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Updated: Jul 23, 2025
The Effect of Anti-Fatigue Decoction on the Behaviors and Serological Indicators in a Central Fatigue Rat Model
Published on: April 12, 2024
Functional connectivity modifications in monoaminergic circuits occur in fatigued MS patients treated with fampridine
Maria A Rocca1,2,3, Paola Valsasina4, Maria Teresa Lamanna4,5
1Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy. rocca.mara@hsr.it.
Background:
Monoaminergic network dysfunction may have a role in multiple sclerosis (MS) fatigue pathogenesis.
Objective:
To investigate modifications of fatigue severity and resting state (RS) functional connectivity (FC) in monoaminergic networks of 45 fatigued MS patients after different symptomatic treatments.
Methods:
Patients were randomly, blindly assigned to fampridine (n = 15), amantadine (n = 15) or placebo (n = 15) treatment and underwent clinical and 3T-MRI evaluations at baseline (t0) and week 4 (w4), i.e. after four weeks of treatment. Fifteen healthy controls (HC) were enrolled. Dopamine-, noradrenaline- and serotonin-related RS FC was assessed by PET-guided constrained independent component analysis.
Results:
At t0, MS patients showed widespread monoamine-related RS FC abnormalities. At w4, fatigue scores decreased in all groups (p = range < 0.001-0.002). Concomitantly, fampridine and amantadine patients showed increased insular RS FC in dopamine-related and noradrenaline-related networks (p < 0.001, uncorrected). Amantadine patients also showed increased RS FC of anterior cingulate cortex in dopamine-related and noradrenaline-related networks (p < 0.001, uncorrected). Placebo patients showed increased precuneus/middle cingulate RS FC in the noradrenaline-related network (p < 0.001, uncorrected). In fampridine and placebo patients, just tendencies towards correlations between RS FC and fatigue modifications were found.
Conclusions:
In MS patients, specific RS FC modifications in PET-guided monoaminergic networks were observed, concomitantly with fatigue improvements following treatment.
Trial Registration Number:
EudraCT 2010-023678-38.
Insights
Fatigue in multiple sclerosis (MS) improved with fampridine and amantadine, linked to changes in brain
Area of Science:
- Neuroscience
- Neurology
- Medical Imaging
Background:
- Monoaminergic network dysfunction is implicated in multiple sclerosis (MS) fatigue.
- Understanding these mechanisms is crucial for developing effective MS fatigue treatments.
Purpose of the Study:
- To investigate changes in fatigue severity and resting-state functional connectivity (FC) within monoaminergic networks in MS patients undergoing symptomatic treatments.
- To compare the effects of fampridine, amantadine, and placebo on fatigue and brain connectivity.
Main Methods:
- 45 fatigued MS patients were randomized to fampridine, amantadine, or placebo for four weeks.
- Clinical assessments and 3T-MRI scans were performed at baseline and week 4.
- Dopamine-, noradrenaline-, and serotonin-related resting-state FC were analyzed using PET-guided independent component analysis.
Main Results:
- MS patients exhibited widespread abnormalities in monoamine-related FC at baseline.
- Fatigue scores significantly decreased across all treatment groups by week 4.
- Fampridine and amantadine treatments led to increased insular and anterior cingulate cortex FC in dopamine- and noradrenaline-related networks.
- Placebo also showed some FC changes, suggesting non-specific effects.
Conclusions:
- Symptomatic treatments for MS fatigue are associated with specific modifications in PET-guided monoaminergic network functional connectivity.
- These findings highlight the role of monoaminergic networks in MS fatigue and treatment response.
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