Substantia Nigra Hyperechogenicity as a Marker for Parkinson's Disease: A Population-Based Study

Background: The clinical diagnosis of Parkinson's disease (PD) is currently anchored in its cardinal motor symptoms. According to hospital-based studies, an enlarged echogenicity in the area of the substantia nigra (SN) assessed with transcranial sonography (TCS) may represent a useful biomarker in the diagnosis of PD. Objective: To evaluate SN hyperechogenicity as a marker for PD in the Bruneck Study cohort, which is representative of the general elderly community. Methods: The diagnostic accuracy of TCS in distinguishing clinically diagnosed PD from nonparkinsonian subjects was assessed in 574 subjects from this cohort. Results: There was a good diagnostic accuracy of TCS in distinguishing PD subjects from nonparkinsonian subjects with an area under the curve value of 0.82. At a receiver-operating characteristic curve analysis-based cutoff value for SN hyperechogenicity of 0.18 cm2, TCS had a sensitivity of 88.2% (95% confidence interval, CI, 64.4-98.0), a specificity of 77.0% (95% CI 72.8-80.6), a positive predictive value of 12.7% (95% CI 7.8-20.0) and a negative predictive value of 99.4% (95% CI 97.8-100.0) for subjects with clinically definite PD at baseline. When analyzing the same population after 5 years with regard to the presence of known and newly diagnosed PD cases, baseline TCS yielded very similar diagnostic accuracy values. Conclusion: SN hyperechogenicity may represent a useful biomarker for PD not only in a hospital-based setting but also in the general community.

[1]  G Becker,et al.  Relationship of substantia nigra echogenicity and motor function in elderly subjects , 2001, Neurology.

[2]  S. Fahn Description of Parkinson's Disease as a Clinical Syndrome , 2003, Annals of the New York Academy of Sciences.

[3]  Matthias Reimold,et al.  The specificity and sensitivity of transcranial ultrasound in the differential diagnosis of Parkinson's disease: a prospective blinded study , 2008, The Lancet Neurology.

[4]  Y Ben-Shlomo,et al.  Cross sectional prevalence survey of idiopathic Parkinson's disease and parkinsonism in London , 2000, BMJ : British Medical Journal.

[5]  R. Benecke,et al.  Value of combined midbrain sonography, olfactory and motor function assessment in the differential diagnosis of early Parkinson's disease , 2012, Journal of Neurology, Neurosurgery & Psychiatry.

[6]  Werner Poewe,et al.  Midbrain sonography in patients with essential tremor , 2007, Movement disorders : official journal of the Movement Disorder Society.

[7]  W. Poewe,et al.  A follow‐up study of substantia nigra echogenicity in healthy adults , 2012, Movement disorders : official journal of the Movement Disorder Society.

[8]  W. Gibb,et al.  The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[9]  J. Jeng,et al.  Transcranial imaging of substantia nigra hyperechogenicity in a Taiwanese cohort of Parkinson's disease , 2007, Movement disorders : official journal of the Movement Disorder Society.

[10]  Uwe Walter,et al.  Transcranial brain sonography findings in discriminating between parkinsonism and idiopathic Parkinson disease. , 2007, Archives of neurology.

[11]  W. Poewe,et al.  Prevalence of movement disorders in men and women aged 50–89 years (Bruneck Study cohort): a population-based study , 2005, The Lancet Neurology.

[12]  Klaus Fassbender,et al.  Transcranial sonography and [123I]FP-CIT SPECT disclose complementary aspects of Parkinson's disease. , 2006, Brain : a journal of neurology.

[13]  U. Dillmann,et al.  Enlarged hyperechogenic substantia nigra is related to motor performance and olfaction in the elderly , 2010, Movement disorders : official journal of the Movement Disorder Society.

[14]  Uwe Walter,et al.  Parkinson's disease-like midbrain sonography abnormalities are frequent in depressive disorders. , 2007, Brain : a journal of neurology.

[15]  Stephen R. Duma,et al.  Substantia nigra echomorphology in the healthy very old: Correlation with motor slowing , 2007, NeuroImage.

