Format

Send to

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

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

Author information

1
Department of Neurology, University of Rostock, Rostock, Germany. Electronic address: uwe.walter@med.uni-rostock.de.
2
XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines; Department of Neurology and Psychiatry, University of Santo Tomas Hospital, Metro Manila, Philippines.
3
Department of Neurology, University of Rostock, Rostock, Germany; Neurology Section, Department of System Medicine, University of Rome "Tor Vergata", Rome, Italy.
4
Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
5
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.
6
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.
7
Institute of Neurogenetics, University of Lübeck, Lübeck, Germany; Department of Neurology, University of Lübeck, Lübeck, Germany.
8
XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines.
9
Movement Disorders Section, Department of Neurology, Hannover Medical School, Hannover, Germany.

Abstract

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

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center