Fatigue and Its Associated Factors in Spinocerebellar Ataxia Type 3/Machado-Joseph Disease

Abstract

Fatigue has been described in several neurodegenerative diseases, reducing quality of life. A systematic evaluation of this clinical feature is lacking in SCA3/MJD. The aim of this study was to evaluate the frequency and the factors associated with fatigue in SCA3/MJD. Patients with SCA3/MJD and matched healthy controls answered the Modified Fatigue Impact Scale (MFIS), Beck Inventory Depression (BDI) and Epworth Sleepiness Scale (ESS). Scale for the assessment and rating of ataxia (SARA) was used to determine ataxia severity. We used Mann-Whitney and Fisher exact tests to compare mean scores and proportions between groups. Linear regression analyses were employed to investigate factors associated with fatigue in SCA3/MJD. Seventy-four patients were included with a mean age and disease duration of 47.2 ± 12.8 and 9.5 ± 6.37 years, respectively. There were 38 men and 36 women. Mean (CAG)n was 72.2 ± 3.8. Mean MFIS score was higher in patients with SCA3/MJD (41.4 ± 16.2 vs 18.4 ± 12.9, p < 0.001). According to BDI scores, relevant depressive symptoms were found in 69.4 % of patients but only in 10.4 % of controls (p < 0.001). The proportion of patients with ESS scores indicating excessive daytime somnolence was also higher than controls (37.5 vs 22.3 %, p = 0.05). In the multiple regression analysis, both BDI and ESS scores were associated with fatigue (r = 0.67, p < 0.001 and p = 0.01). Fatigue is frequent and strongly associated with depression and excessive daytime somnolence in SCA3/MJD.

Ataxic Severity Is Positively Correlated With Fatigue in Spinocerebellar Ataxia Type 3 Patients

“…We also found that daytime somnolence and ataxic severity are risk factors associated with fatigue. While daytime somnolence, the length of expanded CAG repeats, anxiety, and depression have been reported to be associated with fatigue (3,19,20,22,23), it was the first time that ataxic severity was found to be associated with fatigue. The significant correlation between fatigue and disease severity was also revealed in a PD cohort (8).…”

“…Since the study subjects were all Chinese, we adopted a Chinese version of FS-14, which was proved to exhibit optimal sensitivity and specificity in recognizing fatigue among the Chinese-speaking population (28) and was widely used for valuing the severity of fatigue (29)(30)(31)(32)(33)(34). To value the severity of daytime somnolence, sleep disturbances, and depression, which were reported to related to the severity of fatigue (19,20,22), patients were asked to complete the Chinese version of questionnaires of the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and the Beck Depression Inventory (BDI). The ESS assesses sleep propensity in eight different daily situations with a total score ranging from 0 (no excessive daytime sleepiness) to 24 (severe excessive daytime sleepiness).…”

“…As a common symptom, fatigue was found to have great impact on the quality of life in PD (13)(14)(15)(16). Fatigue is also a pronounced non-motor symptom in SCAs (17)(18)(19), especially in SCA3 patients, with a high prevalence around 52.9-63.5% (3,20,21). The significant predictors of fatigue, such as length of expanded CAG repeats, excessive daytime somnolence, and mood disorders such as anxiety and major depression have been explored (3,19,20,22,23).…”

“…Fatigue is also a pronounced non-motor symptom in SCAs (17)(18)(19), especially in SCA3 patients, with a high prevalence around 52.9-63.5% (3,20,21). The significant predictors of fatigue, such as length of expanded CAG repeats, excessive daytime somnolence, and mood disorders such as anxiety and major depression have been explored (3,19,20,22,23). Given that the frequency of fatigue is so high and severity worsens over time with disease progression (4), the question is raised as to whether or not it could affect the clinical symptoms seen in neurodegenerative disorders, which have never been investigated.…”

The Sleeping Cerebellum

“…Vice versa, patients suffering from primary malfunctions of the cerebellum can show a variety of sleep disorders (for a detailed review, see [11,[69][70][71][72][73]). For example, patients with spinocerebellar ataxias [69,70,74,75], which are characterized by degeneration of the cerebellum and its afferent and efferent connections, can show increased daytime somnolence as well as NREM-and REM-related parasomnias. These data underline that the cerebellum fine-tunes neocortical forms of sleeprelated activity.…”