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. 2025 Apr;32(4):e70093.
doi: 10.1111/ene.70093.

Fatigue in the Preataxic and Ataxic Stages of Spinocerebellar Ataxia Type 3

Zhi-Li Chen  1 , Li-Mei Xiao  1 , Chun Li  1 , Liang-Liang Qiu  1   2 , Wei Lin  1 , Zhi-Xian Ye  1 , Yuan-Yuan Zhang  1 , Zhi-Bao Zhu  1 , Meng-Cheng Li  3 , Min-Ting Lin  1 , Wan-Jin Chen  1   2 , Ning Wang  1   2 , Ying Fu  1   2 , Shi-Rui Gan  1   2 ; OSCCAR Investigators
Affiliations

Fatigue in the Preataxic and Ataxic Stages of Spinocerebellar Ataxia Type 3

Zhi-Li Chen et al. Eur J Neurol. 2025 Apr.

Abstract

Objective: Fatigue is a significant symptom in patients with spinocerebellar ataxia type 3 (SCA3). This study explores the role of fatigue in SCA3, examining its impact on quality of life and its potential as an indicator of disease progression.

Methods: We prospectively recruited 128 molecularly confirmed SCA3 patients and 125 sex-, age-, and education-matched healthy controls (HCs). Age at onset, disease duration, length of normal and expanded CAG repeats, and 14-item Fatigue Scale score were compared. MRIs evaluated the cerebellum and brain lesions.

Results: Our study found that the preataxic SCA3 group exhibited lower fatigue incidence and score than HCs (Incidence: 13% vs. 36%, p = 0.031; FS-14 score: 3.0 ± 2.7 vs. 5.6 ± 2.8, p < 0.001). Ataxic SCA3 patients experienced significantly higher fatigue incidence and score compared to both the preataxic SCA3 group (Incidence: 63.8% vs. 13%, p < 0.001; FS-14 score: 8.1 ± 3.9 vs. 3.0 ± 2.7, p < 0.001) and HCs (Incidence: 63.8% vs. 36%, p < 0.001; FS-14 score: 8.1 ± 3.9 vs. 5.6 ± 2.8, p < 0.001). Moreover, fatigue severity in SCA3 correlated with disease duration and expanded CAG repeat length. Neuroanatomical correlations revealed volume reductions in cortical and cerebellar regions linked to higher physical and mental fatigue scores in SCA3 patients.

Conclusions: Monitoring fatigue effectively evaluates a patient's overall quality of life and disease progression, making it a key indicator. Future treatments can target specific brain regions, with their effectiveness being evaluated through FS-14 assessments of fatigue changes.

Keywords: cerebellar volume; cortical volume; fatigue; magnetic resonance imaging; spinocerebellar ataxia type 3 (Machado‐Joseph disease).

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Trial profile. FS‐14, 14‐Item Fatigue Scale; GM, gray matter; HCs, healthy controls; PSM, propensity score matching; SCA3, Spinocerebellar ataxia type 3.
FIGURE 2
FIGURE 2
Violin plots comparing the FS‐14, physical, and mental scores between HCs and SCA3 patients (preataxic SCA3 group, ataxic SCA3 group, and total SCA3 group). The median was represented by the middle dashed line, and the outer dashed lines represented the interquartile ranges. Data was evaluated by Mann–Whitney U test, * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001, ns = not significant. FS‐14, 14‐Item Fatigue Scale; HCs, healthy controls; SCA3, spinocerebellar ataxia type 3.
FIGURE 3
FIGURE 3
Voxel‐based morphometry analysis of the correlation between GM volume loss and (A) FS‐14 score, (B) mental fatigue score, and (C) physical fatigue score increase. Covariates were age, sex, education, and TIV. The color bar displayed p‐values. FS‐14, 14‐Item Fatigue Scale; L, left; R, right.
See this image and copyright information in PMC

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