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Review
. 2021 Dec;11(6):e867-e875.
doi: 10.1212/CPJ.0000000000001116.

CSF and Circulating NfL as Biomarkers for the Discrimination of Parkinson Disease From Atypical Parkinsonian Syndromes: Meta-analysis

Efthalia Angelopoulou  1 , Anastasia Bougea  1 , Andreas Papadopoulos  1 , Nikolaos Papagiannakis  1 , Athina-Maria Simitsi  1 , Christos Koros  1 , Marios K Georgakis  1 , Leonidas Stefanis  1
Affiliations
Review

CSF and Circulating NfL as Biomarkers for the Discrimination of Parkinson Disease From Atypical Parkinsonian Syndromes: Meta-analysis

Efthalia Angelopoulou et al. Neurol Clin Pract. 2021 Dec.

Abstract

Purpose of review: To evaluate whether CSF and circulating neurofilament light chain (NfL), a marker of axonal damage, could discriminate Parkinson disease (PD) from atypical parkinsonian syndromes (APSs).

Recent findings: MEDLINE and Scopus were systematically searched, and 15 studies were included (1,035 patients with PD and 930 patients with APS). CSF NfL levels were 1.26 SDs higher in the APS group compared to the PD group (g = 1.26 [95% confidence interval 0.99-1.53]), and circulating NfL levels were 1.53 SDs higher in the APS group compared to the PD group (g = 1.53 [95% confidence interval 1.15-1.91]); 4 studies, 307 patients with PD, 197 patients with APS. Pooled areas under the curve were 0.941 (0.916-0.965) and 0.874 (0.802-0.946) for CSF and circulating NfL, corresponding to average sensitivities of 86% (79%-90%) and 91% (86%-95%), and specificity of 88% (82%-92%) and 76% (62%-85%), respectively.

Summary: These results strongly support the high diagnostic accuracy of both CSF and circulating NfL in differentiating PD from APS, highlighting their usefulness as promising biomarkers.

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Figures

Figure 1
Figure 1. PRISMA Flowchart for Study Selection
PRISMA flowchart depicting the process for the selection of the included studies for the systematic review and for the data synthesis of the clinical studies investigating the NfL levels in patients with PD vs APS. APS = atypical parkinsonian syndrome; PD = Parkinson disease; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Figure 2
Figure 2. Forest Plots of the Meta-analyses of (A) CSF and (B) Circulating NfL Levels in Patients with APS vs PD
SMDs of each study are depicted as data markers; shaded boxes around the data markers indicate the statistical weight of the respective study; 95% CIs are indicated by the error bars; pooled-effect estimates are reflected as a diamond. APS = atypical parkinsonian syndrome; CI = confidence interval; NfL = neurofilament light chain; PD = Parkinson disease; SMD = standardized mean difference.
Figure 3
Figure 3. HSROC Curves for the Discriminative Ability of (A) CSF and (B) Circulating NfL to Differentiate APS From PD
Each study is depicted as a hollow circle; the diameter of each circle corresponds to the respective weight given to each study. CSF NfL analysis is based on 7 studies: 363 patients with APS and 501 patients with PD; circulating NfL analysis is based on 4 studies: 214 patients with APS and 307 patients with PD. APS = atypical parkinsonian syndrome; HSROC = hierarchical summary receiver operating characteristic; NfL = neurofilament light chain; PD = Parkinson disease.
See this image and copyright information in PMC

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