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. 2025 Mar 1;272(3):235.
doi: 10.1007/s00415-025-12964-x.

Late-onset vestibulocerebellar ataxia: clinical and genetic studies in a long follow-up series of 50 patients

David Genís  1   2 , Berta Alemany  3   4 , David Pellerin  5   6 , Bernard Brais  5 , Marie-Josée Dicaire  5 , Víctor Volpini  7 , Berta Campos  7 , Jordi Corral  7 , Josep Gardenyes  7 , Laura de Jorge  7 , Héctor San Nicolás  7 , Maria Buxó  8 , Joan Martínez Sancho  8 , Maria Obon  9 , Carles Roig  9   10 , Laia Rodriguez-Revenga  11   12 , María Isabel Alvarez-Mora  11   12 , Matt C Danzi  13 , Henry Houlden  6 , Stephan Zuchner  13 , Fabián Márquez  14 , Lluís Ramió I Torrentà  4   15   14
Affiliations

Late-onset vestibulocerebellar ataxia: clinical and genetic studies in a long follow-up series of 50 patients

David Genís et al. J Neurol. .

Abstract

Background: To describe the epidemiology, clinical features, degree of disability and genetic characteristics of a cohort of patients with a vestibulo-cerebellar ataxia of very late onset (LOVCA).

Methods: We analysed the clinical, radiological, and genetic characteristics of a cohort of 50 patients with LOVCA. Where possible, patients were followed over the full course of the disease, including clinical, and molecular genetic analysis of genes known to cause episodic ataxia.

Results: Ten patients are familial and 40 sporadic. Forty-three patients had an episodic onset, with episodes of gait ataxia characterized especially by sudden instability with downbeat nystagmus, visual symptoms, dizziness, and falls. Progression began on average 1.5 years after the onset of episodes. Of the patients followed over the full course of the disease, 87% became disabled. Women seem more prone to disability than men. An FGF14 intronic GAA repeat expansion was found in 61% of patients with available DNA. The prevalence of LOVCA is 5.03/105 inhabitants. Treatment with 4-aminopyridine reduced the number and severity of episodes.

Conclusion: LOVCA appears after the age of 50 and commonly leads to an inability to stand up and walk. The disease caused mild atrophy only in half of the patients and few changes were observed by MRI. The most common genetic cause was a heterozygous GAA expansion in FGF14 (SCA27B). One third of our patients have no aetiological diagnosis. Disability seems to be a result of the complete loss of the vestibulocerebellar function, which is presumably a result of degeneration of this system.

Keywords: Episodic ataxia; Genetic diagnosis; Late-onset ataxia; Vestibulocerebellar ataxia.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose.

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