Peripheral and autonomic nervous system involvement in spinocerebellar ataxia type 3: unveiling an invisible burden

TL;DR

This study shows that peripheral and autonomic nervous system issues are common in SCA3, affecting patients even before symptoms appear and worsening quality of life.

Contribution

The study reveals that peripheral and autonomic symptoms in SCA3 are prevalent and contribute to disease burden, even in pre-ataxic stages.

Findings

Muscle cramps were reported weekly by nearly all ataxic and 60% of pre-ataxic SCA3 individuals.

Neuropathy severity scores were higher in SCA3 individuals and linked to worse functional status and ataxia severity.

Autonomic symptoms were associated with impaired daily life and lower quality of life in SCA3 patients.

Abstract

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.

To investigate the clinical burden of peripheral and autonomic nervous system involvement in SCA3 mutation carriers across the disease spectrum.

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.

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.

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.

The online version contains supplementary material available at 10.1007/s00415-025-13588-x.

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