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Título

Nigroestriatal dysfunction is frequent in RFC-1 related disorder

Resumo

Background: RFC1/CANVAS syndrome is a rare adult-onset heredodegenerative disorder caused by biallelic AAAAG RFC1 expansions and characterized primarily by cerebellar ataxia, sensory neuronopathy (ganglionopathy), as well as bilateral vestibular hypofunction. Parkinsonism is now recognized as an additional feature in the disease, however no systematic evaluation of nigrostriatal dopaminergic function has been published so far.
Objective: To describe striatal dopamine transporter (DAT) density in a sample of RFC1/CANVAS patients using dopaminergic transporter brain scintigraphy with 99mTc-TRODAT-1 (DAT imaging).
Methods: This is an observational, single-center study conducted in a tertiary referral hospital, which analyzed 10 patients with molecular confirmation of RFC1/CANVAS. Disease severity was assessed with the SARA scale. Each subject was carefully evaluated for the presence of parkinsonian features. DAT imaging was acquired and reconstructed in the transverse, coronal and sagittal planes 4 hours after venous injection of 99mTc-TRODAT-1 . An experienced nuclear physician performed the visual analysis of all images. Quantification was performed drawing region of interest (ROI) in the striatum, putamen and caudate bilaterally. The specific uptake (mean uptake ratio) of each region was calculated using occipital region uptake as the reference.
Results: Patients had a mean age of 63 ± 9.2 years, and there were 7 women. The mean SARA score was 16.9 ± 5.8. Seven patients had abnormal DAT imaging results, characterized by reduced uptake in left putamen (100%), right putamen (85.7%), left caudate (71.4%) and right caudate (71.4%). Four patients (57.1%) had bilateral striatum abnormalities. Parkinsonism was noticed in 3/7 patients, all of which had abnormal DAT scans. Interestingly, four subjects had reduced DAT imaging uptake, but no clinical signs of parkinsonism.
Conclusions: Nigrostriatal dysfunction is frequent in RFC1/CANVAS, suggesting that disease pathology is more widespread than previously thought. Additionally, the fact that patients without parkinsonism also had abnormal DAT imaging results might suggest that DAT imaging changes occur early along the disease course. These results have practical therapeutic relevance and suggest that dopaminergic agents might be useful at least for a subgroup of patients with RFC1-related disorder.

Palavras Chave

Nigroestriatal. RFC-1. Scintigraphy. Parkinsonism. Ganglionopathy. Ataxia. Vestibular

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