Exercise and Spinal Muscular Atrophy

November 2020

Introduction

The relationship between exercise and neuromuscular 
conditions has long been a debated issue. In the past the advice given to individuals with neuromuscular conditions was to avoid or limit exercise to prevent damaging muscles. It has now been suggested that some exercise may be beneficial for some types of neuromuscular conditions.
 

Review of the Exercise Studies in SMA

There are many difficulties in investigating SMA and the effects of exercise. SMA is considered a rare condition, and symptoms and its impact varies widely; this means that the results of studies of people who have had a clinical diagnosis of SMA Type 2 and are ‘sitters’ may not necessarily be useful for others who have a different clinical diagnosis and whose SMA has a different impact. Exercise is often more difficult for people with a neuromuscular condition; weakness, pain, 
fatigue and contractures (stiffening of the joints) make recruitment to studies harder. A lack of ability to walk and exercise may also contribute to weight gain, which in turn may make movement more difficult.

Broadly speaking, most types of exercise can be grouped into two categories: aerobic exercise – highly repetitive movements with no, or minimal, weight added (such as swimming); and strength training – moving increasing weights (such as through lifting). It is unclear from studies which type of exercise is most beneficial, if either.

Although only a small number of studies have been published which look specifically into SMA and exercise, there has been an increase in the number of studies since the first summary article I wrote on this subject in 2015. This may be due in part to several animal studies which have looked at exercising mice with SMA1,2. Chali and colleagues found that long term running and swimming of mice with SMA (similar to a clinical diagnosis of SMA Type 3 in humans) helped with resistance to muscle and nerve cell damage, as well as having beneficial effects on breathing measurements1. Another reason for an increase in exercise studies is the new drug treatments which have been developed. The majority of these treatments target production of the protein which is missing in nerve cells in SMA. If the treatment is successful, the nerve cells may be preserved but the muscle is often already weak; therefore it theoretically may be helpful to do exercises to strengthen or work the muscle in order to compensate for this.   

In 2019, Bartels and colleagues3 published a review of previous studies looking at SMA and exercise. While they looked at many studies, they only found one which was designed in a way that gave strong evidence into whether exercise in SMA is beneficial (randomized control trial - see Levels of Evidence article)4.
 

Aerobic Exercise

Montes and colleagues completed a study in late 2015 which looked at a home-based programme which works on muscle strength and uses lying down cycling (recumbent cycle ergometry)4. Fourteen participants with a clinical diagnosis of SMA Type 3 were enrolled and were put through an exercise regimen of either 7 or 12 months. The evidence demonstrated that exercise was safe in this group and didn’t cause increased fatigue. It did show that measures of breathing function improved, but failed to show a significant improvement in tests looking at how far an individual can walk. In the review paper by Bartels and colleagues, the writers summarised these findings as being insufficient to provide evidence of benefits of this form of exercise.

In 2012, Lewelt and colleagues1 published a study which investigated nine people who were aged, on average, ten years old, and who all had clinical diagnoses of SMA Types 2 or 35. Each individual was checked beforehand to make sure they could perform the exercises according to the planned schedule. The study was looking at ‘Progressive resistance training’; an exercise plan performed at home which involves individuals pushing or pulling against weights in the form of weighted wrist bands which gradually get heavier. Children as young as five have used this exercise routine in other studies to increase muscle strength and lose weight. The exercises consisted of 45-60 minute sessions with a physiotherapist three times a week. Exercise days were spaced at least one day apart, with two sets of fifteen repetitions of the exercise carried out, and five minutes of break time in between. The young people started doing the same exercises without weights, then ankle and wrist weights were added once each individual managed to complete the two sets of exercises in a week. Over a twelve week period it was discovered that there was only a small improvement in muscle strength overall, particularly in individuals who already had significant muscle weakness. The authors found that there was a significant overall improvement in some of the measures of how well muscles do particular tasks. The authors of the study point out that individuals may not have noticed this improvement as it was so small.

The studies looking at aerobic exercise by Lewelt, Montes and others seem to demonstrate moderately positive results in those who have a clinical diagnosis of SMA Type 2 or 34,5,6. There are several drawbacks to these studies such as the small number of participants, and often the lack of a group of people to compare to (control group).
 

