Hypothalamic atrophy in CANVAS/RFC1

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.

We aimed to investigate hypothalamic volumetry in CANVAS/RFC1.

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.

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.

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