1. Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis
- Author
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van Wieringen Wn, Marcel M. Verbeek, Ludwig Kappos, van Swieten Jc, Tove Christensen, Edward J. Wild, Lieke H.H. Meeter, Mattias Vågberg, Ross W. Paterson, Tobias Skillbäck, Lu Ch, Markus Axelsson, Shorena Janelidze, Ulf Andreasson, Maria Bjerke, Jonathan M. Schott, José C. Álvarez-Cermeño, Megan K. Herbert, Nadia K. Magdalinou, Michael Jonsson, Betty M. Tijms, Peter Sundström, Troiano M, Fredrik Piehl, Mohsen Khademi, Pyykkö Ot, Rosanna Tortelli, Jens Kuhle, Lena Brundin, Ales Bartos, Joel Jakobsson, Jessen-Krut J, Michael Khalil, Isabella Laura Simone, Stilund M, Julio C. Rojas, Carole Scherling, Lenka Fialová, David Bäckström, Finn Sellebjerg, Anders Wallin, Jette L. Frederiksen, Pieter Jelle Visser, Signe Modvig, Henrik Zetterberg, Mikael Landén, Mehta, Carla Tortorella, Gudmundur Johannsson, Andrea Malaspina, Giancarlo Logroscino, Pijnenburg Yal, Pérez-Santiago J, Claire Bridel, Weiss A, Romme Christensen J, Niklas Mattsson, Martin Gunnarsson, Alessandro Trentini, Sandberg L, Sara Hall, Kaj Blennow, Lars Forsgren, Ragnarsson O, Oskar Hansson, Jan Lycke, Tomas Olsson, Magnus Gisslén, Joachim Burman, Carsten Wikkelsö, Anders Svenningsson, Luisa M. Villar, Leinonen, Martin R Turner, Charlotte E. Teunissen, Elizabeth Gray, A. Boxer, Neurology, Human genetics, Laboratory Medicine, Epidemiology and Data Science, Amsterdam Neuroscience - Neuroinfection & -inflammation, CCA - Imaging and biomarkers, Clinical sciences, and Group, NFL
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NATIONAL INSTITUTE ,medicine.medical_specialty ,Neurology ,neuroaxonal damage ,CLINICAL-DIAGNOSIS ,cerebrospinal fluid ,AMYOTROPHIC-LATERAL-SCLEROSIS ,NO ,AXONAL DAMAGE ,03 medical and health sciences ,0302 clinical medicine ,PARKINSONS-DISEASE ,Internal medicine ,medicine ,Dementia ,030212 general & internal medicine ,Amyotrophic lateral sclerosis ,FIBRILLARY ACIDIC PROTEIN ,Original Investigation ,Medicine(all) ,Neurofilament light protein ,business.industry ,Multiple sclerosis ,MULTIPLE-SCLEROSIS ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,medicine.disease ,Amyotrophic-lateral-sclerosis ,fibrillary acidic protein ,csf neurofilament ,multiple-sclerosis ,alzheimers-disease ,axonal damage ,neurodegenerative diseases ,parkinsons-disease ,clinical-diagnosis ,national institute ,3. Good health ,ALZHEIMERS-DISEASE ,CSF NEUROFILAMENT ,Meta-analysis ,Biomarker (medicine) ,healthy controls ,Neurology (clinical) ,diagnostic value ,Alzheimer's disease ,business ,NEURODEGENERATIVE DISEASES ,030217 neurology & neurosurgery ,Frontotemporal dementia - Abstract
Key PointsQuestionHow do levels of neurofilament light in cerebrospinal fluid (cNfL) compare between neurological conditions and with healthy controls? FindingsAmong 10 059 individuals in this systematic review and meta-analysis, cNfL was elevated in most neurological conditions compared with healthy controls, and the magnitude of the increase varies extensively. Although cNfL overlaps between most clinically similar conditions, its distribution did not overlap in frontotemporal dementia and other dementias or in Parkinson disease and atypical parkinsonian syndromes. MeaningThe cNfL is a marker of neuronal damage and may be useful to differentiate some clinically similar conditions, such as frontotemporal dementia from Alzheimer disease and Parkinson disease from atypical parkinsonian syndromes. This systematic review and meta-analysis assesses the associations of age, sex, and diagnosis with neurofilament light in cerebrospinal fluid and evaluates its potential in discriminating clinically similar conditions. ImportanceNeurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date. ObjectivesTo assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions. Data SourcesPubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC. Study SelectionStudies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex. Data Extraction and SynthesisIndividual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept. Main Outcome and MeasureThe cNfL levels adjusted for age and sex across diagnoses. ResultsData were collected for 10059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n=2795), dementias and predementia stages (n=4284), parkinsonian disorders (n=984), and HC (n=1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes. Conclusions and RelevanceThese data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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- 2019