Structural Cerebellar Abnormalities and Parkinsonism in Patients with 22q11.2 Deletion Syndrome

Background: The phenotypic expression of 22q11.2 deletion syndrome (22q11.2DS) is variable and may include cognitive, psychiatric, and neurological manifestations, e.g., parkinsonism. We investigated brain structural alterations in patients with 22q11.2DS with and without parkinsonism (Park+ and Park-) in comparison with healthy controls (HCs). Methods: Voxel-based morphometry was performed on 3D T1-weighted MR images to explore gray matter volume (GMV) differences between 29 patients (15 Park+, 14 Park-), selected from a consecutive series of 56 adults diagnosed with 22q11.2DS, and 24 HCs. One-way ANOVA and multiple linear regression analyses were performed to explore group differences in GMV and correlations between clinical scores (MDS-UPDR-III and MoCA scores) and structural alterations. Results: Significant between-group differences in GMV were found in the cerebellum, specifically in bilateral lobes VIII and left Crus II, as well as in the left superior occipital gyrus. Although both Park+ and Park- patients showed GMV decrements in these regions with respect to HCs, GMV loss in the right lobe VIII and left Crus II was greater in Park+ than in Park- patients. GMV loss did not correlate with clinical scores. Conclusions: Patients with 22q11.2DS and parkinsonism manifest specific cerebellar volume alterations, supporting the hypothesis of neurodegenerative processes in specific cerebellar regions as a putative pathophysiological mechanism responsible for parkinsonism in patients with 22q11.2DS.

Automated summary

This study found specific grey matter volume (GMV) reductions in the cerebellum (lobes VIII and Crus II) and the left superior occipital gyrus in patients with 22q11.2 deletion syndrome (22q11.2DS) and parkinsonism. Although bothPark+ and Park- patients showed GMV decrements in these regions, the reductions were greater in Park+ patients. However, GMV loss did not correlate with clinical scores.