Objective: To investigate cortical and subcortical atrophy patterns in X-linked dystonia-parkinsonism (XDP).

Background: XDP is a neurodegenerative disorder characterized by severe adult-onset dystonia followed by parkinsonism over the course of disease. Post mortem studies revealed striatal pathology mainly affecting the striosome in the initial dystonic phase, and both striosome and matrisome in the Parkinsonian phase. Upon clinical MR imaging, striatal atrophy can be observed in later disease stages whereas no or only discrete striatal atrophy has been found in the dystonic phase. Quantitative MR analyses were not yet performed in XDP.

Methods: T-1 weighted cranial MRI scans were acquired in 17 male Filipino XDP patients (age: M= 40.12, SD= 7.6; mean disease duration: 3 years) and 17 ethnicity-matched male healthy controls (age: M= 35.67, SD= 7.72). Voxel-based morphometry (VBM) was conducted using SPM8 and DARTEL. In addition to a whole brain analysis, ROIs were defined for putamen, caudate, external and internal pallidum (GPe, GPi), substantia nigra (SN), and the primary motor cortex. Cortical thickness measurement and subcortical volumetry were done using FreeSurfer software.

Results: VBM revealed starkly reduced voxel intensity restricted to putamen, caudate, GPe and GPi bilaterally in XDP patients compared to controls (p<0.001). In contrast, SN voxel intensity was not different between groups (p= 0.240). In keeping with the VBM results, subcortical volumetry revealed distinct volume reductions of the putamen (-45%), caudate (-46%) and pallidum (-44%) (all p<0.001). Cortical thickness and cortical gray matter intensity were not different between groups. Caudate volume correlated with disease duration (p<0.01) whereas the putamen and pallidum volume did not.

Conclusions: Striatal atrophy is severe even in patients with short disease duration and is not associated with a gradual putaminal decline within the first years of overt disease indicating a potential long-lasting presymptomatic degenerative phase. There are no obvious compensatory structural changes on a cortical level. In addition to previously described striatal changes, GPe and GPi also appear to be involved in the neurodegenerative disease process. To investigate possible compensatory mechanisms in presymptomatic mutation carriers and possible predictors for disease onset, follow-up investigations in asymptomatic mutation carriers are warranted.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/severe-striatal-and-pallidal-atrophy-in-early-disease-stages-of-x-linked-dystonia-parkinsonism/