Tainá M Marques1, Anouke van Rumund1, Patrick Oeckl1, H Bea Kuiperij1, Rianne A J Esselink1, Bastiaan R Bloem1, Markus Otto1, Marcel M Verbeek2. 1. From the Department of Neurology (T.M.M., A.v.R., H.B.K., R.A.J.E., B.R.B., M.M.V.), Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen; Department of Laboratory Medicine (T.M.M., H.B.K., M.M.V.), Radboud University Medical Center, Nijmegen; Parkinson Center Nijmegen (T.M.M., A.v.R., R.A.J.E., B.R.B., M.M.V.), the Netherlands; and Department of Neurology (P.O., M.O.), Ulm University Hospital, Germany. 2. From the Department of Neurology (T.M.M., A.v.R., H.B.K., R.A.J.E., B.R.B., M.M.V.), Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen; Department of Laboratory Medicine (T.M.M., H.B.K., M.M.V.), Radboud University Medical Center, Nijmegen; Parkinson Center Nijmegen (T.M.M., A.v.R., R.A.J.E., B.R.B., M.M.V.), the Netherlands; and Department of Neurology (P.O., M.O.), Ulm University Hospital, Germany. Marcel.Verbeek@radboudumc.nl.
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.
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.
Authors: Rong Ye; Joseph J Locascio; Anna E Goodheart; Moqing Quan; Baorong Zhang; Stephen N Gomperts Journal: Parkinsonism Relat Disord Date: 2021-02-17 Impact factor: 4.891
Authors: Jasmini Alagaratnam; Sophia von Widekind; Davide De Francesco; Jonathan Underwood; Paul Edison; Alan Winston; Henrik Zetterberg; Sarah Fidler Journal: BMJ Neurol Open Date: 2021-06-16