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Abstract
Objective To investigate the diagnostic value of serum neurofilament light chain (NFL) in patients with clear signs of parkinsonism but whose specific diagnosis was yet uncertain.
Methods Serum samples were collected from patients with clear signs of parkinsonism but with uncertain diagnosis at the inclusion. Clinical diagnoses of Parkinson disease (PD) and atypical parkinsonism disorders (APDs) were established after 3 years of follow-up and updated again after a maximum of 12 years in case longer follow-up data were available. Serum NFL was quantified by single molecule array in patients with PD (n = 55) and APD (n = 29, multiple system atrophy = 22, progressive supranuclear palsy = 7) and 53 nonneurologic controls.
Results Serum NFL levels were elevated and differentiated the APD group (mean 23.8 ± 10.3 ng/L) from PD (mean 10.4 ± 4.9 ng/L) and controls (mean 11.5 ± 6.5 ng/L, p < 0.0001) with accuracy levels up to 91% (sensitivity = 86% and specificity = 85%). Serum NFL strongly correlated with CSF NFL levels (r = 0.72, p < 0.0001) in all groups and with age in PD (r = 0.78, p < 0.0001) and controls (r = 0.66, p < 0.0001). In our cohort, the probability of having APD was 76% (positive predictive value) and of having PD 92% (negative predictive value).
Conclusion Serum NFL levels are markedly elevated in APD compared to PD and discriminate APDs from PD with high accuracy. Serum NFL may be a useful clinical biomarker to identify APD, even at stages when clinical symptoms are not yet conclusive.
Classification of evidence This study provides Class II evidence that serum NFL levels accurately discriminate APDs from PD.
Glossary
- Aβ42=
- β-amyloid 42;
- α-syn=
- α-synuclein;
- APD=
- atypical parkinsonism disorder;
- AUC=
- area under the curve;
- CBS=
- cortical basal syndrome;
- CI=
- confidence interval;
- H&Y=
- Hoehn and Yahr;
- MMSE=
- Mini-Mental State Examination;
- MSA=
- multiple system atrophy;
- NFL=
- neurofilament light chain;
- PD=
- Parkinson disease;
- PSP=
- progressive supranuclear palsy;
- ROC=
- receiver operating characteristic;
- Simoa=
- single molecule array
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Editorial, page 595
Class of Evidence: NPub.org/coe
- Received July 24, 2018.
- Accepted in final form November 21, 2018.
- © 2019 American Academy of Neurology
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