# Exercise as it relates to Disease/Improving exercise tolerance in patients with Multiple Sclerosis: Can aerobic training help?

This Wikibooks fact sheet is a critique of a study by Rampello et al., 'Effect of Aerobic Training on Walking Capacity and Maximal Exercise Tolerance in Patients with Multiple Sclerosis: A Randomised Crossover Controlled Study', which looked at how aerobic training could potentially improve exercise tolerance and walking capacity in people with MS.

## What is the background to this research?

Multiple sclerosis (MS) is a chronic disease that involves damage to the myelin sheath of neurons in the central nervous system (CNS). This demyelination affects nerve conduction and impulses in the brain, spinal cord and optic nerves. People with MS can often experience fatigue that not only limits their exercise tolerance, but also their ability to carry out daily living activities. They also experience thermosensitivity and therefore run the risk of making their symptoms worse due to their inability to regulate their increased body temperature during physical activity. It's no wonder that patients with MS have previously been told not to participate in physical activity at all.
Unfortunately, avoiding physical activity may become somewhat of a detrimental path for people with MS, as illustrated in the diagram below.
Fortunately, over the last decade, evidence has been building up suggesting that physical activity can benefit people with MS, specifically to help maintain and improve functional strength in order to maintain functional independence. This regulation of functional independence is one of the main aims of rehabilitation for people with MS. Therefore, the ability to tolerate exercise is important for MS patients to be able to participate in physical activity to improve and maintain their functional strength and consequently, their independence.

## Where is the research from?

* Where: Italy
* Who: Patients from MS outpatient clinics who were on a waiting list for a rehabilitation program
* Researchers: Medical doctors with backgrounds in rehabilitation and respiratory diseases
It is important that the interpretations of this study consider cultural differences between various populations. Therefore, while the results may apply to some populations, there are other populations that may respond differently to these interventions.

## What kind of research was this?

The study was conducted as a randomised cross-over control (RCC) study.
* RCC: same as a randomised control study (RCT) where subjects are randomly allocated to different treatment groups, with the added step of having treatment groups swap their treatments after a given period of time (i.e. the crossover).
Previous studies that used different methods looked at aerobic exercise and MS patients, and have generally found that aerobic exercise is well tolerated but only at a low to moderate intensity. A pilot study found that aerobic exercise may improve overall disability and mobility. However, while endurance exercise has been found to have potential beneficial effects on psychological profiles and physiology, results are inconclusive about whether aerobic exercise can help with fatigue.

## What did the research involve?

Subjects either underwent an aerobic training or a neurological rehabilitation intervention for eight weeks. They then had an eight-week washout period where they were told to stop exercising. After this period, they swapped intervention protocols.
This use of a crossover design minimises the number of participants needed, which is more economical. It also allows subjects to access two potentially beneficial interventions, which is ethically sound.
Table 1. Comparison of the two experimental protocols :
| | Aerobic training program | Neurological rehabilitation program |
| Overall duration | 8 weeks | 8 weeks |
| Sessions per week | 3 | 3 |
| Session duration (not including warm-up and cool-down) | 30min | 60min |
| Exercises/Activities done | Based on a protocol previously proposed by Petajan et al. (1996) Warm-up: 5min, relatively low work rate Intervention: 30min cycling on a stationary cycle ergometer at 60% of their maximum work rate Cool-down: 15min of stretching exercises for lower limb and trunk muscles | Focused more on the range of motion and movement of the upper body (upper limbs and trunk) and gait exercises. Exercises were grouped in four parts, separated by 3min pauses, and focused on controlled breathing throughout |

### Limitations

* Large dropout- "high rate of participant loss"
** Increased the potential for type II error (i.e. increased chance that you don't find a significant difference, when there really is one there)
*** Affects the generalisability of the study
** Dropouts due to: relapses in MS, persistent induced fatigue and breathlessness, and stress
*** Indicates that exercise programs can still potentially cause harm to patients with MS
* Learning effect- you get better at a test because you've done it before
** To counteract this, the researchers got their subjects to perform the 6-Minute Walk Test (6MWT) twice on the study day, with an hour of rest in between. They also only took results from the second test.
*** This was done because performance typically plateaus after two tests are completed within the week.
* Carryover effect- when the effects of the first protocol potentially influence the effects of the second protocol
** Previous research has shown that the benefits of an intervention can last 6-9 weeks afterwards in some participants (e.g. Patti F, Ciancio MR, Cacopardo M, et al., 2003; Solari A, Filippino G, Gasco P, et al., 1999)
*** Therefore, the researchers' eight-week washout period may be too short to fully account for the effects of the first intervention.
** According to the researchers, however, the baseline measurements between the two interventions had no significant differences, which they suggest may rule out the carryover effect.
*** But, the mechanisms underlying these baseline variables, and other variables still may have been affected by either intervention.
* Comparison of interventions based on the outcomes for the aerobic training program- e.g. peak oxygen uptake, lung function
** The neurological rehabilitation program may have actually been more superior to the aerobic training program in non-aerobic outcomes that were not measured in the study (i.e. balance, flexibility etc.).

