title: Neuroanatomical changes extend beyond striatal atrophy in X-linked dystonia parkinsonism.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Neurology, University of Lübeck, Lübeck, Germany; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany. Electronic address: norbert.brueggemann@neuro.uni-luebeck.de.
authors.forename: Norbert
authors.initials: N
authors.lastname: Brüggemann
authors.affiliation: Department of Neurology, University of Lübeck, Lübeck, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Heldmann
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
authors.forename: Aloysius
authors.initials: A
authors.lastname: Domingo
authors.affiliation: Department of Neurosurgery, University of Lübeck, Lübeck, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Rasche
authors.affiliation: Department of Neurosurgery, University of Lübeck, Lübeck, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Tronnier
authors.affiliation: XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines; Department of Neurology and Psychiatry, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines.
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Rosales
authors.affiliation: XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines; Department of Neurosciences, College of Medicine-Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.
authors.forename: Roland Dominic G
authors.initials: RD
authors.lastname: Jamora
authors.affiliation: XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines.
authors.forename: Lillian V
authors.initials: LV
authors.lastname: Lee
authors.affiliation: Department of Neurology, University of Lübeck, Lübeck, Germany.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Münte
mesh_terms: D000328:Adult; D016880:Anisotropy; D016022:Case-Control Studies; D038524:Diffusion Magnetic Resonance Imaging; D020821:Dystonic Disorders / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D020955:Striatonigral Degeneration / Q000473:pathology*; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology
keywords: Dystonia; Fractional anisotropy; Mean diffusivity; White matter; X-linked dystonia parkinsonism