Running on Empty: Understanding how fatigue affects quality of life in Spinocerebellar ataxias

Spinocerebellar ataxias (SCAs) are characterized by various symptoms, but fatigue is not often included on this list. Fatigue is clinically defined as difficulty initiating or sustaining voluntary mental and physical activities. In this study, Lai and colleagues study how common fatigue is and how it affects quality of life in people with SCA1, SCA2, SCA3, or SCA6. They find that fatigue is common across these diseases and that patients experiencing fatigue have more severe ataxia and depressive symptoms, and report worse quality of life. This is important because understanding how fatigue affects patients will help doctors and researchers better address patient concerns and develop treatments. 

In this specific study, the researchers monitored the ataxia, fatigue, and depressive symptoms of over 400 people with either SCA1, SCA2, SCA3, or SCA6. This was accomplished by asking participants to complete several tests:  

1. The Scale for the Assessment and Rating of Ataxia (SARA): measures ataxia severity by having participants perform a series of movements such as walking and standing. A higher score indicates more severe ataxia. 
2. The Fatigue Severity Scale (FSS): measures mental and physical fatigue during the past week using a 9-item questionnaire, with higher scores meaning greater fatigue.  
3. The Patient Health Questionnaire-9 (PHQ-9): measures depression symptoms during the past two weeks, with higher scores indicating more severe depression. 

Participants were also asked to rate their quality of life by describing their health problems in five areas – anxiety/depression, pain/discomfort, usual activities, self-care, and mobility. This was done using a test called the EuroQol-5 Dimension (EQ-5D).  

With this information, Lai and colleagues compared the results across the SCA subtypes. They emphasized four main takeaways: 

1. Fatigue was found in all the SCA subtypes studied. Fatigue was most common in SCA3, followed by SCA1, SCA6, and SCA2.  
2. Fatigue was correlated to depression in all SCA subtypes investigated. More severe depression (but not more severe ataxia) was associated with more severe fatigue. This means that depressive symptoms could be related to fatigue in SCAs. 
3. In SCA3 and SCA6 – Fatigue was associated with worse quality of life, regardless of ataxia and depression. In SCA3, those with fatigue had longer disease duration and longer pathological CAG repeat numbers. 
4. In all SCA subtypes – Over six years, fatigue continued to be linked with a worse quality of life. Of note, during this period, ataxia symptoms got worse, but fatigue symptoms did not.  

In summary, fatigue is a prevalent symptom across the SCA subtypes and represents a challenge to quality of life. While the large number of participants is a strength of this study, there are a few caveats. It would be helpful to compare patients with SCA to healthy controls to understand how fatigue may change across the lifespan. Additionally, the study did not consider other factors that may have contributed to fatigue, including sleep disorders, work schedules, diet, and exercise. For example, SCAs are associated with weight loss due to muscle wasting and autonomic dysfunction such as heart rate variability, which makes fatigue a secondary effect. Finally, this study did not address the primary type of fatigue observed– mental and physical. Therefore, future studies could expand upon these findings and investigate the source of fatigue to gain a better understanding of this in SCAs. Finally, action points that could help improve fatigue, such as mobility-enhancing techniques and exercise regimes in SCA patients, could prove helpful.  

For now, this study highlights that fatigue should be considered when caring for patients with SCAs. It highlights the importance of reassuring patients and caregivers that fatigue is an actual symptom of SCAs. This is a step forward for clinical care and future research, as uncovering symptoms opens new avenues for potential treatments and better control for quality of life.