Nigrostriatal dysfunction in RFC1-related disorder/CANVAS

Area of Science:

• Neurology
• Neuroimaging
• Genetics

Background:

• Parkinsonism is an emerging clinical feature of RFC1-associated CANVAS syndrome.
• Systematic evaluations of nigrostriatal dopaminergic function in RFC1/CANVAS are lacking.

Purpose of the Study:

• To investigate nigrostriatal dopaminergic integrity in patients with molecularly confirmed RFC1/CANVAS syndrome.
• To assess the correlation between dopaminergic dysfunction and clinical presentation.

Main Methods:

• Observational, single-center study of 13 RFC1/CANVAS patients.
• Clinical assessment using the SARA scale and evaluation for parkinsonian features.
• Dopamine transporter (DAT) imaging using 99mTc-TRODAT-1.

Main Results:

• Nine out of 13 patients showed abnormal DAT imaging, with putamen more affected than the caudate nucleus.
• Clinical parkinsonism was present in 3 patients, all with abnormal DAT scans.
• Six patients had reduced DAT uptake without clinical parkinsonism, suggesting early subclinical dopaminergic deficits.

Conclusions:

• Nigrostriatal dopaminergic dysfunction is prevalent in RFC1/CANVAS syndrome.
• DAT imaging abnormalities can occur even in the absence of clinical parkinsonism.
• Dopaminergic changes may represent an early feature of the disease course.