Neocortical Atrophy in Machado‐Joseph Disease: A Longitudinal Neuroimaging Study

Abstract

Previous imaging studies in the Machado-Joseph disease (MJD/SCA3) have mostly concentrated on the cerebellum and brainstem. Our goal was to perform a whole brain longitudinal evaluation. METHODSWe included 45 patients and 51 controls, who underwent two brain magnetic resonance imaging and magnetic resonance spectroscopy (mean interval of 12.5 ± 1.5 months). We used voxel-based morphometry (VBM) and the MarsBar analysis toolbox to extract grey matter density (GMD) values from regions of interest. We used a linear regression model and a general linear model to correlate GMD with clinical markers, and paired t-test for the longitudinal evaluation. RESULTSWe observed decreased GMD (P < .01) at frontal, parietal, temporal and occipital lobes, subcortical grey matter, cerebellum, and brainstem. White matter atrophy was restricted to the cerebellum. Age, CAG, and disease duration predicted GMD in different areas, but age and CAG were the most important predictors. The longitudinal analysis failed to demonstrate changes. Changes in regions other than the cerebellum appeared to contribute significantly to the final International Cooperative Ataxia Rating Scale score. CONCLUSIONWe confirmed cortical involvement in MJD/SCA3. The most important factors in predicting GMD were age and CAG. The lack of progression of atrophy may indicate floor effect and/or short duration of follow-up.

MR Imaging in Spinocerebellar Ataxias: A Systematic Review

“…16,17 Both studies assessed volumetric analysis, and 1 of them assessed MR spectroscopy changes with time. 16 Volumetric studies used voxel-based morphometry (VBM) and surface-based analysis.…”

“…16,17 Both studies assessed volumetric analysis, and 1 of them assessed MR spectroscopy changes with time. 16 Volumetric studies used voxel-based morphometry (VBM) and surface-based analysis. VBM analysis, implemented in differ-ent versions of the SPM software (SPM2, SPM5, and SPM8; tools; http://www.fil.ion.ucl.ac.uk/spm/software/spm8), varied among selected studies, which used ROIs or VOI analysis and/or wholebrain volume analysis with standardization maps.…”

“…VBM analysis, implemented in differ-ent versions of the SPM software (SPM2, SPM5, and SPM8; tools; http://www.fil.ion.ucl.ac.uk/spm/software/spm8), varied among selected studies, which used ROIs or VOI analysis and/or wholebrain volume analysis with standardization maps. Seven studies used ROI or VOI 16,[18][19][20][21][22][23] analysis (2 with manual outlining), and 8 studies performed whole brain analysis (5 automated 24-28 and 3 semiautomated 17,29,30 processing). One study performed both manual and automated morphometric measurement of the thalamus.…”

“…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.…”