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. 2025 Jun 17;272(7):465.
doi: 10.1007/s00415-025-13194-x.

Hypothalamic atrophy in CANVAS/RFC1

Verena Miranda Souza #  1 , Camila Caroso Lobo #  1 , Thiago Junqueira Ribeiro Rezende  1 , Gabriel Silva Schmitt  1 , Paula Camila Alves de Assis Pereira Matos  2 , Fabrício Diniz de Lima  1 , Alberto Rolim Muro Martinez  1 , Orlando Graziani Povoas Barsottini  2 , José Luiz Pedroso  2 , Wilson Marques Jr  3 , Marcondes Cavalcante França Jr  4
Affiliations

Hypothalamic atrophy in CANVAS/RFC1

Verena Miranda Souza et al. J Neurol. .

Abstract

Background: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a late-onset multisystem disorder related to the RFC1 gene. Despite evidence of dysautonomia and sleep disturbances, hypothalamic involvement is unknown.

Objective: We aimed to investigate hypothalamic volumetry in CANVAS/RFC1.

Methods: We analyzed 19 CANVAS/RFC1 patients and 19 healthy controls using automated hypothalamic segmentation from 3 T-MRI scans. Volumetric comparisons were performed using ANCOVA, while correlations with Scale for the Assessment and Rating of Ataxia (SARA) and Scales for Outcomes in Parkinson's Disease-Autonomic questionnaire (SCOPA-AUT) scores were assessed by Pearson's correlation.

Results: CANVAS/RFC1 group had a significantly lower total hypothalamic volume (RFC1: 734.84 ± 160.49 mm3 vs Controls: 878.83 ± 136.55 mm3; P = 0.03; d = 0.99) and a reduced left tuberal superior (LTS) volume (RFC1: 71.21 ± 21.85 mm3 vs Controls: 90.30 ± 15.67 mm3; P = 0.02; d = 0.99). LTS volume inversely correlated with SARA score (R = -0.51, P = 0.049), but no associations were found with SCOPA-AUT.

Conclusion: This study reveals hypothalamic atrophy in CANVAS, suggesting its role in disease pathophysiology. Further research should investigate broader hypothalamic dysfunctions and clinical implications.

Keywords: Ataxia; Dysautonomia; Hypothalamus; MRI; RFC1 expansion.

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Conflict of interest statement

Declarations. Conflict of interest: No conflicts of interest related to the research in this manuscript were declared by any of the authors. Ethical approval: The study protocol was approved by the Ethics Committee of the Clinics Hospital at the University of Campinas (registered as “CAAE 29869520.8.3001.5404”). The study was conducted in accordance with the principles outlined in the Declaration of Helsinki. The authors declare that they have no conflicts of interest.

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