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Randomized Controlled Trial
. 2023 Mar;270(3):1672-1681.
doi: 10.1007/s00415-022-11513-0. Epub 2022 Dec 12.

The insula modulates the effects of aerobic training on cardiovascular function and ambulation in multiple sclerosis

Matteo Albergoni  1 , Loredana Storelli  1 , Paolo Preziosa  1   2   3 , Maria A Rocca  1   2   3 , Massimo Filippi  4   5   6   7   8
Affiliations
Randomized Controlled Trial

The insula modulates the effects of aerobic training on cardiovascular function and ambulation in multiple sclerosis

Matteo Albergoni et al. J Neurol. 2023 Mar.

Abstract

Background: Impairment of cardiovascular control is common in multiple sclerosis (MS), possibly due to damage of strategic brain regions such as the insula. Aerobic training (AT) targets cardiopulmonary system and may represent a neuroprotective strategy.

Purpose: To investigate whether insular damage (T2-hyperintense lesions and volume) is associated with cardiovascular fitness (CF) and influences AT effects in MS.

Methods: Sixty-one MS patients were randomized to an AT intervention group (MS-AT) and a motor training control group (MS-C). At baseline and after training (24 sessions over 2-3 months), peak of oxygen consumption (VO2max), heart rate reserve (HRR), 6-min walk test (6MWT) and whole brain and insula MRI data were collected. Two healthy control (HC) groups were enrolled for CF and MRI data analysis.

Results: At baseline, MS patients vs HC showed impaired VO2max, HRR and 6MWT (p < 0.001) and widespread gray matter atrophy, including bilateral insula. In MS patients, left insula T2-lesion volume correlated with HRR (r = 0.27, p = 0.042). After training, MS-AT, especially those without insular T2-hyperintense lesions, showed 6MWT improvement (p < 0.05) and a stable insular volume, whereas MS-C showed left insular volume loss (p < 0.001).

Conclusions: By increasing 6MWT performance, our results suggest that AT may improve walking capacity and submaximal measure of CF in MS patients. Such beneficial effect may be modulated by insula integrity.

Keywords: Aerobic training; Exercise; Insula; Magnetic resonance imaging; Multiple sclerosis.

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Conflict of interest statement

M. Albergoni has nothing to disclose. L. Storelli declared the receipt of grants and contracts from FISM—Fondazione Italiana Sclerosi Multipla—within a fellowship program (cod. 2019/BR/009). P. Preziosa received speaker honoraria from Roche, Biogen, Novartis, Merck Serono, Bristol Myers Squibb and Genzyme. He has received research support from Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. M.A. Rocca received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche; and speaker honoraria from Bayer, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Merck Healthcare Germany, Merck Serono SpA, Novartis, Roche, and Teva. She receives research support from the MS Society of Canada 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, Associate Editor of Radiology, and Associate Editor of Neurological Sciences; 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, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Figures

Fig. 1
Fig. 1
Baseline voxel-based morphometry results. SPM analysis showing significant differences in GM volume (lower volume encoded in blue/light blue color-coded, p < 0.05 family-wise corrected, cluster extent = 10) superimposed on the custom GM template. (a) Clusters showing widespread pattern of lower GM volume in MS patients compared to HC-MRI. (b) The insula masks used for local VBM analysis (left mask in red and right mask in blue), (c) clusters showing lower GM volume within bilateral insula areas in MS compared to HC-MRI. GM gray matter, HC-MRI healthy control group for baseline magnetic resonance imaging comparison, MS multiple sclerosis, SPM statistical parametric mapping
Fig. 2
Fig. 2
Longitudinal tensor-based morphometry results. SPM analysis showing significant GM volume changes (increased volumes are encoded in red–yellow, while decreased volumes are encoded in blue–light blue, p < 0.001 uncorrected, cluster extent = 10). (a) Clusters showing GM volume increase within MS-AT group after training. (b) Clusters showing GM volume increase within MS-C group after training. (c) Clusters showing GM atrophy within MS-AT group after training. (d) Clusters showing GM atrophy within MS-C group after training. (e) Clusters showing greater GM volume increase in MS-AT compared to MS-C. (f) Clusters showing greater GM atrophy in MS-AT compared to MS-C. GM gray matter, MS multiple sclerosis, MS-AT MS group that performed aerobic training, MS-C MS group that performed motor control training without direct involvement of cardiopulmonary system, SPM statistical parametric mapping. The arrow in (d) points out the atrophy process experienced by MS-C within left insula area
See this image and copyright information in PMC

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