Contributions
Abstract: P1177
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: The default mode network (DMN) is one of the most relevant functional networks of the human brain, whose resting state (RS) functional connectivity (FC) has been found to be disrupted with aging and in several neurological conditions. Fingolimod (FTY) and natalizumab (NAT) are effective in reducing disease activity, disability progression and brain volume loss in relapsing-remitting multiple sclerosis (RRMS). However, the effect of such treatments on RS FC has not been investigated yet. Aim of this study was to assess DMN RS FC changes in RRMS patients treated with FTY and NAT over two years of treatment.
Methods: Fifty right-handed RRMS patients starting FTY (n=23) or NAT (n=27) underwent 3T RS fMRI brain scans at baseline (T0), month6 (M6), year1 (Y1) and year2 (Y2). A neurological evaluation, with rating of the expanded disability status scale (EDSS) score, was performed at each timepoint. Fifteen age- and sex-matched right-handed healthy controls (HC), who underwent RS fMRI acquisitions at T0 and after a median period of 2.2 years, were also evaluated as reference. Independent component analysis (ICA) was used to decompose RS fMRI data into spatially independent maps and time courses using the GIFT software. SPM12 was then used to assess the longitudinal pattern of DMN RS FC change in each patients' group during the two years of treatment as well as in HC.
Results: At baseline, the two groups were matched for demographic and clinical characteristics. Significant reduction of disease activity was found in both groups over time, with stability of EDSS. ICA allowed to identify two components related to the DMN. At T0, compared with HC, both FTY- and NAT-groups showed a significant lower RS FC in the bilateral posterior cingulate cortex and precuneus. A significant increase of RS FC over time was found in the right posterior cingulate cortex and left precuneus for the FTY-group, and in the bilateral precuneus for the NAT-group, with no significant time x group interaction. No DMN RS FC changes were detected in HC over the same period of time.
Conclusions: A significant increase of RS FC in core regions of the DMN was detected in FTY- and NAT-groups during the first two years of treatment, possibly reflecting a recovery from disease activity occurred before treatment start and a subsequent disease stability. RS FC seems to provide useful information to monitor the effect of therapeutic interventions in patients with MS.
Disclosure: M.A. Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.
P. Preziosa received speakers honoraria from Biogen Idec, Novartis and ExceMED.
G. Comi has received consulting fees for participating on advisory boards from Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Actelion and honorarium for speaking activities for Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Biogen, ExceMED.
M. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
C. Marchetti, P. Valsasina, M. Rodegher, and L. Moiola have nothing to disclose.
Abstract: P1177
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: The default mode network (DMN) is one of the most relevant functional networks of the human brain, whose resting state (RS) functional connectivity (FC) has been found to be disrupted with aging and in several neurological conditions. Fingolimod (FTY) and natalizumab (NAT) are effective in reducing disease activity, disability progression and brain volume loss in relapsing-remitting multiple sclerosis (RRMS). However, the effect of such treatments on RS FC has not been investigated yet. Aim of this study was to assess DMN RS FC changes in RRMS patients treated with FTY and NAT over two years of treatment.
Methods: Fifty right-handed RRMS patients starting FTY (n=23) or NAT (n=27) underwent 3T RS fMRI brain scans at baseline (T0), month6 (M6), year1 (Y1) and year2 (Y2). A neurological evaluation, with rating of the expanded disability status scale (EDSS) score, was performed at each timepoint. Fifteen age- and sex-matched right-handed healthy controls (HC), who underwent RS fMRI acquisitions at T0 and after a median period of 2.2 years, were also evaluated as reference. Independent component analysis (ICA) was used to decompose RS fMRI data into spatially independent maps and time courses using the GIFT software. SPM12 was then used to assess the longitudinal pattern of DMN RS FC change in each patients' group during the two years of treatment as well as in HC.
Results: At baseline, the two groups were matched for demographic and clinical characteristics. Significant reduction of disease activity was found in both groups over time, with stability of EDSS. ICA allowed to identify two components related to the DMN. At T0, compared with HC, both FTY- and NAT-groups showed a significant lower RS FC in the bilateral posterior cingulate cortex and precuneus. A significant increase of RS FC over time was found in the right posterior cingulate cortex and left precuneus for the FTY-group, and in the bilateral precuneus for the NAT-group, with no significant time x group interaction. No DMN RS FC changes were detected in HC over the same period of time.
Conclusions: A significant increase of RS FC in core regions of the DMN was detected in FTY- and NAT-groups during the first two years of treatment, possibly reflecting a recovery from disease activity occurred before treatment start and a subsequent disease stability. RS FC seems to provide useful information to monitor the effect of therapeutic interventions in patients with MS.
Disclosure: M.A. Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.
P. Preziosa received speakers honoraria from Biogen Idec, Novartis and ExceMED.
G. Comi has received consulting fees for participating on advisory boards from Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Actelion and honorarium for speaking activities for Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Biogen, ExceMED.
M. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).
C. Marchetti, P. Valsasina, M. Rodegher, and L. Moiola have nothing to disclose.