Fatigue in SMA: making it measurable, mapping it, and treating it
Fatigue, the inability to sustain activities such as writing, drinking from a cup, and walking, is a major complaint that SMA patients face daily. However, little is known about the frequency of fatigue, its causes, and how it can be treated. The development of good measurement instruments that can be used to investigate fatigue and determine the effect of training and medication is an important first step. This is according to researcher and pediatric physiotherapist Bart Bartels of the SMA Expertise Center at UMC Utrecht, who is receiving his PhD today.
Mapping fatigue
Spinal muscular atrophy (SMA) is a hereditary condition that can lead to severe muscle weakness, limitations in daily life, and death. Fatigue, the inability to sustain activities, is also a common complaint. “Because little is known about fatigue in SMA, it is important to gain insight into this complaint,” says Bartels. His research shows that fatigue occurs in both weak and relatively strong patients with SMA. There are also patients with significant muscle weakness who can easily sustain the activities they are still able to perform.
It is also noteworthy that while patients with SMA tire easily during activities, they generally do not feel more fatigued than healthy peers. These findings support the notion that fatigue is an important co-occurring symptom related to the disease, but is not synonymous with muscle weakness and perceived fatigue. According to Bartels, this must be taken into account during treatment. In his research, he also demonstrates that there is still insufficient evidence regarding the effect and safety of physical training in SMA and that further research is needed into an SMA-specific optimal training dose.
To measure is to know
But how do you measure fatigue in a group of patients where the differences in limitations are so great? Bartels: “Fatigue in SMA is a difficult complaint to assess with a single test, because one person may still be able to walk, while another can only move their arm or hand. Over the past six years, therefore, together with colleagues from the SMA Expertise Center and the Children's Movement Center, he has developed a number of fatigue tests that allow fatigue to be measured and compared for the first time in patients with both a severe and a relatively mild form of SMA. Bartels’ research shows that 85% of patients with SMA experience fatigue and that this can be reliably determined using so-called ‘Endurance Shuttle Tests’. The researchers have also ensured that these fatigue tests are now being applied in several international scientific studies.”
Treatment of fatigue
The renewed insights into fatigue, and the fatigue tests developed by Bartels, made it possible to examine treatment. Researchers at the SMA Expertise Center, therefore, under the leadership of Professor Ludo van der Pol, investigated whether the drug Pyridostigmine is effective for SMA. Pyridostigmine is a medication used in the treatment of the muscle disease Myasthenia Gravis, among others, to improve nerve impulse transmission and thereby reduce fatigue. Previous research by one of the researchers at the SMA Expertise Center, Dr. Wadman, showed that approximately half of patients with SMA suffer from impaired nerve impulse transmission.
Bartels: “Pyridostigmine also appears to lead to improvements in endurance in SMA patients, and we were able to detect this using our newly developed fatigue tests. Patients report being better able to finish their meals, propel their (electric) wheelchair, or walk for longer periods without breaks. This study shows that the development and/or selection of reliable measuring instruments are essential components of conducting effective drug trials. The fact that we started with limited knowledge about fatigue and have now found a drug that significantly improves the quality of life for SMA patients is, of course, fantastic.”