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Abstract Details

Patterns of Cerebellar Atrophy and Resting State Functional Connectivity Changes in Relapsing-Remitting MS Patients Starting Fingolimod and Natalizumab: A 2-Year Study
Multiple Sclerosis
S5 - Multiple Sclerosis: Clinical Trials and Disease-modifying Therapy (2:12 PM-2:24 PM)
007
To compare the effects of fingolimod and natalizumab on cerebellar atrophy and resting state (RS) functional connectivity (FC) in relapsing-remitting multiple sclerosis (RRMS) after two years of treatment.
Fingolimod and natalizumab significantly reduce disease activity, but their effects on cerebellar structural and functional abnormalities have not been investigated yet.
RRMS patients starting fingolimod (n=23) or natalizumab (n=27) underwent 3T MRI scans at baseline (T0), month-6 (M6), year-1 (Y1) and year-2 (Y2). Fifteen healthy controls (HC) were also acquired at T0 and Y2. Baseline cerebellar fraction and its longitudinal changes were estimated using SUIT, SPM12 and a Jacobian integration method. Seed-based cerebellar RS FC of the bilateral CrusI/CrusII was also calculated.

At T0, no between-group cerebellar volume differences were found, while reduced intra- and inter-cerebellar and thalamo-cerebellar RS FC was found in both patients’ groups vs HC. Fingolimod-patients experienced a significantly higher cerebellar atrophy rate compared to natalizumab-patients  at M6 vs T0 (-1.28% vs -0.06%), still occurring at Y2 vs M6 (-1.38% vs +0.01%, p<0.001). At Y2 vs T0, fingolimod-patients developed a more severe cerebellar atrophy (-0.93%) compared to HC (-0.29%) and natalizumab-group (-0.10%) (p<0.001). While RS FC was stable in HC longitudinally, both patients’ groups showed a progressive reduction of cerebellar RS FC with fronto-parietal regions and a progressive increase of cerebellar RS FC with bilateral cerebellar regions and deep gray matter. In natalizumab-patients, RS FC changes were linear over time and independent from cerebellar atrophy. Conversely, in fingolimod-patients, cerebellar RS FC reduction was mainly detected at M6 vs T0, while RS FC increase mainly occurred at Y2 vs M6 and was partially associated with lower cerebellar atrophy progression. 
Natalizumab is superior to fingolimod in limiting cerebellar atrophy progression. Both drugs promote cerebellar networks reorganization after two years of treatment. Increased RS FC may compensate cerebellar structural damage accumulation.
Authors/Disclosures
Paolo Preziosa (Ospedale San Raffaele)
PRESENTER 		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.
Paola Valsasina No disclosure on file
Loredana Storelli Loredana Storelli has nothing to disclose.
Elisabetta Pagani Elisabetta Pagani has nothing to disclose.
Lucia Moiola, MD, PhD (Fondazione Centro San Raffaele) Dr. Moiola has nothing to disclose.
No disclosure on file
Maria A. Rocca (Neuroimaging Research Unit) 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.
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.