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

Abstract

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.

Prodromal Parkinson's disease as defined per MDS research criteria in the general elderly community

“…5 The study protocol of the Bruneck Study had been approved by the local ethics committee, and all participants gave written informed consent according to the Declaration of Helsinki. Interviews and examinations were carried out by 2 neurologists with special expertise in movement disorders.…”

“…Participants underwent a standard interview including drug history and a standardized neurological examination including the Unified PD Rating Scale motor section (UPDRS-III). 5 Presence of clinically defined PD was ascertained per United Kingdom PD Society Brain Bank criteria. 6 Follow-up visits with a similar protocol took place after a median (range) of 3.0 years The following data on risk markers included in the MDS criteria were available: male sex, regular pesticide exposure, occupational solvent exposure, nonuse of caffeine, smoking status, family history (any first-degree relative with PD), and substantia nigra hyperechogenicity on transcranial sonography as described elsewhere.…”

“…6 Follow-up visits with a similar protocol took place after a median (range) of 3.0 years The following data on risk markers included in the MDS criteria were available: male sex, regular pesticide exposure, occupational solvent exposure, nonuse of caffeine, smoking status, family history (any first-degree relative with PD), and substantia nigra hyperechogenicity on transcranial sonography as described elsewhere. 5 The following prodromal markers included in the MDS criteria were assessed in 2005: possible subthreshold parkinsonism (assessed by UPDRS-III), olfactory loss (assessed with the Sniffin' Sticks 12-item odor identification test; Burghart Medizintechnik, Germany), 7 constipation, urinary dysfunction, severe erectile dysfunction requiring medical intervention, and depression/anxiety. Three additional prodromal markers had been assessed during the Bruneck Study 2000, 8 and the respective data were imputed in this analysis: probable REM-sleep behavior disorder (RBD), excessive daytime somnolence, and orthostatic hypotension.…”

Optimizing odor identification testing as quick and accurate diagnostic tool for Parkinson's disease

“…For the present study, data from a total of 134 PD patients and 46 patients with atypical parkinsonism (23 multiple system atrophy [MSA], 23 progressive supranuclear palsy [PSP]), who participated in three independent prospective, cross‐sectional clinical studies at the Department of Neurology, Innsbruck Medical University (Innsbruck, Austria)14, 15 and from 336 age‐matched healthy controls (HCs) and 29 subjects with ET from the prospective population‐based Bruneck Study16, 17 were analyzed (center A). Patients were regularly followed over at least 24 months to reassess their clinical diagnosis, and 4 cases were reclassified as MSA (n = 1) or PSP (n = 3) during clinical follow‐up.…”

Transcranial Brain Parenchymal Sonography in Neurodegenerative and Psychiatric Diseases

“…These transcranial sonographic findings suggest that the occurrence and degree of a hyperechoic signal in the substantia nigra do not represent the extent of dopaminergic neurons' progressive degeneration in patients with PD. Substantia nigra hyperechogenicity has also been detected in 8% to 10% of healthy people 18 , 19 . Healthy individuals with substantia nigra hyperechogenicity may show functional deficits in the nigrostriatal dopaminergic pathways, with “soft motor sign and symptom” occurrence.…”