2024 American Academy of Neurology Abstract Website

Monica Margoni¹, Paola Valsasina², Lucia Moiola³, Damiano Mistri², Maria Rocca⁴, Massimo Filippi⁵
¹Neuroimaging Research Unit, Division of Neuroscience; Neurology Unit; and Neurorehabilitation Unit, ²Neuroimaging Research Unit, Division of Neuroscience, ³Neurology Unit, IRCCS San Raffaele Scientific Institute, ⁴Neuroimaging Research Unit, Division of Neuroscience; and Neurology Unit, ⁵Neuroimaging Research Unit, Division of Neuroscience; Neurology Unit; Neurorehabilitation Unit; and Neurophysiology Service, IRCCS San Raffaele Scientific Institute; and Vita-Salute San Raffaele University

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).

Background:

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

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.