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Does aerobic training alleviate fatigue with MSers? Maybe not

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  • Does aerobic training alleviate fatigue with MSers? Maybe not

    Despite a number of studies that have found trends toward the reverse, this new study says that aerobic training does not ameliorate extreme fatigue in MS. Disappointing. Was the study flawed? Are we too optimistic about exercise's effect on our disease? Sometimes science doesn't mesh with our wants. The full study won't be released until December 2016 for us to examine their research.

    Here is how the lead researcher summed it up soberingly: "There were a few people who said they felt better, but that wasn't enough to make the study meaningful. If I look at all the measures we have, I don't think we can treat fatigue with exercise training."

    For folks who struggle with extreme fatigue, this study says don't beat yourself up trying to exercise your way out of this crushing symptom of MS. Until evidence says otherwise, I have to begrudgingly go along. - D


    Does aerobic training alleviate fatigue and improve societal participation in patients with multiple sclerosis? The TREFAMS-A multicentre randomised trial

    M. Heine1,2, O. Verschuren2, E. Hoogervorst3, E. van Munster4, H. Hacking3, A. Visser-Meily2, J. Twisk5,6, H. Beckerman1,6, V. de Groot1,6, G. Kwakkel1,7,8, TREFAMS-ACE Study Group 1Rehabilitation Medicine, VUmc MS Center, VU University Medical Center, Amsterdam, 2Brain Center Rudolf Magnus and Center of Excellence for Rehabilitation Medicine, University Medical Center Utrecht and Rehabilitation Center de Hoogstraat, Utrecht, 3Multiple Sclerosis Center, St. Antonius Hospital, Nieuwegein, 4Neurology, Jeroen Bosch Hospital, Den Bosch, 5Epidemiology and Biostatistics, 6EMGO+ Institute for Health and Care Research, VU University Medical Center, 7Neurorehabilitation, Reade Centre of Rehabilitation and Rheumatology, Amsterdam, The Netherlands, 8Physical Therapy and Human Movement Sciences, Northwestern University, Evanston, IL, United States

    Background: Aerobic training may prove a viable treatment to alleviate the commonly reported fatigue in patients with multiple sclerosis (MS). However, limited evidence is available for its effectiveness in fatigued patients with MS.

    Methods: Treating fatigue in multiple sclerosis - Aerobic training (TREFAMS-A) is a multicentre, observer-blinded, randomised controlled trial in 90 ambulant patients with MS suffering from severe fatigue. Patients were allocated 1:1 to 16 weeks individual, partly supervised, aerobic training or a control intervention consisting of three consultations with an MS-specialized nurse. Primary outcomes were perceived fatigue (Checklist Individual Strength [CIS] fatigue subscale) with, and societal participation (Impact on Participation and Autonomy [IPA] scale). An improvement of ≥ 8 points on the CIS fatigue subscale was considered clinically relevant. Secondary outcomes included measures of physical fitness, and complementary fatigue measures. Assessments were performed at baseline, 8, 16, 26, and 52 weeks. Random coefficient analysis was used to assess the group-by-time interaction effects. This study is registered with number ISRCTN69520623.

    Findings: Between 1 October 2011 and 1 October 2014, over 925 patients were approached, 207 patients with MS were assessed for eligibility, and 90 were included. The mean difference (MD) between-groups, post-intervention on the CIS fatigue subscale was 4.708 (Standard Error [SE] = 1.890; P = .014) in favour of aerobic training. This was preceded by a significant increase in peak power output following 8 weeks of training (MD = 11.701; SE = 5.868; P = .048). At 8 weeks, also a significant reduction on the Modified Fatigue Impact Scale psychosocial subscale (MD = -0.771; SE = 0.325, P = .019) was shown. No significant effect was found on societal participation.

    Interpretation: Aerobic training in MS patients with severe fatigue does not lead to clinically meaningful reductions in fatigue and does not improve societal participation when compared to three consultations offered by an MS-specialized nurse.


    Heine, M

    (2016) UMC Repository



    Multiple sclerosis (MS) is considered a chronic and debilitating autoimmune-mediated inflammatory and neurodegenerative disorder of the central nervous system. It is the number one neurological condition in young adults, affecting approximately 17.000 people in the Netherlands. Patients with MS often experience severe levels of chronic fatigue which, amongst others, affects societal participation. In the context of a progressive neurological disease patients often adopt a relative sedentary lifestyle. This, in turn may negatively affect their physical fitness and general health which subsequently increases the perceived fatigue severity. Following a vicious cycle, this may then lead to a more sedentary lifestyle.

