Comprehensive neuropsychological assessment and FDG-PET imaging in patients with RFC1-related disorder

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a disorder characterized by biallelic intronic (AAGGG) expansions in the RFC1 gene. However, the characterization of the cognitive and behavioral disturbances of these patients is still largely unknown.

To determine the frequency and characteristics of cognitive dysfunction in patients with RFC1 disease using a comprehensive neuropsychological assessment, and to evaluate the brain regions involved using ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET).

Eleven participants diagnosed with CANVAS underwent FDG-PET neuroimaging and comprehensive neuropsychological assessment, including evaluation of psychiatric and behavioral symptoms. Test scores were converted to adjusted scaled scores and dichotomized as intact or impaired.

We detected executive dysfunction, followed by deficits in social cognition and episodic memory. Almost no cognitive test showed correlations with fine motor coordination. Depression, anxiety, and irritability were relatively high, whereas apathy and disinhibition were rare. FDG-PET imaging revealed cerebellar hypometabolism, with no evidence of involvement of other brain regions.

Our study found executive dysfunction, followed by deficits in social cognition and episodic memory, as the main cognitive features of CANVAS syndrome. Cerebellar hypometabolism observed on FDG-PET suggests a role of the cerebellum in the cognitive deficits seen in these patients.