Multiple Sclerosis Journal - October 2017 - 1517
696596
research-article2017
MSJ0010.1177/1352458517696596Multiple Sclerosis JournalM Heine, O Verschuren
MULTIPLE
SCLEROSIS
JOURNAL
MSJ
Original Research Paper
Does aerobic training alleviate fatigue and
improve societal participation in patients with
multiple sclerosis? A randomized controlled trial
Martin Heine, Olaf Verschuren, Erwin LJ Hoogervorst, Erik van Munster, Hub GA Hacking,
Anne Visser-Meily, Jos WR Twisk, Heleen Beckerman, Vincent de Groot, Gert Kwakkel,
on behalf of the TREFAMS-ACE study group
Abstract
Background: Evidence supporting the effectiveness of aerobic training, specific for fatigue, in severely
fatigued patients with multiple sclerosis (MS) is lacking.
Objective: To estimate the effectiveness of aerobic training on MS-related fatigue and societal participation in ambulant patients with severe MS-related fatigue.
Methods: Patients (N = 90) with severe MS-related fatigue were allocated to 16-week aerobic training or
control intervention. Primary outcomes were perceived fatigue (Checklist Individual Strength (CIS20r)
fatigue subscale) and societal participation. An improvement of ⩾8 points on the CIS20r fatigue subscale
was considered clinically relevant. Outcomes were assessed by a blinded observer at baseline, 2, 4, 6 and
12 months.
Results: Of the 89 patients that started treatment (median Expanded Disability Status Scale (interquartile
range), 3.0 (2.0-3.6); mean CIS20r fatigue subscale (standard deviation (SD)), 42.6 (8.0)), 43 received
aerobic training and 46 received the control intervention. A significant post-intervention between-group
mean difference (MD) on the CIS20r fatigue subscale of 4.708 (95% confidence interval (CI) = 1.003-
8.412; p = 0.014) points was found in favour of aerobic training that, however, was not sustained during
follow-up. No effect was found on societal participation.
Conclusion: Aerobic training in MS patients with severe fatigue does not lead to a clinically meaningful
reduction in fatigue or societal participation when compared to a low-intensity control intervention.
Keywords: Multiple sclerosis, rehabilitation, exercise therapy, fatigue, randomized controlled trial
Date received: 13 November 2016; revised: 7 February 2017; accepted: 8 February 2017
Introduction
Multiple sclerosis (MS) is considered an immunemediated chronic disorder of the central nervous system and is the most common neurological disease
causing disability in young and middle-aged people.1
MS-related fatigue is one of the most often reported
symptoms that leads to restrictions in societal participation and performance in daily life at home, at work
and in leisure activities.2,3 MS-related fatigue can be
defined as 'a subjective lack of mental or physical
energy as perceived by the individual (or caregiver) to
interfere with usual and desired activities'.4 It can be
of central or peripheral origin and may affect physical, cognitive or psychosocial functions.5
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Exercise therapy may positively affect MS-related
fatigue, and a variety of mechanisms have been proposed to explain possible beneficial effects including
a neuroprotective effect,6 normalization of hypothalamic-pituitary-adrenal axis imbalances5 or an antiinflammatory effect.7,8 In addition, aerobic training or
exercise in general may reduce the imminent effects
of reduced physical activity and the vicious cycle of
deconditioning leading to a reduced physical fitness,
reduced general health and a higher incidence of
comorbidity.9,10 A meta-analysis evaluating current
evidence on the effectiveness of exercise therapy on
fatigue in patients with MS found a significant heterogeneous moderate effect in favour of exercise therapy
Multiple Sclerosis Journal
2017, Vol. 23(11) 1517-1526
DOI: 10.1177/
https://doi.org/10.1177/1352458517696596
1352458517696596
https://doi.org/10.1177/1352458517696596
© The Author(s), 2017.
Reprints and permissions:
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Correspondence to:
M Heine
VUmc MS Center
Amsterdam and Department
of Rehabilitation Medicine,
VU University Medical
Center, PO Box 7057,
1007 MB Amsterdam, The
Netherlands.
m.heine@vumc.nl
Martin Heine
VUmc MS Center
Amsterdam and Department
of Rehabilitation Medicine,
VU University Medical
Center, Amsterdam, The
Netherlands/Brain Center
Rudolf Magnus and Center of
Excellence for Rehabilitation
Medicine, University
Medical Center Utrecht and
Rehabilitation Center De
Hoogstraat, Utrecht, The
Netherlands
Olaf Verschuren
Anne Visser-Meily
Brain Center Rudolf Magnus
and Center of Excellence
for Rehabilitation Medicine,
University Medical Center
Utrecht and Rehabilitation
Center De Hoogstraat,
Utrecht, The Netherlands
Erwin LJ Hoogervorst
Hub GA Hacking
Multiple Sclerosis Center,
St Antonius Hospital,
Nieuwegein, The Netherlands
Erik van Munster
Department of Neurology,
Jeroen Bosch Ziekenhuis,
Den Bosch, The Netherlands
Jos WR Twisk
Department of Epidemiology
and Biostatistics, VU
University Medical
Center, Amsterdam, The
Netherlands/EMGO+
Institute for Health and Care
Research, VU University
Medical Center, Amsterdam,
The Netherlands
Heleen Beckerman
Vincent de Groot
VUmc MS Center
Amsterdam and Department
of Rehabilitation Medicine,
VU University Medical
Center, Amsterdam, The
1517
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Table of Contents for the Digital Edition of Multiple Sclerosis Journal - October 2017
Contents
Multiple Sclerosis Journal - October 2017 - Cover1
Multiple Sclerosis Journal - October 2017 - Cover2
Multiple Sclerosis Journal - October 2017 - Contents
Multiple Sclerosis Journal - October 2017 - ii
Multiple Sclerosis Journal - October 2017 - iii
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Multiple Sclerosis Journal - October 2017 - 1438
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Multiple Sclerosis Journal - October 2017 - Cover3
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