Imaging correlates of pathology in corticobasal syndrome

Abstract

Background: Corticobasal syndrome (CBS) can be associated with different underlying pathologies that are difficult to predict based on clinical presentation. The aim of this study was to determine whether patterns of atrophy on imaging could be useful to help predict underlying pathology in CBS.

Methods: This was a case-control study of 24 patients with CBS who had undergone MRI during life and came to autopsy. Pathologic diagnoses included frontotemporal lobar degeneration (FTLD) with TDP-43 immunoreactivity in 5 (CBS-TDP), Alzheimer disease (AD) in 6 (CBS-AD), corticobasal degeneration in 7 (CBS-CBD), and progressive supranuclear palsy in 6 (CBS-PSP). Voxel-based morphometry and atlas-based parcellation were used to assess atrophy across the CBS groups and compared to 24 age- and gender-matched controls.

Results: All CBS pathologic groups showed gray matter loss in premotor cortices, supplemental motor area, and insula on imaging. However, CBS-TDP and CBS-AD showed more widespread patterns of loss, with frontotemporal loss observed in CBS-TDP and temporoparietal loss observed in CBS-AD. CBS-TDP showed significantly greater loss in prefrontal cortex than the other groups, whereas CBS-AD showed significantly greater loss in parietal lobe than the other groups. The focus of loss was similar in CBS-CBD and CBS-PSP, although more severe in CBS-CBD.

Conclusions: Imaging patterns of atrophy in CBS vary according to pathologic diagnosis. Widespread atrophy points toward a pathologic diagnosis of FTLD-TDP or AD, with frontotemporal loss suggesting FTLD-TDP and temporoparietal loss suggesting AD. On the contrary, more focal atrophy predominantly involving the premotor and supplemental motor area suggests CBD or PSP pathology.

Figure 1 Patterns of gray matter loss in each corticobasal syndrome (CBS) pathologic group compared to controls Surface renderings showing regions of gray matter loss in the dominant and nondominant hemisphere of CBS-TDP, CBS-AD, CBS-CBD, and CBS-PSP compared to controls. All results are shown after correction for multiple comparisons using the false discovery rate (FDR) at p < 0.001, except for the results from the CBS-PSP group, which are shown uncorrected at p < 0.001. AD = Alzheimer disease; CBD = corticobasal degeneration; PSP = progressive supranuclear palsy; TDP = TDP-43 immunoreactivity.

Figure 2 Regions of gray matter loss common to all corticobasal syndrome (CBS) pathologic groups and different across groups Surface renderings showing the results of 3 statistical comparisons: 1) regions of gray matter loss that were common to all CBS pathologic groups using a conjunction analysis, 2) regions of gray matter loss in the CBS-TDP group compared to all other CBS pathologic groups, and 3) regions of gray matter loss in the CBS-AD group compared to all other CBS pathologic groups. Results are shown uncorrected for multiple comparisons at p < 0.001. AD = Alzheimer disease; CBD = corticobasal degeneration; TDP = TDP-43 immunoreactivity.

Figure 3 Scatterplots showing individual level volumetric data for 2 regions of interest Z scores of the superior frontal lobe (A) and parietal lobe (B) in the dominant hemisphere are plotted for each corticobasal syndrome (CBS) pathologic group and controls. The boxes indicate the median and interquartile range of the distributions while the horizontal lines extending from the boxes stop at the most extreme data points. All CBS pathologic groups showed greater negative Z scores than controls for both regions. CBS-TDP showed the greatest negative Z score for the superior frontal lobe, whereas CBS-AD showed the greatest negative Z score for the parietal lobe. AD = Alzheimer disease; CBD = corticobasal degeneration; PSP = progressive supranuclear palsy; TDP = TDP-43 immunoreactivity.