Objective: To characterize a metabolic brain network associated with X-linked dystonia-parkinsonism (XDP).

Background: X-linked dystonia-parkinsonism (XDP, DYT/PARK-TAF1, Lubag) is an X-linked recessive movement disorder characterized by torsion dystonia as well as parkinsonism.The majority of patients presents with dystonia. Parkinsonism is present at onset in a minority of cases, but typically develops over time in the remainder. Neuropathologically, the caudate and putamen are affected in XDP, with neuronal loss and gliosis.  Although a rare disorder, these clinical and pathological features make XDP a potential model disease for both dystonia and parkinsonism. To date, most imaging studies in this disease have used MRI, with metabolic imaging limited to single cases.

Method: 30 right-handed Filipino men with XDP (age 44.4±8.5 years) and 30 gene negative healthy men from the same population (age 37.4 ±10.5 years) underwent FDG PET. The scans were analyzed using spatial covariance mapping to identify a significant XDP-related metabolic pattern (termed XDPRP). Patients were rated clinically at the time of imaging according to the XDP-MDSP scale.

Results: We identified a significant XDPRP topography from 15 randomly selected XDP subjects and 15 controls. This pattern was characterized by bilateral metabolic reductions in caudate/putamen, frontal operculum and cingulate cortex, with relative increases in the bilateral somatosensory cortex and cerebellar vermis. Age-corrected XPDRP expression was significantly elevated in XDP compared to controls in the derivation set (p<0.0001), and in the remaining patients vs. controls in the testing set (p<0.0001). We validated the XDPRP topography by identifying a similar pattern in the original testing set (r=0.90, p<0.0001; voxel-wise correlation between both patterns). Significant correlations between XDPRP expression and clinical ratings for parkinsonism, but not dystonia, were observed in both XDP groups. Further network analysis revealed abnormalities of information transfer through the XDPRP space, with loss of normal connectivity and gain of abnormal functional connections linking network nodes with outside brain regions.

Conclusion: XDP is associated with a characteristic metabolic network associated with abnormal functional connectivity between the basal ganglia, thalamus, motor regions, and cerebellum. Clinical signs may relate to faulty information transfer through the network to outside brain regions.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-network-imaging-biomarker-of-x-linked-dystonia-parkinsonism/