Abstract
Background X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative adult-onset basal ganglia model disease associated with severe striatal atrophy. Anatomical changes exceeding striatal pathology were not yet described in XDP. The present study aimed to assess the microstructure of white matter tracts in XDP using magnetic resonance tomography. Methods Diffusion-weighted imaging was done in 10 XDP patients, aged 42.2 years (SD 8.1), and 14 ethnicity and age-matched controls, aged 40.2 years (SD 6.4). Based on diffusion tensor images, mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated. Results Except for in the occipital lobe, XDP patients showed generally increased MD values across the entire white matter. FA map analysis identified four significant clusters with controls showing higher FA values than XDP patients. Involved regions included the fornix, anterior thalamic radiation, corticospinal tract, and superior corona radiata bilaterally. In the fornix and the anterior thalamic radiation, the UPDRSIII total score showed a negative correlation with mean FA values at a trend level (tau = −0.40, p = 0.053). Volumetric analysis revealed significant gray matter volume loss of putamen (F(1,19) = 44.2, p < 0.001), caudate nucleus (F(1,19) = 54.3, p < 0.001), and pallidum (F(1,19) = 8.9, p = 0.007). Conclusions The present study confirms striatal atrophy in XDP and provides evidence for a strong involvement of the white matter and the pallidum. This calls into question the previously held concept of exclusive striatal atrophy in this unique movement disorder. The spared occipital region may point towards a lack of anatomical connections with the atrophied striatum.
| Original language | English |
|---|---|
| Journal | Parkinsonism and Related Disorders |
| Volume | 31 |
| Pages (from-to) | 91-97 |
| Number of pages | 7 |
| ISSN | 1353-8020 |
| DOIs | |
| Publication status | Published - 01.10.2016 |
Funding
Dr. Brüggemann was funded by the German Research Foundation (BR 4328/1-1) and the Collaborative Center for X-linked Dystonia-Parkinsonism. He received speaker's honoraria from the German Neurological Society. He received travel grants from Ipsen, Merz and St. Jude Medical. Dr. Heldmann reports no disclosures. Dr. Klein is a member of the editorial board of “Neurology” and has served as editor of the “Continuum Issue Neurogenetics 2008” and as faculty at the Annual Meetings of the American Academy of Neurology since 2004. She serves as a medical advisor to Centogene. She is the recipient of a career development award from the Hermann and Lilly Schilling Foundation. She is funded by the Deutsche Forschungsgemeinschaft, the Possehl Foundation and received institutional support from the University of Luebeck for genetics research. Dr. Domingo reports no disclosures. Dr. Rasche reports no disclosures. Dr. Tronnier received honoraria from St. Jude, Medtronic, EISAI and Codman for scientific presentation. He is member of the advisory boards of EISAI and Medtronic. Dr. Rosales reports no financial disclosures. Dr. Jamora reports no disclosures. Dr. Lee reports no disclosures. Dr. Münte received the following support during the previous 12 months: several grants by the German National Science Foundation (Deutsche Forschungsgemeinschaft), several grants by the Federal Ministry of Research (Bundesministerium für Bildung und Forschung), an unrestricted grant by Willmar-Schwabe AG (pharmaceutical company). We gratefully thank all participants for their invaluable collaboration. This study was supported by funding by the Collaborative Center for X-linked Dystonia Parkinsonism. CK is the recipient of a career development award from the Hermann and Lilly Schilling Foundation. The funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Appendix A
