Background: Spinocerebellar ataxia type 3 (SCA3) is an inherited form of ataxia that leads to progressive neurodegeneration. Fatigue is a common non-motor symptom in SCA3 and other neurodegenerative diseases, such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Although risk factors to fatigue in these diseases have been thoroughly studied, whether or not fatigue can affect clinical phenotypes has yet to be investigated. Methods: Ninety-one molecularly confirmed SCA3 patients and 85 age-and sex-matched controls were recruited for this study. The level of fatigue was measured using the 14-item Fatigue Scale (FS-14), and the risk factors to fatigue and how fatigue correlates with clinical phenotypes were studied using multivariable linear regression models. Results: We found that the severity was significantly higher in the SCA3 group than in the control group (9.30 ± 3.04% vs. 3.94 ± 2.66, P = 0.000). Daytime somnolence (β = 0.209, P = 0.002), severity of ataxia (β = 0.081, P = 0.006), and poor sleep quality (β = 0.187, P = 0.037) were found to have a positive relationship with fatigue. Although fatigue had no relationship with age at onset or ataxic progression, we found that it did have a positive relationship with the severity of ataxia (β = 7.009, P = 0.014). Conclusions: The high level of fatigue and the impact of fatigue on the clinical manifestation of SCA3 patients suggest that fatigue plays a large role in the pathogenesis of SCA3, thus demonstrating the need for intervention and treatment options in this patient cohort.

BackgroundSpinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant hereditary ataxia, and, thus far, effective treatment remains low. Repetitive transcranial magnetic stimulation (rTMS) can improve the symptoms of spinal cerebellar ataxia, but the mechanism is unclear; in addition, whether any improvement in the symptoms is related to cerebellar metabolism has not yet been investigated. Therefore, the purpose of this study was to investigate the effects of low-frequency rTMS on local cerebellar metabolism in patients with SCA3 and the relationship between the improvement in the symptoms and cerebellar metabolism.MethodsA double-blind, prospective, randomized, sham-controlled trial was carried out among 18 SCA3 patients. The participants were randomly assigned to the real stimulation group (n = 9) or sham stimulation group (n = 9). Each participant in both the groups underwent 30 min of 1 Hz rTMS stimulation (a total of 900 pulses), differing only in terms of stimulator placement, for 15 consecutive days. To separately compare pre- and post-stimulation data (magnetic resonance spectroscopy (MRS) data and the International Cooperative Ataxia Rating Scale (ICARS) score) in the real and sham groups, paired-sample t-tests and Wilcoxon’s signed-rank tests were used in the analyses. The differences in the ICARS and MRS data between the two groups were analyzed with independent t-tests and covariance. To explore the association between the changes in the concentration of cerebellar metabolism and ICARS, we applied Pearson’s correlation analysis.ResultsAfter 15 days of treatment, the ICARS scores significantly decreased in both the groups, while the decrease was more significant in the real stimulation group compared to the sham stimulation group (p < 0.001). The analysis of covariance further confirmed that the total ICARS scores decreased more dramatically in the real stimulation group after treatment compared to the sham stimulation group (F = 31.239, p < 0.001). The values of NAA/Cr and Cho/Cr in the cerebellar vermis, bilateral dentate nucleus, and bilateral cerebellar hemisphere increased significantly in the real stimulation group (p < 0.05), but no significant differences were found in the sham stimulation group (p > 0.05). The analysis of covariance also confirmed the greater change in the real stimulation group. This study also demonstrated that there was a negative correlation between NAA/Cr in the right cerebellar hemisphere and ICARS in the real stimulation group (r = − 0.831, p = 0.02).ConclusionThe treatment with rTMS over the cerebellum was found to induce changes in the cerebellar local metabolism and microenvironment in the SCA3 patients. The alterations may contribute to the improvement of the symptoms of ataxia in SCA3 patients.

Objective Spinocerebellar ataxia type 3 (SCA3) is one of the most common hereditary neurodegenerative diseases, with balance instability as main symptom. Balance quantification is crucial for evaluating the efficacy of therapeutic interventions. However, balance evaluation in SCA3 is often subject to bias. Here, we aimed to quantitatively evaluate postural instability and investigate the relationship between postural instability and clinical characteristics in SCA3 patients. Methods Sixty‐two SCA3 patients and 62 normal controls were recruited, and their postural balance was measured using a posturographic platform. Principal component analysis was performed as data reduction to identify postural instability factors. Multivariable linear regression was used to investigate potential risk factors for postural instability and to explore whether postural instability predicts the severity and progression of ataxia in SCA3 patients. Results We found SCA3 patients experience postural instability characterized by significant impairment in static and dynamic stability. The condition without visual feedback was the most sensitive measure in differentiating SCA3 from controls. Regression analyses revealed that ataxia severity predicted both static (P = 0.014) and dynamic stability (P = 0.001). Likewise, along with expanded CAG repeats (P < 0.001), both static (P < 0.001) and dynamic stability (P < 0.001) predicted ataxia severity, but not ataxia progression. Interpretation Our findings demonstrate the validity of using the Pro‐kin system for assessing postural instability in SCA3 patients. This type of quantitative assessment of balance dysfunction can contribute to clinical trials and balance rehabilitation in SCA3 patients.

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Background Spinocerebellar ataxia type 3 (SCA3) is a rare, inherited form of ataxia that leads to progressive neurodegeneration. The initial symptoms could affect clinical phenotypes in neurodegenerative diseases, such as Parkinson's disease and amyotrophic lateral sclerosis. However, the contribution of initial symptoms to the phenotypes of SCA3 has been scarcely investigated. Methods In the present study, 143 SCA3 patients from China were recruited and divided into two groups of gait‐onset and non‐gait‐onset. For determining the influences of initial symptoms on age at onset (AAO), the severity and progression of ataxia, and the possible factors affecting the initial symptoms, multivariable linear regression, and multivariate logistic regression were performed. Results We found that the frequency of gait‐onset was 87.41%, and the frequency of non‐gait‐onset was 12.59% (diplopia: 7.69%, dysarthria: 4.20%, dystonia: 0.70%). Compared to the non‐gait‐onset group, the gait‐onset group had significantly more severe ataxia ( p = 0.046), while the initial symptoms had no effect on AAO ( p = 0.109) and progression of ataxia ( p = 0.265). We failed to find the existence of any factors affecting initial symptoms. Conclusion These findings collectively suggested that initial symptoms influenced phenotypes in SCA3 and that neurodegeneration in different parts of brain may induce different disease severity in SCA3.