Basal ganglia and cerebellar pathology in X-linked dystonia-parkinsonism

X-linked dystonia-parkinsonism is a hereditary, neurodegenerative movement disorder. Hanssen et al. report severe atrophy in the striatum, most pronounced in the striosome-enriched rostral region. Additional structural changes in the cerebellum highlight the significance of this structure in the pathophysiology of dystonia. Abstract X-linked dystonia-parkinsonism is a neurodegenerative movement disorder characterized by adult-onset dystonia combined with parkinsonism over the disease course. Previous imaging and pathological findings indicate exclusive striatal atrophy with predominant pathology of the striosomal compartment in the dystonic phase of X-linked dystonia-parkinsonism. The striosome occupies 10-15% of the entire striatal volume and the density of striosomes follows a rostrocaudal gradient with the rostral striatum being considered striosome-rich. Recent quantitative MRI analyses provided evidence for an additional involvement of the white matter and the pallidum. In this study, we aimed to (i) disentangle the degree of atrophy in the different subdivisions of the striatum; (ii) investigate changes of cortical morphology; and (iii) elucidate the role of the cerebellum in X-linked dystonia-parkinsonism. T1-weighted MRI scans were acquired in 17 male X-linked dystonia-parkinsonism patients with predominant dystonia (40.1 ± 7.5 years) and 17 ethnicity-matched male healthy controls (35.2 ± 7.4 years). Voxel-based morphometry used a region of interest-based approach for the basal ganglia and primary motor cortex, whole brain analysis, and a separate analysis of the cerebellum. Cortical thickness and subcortical volume were measured. Volume loss in X-linked dystonia-parkinsonism affected all parts of the striatum (−29% voxel intensity) but was most pronounced in the associative subdivision (−41%; P < 0.001). The volume loss also involved the external and internal pallidum, albeit to a lesser extent than the striatum (−19% and −12%, P