Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury

Arch Neurol. 2002 Jun;59(6):999-1005. doi: 10.1001/archneur.59.6.999.


Background: Patients with Parkinson disease characteristically exhibit an increased echogenicity of the substantia nigra (SN) on transcranial sonography, a new neuroimaging technique. The same echo feature of the SN can be identified in 9% of healthy adults.

Objective: To evaluate the relevance of the echogenic SN in healthy adults.

Design: In the first part of the study, 10 healthy subjects younger than 40 years with a distinct SN hyperechogenicity underwent extensive neurological, motor, neuropsychological, and fluorine 18-dopa positron emission tomographic ([18F]-dopa PET) examinations. Results were compared with those of 10 subjects with a low echogenic SN. In the second part of the study, the postmortem brains of 20 patients without extrapyramidal disorders during their lifetime were sonographically examined with a particular focus on SN echogenicity. Subsequently, one half of the brain was prepared for heavy metal analysis, the other for a histological examination.

Results: Healthy subjects with SN hyperechogenicity exhibited a significant reduction of the [18F]-dopa uptake, especially in the putamen (Wilcoxon matched pair test: left side, P =.006; right side, P =.009), whereas their neuropsychological and motor performance were normal. Postmortem studies showed that the echogenicity of the SN correlated with its iron content.

Conclusions: Increased echogenicity of the SN, characteristically seen in Parkinson disease, is related to a functional impairment of the nigrostriatal system (even in young healthy adults) that can be revealed by [18F]-dopa PET studies. Substantia nigra hyperechogenicity is related to a higher tissue iron level, which is known to enhance the cells' generation of reactive oxygen specimens. Therefore, we hypothesize that transcranial sonography may identify a susceptibility marker for the development of nigral injury that can be detected early in life, prior to the onset of Parkinson disease.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / analysis
  • Biomarkers / chemistry
  • Corpus Striatum / chemistry
  • Corpus Striatum / metabolism*
  • Corpus Striatum / pathology*
  • Female
  • Humans
  • Iron / analysis
  • Iron / metabolism*
  • Male
  • Postmortem Changes
  • Statistics, Nonparametric
  • Substantia Nigra / chemistry
  • Substantia Nigra / metabolism*
  • Substantia Nigra / pathology*
  • Tomography, Emission-Computed / methods
  • Tomography, Emission-Computed / statistics & numerical data
  • Ultrasonography, Doppler, Transcranial* / methods
  • Ultrasonography, Doppler, Transcranial* / statistics & numerical data


  • Biomarkers
  • Iron