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Abstract Details

Functional Connectivity Modifications in Monoaminergic Circuits Underpin Fatigue Development in MS Patients
Multiple Sclerosis
P11 - Poster Session 11 (5:30 PM-6:30 PM)
6-008
Fatigue affects a large proportion of MS patients. Dysregulation of monoaminergic networks might have a role in fatigue pathogenesis.
To investigate changes over time of resting state (RS) functional connectivity (FC) in monoaminergic networks and their association with fatigue development in multiple sclerosis (MS).

Eighty-nine right-handed MS patients and 49 matched healthy controls (HC) underwent neurological, fatigue and 3.0T RS functional MRI assessment at baseline and after 1.3 year median follow-up (interquartile range=1.01-2.01 years). Fatigue was evaluated at baseline and follow-up using the modified fatigue impact scale (MFIS) score. Patients were considered as fatigued if MFIS was >38. Monoaminergic-related RS FC was estimated using an independent component analysis constrained to PET atlases for dopamine, noradrenaline and serotonin transporters.

At baseline, 24 (27%) MS patients were fatigued (F) and 65 were not fatigued (NF). Of these, 22 (34%) developed fatigue (devFAT) at follow-up and 43 remained NF (noFAT). At baseline, F-MS patients were characterized by increased monoaminergic-related RS FC in hippocampal, postcentral, temporal and occipital cortices, as well as by decreased RS FC in the insular cortex. During the follow-up, noFAT MS patients showed limited dopamine-related RS FC changes over time. Conversely, devFAT MS patients showed increased dopamine-related RS FC in the left hippocampus, significant at time-by-group interaction analysis. In the noradrenaline-related network, noFAT patients showed decreased RS FC over time in the left superior frontal gyrus. This region showed increased RS FC in both devFAT and F-MS patients; this divergent behavior was significant at time-by-group interaction analysis. Finally, devFAT MS patients presented increased serotonin-related RS FC over time in the angular and middle occipital gyri, while this latter region showed decreased serotonin-related RS FC at follow-up vs baseline in F-MS.

Specific patterns of monoaminergic networks changes over time characterized MS patients according to fatigue status.

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.
Monica Margoni Monica Margoni has received research support from MAGNIMS. Monica Margoni has received research support from Merck-Serono. Monica Margoni has received research support from Sanofi-Genzyme.
Paola Valsasina No disclosure on file
Anna Bacchetti No disclosure on file
Damiano Mistri, MSC (Università Vita-Salute San Raffaele) Mr. Mistri has nothing to disclose.
Nicolò Tedone (San Raffaele hospital) 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 $5,000-$9,999 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.