[16]  Daniela Berg,et al.  Echogenicity of the substantia nigra in Parkinson's disease and its relation to clinical findings , 2001, Journal of Neurology.

[17]  R. Hilker,et al.  Reproducibility and diagnostic accuracy of substantia nigra sonography for the diagnosis of Parkinson's disease , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[18]  R. Benecke,et al.  Substantia nigra echogenicity is normal in non-extrapyramidal cerebral disorders but increased in Parkinson's disease , 2002, Journal of Neural Transmission.

[19]  Yoav Ben-Shlomo,et al.  The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. , 2002, Brain : a journal of neurology.

[20]  J. A. Cook,et al.  Heterogeneity in male to female risk for Parkinson’s disease , 2007, Journal of Neurology, Neurosurgery & Psychiatry.

[21]  Andrew J. Lees,et al.  Improved accuracy of clinical diagnosis of Lewy body Parkinson’s disease , 2001, Neurology.

[22]  Daniela Berg,et al.  Five‐year follow‐up study of hyperechogenicity of the substantia nigra in Parkinson's disease , 2005, Movement disorders : official journal of the Movement Disorder Society.

[23]  Klaus Fassbender,et al.  Enlarged hyperechogenic substantia nigra as a risk marker for Parkinson's disease , 2013, Movement disorders : official journal of the Movement Disorder Society.

[24]  J. Fleiss,et al.  Intraclass correlations: uses in assessing rater reliability. , 1979, Psychological bulletin.

[25]  D. Dressler,et al.  Transcranial brain sonography findings in clinical subgroups of idiopathic Parkinson's disease , 2007, Movement disorders : official journal of the Movement Disorder Society.

[26]  W. Poewe,et al.  Defining at‐risk populations for Parkinson's disease: Lessons from ongoing studies , 2012, Movement disorders : official journal of the Movement Disorder Society.

[27]  Jochen Klenk,et al.  Enlarged substantia nigra hyperechogenicity and risk for Parkinson disease: a 37-month 3-center study of 1847 older persons. , 2011, Archives of neurology.

[28]  E. Katunina,et al.  [Epidemiology of Parkinson's disease]. , 2013, Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova.

[29]  D. Dressler,et al.  Assessment of Substantia Nigra Echogenicity in German and Filipino Populations Using a Portable Ultrasound System , 2012, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[30]  A J Lees,et al.  What features improve the accuracy of clinical diagnosis in Parkinson's disease: A clinicopathologic study , 2001, Neurology.

[31]  Klaus Seppi,et al.  Neuroimaging: Current role in detecting pre‐motor Parkinson's disease , 2012, Movement disorders : official journal of the Movement Disorder Society.

[32]  G Becker,et al.  Vulnerability of the nigrostriatal system as detected by transcranial ultrasound , 1999, Neurology.

[33]  W. Poewe,et al.  Is Transcranial Sonography Useful to Distinguish Scans Without Evidence of Dopaminergic Deficit Patients From Parkinson's Disease? , 2012, Movement disorders : official journal of the Movement Disorder Society.

[34]  K. Bötzel,et al.  Prevalence and incidence of Parkinson's disease in Europe , 2005, European Neuropsychopharmacology.

[35]  D. Berg,et al.  In vivo detection of iron and neuromelanin by transcranial sonography – a new approach for early detection of substantia nigra damage , 2006, Journal of Neural Transmission.

[36]  D. Schwartz,et al.  Toll-like receptor 4 polymorphisms and atherogenesis in humans. , 2002 .

[37]  Daniela Berg,et al.  Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury. , 2002, Archives of neurology.

[38]  G. Cooke,et al.  Toll-like receptor 4 polymorphisms and atherogenesis. , 2002, The New England journal of medicine.

[39]  Michal Bar,et al.  Transcranial sonography in movement disorders. , 2008, Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia.

[40]  J. Molinuevo,et al.  Midbrain hyperechogenicity in idiopathic REM sleep behavior disorder , 2009, Movement disorders : official journal of the Movement Disorder Society.

[41]  W. Poewe,et al.  Is Transcranial Sonography Useful to Distinguish Drug-Induced Parkinsonism From Parkinson ’ s Disease ? , 2012 .