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December 2021; 11 (6) Review

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

Meta-analysis

Efthalia Angelopoulou, View ORCID ProfileAnastasia Bougea, View ORCID ProfileAndreas Papadopoulos, View ORCID ProfileNikolaos Papagiannakis, View ORCID ProfileAthina-Maria Simitsi, View ORCID ProfileChristos Koros, View ORCID ProfileMarios K. Georgakis, View ORCID ProfileLeonidas Stefanis
First published July 1, 2021, DOI: https://doi.org/10.1212/CPJ.0000000000001116
Efthalia Angelopoulou
Department of Neurology (EA, AB, NP, A-MS, CK, LS), National and Kapodistrian University of Athens, Eginition Hospital; Post-graduate Intern at “Hygeia” Hospital (AP), “Andreas Vgenopoulos” Scholarship, Athens, Greece; and Institute for Stroke and Dementia Research (ISD) (MKG), University Hospital, Ludwig-Maximilians University (LMU) Munich, Germany.
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Anastasia Bougea
Department of Neurology (EA, AB, NP, A-MS, CK, LS), National and Kapodistrian University of Athens, Eginition Hospital; Post-graduate Intern at “Hygeia” Hospital (AP), “Andreas Vgenopoulos” Scholarship, Athens, Greece; and Institute for Stroke and Dementia Research (ISD) (MKG), University Hospital, Ludwig-Maximilians University (LMU) Munich, Germany.
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  • ORCID record for Anastasia Bougea
Andreas Papadopoulos
Department of Neurology (EA, AB, NP, A-MS, CK, LS), National and Kapodistrian University of Athens, Eginition Hospital; Post-graduate Intern at “Hygeia” Hospital (AP), “Andreas Vgenopoulos” Scholarship, Athens, Greece; and Institute for Stroke and Dementia Research (ISD) (MKG), University Hospital, Ludwig-Maximilians University (LMU) Munich, Germany.
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Nikolaos Papagiannakis
Department of Neurology (EA, AB, NP, A-MS, CK, LS), National and Kapodistrian University of Athens, Eginition Hospital; Post-graduate Intern at “Hygeia” Hospital (AP), “Andreas Vgenopoulos” Scholarship, Athens, Greece; and Institute for Stroke and Dementia Research (ISD) (MKG), University Hospital, Ludwig-Maximilians University (LMU) Munich, Germany.
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Athina-Maria Simitsi
Department of Neurology (EA, AB, NP, A-MS, CK, LS), National and Kapodistrian University of Athens, Eginition Hospital; Post-graduate Intern at “Hygeia” Hospital (AP), “Andreas Vgenopoulos” Scholarship, Athens, Greece; and Institute for Stroke and Dementia Research (ISD) (MKG), University Hospital, Ludwig-Maximilians University (LMU) Munich, Germany.
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Christos Koros
Department of Neurology (EA, AB, NP, A-MS, CK, LS), National and Kapodistrian University of Athens, Eginition Hospital; Post-graduate Intern at “Hygeia” Hospital (AP), “Andreas Vgenopoulos” Scholarship, Athens, Greece; and Institute for Stroke and Dementia Research (ISD) (MKG), University Hospital, Ludwig-Maximilians University (LMU) Munich, Germany.
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Marios K. Georgakis
Department of Neurology (EA, AB, NP, A-MS, CK, LS), National and Kapodistrian University of Athens, Eginition Hospital; Post-graduate Intern at “Hygeia” Hospital (AP), “Andreas Vgenopoulos” Scholarship, Athens, Greece; and Institute for Stroke and Dementia Research (ISD) (MKG), University Hospital, Ludwig-Maximilians University (LMU) Munich, Germany.
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Leonidas Stefanis
Department of Neurology (EA, AB, NP, A-MS, CK, LS), National and Kapodistrian University of Athens, Eginition Hospital; Post-graduate Intern at “Hygeia” Hospital (AP), “Andreas Vgenopoulos” Scholarship, Athens, Greece; and Institute for Stroke and Dementia Research (ISD) (MKG), University Hospital, Ludwig-Maximilians University (LMU) Munich, Germany.
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Citation
CSF and Circulating NfL as Biomarkers for the Discrimination of Parkinson Disease From Atypical Parkinsonian Syndromes
Meta-analysis
Efthalia Angelopoulou, Anastasia Bougea, Andreas Papadopoulos, Nikolaos Papagiannakis, Athina-Maria Simitsi, Christos Koros, Marios K. Georgakis, Leonidas Stefanis
Neurol Clin Pract Dec 2021, 11 (6) e867-e875; DOI: 10.1212/CPJ.0000000000001116

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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.

Footnotes

  • Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.

  • ↵* These authors contributed equally to this work.

  • Received March 1, 2021.
  • Accepted May 21, 2021.
  • © 2021 American Academy of Neurology
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