Strength Training

Madsen and colleagues from University of Copenhagen, Denmark, published a study in 2015 looking at six individuals with a clinical diagnosis of SMA Type 3, and compared these to nine individuals without SMA7. Both groups rode special types of exercise bikes two to four times per week for twelve weeks. Sessions were thirty minutes long. Madsen and colleagues were interested in how much oxygen could be used by the body during exercise; in this study they refer to this measurement as ‘VO2 max’. This measures how the body improves in taking in oxygen during exercise; if your breathing muscles are weak, as they might be with SMA Type 2, this would interfere with the results and you couldn’t be sure if the response was due to the exercise or to improvement of the breathing muscles. It is likely that individuals with SMA Type 3 were chosen to take part because they don’t get breathing muscle weakness until late in life, if at all. Madsen and colleagues showed a significant increase in how well individuals could exercise and take oxygen into the body during exercise, but there was no change in individuals’ muscle strength or in their ability to perform tasks. A lot of the individuals with SMA also reported fatigue, but had no increase in blood test results that showed muscle damage. Overall, the results of this study suggest that this form of exercise may provide some benefit to how much oxygen can be taken into the body, but it was unclear how beneficial and noticeable this would be to individuals. Participants reported experiencing fatigue after the exercise, and this led to one individual leaving before the end of the study.
 

Other Methods of Exercise

One review in 2013 by Anziska and colleagues8, which looks at exercise and its role in neuromuscular conditions, suggested that ‘submaximal aerobic training’ (doing aerobic exercise but not quite as hard as you possibly can) should be advised in conditions like SMA, as individuals are more likely to damage muscles if they are pushing themselves to the limit of their abilities. The authors also suggested that it may be better to focus on training specific groups of muscles, by choosing carefully which exercises to concentrate on; although the authors of this review don’t suggest which specific muscle groups to focus on in the case of SMA.

No recent studies have looked at hydrotherapy and water based exercise in SMA specifically. Hydrotherapy has historically been suggested to help to prevent contracture development, and has been beneficial to individuals with other neuromuscular conditions. One study was published in 19969, which looked at the response of individuals with a clinical diagnosis of SMA Type 2 or 3 to hydrotherapy. The authors suggested that there was some stabilisation of muscle strength, and even improved strength reported in some individuals. There was also a reported improvement in activities of daily living. In this study, individuals had bi-weekly hydrotherapy sessions which lasted between 30-45 minutes. The provision of hydrotherapy in the UK is very variable, and individuals may not have access to these therapies as frequently as the participants did in this study.

Another method which has been trialed in other, similar conditions is direct electrical stimulation of muscle groups. In the past, this therapy has not been shown to be successful over a reasonably long period (1 year) at improving measures of muscle function in children with a clinical diagnosis of SMA Type 2 or 310. This technology has been revisited in 2019 by Gobbo and colleagues, who reported its use in a thirteen-year-old, along with cycling. The participant demonstrated an increase in thigh muscle mass and increase in his ability to perform tasks. There is currently more evidence against the use of this technology, which needs to be studied in larger well designed trials11.
 

Conclusion

Over the past decade, guidance on exercise in SMA has changed, with more studies showing that there may be beneficial effects of different types of exercise. The studies over the past three years have added to our knowledge of how exercise can affect individuals with SMA, but there is much that is not yet known. Studies so far haven’t been big enough and may suggest potential benefits which may not make a big enough difference to be noticeable to individuals.

There is probably enough evidence now however, that exercise is helpful for some individuals with SMA, but the jury is still out on what type of exercise is best, how long to exercise for, and how best to avoid fatigue or pain. Possibly the exercise with the most evidence is aerobic such as recumbent cycling, as this has been shown to give small benefits in function and may help with breathing. One thing that all of the authors of the studies above agree on, is that individuals with SMA should discuss their plans with a physician or physiotherapist who knows them and understands the impact SMA is having on them before beginning an exercise routine.
 

