Abstract Details

Title Modulation of Large-Scale Functional Networks Occurs in MS Patients Starting Fingolimod or Natalizumab: A 2-Year Resting State Functional Connectivity Study

Topic Multiple Sclerosis

Presentation(s) S31 - MS and CNS Inflammatory Disease: Imaging (3:52 PM-4:03 PM)

Poster/Presentation
Number 003

Background FTY and NAT are effective in reducing disease activity, disability progression and brain volume loss in RRMS patients. The effect of such treatments on brain RS FC has not been investigated yet.

Objective To investigate longitudinal changes of resting state (RS) functional connectivity (FC) in relapsing-remitting (RR) multiple sclerosis (MS) patients treated with fingolimod (FTY) and natalizumab (NAT) over two years of treatment.

Design/Methods Fifty right-handed RRMS patients starting FTY (n=23) or NAT (n=27) underwent 3T RS fMRI acquisitions at baseline (T0), month 6 (M6), year 1 (Y1) and year 2 (Y2). Neurological examinations, with rating of the expanded disability status scale (EDSS) score, and neuropsychological evaluations were performed at each time-point. Fifteen matched right-handed healthy controls (HC), who underwent RS fMRI at T0 and after a median period of 2.2 years, were also recruited. Independent component analysis was used to derive the main large-scale motor and cognitive functional networks. RS FC changes over time were assessed in study group.

Results

At T0, the two patients’ groups were demographically and clinically matched. Significant reduction of disease activity, stability of the EDSS score, and improvement of cognitive performances were found in both groups over time. At T0, both FTY- and NAT-groups showed a significantly lower RS FC in the sensorimotor, default-mode (DMN), fronto-parietal and salience networks vs HC. At Y2, no RS FC changes were detected in HC, whereas a significant RS FC increase was found in sensorimotor, cerebellar, DMN and fronto-parietal networks in both FTY- and NAT-groups, which was correlated with concomitant cognitive improvements.

Conclusions RS FC significantly increased in the main large-scale RS functional networks 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.

Authors/Disclosures
Maria A. Rocca (Neuroimaging Research Unit) PRESENTER	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
	No disclosure on file
Paola Valsasina	No disclosure on file
Paolo Preziosa (Ospedale San Raffaele)	Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Gianna Carla Riccitelli (San Raffaele)	No disclosure on file
	No disclosure on file
Lucia Moiola, MD, PhD (Fondazione Centro San Raffaele)	Dr. Moiola has nothing to disclose.
	No disclosure on file
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.

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