title: Sonographic alteration of substantia nigra is related to parkinsonism-predominant course of X-linked dystonia-parkinsonism.
abstract: X-linked recessive dystonia-parkinsonism (XDP, DYT3) is highly prevalent in the Philippines and manifests with varying phenotype. We sought to evaluate the significance of transcranial brain sonography as a biomarker for parkinsonism-predominant phenotype.
  
  
  
  90 Filipino participants were enrolled into a cross-sectional study: 39 patients with XDP, 21 asymptomatic first-degree relatives of XDP patients, and 30 healthy control subjects. Echogenicity of the substantia nigra and the lenticular nuclei was digitally quantified. Brain sonography data were compared with video-based clinical assessment, genetic status and pedigree charts.
  
  
  
  The majority of patients had hyperechogenicity of the substantia nigra (79%) and/or the lenticular nuclei (81%). Disease duration correlated with echointensity of lenticular nuclei (Pearson test, r = 0.55, p = 0.029) but not substantia nigra (p = 0.31). Abnormal substantia-nigra hyperechogenicity was more frequent in patients with prominent parkinsonism (100%) compared to those without (68%; χ2test, p = 0.035). The grading of substantia-nigra echogenicity (normal/increased) in patients was in all cases identical to that in their respective asymptomatic relatives. All patients with "familial" substantia-nigra normoechogenicity presented with a phenotype of predominant dystonia and only mild parkinsonism. In turn, "familial" substantia-nigra hyperechogenicity indicated a phenotype with moderate to severe parkinsonism (sensitivity, 100%; specificity, 67%; Fisher test, p = 0.021).
  
  
  
  Findings imply early alteration of the substantia nigra in XDP mutation carriers prone to develop parkinsonism. Thus, substantia-nigra hyperechogenicity may be regarded as a preclinical risk marker of parkinsonism-predominant XDP. Furthermore, this biomarker is clustered in some families suggesting the existence of one or more genetic co-factors influencing the phenotype of the disease.
authors.affiliation: Department of Neurology, University of Rostock, Rostock, Germany. Electronic address: uwe.walter@med.uni-rostock.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Walter
authors.affiliation: XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines; Department of Neurology and Psychiatry, University of Santo Tomas Hospital, Metro Manila, Philippines.
authors.forename: Raymond
authors.initials: R
authors.lastname: Rosales
authors.affiliation: Department of Neurology, University of Rostock, Rostock, Germany; Neurology Section, Department of System Medicine, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rocco
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Westenberger
authors.affiliation: XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany; Graduate School, University of Lübeck, Lübeck, Germany.
authors.forename: Aloysius
authors.initials: A
authors.lastname: Domingo
authors.affiliation: Department of Neurology, University of Rostock, Rostock, Germany; XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines; Department of Neurology and Psychiatry, University of Santo Tomas Hospital, Metro Manila, Philippines.
authors.forename: Criscely L
authors.initials: CL
authors.lastname: Go
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Lübeck, Germany; Department of Neurology, University of Lübeck, Lübeck, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Brüggemann
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
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: Movement Disorders Section, Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Dressler
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D018450:Disease Progression; D020821:Dystonic Disorders / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020734:Parkinsonian Disorders / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics; D010679:Philippines; D013378:Substantia Nigra / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D014463:Ultrasonography; D014743:Videotape Recording
keywords: Dystonia; Endophenotype; Parkinsonism; Ultrasound; X-linked dystonia-parkinsonism