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Thalamic nuclei volume partially mediates the effects of aerobic capacity on fatigue in people with multiple sclerosis

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Abstract

Background

Fatigue is frequent in people with multiple sclerosis (pwMS) impacting physical and cognitive functions. Lower aerobic capacity and regional thalamic volume may be involved in the pathophysiology of fatigue in pwMS.

Objectives

To identify associations between thalamic nuclei volumes, aerobic capacity and fatigue and to investigate whether the influence of aerobic capacity on fatigue in pwMS is mediated by thalamic integrity.

Methods

Eighty-three pwMS underwent a clinical evaluation with assessment of fatigue (Modified Fatigue Impact Scale [MFIS]), including physical (pMFIS) and cognitive (cMFIS) components, and peak of oxygen uptake (VO2peak). PwMS and 63 sex- and age-matched healthy controls (HC) underwent a 3 T brain MRI to quantify volume of the whole thalamus and its nuclei.

Results

Compared to HC, pwMS showed higher global MFIS, pMFIS and cMFIS scores, and lower VO2peak and thalamic volumes (p < 0.001). In pwMS, higher VO2peak was significantly associated with lower MFIS and pMFIS scores (r value = − 0.326 and − 0.356; pFDR ≤ 0.046) and higher laterodorsal thalamic nucleus (Dor) cluster volume (r value = 0.300; pFDR = 0.047). Moreover, lower Dor thalamic cluster volume was significantly associated with higher MFIS, pMFIS and cMFIS scores (r value range = − 0.305; − 0.293; pFDR ≤ 0.049). The volume of Dor thalamic cluster partially mediated the positive effects of VO2peak on both MFIS and cMFIS, with relative indirect effects of 21% and 32% respectively. No mediation was found for pMFIS.

Conclusions

Higher VO2peak is associated with lower fatigue in pwMS, likely acting on Dor thalamic cluster volume integrity. Such an effect might be different according to the type of fatigue (cognitive or physical).

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Data availability

The data sets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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Funding

This study has been supported by grant from Italian Ministry of Health (GR-2019–12369599).

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Authors and Affiliations

  1. Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy

    Matteo Albergoni, Elisabetta Pagani, Paolo Preziosa, Alessandro Meani, Monica Margoni, Maria A. Rocca & Massimo Filippi

  2. Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Paolo Preziosa, Monica Margoni, Maria A. Rocca & Massimo Filippi

  3. Vita-Salute San Raffaele University, Milan, Italy

    Paolo Preziosa, Maria A. Rocca & Massimo Filippi

  4. Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Monica Margoni & Massimo Filippi

  5. Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Massimo Filippi

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  1. Matteo Albergoni
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Corresponding author

Correspondence to Massimo Filippi.

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Conflicts of interest

M. Albergoni has nothing to disclose; E. Pagani has nothing to disclose; P. Preziosa received speaker honoraria from Roche, Biogen, Novartis, Merck Serono, Bristol Myers Squibb, Genzyme, Horizon and Sanofi, he has received research support from Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla; A. Meani has nothing to disclose; M.A. Rocca received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche; and speaker honoraria from AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. She receives research support from the MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla. She is Associate Editor for Multiple Sclerosis and Related Disorders. M. Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology; received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme; he receives 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.

Ethical approval

Approval was received from the institutional ethical standards committee on human experimentation of IRCCS Ospedale San Raffaele (Protocol number 59/INT/2015). Written informed consent was obtained from all subjects prior to study participation according to the Declaration of Helsinki.

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Albergoni, M., Pagani, E., Preziosa, P. et al. Thalamic nuclei volume partially mediates the effects of aerobic capacity on fatigue in people with multiple sclerosis. J Neurol (2024). https://doi.org/10.1007/s00415-024-12277-5

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  • DOI: https://doi.org/10.1007/s00415-024-12277-5

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