title: Lenticular nucleus hyperechogenicity in Wilson's disease reflects local copper, but not iron accumulation.
abstract: In patients with Wilson's disease (WD) transcranial brain sonography typically reveals areas of increased echogenicity (hyperechogenicity) of the lenticular nucleus (LN). Correlation with T2-hypointensity on magnetic resonance images suggested that LN hyperechogenicity in WD is caused by trace metal accumulation. Accumulation of both, copper and iron, in the brain of WD patients has been reported. The present study was designed to elucidate whether LN hyperechogenicity in WD reflects accumulation of copper or iron. Post-mortem brains of 15 WD patients and one non-WD subject were studied with ultrasonography in an investigator-blinded fashion. LN hyperechogenicity was measured planimetrically by manual tracing as well as using digitized image analysis. The putaminal copper content was determined in samples of 11 WD brains and the non-WD brains using inductively coupled plasma mass spectrometry, and iron content was assessed using flame atomic absorption spectroscopy. LN was normal on ultrasonography only in the non-WD brain, but abnormal (hyperechogenic) in all WD brains. Digitized image analysis measures of LN hyperechogenicity and, by trend, manual measures correlated with putaminal copper content (Pearson test; digitized: r = 0.77, p = 0.04; manual: r = 0.57, p = 0.051) but not with iron content (each, p > 0.18). LN hyperechogenicity measures were unrelated to age at death of patients, age at onset of WD, WD duration, age of brain specimen, serum copper or serum ceruloplasmin (each, p > 0.1). We conclude that LN hyperechogenicity in WD reflects copper, but not iron accumulation. Further studies are warranted to elucidate the use of transcranial brain sonography for monitoring therapeutic effects of chelating agents in WD patients.
authors.affiliation: Department of Neurology, University of Rostock, Rostock, Germany, uwe.walter@med.uni-rostock.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Walter
authors.forename: Marta
authors.initials: M
authors.lastname: Skowrońska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Litwin
authors.forename: Grażyna Maria
authors.initials: GM
authors.lastname: Szpak
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jabłonka-Salach
authors.forename: David
authors.initials: D
authors.lastname: Skoloudík
authors.forename: Ewa
authors.initials: E
authors.lastname: Bulska
authors.forename: Anna
authors.initials: A
authors.lastname: Członkowska
mesh_terms: D000328:Adult; D003300:Copper / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006527:Hepatolenticular Degeneration / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007501:Iron / Q000378:metabolism*; D008297:Male; D013057:Spectrum Analysis; D014463:Ultrasonography
chemical_list: D003300:Copper; D007501:Iron