## What were the basic results?

Researchers found that neither program significantly affected lung function or respiratory muscle strength. The results of the study are summarised below.
Table 2. Summary of results :
| Variable | Pre- vs Post-: Aerobic training | Pre- vs Post-: Neurological Rehabilitation | Aerobic vs Neurological: Post-intervention values |
| Walking distance (metres) | Pre: 308 ± 98 m Post: 332 ± 108 m Significantly improved | Pre: 298 ± 114 m Post: 308 ± 110 m No significant difference | No significant difference |
| Walking speed (metres/minute) | Pre: 51 ± 16 m/min Post: 55 ± 18 m/min Significantly improved | Pre: 50 ± 19 m/min Post: 51 ± 18 m/min No significant difference | No significant difference |
| Cost of walking (milliletres of oxygen per kilogram body weight per metre walked) | Pre: 0.20 ± 0.07 mL O2/kg/m Post: 0.20 ± 0.07 mL O2/kg/m No significant difference | Pre: 0.23 ± 0.1 mL O2/kg/m Post: 0.22 ± 0.09 mL O2/kg/m No significant difference | No significant difference |
| Peak oxygen uptake (VO2; millilitres/minute/kilogram) | Pre: 17.1 ± 7.0 mL/min/kg Post: 20.0 ± 6.6 mL/min/kg Significantly increased | Pre: 16.8 ± 6.5 mL/min/kg Post: 16.9 ± 6.1 mL/min/kg No significant difference | Significant difference |
| Maximum work rate (Watts) | Pre: 82 ± 43 W Post: 103 ± 48 W Significantly increased | Pre: 79 ± 45 W Post: 82 ± 42 W No significant difference | Significant difference |
| Peak VO2/Heart rate (millilitres/beats per minute) | Pre: 7.8 ± 3.0 mL/bpm Post: 8.7 ± 3.2 mL/bpm Significantly increased | Pre: 7.8 ± 2.9 mL/bpm Post: 8.1 ± 3.5 mL/bpm No significant difference | No significant difference |
The researchers interpreted these significant improvements to suggest that while both programs improved maximum exercise tolerance and walking capacity when compared to baseline measures (i.e. pre- vs post-intervention), aerobic training may be more effective in improving exercise tolerance and walking capacity compared to neurological rehabilitation.
Interestingly, while there was a significant difference in pre- and post-intervention outcomes for the aerobic training group, there was no significant difference in the post-intervention outcomes between the programs (i.e. aerobic vs neurological) except in two aerobic outcomes; peak oxygen uptake and maximum work rate. This may be due to the sensitivity of the statistical analyses used, which may not have been able to detect a small change in outcomes.

## What conclusions can we take from this research?

* Aerobic training appears to have the potential to improve walking capacity and exercise tolerance in MS patients.
** This is important because it suggests that aerobic training can help improve the ability of MS patients to move and walk independently.
* However, given the statistical analysis of the results, aerobic training may not be superior to a neurological rehabilitation program in improving exercise tolerance and walking capacity.
* Some recent research supports the idea that aerobic training may improve walking capacity. However, more evidence is required to solidify the relationship between aerobic training and exercise tolerance.

## Practical advice

Research appears to be leaning more towards investigating the effect of aerobic exercise on walking capacity and gait, rather than on exercise tolerance. More research needs to be undertaken if the relationship between exercise tolerance and aerobic training is to be better understood.
Clearly, great care should be taken when deciding to undertake aerobic exercise with MS patients.
* Aerobic training...
** Can provide potential improvements in walking capacity and aerobic outcomes, but these may not always transfer into all skills that assist in daily living (e.g. getting up out of a chair etc.).
** Still has the potential to exacerbate negative MS symptoms, so strict control of exercise intensity should be applied.
* Research in aerobic exercise has mostly been done with patients who had moderate MS.
** Patients with higher degrees of disability and MS severity may have negative responses to aerobic exercise.

### Further information

* For more information about MS, visit the MS Australia website, which also includes a section about MS and exercise.

## References

* 1 2 3 4 5 6 7 8 9 Rampello A., Franceschini M., Piepoli M., Antenucci R., Lenti G., Olivieri D., & Chetta A. Effect of Aerobic Training on Walking Capacity and Maximal Exercise Tolerance in Patients With Multiple Sclerosis: A Randomised Crossover Controlled Study. Physical Therapy. 2007 May; 87(5):545-555.
* ↑ MS Australia [Internet]. MS Australia; 2017. What is MS; 2017. Available from: https://www.msaustralia.org.au/what-ms
* 1 2 3 Petajan J & White A. Recommendation for Physical Activity in Patients with Multiple Sclerosis. Sports Medicine. 1999 Mar;27(3):179-191
* 1 2 3 4 5 6 Dalgas U, Stenager E, & Ingemann-Hansen T. Multiple sclerosis and physical exercise: recommendations for the application of resistance-, endurance- and combined training. Multiple Sclerosis Journal. 2008 Jan;14(1):35-53.
* 1 2 Kileff J. & Ashburn A. A pilot study of the effect of aerobic exercise on people with moderate disability multiple sclerosis. Clinical Rehabilitation. 2005 Mar; 19(2): 165-169.
* ↑ Petajan JH, Gappmaier E, White AT, et al. Impact of aerobic training on fitness and quality of life in multiple sclerosis. Annals of Neurology. 1996;39:432–441.
* ↑ Ahmadi A., Arastoo A.A., Nikbakht M., Zahednejad S., & Rajabpour M. Comparison of the Effect of 8 weeks Aerobic and Yoga Training on Ambulatory Function, Fatigue and Mood Status in MS Patients. Iran Red Crescent Medical Journal. 2013 Jun; 15(6): 449-454.
* ↑ Benedetti M.G., Gasparroni V, Stecchi S., Zilioli R., Straudi S. and Piperno R. Treadmill exercise in early multiple sclerosis: a case series study. European Journal of Physical and Rehabilitation Medicine. 2009;45:53-59.