    The exact pathophysiology of MS-related fatigue is poorly understood leading to lack of consensus regarding definition and assessment tools (chapter 10). Various mechanisms have been proposed through which a structural exercise program may alleviate fatigue including an anti-inflammatory effect, a psychosocial effect, a neuroprotective effect, and an increase in physical fitness and general health.

    The first part of this thesis assessed the psychometric properties of the gold standard cardiopulmonary exercise test (CPET) for physical fitness, in patients with MS. CPET is reliable (chapter 3) and valid (chapter 4) in ambulant patients with MS. In patients that are not ambulant, the oxygen uptake efficiency slope (OUES) may prove a valid and reliable alternative measure for physical fitness in comparison to the convention peak oxygen uptake (chapter 5). The combined evidence of 40 studies that used CPET to assess aerobic capacity (i.e. physical fitness) in patients with MS suggested that aerobic capacity is on average ~17% lower in patients with MS compared to healthy controls (chapter 2), and further declines with an increase in disease severity (chapter 2 and 6). The magnitude of this decline is associated with secondary healthy risks.

    A systematic review (chapter 7) indicated a moderate effect of aerobic training on fatigue, however in the studies underlying this review fatigue was often a secondary outcome which had implications on our confidence in the found effect size. In the second part if this thesis we described the protocol (chapter 8)and results (chapter 9) of a multi-center randomized clinical trial to study the effects of aerobic training on fatigue and societal participation in 90 severely fatigued patients with MS.

    The patients allocated to the aerobic training intervention, compared to the control condition, significantly improved their fatigue levels by 4.7 points on the primary fatigue outcome (checklist individual strength fatigue subscale, range 8 – 56). Unfortunately, the magnitude of improvement was below the a priory defined cut-off of 8 points to be clinically relevant. This notion was further supported by (1) the lack of improvement on the complementary fatigue questionnaires included, (2) by the finding the improvement did not sustain during the 10 weeks, and 36 weeks follow-up; and (3) that the improvement in fatigue did not lead to an improvement in societal participation.

    This, in the context of previous studies, led to the conclusion that aerobic training does not lead to clinically relevant reductions of MS-related fatigue nor improvements in societal participation.

    The editors at Neurology Now put together this blog after talking to the author and others at ECTRIMS:
    Dave Bexfield

  • #2
    I don't know Dave. There are quite a few studies that show down at cellular level how beneficial exercise is for people with MS. As a fatigue fighter, I feel a bit vindicated, but at a gut level I'm thinking like you, perhaps the study is flawed by the way it takes measurement of fatigue. You or someone on this forum posted an article about needing a better definition of fatigue. Seems like it's Hard to say exercise doesn't improve fatigue if you haven't fully defined fatigue.


    • #3
      I personally felt better awhile after two bike rides for 15-20 minutes on Sunday. After the first bike ride, I felt horrible. After the second in the evening, I made it until midnight without crashing fatigue.

      I also made it until 6pm yesterday without crashing fatigue, which mine usually starts around 2pm. I was also more positive mentally at work. Some of my coworkers noticed that I seemed more energetic and happy yesterday. They know what I've been going through lately. Last night, I did a bike ride and felt horrible afterwards. It was difficult taking a shower, but after dinner, I got an extra two hours without crashing fatigue.

      I started getting crashing fatigue around 2pm today and it sucks, but those little spurts will make me keep doing it. I will keep going no matter what. Except for tonight, I'm giving myself the night off
      Last edited by funnybutnotfunny; 09-20-2016, 07:54 PM.


      • #4
        I have to wonder if this depends on the severity of the fatigue as well. Mine is rather mild and very intermittent. Aerobic exercise is invigorating to me.

        But maybe if the fatigue is crushing and aerobic exercise leaves you feeling even worse after a day or two its time to tone it done?


        • #5
          Yes, my muscles fatigue quickly and overall weakness ensues. I personally think that FES is one part of the solution - it seems that it would allow one to build up some muscle strength without a lot of physical exertion. It might help remind the mind how to contract muscles and move quicker. It makes no sense to me why FES is used for rehab of people with strokes and paralyzed but not accepted treatment for MS until one is paralyzed!!! [I wish Dr. Whals' had been given a million dollars to study FES with MS. (I'm not ready to turn myself into my own electrified guinea pig yet-- the cost is high and I don't think I can do 5 hours of zapping a day like dr wahls did to recover herself.)Maybe that study is next on her list?!? ]