Abstract
BACKGROUND: Neuropathological examinations in spinocerebellar ataxia type 3 (SCA3) have demonstrated peripheral and autonomic nervous system degeneration, but the impact of associated symptoms on genetically affected individuals at different disease stages remains understudied. OBJECTIVE: To investigate the clinical burden of peripheral and autonomic nervous system involvement in SCA3 mutation carriers across the disease spectrum. METHODS: Forty SCA3 mutation carriers, including ten pre-ataxic individuals, completed questionnaires about muscle cramps, neuropathic pain, autonomic symptoms, activities of daily living, and quality of life, and underwent a standardized clinical examination of ataxia and neuropathy severity. Data were compared with 16 healthy controls. RESULTS: All but one of the ataxic and 60% of pre-ataxic individuals experienced muscle cramps at least weekly. Neuropathic pain was reported by 20% of pre-ataxic and 16.7% of ataxic mutation carriers, while the average number of autonomic symptoms in both groups was 2 and 4.7, respectively. Neuropathy severity scores were significantly higher in pre-ataxic and ataxic individuals than in healthy controls and associated with (i) worse self-reported functional status and (ii) clinician-reported ataxia severity. The number of autonomic symptoms was associated with patient-reported impairments in daily life and quality of life. CONCLUSION: Clinical features of peripheral and autonomic nervous system degeneration are very common in SCA3, may already be observed in pre-ataxic individuals, and independently contribute to patient-reported disease burden and clinician-rated overall ataxia severity.