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.

Disease-related patterns of in vivo pathology in Corticobasal syndrome

“…Microstructural white matter changes were also observed in frontal and parietal cortices in the hemisphere contralateral to the clinically most affected body side of patients with CBS compared to healthy controls and patients with MCI. This is in line with previous studies showing significant asymmetric regional grey matter loss and white matter changes in motor cortex areas [ 10 , 11 ].…”

“…Another [ 18 F]AV1451 PET study has demonstrated increased tau binding in the putamen, globus pallidus, thalamus and precentral grey and white matter in the hemisphere contralateral to the clinically most affected side in six CBS patients [ 9 ]. Previous MRI studies have shown grey matter loss and white matter changes in precentral, superior frontal, and fusiform gyri, putamen and globus pallidus in CBS patients [ 10 , 11 ].…”

Frontal Pole Hypometabolism Linked to Reduced Prosocial Sexual Behaviors in Frontotemporal Dementia and Corticobasal Syndrome

“…Demographic and clinical data are presented in Table 1. CBS patients were used as clinical controls, as CBS is also neurodegenerative, but is associated with fewer neuropsychiatric and behavioral changes than FTD [14] and is predominantly characterized by atrophy in the posterior frontal lobes and basal ganglia [15,16], regions hypothesized to have fewer associations with sexual symptoms than anterior frontal and temporolimbic regions, as described above.…”

“…To restrict analyses to the hypothesized regions, ROIs were chosen based on established regions of atrophy in FTD (all phenotypes) [27][28][29][30][31] and CBS [15,16]. A mask of these regions was created using the Harvard Oxford Cortical and Subcortical atlases, available through the Functional MRI of the Brain Software Library [32] (Supplementary Material).…”

Neuroimaging of Sleep Disturbances in Movement Disorders

“…There have been no studies, to-date, exploring the neuropathological basis of sleep disturbances in CBS using neuroimaging techniques. A data-driven meta-analysis identifying and comparing the neural correlates of CBS for atrophy measurements included 200 CBS patients and 318 controls ( 187 ). This study identified four brain regions with significant atrophy: (1) the bilateral anterior thalamus; (2) the posterior midcingulate cortex, bilateral posterior frontomedian cortex and the premotor area/supplementary motor area; (3) the posterior superior frontal sulcus and precentral gyrus/middle frontal gyrus; (4) the left posterior superior frontal sulcus and middle frontal gyrus.…”