Abstract
Background: X-linked dystonia-parkinsonism (XDP) is characterized by the unique transition of dystonia to parkinsonism and striatal degeneration. Slowing of saccades on clinical examination has been taken as suggestive of a progressive supranuclear palsy (PSP) phenotype. Objectives: To elucidate whether eye movement abnormalities in XDP patients reflect striatonigral impairment or deficits in the brainstem saccade generator as present in PSP. Methods: Eye movements of 18 male XDP patients from the Philippines and 16 ethnically and age-matched, healthy control participants were analyzed and the results related to morphometric frontostriatal changes. Results: There was moderate saccade hypometria in XDP but velocity of visually guided saccades was normal. XDP patients showed an increased antisaccade error rate which correlated with the reduction of (i) the volume of the pallidum and putamen as well as (ii) the volume and cortical thickness in dorsolateral prefrontal cortex. Amplitude of memory-guided saccades was smaller and latency prolonged. Horizontal smooth pursuit eye movements were impaired. Conclusions: Oculomotor abnormalities in XDP resemble those of patients with the Parkinsonian type of multiple system atrophy and - to a lesser degree - Parkinson's disease, but are not compatible with PSP. They indicate striatal impairment and may represent preclinical signs of the parkinsonian stage of XDP. The increasing failure of response inhibition in the antisaccade task with increasing striatal atrophy may indicate an endophenotype for striatal degeneration. Dorsolateral prefrontal degeneration can be inferred from the failure in initiating antisaccades, prolonged latency of memory-guided saccades and the reduction of dorsolateral prefrontal volume and cortical thickness.
| Original language | English |
|---|---|
| Journal | Parkinsonism and Related Disorders |
| Volume | 61 |
| Pages (from-to) | 170-178 |
| Number of pages | 9 |
| ISSN | 1353-8020 |
| DOIs | |
| Publication status | Published - 01.04.2019 |
Funding
This study was supported by funding by the Collaborative Center for X-linked Dystonia Parkinsonism (NB) and the Deutsche Forschungsgemeinschaft ( FOR2488 to CK and NB, SFB936 ). A.S.: Employment: University of Luebeck and University Hospital of Schleswig-Holstein. H.H.: Employment: University Hospital of Schleswig-Holstein. I.H.: Employment: General Hospital Celle, Dept. of Paediatrics. J.P.: Employment: University Hospital of Schleswig-Holstein. R.L.R: Advisory board: Ipsen Neuroscience; Travel honorarium and Principal Clinical trial investigator: Ipsen Neuroscience. R.D.G.J.: Advisory Boards: Lundbeck Phils., Torrent Phils.; Honoraria: Philippine offices of Allergan, Lundbeck, Medichem, Medtronic, Natrapharm, Sun, Torrent; Grants: Collaborative Center for XDP (CCXDP), MGH . C.C.D.: no disclosures. A.D.: Recipient of research and training grants from the Dystonia Medical Research Foundation (Chicago, IL, USA) and the Collaborative Center for XDP (Boston, MA, USA). C.K.: Advisory Boards: Centogene, Biogen; Honoraria: Wellcome Trust (Expert Review Group member), Else Kroener Fresenius Foundation (Scientific Board Member), Annals of Neurology (Associate Editor); Grants: Hermann and Lilly Schilling Foundation , German Research Foundation , EU; Employment: University of Luebeck and University Hospital of Schleswig-Holstein; Royalties: Oxford University Press . N.B.: Employment: University of Luebeck and University Hospital of Schleswig-Holstein; Grants: Else-Kroener Fresenius Foundation , German Research Foundation ; Collaborative Center for X-Linked Dystonia-Parkinsonism, MGH, Boston . Ch.H.: Employment: University of Luebeck and University Hospital of Schleswig-Holstein; Honoraria: Henning Pharma, Pierre-Fabre, Heel and Sensorion. All authors report no conflict of interest. The study has not been sponsored by industry. Financial disclosures: A. Sprenger, H. Hanssen, I. Hagedorn, J. Prasuhn, R.L. Rosales and C.C.Diesta report no disclosures. R.D.G. Jamora is on the advisory boards of the Philippine offices of Lundbeck and Torrent and has received honoraria/CME grants from the Philippine offices of Allergan, Lundbeck, Medichem, Natrapharm, Sun and Torrent and the international regional office of Medtronic. He has received a research grant from the Collaborative Center for XDP (CCXDP), MGH, Boston . He has ongoing clinical trials for Allergan and Ipsen as a primary site investigator in Manila. He has no owner interest in any pharmaceutical company. A. Domingo is the recipient of an award from the Dystonia Medical Research Foundation. C. Klein is the recipient of a career development award from the Hermann and Lilly Schilling Foundation and this study is part of the SFB936 Project C5 (to CK). N. Brueggemann is a recipient of the research grant for the Collaborative Center for X-Linked Dystonia-Parkinsonism, MGH, Boston . Ch. Helmchen reports no disclosures.
Research Areas and Centers
- Research Area: Medical Genetics
