Dados do Trabalho

Título

RFC1-related disorder: In vivo evaluation of spinal cord damage

Resumo

Background: RFC1-related disorder is a recently described neurodegenerative condition related to biallelic intronic expansions in RFC1, leading to CANVAS syndrome. This condition is typically characterized by a clinical triad of cerebellar ataxia, sensory neuronopathy and vestibular areflexia, but also with a broad phenotypic spectrum, including dopa-responsive parkinsonism, spasmodic cough and dysautonomia. Cerebellar and encephalic MRI changes have been described in this disease, but little is known regarding spinal cord involvement.
Objectives: The present study aims to determine spinal cord alterations in RFC1-related disorder and its clinical correlates.
Methods: Seventeen subjects with biallelic RFC1 (AAGGG)n expansions and 11 age and sex-matched healthy controls were enrolled between 2019 and 2021. All individuals underwent multimodal MRI spinal cord acquisitions in a 3T Philips Achieva scanner and patients were evaluated including SARA scores and time from ataxia onset (disease duration) to quantify disease severity. The Spinal Cord Toolbox (SCT) was used to assess spinal cord cross-sectional area (CSA), eccentricity (ECC), spinal cord gray matter area and diffusivity parameters of fasciculus cuneatus, fasciculus gracilis and lateral corticospinal tract across C2-C5 levels. Between-group comparisons were assessed using Mann-Whitney U test, employing age and gender as covariate. A Bonferroni test correction was used to control for multiple comparisons. Correlations between MRI findings and clinical data were assessed through Spearman correlation test.
Results: RFC1 group had significant spinal cord CSA reduction along all cervical levels, increased ECC in lower cervical levels and gray matter atrophy when compared to controls. Regarding white matter alterations, diffusivity abnormalities were found only in the dorsal columns. There was no significant correlation between clinical data and imaging parameters.
Conclusion: RFC1-related disorder patients have prominent gray matter atrophy and white matter degeneration in cervical spine, mostly on dorsal columns, showing that spinal cord damage is a hallmark of this disease. More studies are needed to assess the usefulness of these findings as clinical biomarkers.

Palavras Chave

Spinal Cord, MRI, RFC1, CANVAS