Disentangling the neural correlates of corticobasal syndrome and corticobasal degeneration with systematic and quantitative ALE meta-analyses

Abstract

Corticobasal degeneration is a scarce neurodegenerative disease, which can only be confirmed by histopathological examination. Reported to be associated with various clinical syndromes, its classical clinical phenotype is corticobasal syndrome. Due to the rareness of corticobasal syndrome/corticobasal degeneration and low numbers of patients included in single studies, meta-analyses are particularly suited to disentangle features of the clinical syndrome and histopathology. Using PubMed, we identified 11 magnetic resonance imaging studies measuring atrophy in 22 independent cohorts with 200 patients contrasted to 318 healthy controls. The anatomic likelihood estimation method was applied to reveal affected brain regions across studies. Corticobasal syndrome was related to gray matter loss in the basal ganglia/thalamus, frontal, parietal, and temporal lobes. In corticobasal degeneration patients, atrophy in the thalamus, frontal, temporal, and occipital lobes were found. Finally, in a conjunction analysis, the bilateral thalamus, the bilateral posterior frontomedian cortex, posterior midcingulate cortex and premotor area/supplementary motor area, and the left posterior superior and middle frontal gyrus/precentral gyrus were identified as areas associated with both, corticobasal syndrome and corticobasal degeneration. Remarkably, atrophy in the premotor area/supplementary motor area and posterior midcingulate/frontomedian cortex seems to be specific for corticobasal syndrome/corticobasal degeneration, whereas atrophy in the thalamus and the left posterior superior and middle frontal gyrus/precentral gyrus are also associated with other neurodegenerative diseases according to anatomic likelihood estimation method meta-analyses. Our study creates a new conceptual framework to understand, and distinguish between clinical features (corticobasal syndrome) and histopathological findings (corticobasal degeneration) by powerful data-driven meta-analytic approaches. Furthermore, it proposes regional-specific atrophy as an imaging biomarker for diagnosis of corticobasal syndrome/corticobasal degeneration ante-mortem.

Fig. 1

PRISMA statement flow diagram. Flow of information through different phases of the systematic literature search identifying the neural correlates of CBS and CBD according to the PRISMA statement, as suggested by Moher, Liberati, Tetzlaff and Altman. ROI region of interest

Fig. 2

Impaired regions in CBS and CBD. Impaired brain regions in CBS and CBD in comparison with healthy control subjects–anatomical likelihood estimates meta-analyses. Atrophy was measured by MRI. The CBS analysis (red) included 184 patients from 17 cohorts contrasted to 265 healthy subjects. The CBD analysis (blue) included 34 patients from seven cohorts contrasted to 121 healthy subjects. The analysis of the combined cohort of CBS and CBD (white) included 200 patients contrasted to 318 healthy control subjects. Coordinates are reported in MNI space. L left

Fig. 3

Conjunction analysis. Conjunction analysis for impaired brain regions in CBS and CBD in comparison with healthy control subjects–anatomical likelihood estimates meta-analyses. White clusters indicate overlap of both meta-analyses (CBS and CBD). Atrophy was measured by MRI. Coordinates are reported in MNI space. L left