Abstract Details

Title Monoaminergic Network Abnormalities Explain Fatigue in Pediatric Multiple Sclerosis

Topic Child Neurology and Developmental Neurology

Presentation(s) S8 - State-of-the-art Diagnostics in Child Neurology (4:54 PM-5:06 PM)

Poster/Presentation
Number 008

Background

Although fatigue is frequently observed in pedMS, little is known about its pathological substrates in these patients.

Objective To investigate monoaminergic network abnormalities in pediatric multiple sclerosis (pedMS) patients according to their fatigue status, through a positron emission tomography (PET)-based constrained independent component analysis (ICA) on resting state (RS) functional MRI (fMRI).

Design/Methods

Fifty-five right-handed pedMS and 23 matched pediatric healthy controls (HC) underwent neurological, fatigue, depression and RS fMRI assessment. Patients were classified as fatigued (F) or non-fatigued (nF) according to their fatigue severity scale (FSS) score. Patterns of dopamine-, noradrenaline- and serotonin-related RS functional connectivity (FC) were derived by ICA, constrained to PET atlases for dopamine, norepinephrine and serotonin transporters, obtained in HCs' brain.

Results

None of pedMS patients had depression and fifteen of them were F. Compared to nF-pedMS patients and HC, F-pedMS patients showed decreased dopamine-related RS FC in the right postcentral gyrus. In addition, F-pedMS patients showed decreased dopamine-related RS FC in the left insula vs HC and increased dopamine-related RS FC in the left middle temporal gyrus and cerebellar lobule VI vs nF-pedMS. In the noradrenaline-related network, F-pedMS patients showed decreased RS FC in the left superior parietal lobule and increased RS FC in the right thalamus compared to HC and nF-pedMS. In addition, F-pedMS patients showed decreased RS FC in the right calcarine cortex and increased RS FC in the right middle frontal gyrus vs HC. Finally, in the serotonin-related network, F-pedMS patients showed decreased RS FC in the right angular gyrus and increased RS FC in the right postcentral gyrus vs nF-pedMS patients and HC.

Conclusions

PedMS patients with fatigue showed specific abnormalities within monoaminergic networks, providing pathological markers for this bothersome symptom and putative targets for its treatment.

Authors/Disclosures
Monica Margoni PRESENTER	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
Lucia Moiola, MD, PhD (Fondazione Centro San Raffaele)	Dr. Moiola has nothing to disclose.
Damiano Mistri, MSC (Università Vita-Salute San Raffaele)	Mr. Mistri has nothing to disclose.
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 $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.