MRI Shows a Region-Specific Pattern of Atrophy in Spinocerebellar Ataxia Type 2

Brian C. Jung, Soo I. Choi, Annie X. Du, Jennifer L. Cuzzocreo, Howard S. Ying, Bennett A. Landman, Susan L. Perlman, Robert W. Baloh, David S. Zee, Arthur W. Toga, Jerry L. Prince, Sarah H. Ying

In this study, we used manual delineation of high-resolution magnetic resonance imaging (MRI) to determine the spatial and temporal characteristics of the cerebellar atrophy in spinocerebellar ataxia type 2 (SCA2). Ten subjects with SCA2 were compared to ten controls. The volume of the pons, the total cerebellum, and the individual cerebellar lobules were calculated via manual delineation of structural MRI. SCA2 showed substantial global atrophy of the cerebellum. Furthermore, the degeneration was lobule specific, selectively affecting the anterior lobe, VI, Crus I, Crus II, VIII, uvula, corpus medullare, and pons, while sparing VIIB, tonsil/paraflocculus, flocculus, declive, tuber/folium, pyramis, and nodulus. The temporal characteristics differed in each cerebellar subregion: (1) duration of disease: Crus I, VIIB, VIII, uvula, corpus medullare, pons, and the total cerebellar volume correlated with the duration of disease; (2) age: VI, Crus II, and flocculus correlated with age in control subjects; and (3) clinical scores: VI, Crus I, VIIB, VIII, corpus medullare, pons, and the total cerebellar volume correlated with clinical scores in SCA2. No correlations were found with the age of onset. Our extrapolated volumes at the onset of symptoms suggest that neurodegeneration may be present even during the presymptomatic stages of disease. The spatial and temporal characteristics of the cerebellar degeneration in SCA2 are region specific. Furthermore, our findings suggest the presence of presymptomatic atrophy and a possible developmental component to the mechanisms of pathogenesis underlying SCA2. Our findings further suggest that volumetric analysis may aid in the development of a non-invasive, quantitative biomarker.