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Diagnostic Accuracy of Transcranial Sonography of the Substantia Nigra in Parkinson's disease: A Systematic Review and Meta-analysis.

ABSTRACT: A large number of articles have reported substantia nigra hyperechogenicity in Parkinson's disease (PD) and have assessed the diagnostic accuracy of transcranial sonography (TCS); however, the conclusions are discrepant. Consequently, this systematic review and meta-analysis aims to consolidate the available observational studies and provide a comprehensive evaluation of the clinical utility of TCS in PD. Totally, 31 studies containing 4,386 participants from 13 countries were included. A random effects model was utilized to pool the effect sizes. Meta-regression and sensitivity analysis were performed to explore potential heterogeneity. Overall diagnostic accuracy of TCS in differentiating PD from normal controls was quite high, with a pooled sensitivity of 0.83 (95% CI: 0.81-0.85) and a pooled specificity of 0.87 (95% CI: 0.85-0.88). The positive likelihood ratio, the negative likelihood ratio and diagnostic odds ratio were calculated 6.94 (95% CI: 5.09-9.48), 0.19 (95% CI: 0.16-0.23), and 42.89 (95% CI: 30.03-61.25) respectively. Our systematic review of the literature and meta-analysis suggest that TCS has high diagnostic accuracy in the diagnosis of PD when compared to healthy control.

SUBMITTER: Li DH

PROVIDER: S-EPMC4754637 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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Project description:ObjectiveNumerous ultrasound studies have suggested that a typical enlarged area of echogenicity in the substantia nigra (SN+) can help diagnose idiopathic Parkinson's disease (IPD). Almost all these studies were retrospective and involved patients with well-established diagnoses and long-disease duration. In this study the diagnostic accuracy of transcranial sonography (TCS) of the substantia nigra in the patient with an undiagnosed parkinsonian syndrome of recent onset has been evaluated.DesignProspective cohort study for diagnostic accuracy.SettingNeurology outpatient clinics of two teaching hospitals in the Netherlands.Patients196 consecutive patients, who were referred to two neurology outpatient clinics for analysis of clinically unclear parkinsonism. Within 2 weeks of inclusion all patients also underwent a TCS and a (123)I-ioflupane Single Photon Emission CT (FP-CIT SPECT) scan of the brain (n=176).Outcome measuresAfter 2 years, patients were re-examined by two movement disorder specialist neurologists for a final clinical diagnosis, that served as a surrogate gold standard for our study.ResultsTemporal acoustic windows were insufficient in 45 of 241 patients (18.67%). The final clinical diagnosis was IPD in 102 (52.0%) patients. Twenty-four (12.3%) patients were diagnosed with atypical parkinsonisms (APS) of which 8 (4.0%) multisystem atrophy (MSA), 6 (3.1%) progressive supranuclear palsy (PSP), 6 (3.1%) Lewy body dementia and 4 (2%) corticobasal degeneration. Twenty-one (10.7%) patients had a diagnosis of vascular parkinsonism, 20 (10.2%) essential tremor, 7 (3.6%) drug-induced parkinsonism and 22 (11.2%) patients had no parkinsonism but an alternative diagnosis. The sensitivity of a SN+ for the diagnosis IPD was 0.40 (CI 0.30 to 0.50) and the specificity 0.61 (CI 0.52 to 0.70). Hereby the positive predictive value (PPV) was 0.53 and the negative predictive value (NPV) 0.48. The sensitivity and specificity of FP-CIT SPECT scans for diagnosing IPD was 0.88 (CI 0.1 to 0.95) and 0.68 (CI 0.58 to 0.76) with a PPV of 0.75 and an NPV of 0.84.ConclusionsThe diagnostic accuracy of TCS in early stage Parkinson's disease is not sufficient for routine clinical use. CLINICALTRIALS.GOV IDENTIFIER: NCT0036819.

Project description:BackgroundParkinson's disease (PD) is the most common neurodegenerative disorder involving the motor system. Although not being the only region involved in PD, affection of the substantia nigra and its projections is responsible for some of the most debilitating features of the disease. To further advance a comprehensive understanding of nigral pathology, we conducted a tissue based comparative proteome study of healthy and diseased human substantia nigra.ResultsThe gross number of differentially regulated proteins in PD was 221. In total, we identified 37 proteins, of which 16 were differentially expressed. Identified differential proteins comprised elements of iron metabolism (H-ferritin) and glutathione-related redox metabolism (GST M3, GST P1, GST O1), including novel redox proteins (SH3BGRL). Additionally, many glial or related proteins were found to be differentially regulated in PD (GFAP, GMFB, galectin-1, sorcin), as well as proteins belonging to metabolic pathways sparsely described in PD, such as adenosyl homocysteinase (methylation), aldehyde dehydrogenase 1 and cellular retinol-binding protein 1 (aldehyde metabolism). Further differentially regulated proteins included annexin V, beta-tubulin cofactor A, coactosin-like protein and V-type ATPase subunit 1. Proteins that were similarly expressed in healthy or diseased substantia nigra comprised housekeeping proteins such as COX5A, Rho GDI alpha, actin gamma 1, creatin-kinase B, lactate dehydrogenase B, disulfide isomerase ER-60, Rab GDI beta, methyl glyoxalase 1 (AGE metabolism) and glutamine synthetase. Interestingly, also DJ-1 and UCH-L1 were expressed similarly. Furthermore, proteins believed to serve as internal standards were found to be expressed in a constant manner, such as 14-3-3 epsilon and hCRMP-2, thus lending further validity to our results.ConclusionUsing an approach encompassing high sensitivity and high resolution, we show that alterations of SN in PD include many more proteins than previously thought. The results point towards a heterogeneous aetiopathogenesis of the disease, including alterations of GSH-related proteins as well as alterations of proteins involved in retinoid metabolism, and they indicate that proteins involved in familial PD may not be differentially regulated in idiopathic Parkinson's disease.

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Diagnostic Accuracy of Transcranial Sonography of the Substantia Nigra in Parkinson's disease: A Systematic Review and Meta-analysis.

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