Cerebrospinal fluid NFL in the differential diagnosis of parkinsonian disorders: A meta-analysis

Neurosci Lett. 2018 Oct 15;685:35-41. doi: 10.1016/j.neulet.2018.07.030. Epub 2018 Jul 20.


Neurofilament light chain (NFL) in cerebrospinal fluid (CSF) is a promising biomarker candidate which may discriminate atypical parkinsonian disorders (APD), mainly including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), from Parkinson's disease (PD). We aim to evaluate the diagnostic accuracy of CSF NFL level as a differentiating biomarker between APD and PD. Databases of PubMed, OVID and Web of Science were searched for studies (published until May 31, 2017) that reported on CSF NFL as a diagnostic biomarker between APD and PD. Eight studies were pooled in this meta-analysis, including 341 PD and 396 APD patients and 388 healthy controls. The pooled sensitivity was 82% (95% CI, 68%-91%) and specificity was 85% (95% CI, 79%-89%) in differentiating APD from PD. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were 5.4 (95% CI, 3.6%-8.1%), 0.21 (95% CI, 0.11%-0.40%), and 25 (95% CI, 9%-69%) respectively; and the area under the curve (AUC) was 0.89 (95% CI, 0.86%-0.91%). Subgroup analysis revealed sensitivity and specificity were significantly influenced by study design. The APD subtypes, disease duration and severity were the main heterogeneity sources in specificity. The results of Deeks' test revealed a low risk of publication bias. The CSF NFL level may be used as a biomarker in discriminating APD from PD with high diagnostic accuracy at an early stage of disease. Large and longitudinal studies are still needed on individuals who are suspected to have APD.

Keywords: Atypical parkinsonian disorders; Meta-analysis; Multiple system atrophy; Neurofilament light chain; Parkinson's disease.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Aged
  • Biomarkers / cerebrospinal fluid
  • Diagnosis, Differential
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple System Atrophy / cerebrospinal fluid
  • Multiple System Atrophy / diagnosis
  • Neurofilament Proteins / cerebrospinal fluid*
  • Parkinson Disease / cerebrospinal fluid*
  • Parkinson Disease / diagnosis*
  • Parkinsonian Disorders / cerebrospinal fluid*
  • Parkinsonian Disorders / diagnosis*
  • Sensitivity and Specificity


  • Biomarkers
  • Neurofilament Proteins