Modulation of cortico-subcortical functional connectivity occurs after symptomatic treatment of fatigue in patients with multiple sclerosis
Author(s): ,
M.A. Rocca
Affiliations:
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience; Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience
,
P. Valsasina
Affiliations:
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience
,
B. Colombo
Affiliations:
Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience
,
V. Martinelli
Affiliations:
Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience
,
A. Falini
Affiliations:
Department of Neuroradiology and CERMAC, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
,
G. Comi
Affiliations:
Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience
M. Filippi
Affiliations:
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience; Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience
ECTRIMS Online Library. Rocca M. 10/10/18; 228478; P634
Dr. Maria Assunta Rocca
Dr. Maria Assunta Rocca
Contributions
Abstract

Abstract: P634

Type: Poster Sessions

Abstract Category: Therapy - Symptomatic treatment

Background: Fatigue affects a large proportion of patients with MS and has been associated with functional abnormalities of cortico-subcortical circuits, involving fronto-parietal regions and basal ganglia. Aim of this study was to investigate longitudinal changes of brain resting state (RS) functional connectivity (FC) in MS patients with fatigue undergoing different treatments for this symptom.
Methods: Forty-five fatigued MS patients were randomly, blindly assigned to treatment with fampridine (n=15), amantadine (n=15) or placebo (n=15) and underwent clinical, neuropsychological (including fatigue assessment) and 3T RS fMRI at baseline (T0) and after four weeks (W4) of treatment. Fifteen matched healthy controls were acquired twice. RS FC analysis of the main brain functional networks was performed using independent component analysis and statistical parametric mapping.
Results: At T0, compared with controls, MS patients showed increased RS FC of deep grey matter regions in the basal ganglia network, as well as several clusters of higher fronto-parietal RS FC in the sensorimotor, visual, and fronto-parietal attention networks. Decreased RS FC in the left postcentral gyrus was also detected. At W4, significantly decreased global, physical and cognitive (p=0.001/0.003/0.01) modified fatigue impact scale (MFIS) scores were found in fampridine patients and, to a lesser extent, in amantadine patients (cognitive and psycho-social MFIS, p=0.04). Placebo patients also showed improved global, physical and psycho-social MFIS (p=0.02/0.01/0.02). At W4, fampridine patients showed increased RS FC of the bilateral precuneus in the default mode and left fronto-parietal networks, as well as increased RS FC of the right inferior frontal gyrus in the salience and right fronto-parietal attention networks. At W4, small clusters of increased RS FC in frontal regions and decreased RS FC in temporo-parietal regions were detected in placebo and amantadine patients. A significant decrease over time of RS FC within the thalamus and other deep grey matter regions was found in fampridine and amantadine patients.
Conclusions: Treatment with fampridine (and, to a lesser extent, with amantadine) ameliorates fatigue in MS patients. Concomitant modifications of RS FC suggest an improved regulation of cortico-subcortical functional circuits.
Support: Partially supported by Italian Ministry of Healthy (GR-2008-1138784) and Fondazione Italiana Sclerosi Multipla (FISM 2018/S/3).
Disclosure: M.A. Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.
P. Valsasina, B Colombo, and A Falini have nothing to disclose.
V. Martinelli V.M. reports consultancy, speaking fees and/or travel expenses from Biogen‐Dompé SG, Merck Serono, Bayer Schering, Novartis, Sanofi‐Aventis, Genzyme Europe and Teva Pharmaceuticals
G. Comi has received consulting fees for participating on advisory boards from Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Actelion and honorarium for speaking activities for Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Biogen, ExceMED.
M. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Abstract: P634

Type: Poster Sessions

Abstract Category: Therapy - Symptomatic treatment

Background: Fatigue affects a large proportion of patients with MS and has been associated with functional abnormalities of cortico-subcortical circuits, involving fronto-parietal regions and basal ganglia. Aim of this study was to investigate longitudinal changes of brain resting state (RS) functional connectivity (FC) in MS patients with fatigue undergoing different treatments for this symptom.
Methods: Forty-five fatigued MS patients were randomly, blindly assigned to treatment with fampridine (n=15), amantadine (n=15) or placebo (n=15) and underwent clinical, neuropsychological (including fatigue assessment) and 3T RS fMRI at baseline (T0) and after four weeks (W4) of treatment. Fifteen matched healthy controls were acquired twice. RS FC analysis of the main brain functional networks was performed using independent component analysis and statistical parametric mapping.
Results: At T0, compared with controls, MS patients showed increased RS FC of deep grey matter regions in the basal ganglia network, as well as several clusters of higher fronto-parietal RS FC in the sensorimotor, visual, and fronto-parietal attention networks. Decreased RS FC in the left postcentral gyrus was also detected. At W4, significantly decreased global, physical and cognitive (p=0.001/0.003/0.01) modified fatigue impact scale (MFIS) scores were found in fampridine patients and, to a lesser extent, in amantadine patients (cognitive and psycho-social MFIS, p=0.04). Placebo patients also showed improved global, physical and psycho-social MFIS (p=0.02/0.01/0.02). At W4, fampridine patients showed increased RS FC of the bilateral precuneus in the default mode and left fronto-parietal networks, as well as increased RS FC of the right inferior frontal gyrus in the salience and right fronto-parietal attention networks. At W4, small clusters of increased RS FC in frontal regions and decreased RS FC in temporo-parietal regions were detected in placebo and amantadine patients. A significant decrease over time of RS FC within the thalamus and other deep grey matter regions was found in fampridine and amantadine patients.
Conclusions: Treatment with fampridine (and, to a lesser extent, with amantadine) ameliorates fatigue in MS patients. Concomitant modifications of RS FC suggest an improved regulation of cortico-subcortical functional circuits.
Support: Partially supported by Italian Ministry of Healthy (GR-2008-1138784) and Fondazione Italiana Sclerosi Multipla (FISM 2018/S/3).
Disclosure: M.A. Rocca received speakers honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche and receives research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla.
P. Valsasina, B Colombo, and A Falini have nothing to disclose.
V. Martinelli V.M. reports consultancy, speaking fees and/or travel expenses from Biogen‐Dompé SG, Merck Serono, Bayer Schering, Novartis, Sanofi‐Aventis, Genzyme Europe and Teva Pharmaceuticals
G. Comi has received consulting fees for participating on advisory boards from Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Actelion and honorarium for speaking activities for Novartis, Teva Pharmaceutical Ind. Ltd, Sanofi, Genzyme, Merck Serono, Bayer, Biogen, ExceMED.
M. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

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