Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and individual participant data meta-analysis of diagnostic cohorts
PubMed 31206160 · doi:10.1001/jamaneurol.2019.1534
What was done
Authors conducted a systematic review and individual participant data meta-analysis by searching PubMed (2006–2016) for studies reporting lumbar CSF neurofilament light protein (cNfL) measured via commercial immunoassay along with age and sex in neurological or psychiatric conditions and healthy controls. Individual-level data were obtained and analyzed using generalized linear mixed-effects models to assess the effects of age, sex, and diagnosis on log-transformed cNfL levels, adjusting for cohort of origin.
What was found
Data were pooled from 10,059 individuals (mean age 59.7 years; 54.1% female) spanning 35 diagnoses, including inflammatory CNS diseases (n = 2,795), dementias/predementia stages (n = 4,284), parkinsonian disorders (n = 984), and healthy controls (n = 1,332). cNfL was elevated compared with healthy controls in most conditions, peaking in cognitively impaired HIV, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. Levels increased with age across controls and most conditions, and were higher in men than women in 33.3% of diagnoses (including controls, multiple sclerosis, Alzheimer disease, and Parkinson disease). Values overlapped across most clinically similar diagnoses, but cNfL segregated FTD and cognitively impaired HIV from other dementias, and Parkinson disease from atypical parkinsonian syndromes.
Why it matters
This large meta-analysis establishes that diagnostic interpretation of CSF NfL requires age- and sex-specific reference ranges. It confirms that while cNfL is a general marker of neuroaxonal damage, it reliably discriminates FTD from Alzheimer disease and Parkinson disease from atypical parkinsonism.
Limits
The abstract does not state the total number of studies included. The search was limited to PubMed and studies using commercial immunoassays published through January 2016. Substantial overlap in cNfL levels across most clinically similar conditions limits its utility as a standalone differential diagnostic marker for many disorders.
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- supports Neurofilament light is a general marker of neuronal death present in anyone with neurodegenerative disease rather than being specific to a particular disease.