an editor of Multiple Sclerosis Journal, a member of the editorial boards of BMC Neurology, Neurology and Frontiers in Neurology, and serves as a consultant for Biogen and Genzyme.
MM Schoonheim receives research support from the Dutch MS Research Foundation, grant number 13-820, and has received compensation for consulting services or speaker honoraria from ExceMed, Genzyme and Biogen, and serves on the editorial board of Frontiers in Neurology
Abstract: EP1540
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: Natalizumab treatment is highly effective in limiting the formation of new white matter (WM) lesions in multiple sclerosis (MS). It is currently unknown, however, in which way natalizumab influences the functional brain network. In this study, we longitudinally examined the severity of functional network changes in MS patients treated by either interferon-β/glatiramer acetate (IFNb/GA) or natalizumab over a period of one year.
Methods: For a period of one year, we followed relapsing-remitting MS patients initiating natalizumab at baseline (N=20), continuing IFNb/GA (N=17) and healthy controls (HC; N=13). All participants underwent resting-state fMRI and structural MRI, as well as cognitive and clinical assessments. For each subject, a whole-brain functional network was constructed by calculating the functional connectivity between all pairs of brain regions in the automated anatomical labeling (AAL) atlas. For each network connection a Z-score was calculated relative to HC and the average increase or decrease in Z-scores at baseline and after one year were defined as the severity of functional network change. Progression in severity of functional network changes was related to lesion load, whole-brain WM integrity and deep grey matter volume, as well as longitudinal changes in average cognition, nine-hole peg test (9-HPT) performance and EDSS.
Results: At baseline, only significant increases in connectivity were observed in MS compared to HC (p< 0.05), without differences between the natalizumab and IFNb/GA groups. After one year, functional connectivity levels further increased, but only in patients treated with IFNb/GA (24%; p< 0.05), whereas functional connectivity levels remained stable in the natalizumab and HC group. In MS, this change in functional connectivity was associated with increasing lesion load and loss of WM integrity (resp. rho=0.408 and rho=-0.383) and a decline in performance on the 9-HPT (rho=0.419).
Conclusion: In MS patients initiating natalizumab treatment, the severity of functional network changes remained stable in the first year of treatment, while the functional connectivity of those patients treated with IFNb/GA therapy increased over a 1-year period. These findings indicate that natalizumab may stabilize the functional network in MS.
Disclosure: KA Meijer receives research support from a research grant from Biogen Idec.
O Wiebenga has nothing to disclose.
AJC Eijlers receives research support from the Dutch MS Research Foundation, grant number 14-358e.
MD Steenwijk has nothing to disclose.
JJG Geurts is an editor of Multiple Sclerosis Journal, a member of the editorial boards of BMC Neurology, Neurology and Frontiers in Neurology, and serves as a consultant for Biogen and Genzyme.
MM Schoonheim receives research support from the Dutch MS Research Foundation, grant number 13-820, and has received compensation for consulting services or speaker honoraria from ExceMed, Genzyme and Biogen, and serves on the editorial board of Frontiers in Neurology