Extra-Cerebellar Signs and Non-motor Features in Chinese Patients With Spinocerebellar Ataxia Type 3

Abstract

Objectives: Our study attempted to systematically explore the prevalence of extra-cerebellar signs and non-motor symptoms, such as anxiety, depression, fatigue, excessive daytime sleepiness (EDS) and sleep disturbances in a cohort of Chinese patients with spinocerebellar ataxia type 3 (SCA3), and further investigated the correlations between non-motor symptoms and clinical characteristics in SCA3 patients. Methods: This study included 68 molecular-proven SCA3 patients. Extra-cerebellar signs were evaluated with the Inventory of Non-Ataxia Symptoms (INAS). The INAS count indicated the number of non-ataxia signs in each patient. The severity of ataxia, fatigue, EDS, sleep quality, anxiety, and depression were assessed using the Scale for the assessment and rating of ataxia (SARA), Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Rating Scale (HAMA), and the Hamilton Depression Rating Scale (HAMD) (24 items), respectively. Results: Extra-cerebellar signs were detected in 91.2% of all SCA3 patients and the mean total INAS count was 2.72 ± 1.88. Rigidity was the most frequent extra-cerebellar sign (47.1%, N = 32). Sensory symptoms (2.9%, N = 2) and chorea (5.9%, N = 4) were rare, and myoclonus (0%) was not found in this cohort. High frequencies of sleep disturbances (64.7%), fatigue (52.9%), depression (48.5%), and anxiety (42.6%) were detected in SCA3 patients. The Spearman correlation indicated that the HAMD score was associated with the CAG repeat length and HAMA score, while the PSQI score was correlated with the SARA and FSS score. In addition, multivariate linear regression analysis showed that the CAG repeat length, age of onset, sleep disturbances and depression were significant predictors of fatigue in SCA3 patients. Conclusions: Our study indicates that the vast majority of SCA3 patients display extra-cerebellar signs. Except for EDS, anxiety, depression, fatigue and impaired sleep quality are present in SCA3 patients. The CAG repeat length, age of onset, sleep disturbances and depression are predictors of fatigue in SCA3 patients.

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).…”

“…It is clinically characterized by progressive cerebellar ataxia, dysphagia, oculomotor disturbances, and extrapyramidal signs. In addition to the cardinal motor manifestations, SCA3 may also exhibit several non-motor clinical manifestations such as sleep behavior disorders, cognitive deficits, olfactory dysfunction, psychiatric symptoms, nutritional problems, autonomic nervous function disturbances, and fatigue (2,3).…”

“…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.…”

An observational study of balance and proprioception function in patients with spinocerebellar ataxias type 3

“…Balance impairments in SCA3 are characterised by increased postural sway and poor balance control during both static and dynamic tasks [7] . These impairments are the most frequent initial clinical manifestation in SCA3, which can be quickly recognised by patients as a sign of onset [8] .…”