Dados do Trabalho

Título

Spinocerebellar ataxia type 6 is not a pure cerebellar disease: data from spinal cord imaging

Resumo

Background: Spinocerebellar ataxia type 6 (SCA6) is a rare autosomal dominantly inherited disorder caused by abnormal CAG trinucleotide repeat expansions in the CACNA1A gene (19p13.13). SCA6 is considered a prototype of pure cerebellar ataxia, with late onset and slowly progressive course, but extracerebellar findings have been described. The pathological hallmark of SCA6 is cerebellum and inferior olive atrophy, but degeneration has also been found on brainstem nuclei and spinal cord in autopsy studies. Previous MRI studies found cerebellar damage in SCA6 cohorts, but little is known regarding spinal cord imaging changes in these patients.
Objective: To assess spinal cord involvement through MRI and its clinical correlates in a SCA6 cohort.
Methods: We enrolled 17 SCA6 patients with genetic confirmation, but 4 patients were excluded due to compressive myelopathy. They underwent clinical evaluation, including SARA, INAS and ICARS scales, and MRI examination on a 3T Phillips scanner at the same day. Thirteen age and sex-matched healthy controls were also assessed. The Spinal Cord Toolbox (SCT) was employed to measure spinal cord area and eccentricity in C1-T2 levels and white matter tracts integrity by assessing diffusion parameters, which are fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD), in C2-C5 levels. Imaging data were compared between SCA6 and controls groups through a Mann-Whitney U test, employing age and sex as covariates. Bonferroni correction for multiple comparisons was performed. Correlations between imaging and clinical data were assessed through Spearman’s rank correlation coefficients.
Results: Mean age of the patients and disease duration were 68,1±7,0 and 15,3±6,9 years, respectively. Mean SARA score was 15,0±6,9. SCA6 group had increased AD in left tectospinal tract (p=0.023), left lateral vestibulospinal tract (p=0.027) and left ventral corticospinal tract (p=0.045), increased MD in right lateral vestibulospinal tract (p=0.032) and left tectospinal tract (p=0.019), and increased RD in right lateral vestibulospinal tract (p=0.032). These MRI parameters did not correlate with clinical data but, in an exploratory approach, left ventral corticospinal tract RD were directly related to INAS scale (p=0.011, r=0.699).
Discussion: These findings indicate that not only the cerebellum, but also the spinal cord is involved in SCA6. Quantitative spinal cord MRI might be a useful biomarker in SCA6.