Spinal Cord Damage in Machado-Joseph Disease

Abstract

Machado-Joseph disease (SCA3) is the most frequent spinocerebellar ataxia worldwide and characterized by remarkable phenotypic heterogeneity. MRI-based studies in SCA3 focused in the cerebellum and connections, but little is known about cord damage in the disease and its clinical relevance. To evaluate the spinal cord damage in SCA3 through quantitative analysis of MRI scans. A group of 48 patients with SCA3 and 48 age and gender-matched healthy controls underwent MRI on a 3T scanner. We used T1-weighted 3D images to estimate the cervical spinal cord area (CA) and eccentricity (CE) at three C2/C3 levels based on a semi-automatic image segmentation protocol. The scale for assessment and rating of ataxia (SARA) was employed to quantify disease severity. The two groups-SCA3 and controls-were significantly different regarding CA (49.5 ± 7.3 vs 67.2 ± 6.3 mm(2), p < 0.001) and CE values (0.79 ± 0.06 vs 0.75 ± 0.05, p = 0.005). In addition, CA presented a significant correlation with SARA scores in the patient group (p = 0.010). CE was not associated with SARA scores (p = 0.857). In the multiple variable regression, we found that disease duration was the only variable associated with CA (coefficient = -0.629, p = 0.025). SCA3 is characterized by cervical cord atrophy and antero-posterior flattening. In addition, the spinal cord areas did correlate with disease severity. This suggests that quantitative analyses of the spinal cord MRI might be a useful biomarker in SCA3.

MR Imaging in Spinocerebellar Ataxias: A Systematic Review

“…Both cerebellar and brain stem structures presented significant correlation with SARA, 29,32,33 ICARS, 16,33 disease duration, 32,33 and CAG repeat expansions length (On-line Table 1 and Fig 2). A single study evaluated semiautomated cervical spine volumetric analysis and found significant atrophy in SCA3/MJD, which correlated with longer disease duration.…”

“…Regarding volumetric studies, cerebellar hemispheres and vermis, whole brain stem, midbrain, pons, medulla oblongata, cervical spine, caudate and putamen nuclei, and thalamus seem to be the best target regions as surrogate outcomes in SCA3/MJD according to cross-sectional studies. 16,29,24,32,33 In the study by Schulz et al, 29 the stepwise inclusion of the pons and medulla oblongata together explained 53% of the variance in SARA in a linear regression model, and in another study, the cross-sectional area of the cervical spine explained 49.1% of SARA scores in a regression model built with disease duration and cerebellar volume. 9 Some minor differences in the results across studies might be related to technical differences between semiautomated and automated analyses and differences between VBM and surface analysis (FreeSurfer).…”

“…Six studies evaluated volumetric changes in patients with SCA3/MJD and control individuals, 4 with VBM, 1 with FreeSurfer analysis, 16,29,30,32,33 and 3 with semiautomated analysis, 29,31,34 comprising a total of 246 patients with SCA3/MJD evaluated. Five of the 6 cross-sectional studies were performed by the same group in a single center in Brazil.…”

“…All 4 studies that analyzed cerebellar volume with VBM and FreeSurfer found significant atrophy for the total cerebellum or cerebellar hemispheres 16,29,32,33 ; 3 studies also reported vermian atrophy. 16,29,33 One study reported dentate nucleus atrophy, 33 while another study reported no differences in this region. 29 Two studies reported cerebellar peduncle atrophy.…”

“…29,33 Four studies reported whole brain stem atrophy, 16,29,32,33 and 3 studies, pontine atrophy. 16,32,33 Two studies reported midbrain 16,29 and medulla oblongata atrophy, 16,33 while 1 study found no differences for midbrain 33 and 1, for medulla oblongata volumes. 29 Semiautomated volume analysis from a single study 29 showed…”