References

1. Chali F, Desseille C, Houdebine L, Benoit E, Rouquet T, Bariohay B, Lopes P, Branchu J, Della Gaspera B, Pariset C, Chanoine C, Charbonnier F, Biondi O. Long-term exercise-specific neuroprotection in spinal muscular atrophy-like mice. J Physiol. 2016 Apr 1;594(7):1931-52. doi: 10.1113/JP271361. Epub 2016 Feb 27. PMID: 26915343; PMCID: PMC4818605.  

2. Ng SY, Mikhail A, Ljubicic V. Mechanisms of exercise-induced survival motor neuron expression in the skeletal muscle of spinal muscular atrophy-like mice. J Physiol. 2019 Sep;597(18):4757-4778. doi: 10.1113/JP278454. Epub 2019 Aug 22. PMID: 31361024; PMCID: PMC6767691.

3.  Bartels B, Montes J, van der Pol WL, de Groot JF. Physical exercise training for type 3 spinal muscular atrophy. Cochrane Database Syst Rev. 2019 Mar 1;3(3):CD012120. doi: 10.1002/14651858.CD012120.pub2. PMID: 30821348; PMCID: PMC6396106.

4. Montes J, Garber CE, Kramer SS, Montgomery MJ, Dunaway S, Kamil-Rosenberg S, Carr B, Cruz R, Strauss NE, Sproule D, De Vivo DC. Single-Blind, Randomized, Controlled Clinical Trial of Exercise in Ambulatory Spinal Muscular Atrophy: Why are the Results Negative? J Neuromuscul Dis. 2015 Oct 7;2(4):463-470. doi: 10.3233/JND-150101. PMID: 27858749; PMCID: PMC5240606.

5. Lewelt A, Krosschell KJ, Stoddard GJ, Weng C, Xue M, Marcus RL, et al. Resistance Strength Training Exercise in Children with Spinal Muscular Atrophy. Muscle & nerve. 2015 Jan 19. PubMed PMID: 25597614. Pubmed Central PMCID: Pmc4506899. Epub 2015/01/20. Eng.

6. Gobbo M, Lazzarini S, Vacchi L, Gaffurini P, Bissolotti L, Padovani A, Filosto M. Exercise Combined with Electrotherapy Enhances Motor Function in an Adolescent with Spinal Muscular Atrophy Type III. Case Rep Neurol Med. 2019 Jul 22;2019:4839793. doi: 10.1155/2019/4839793. PMID: 31428487; PMCID: PMC6679856.

7. Madsen KL, Hansen RS, Preisler N, Thogersen F, Berthelsen MP, Vissing J. Training improves oxidative capacity, but not function, in spinal muscular atrophy type III. Muscle & nerve. 2015 Aug;52(2):240-4. PubMed PMID: 25418505. Epub 2014/11/25. eng.

8. Anziska Y, Sternberg A. Exercise in neuromuscular disease. Muscle & nerve. 2013;48(1):3-20.

9. Cunha MCB, Oliveira ASB, Labronici RHDD, Gabbai AA. Spinal muscular atrophy type II (intermediary) and III (Kugelberg-Welander): evolution of 50 patients with physiotherapy and hydrotherapy in a swimming pool. Arquivos de Neuro-Psiquiatria. 1996;54:402-6.

10. Fehlings DL, Kirsch S, McComas A, Chipman M, Campbell K. Evaluation of therapeutic electrical stimulation to improve muscle strength and function in children with types II/III spinal muscular atrophy. Developmental medicine and child neurology. 2002 Nov;44(11):741-4. PubMed PMID: 12418614. Epub 2002/11/07. eng.

11. Bora G, Subaşı-Yıldız Ş, Yeşbek-Kaymaz A, Bulut N, Alemdaroğlu İ, Tunca-Yılmaz Ö, Topaloğlu H, Karaduman AA, Erdem-Yurter H. Effects of Arm Cycling Exercise in Spinal Muscular Atrophy Type II Patients: A Pilot Study. J Child Neurol. 2018 Mar;33(3):209-215. doi: 10.1177/0883073817750500. Epub 2018 Jan 12. PMID: 29327642.