Sonographic alteration of substantia nigra is related to parkinsonism-predominant course of X-linked dystonia-parkinsonism

Parkinsonism Relat Disord. 2017 Apr;37:43-49. doi: 10.1016/j.parkreldis.2017.01.006. Epub 2017 Jan 10.


Introduction: 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.

Methods: 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.

Results: 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%; χ2 test, 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).

Conclusion: 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.

Keywords: Dystonia; Endophenotype; Parkinsonism; Ultrasound; X-linked dystonia-parkinsonism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Disease Progression
  • Dystonic Disorders* / complications
  • Dystonic Disorders* / diagnostic imaging
  • Dystonic Disorders* / genetics
  • Genetic Diseases, X-Linked* / complications
  • Genetic Diseases, X-Linked* / diagnostic imaging
  • Genetic Diseases, X-Linked* / genetics
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics
  • Parkinsonian Disorders* / complications
  • Parkinsonian Disorders* / diagnostic imaging
  • Parkinsonian Disorders* / genetics
  • Philippines
  • Substantia Nigra / diagnostic imaging*
  • Substantia Nigra / physiopathology*
  • Ultrasonography*
  • Videotape Recording

Supplementary concepts

  • Dystonia 3, Torsion, X-Linked