Annals of Neurology· 2017Q1
Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis
- 1,164citations
- Q1SCImago
- 2017year
Short summary
Serum neurofilament light chain (sNfL) levels, measured via an ultrasensitive assay, are higher in multiple sclerosis (MS) patients than healthy controls and strongly correlate with cerebrospinal fluid (CSF) NfL levels.
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Key points
- sNfL levels were significantly higher in MS patients compared to healthy controls (n=254 HC, n=142 MS cohort 1, n=246 MS cohort 2).
- sNfL showed a strong association with CSF NfL (β = 0.589, p < 0.001).
- Higher sNfL levels correlated with the presence of gadolinium-enhancing lesions (brain/spinal: β = 1.461, p = 0.005; both: β = 1.902, p = 0.002).
- sNfL was independently associated with disability (EDSS) and relapses (p < 0.001 for both).
- Patients at the 97.5th percentile of sNfL had a 1.94-fold higher risk of relapses and a 2.41-fold higher odds of EDSS worsening.
AI-generated from the title and abstract; the full text is not read.
Abstract
OBJECTIVE: Neurofilament light chains (NfL) are unique to neuronal cells, are shed to the cerebrospinal fluid (CSF), and are detectable at low concentrations in peripheral blood. Various diseases causing neuronal damage have resulted in elevated CSF concentrations. We explored the value of an ultrasensitive single-molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS). METHODS: sNfL levels were measured in healthy controls (HC, n = 254) and two independent MS cohorts: (1) cross-sectional with paired serum and CSF samples (n = 142), and (2) longitudinal with repeated serum sampling (n = 246, median follow-up = 3.1 years, interquartile range [IQR] = 2.0-4.0). We assessed their relation to concurrent clinical, imaging, and treatment parameters and to future clinical outcomes. RESULTS: sNfL levels were higher in both MS cohorts than in HC (p < 0.001). We found a strong association between CSF NfL and sNfL (β = 0.589, p < 0.001). Patients with either brain or spinal (43.4pg/ml, IQR = 25.2-65.3) or both brain and spinal gadolinium-enhancing lesions (62.5pg/ml, IQR = 42.7-71.4) had higher sNfL than those without (29.6pg/ml, IQR = 20.9-41.8; β = 1.461, p = 0.005 and β = 1.902, p = 0.002, respectively). sNfL was independently associated with Expanded Disability Status Scale (EDSS) assessments (β = 1.105, p < 0.001) and presence of relapses (β = 1.430, p < 0.001). sNfL levels were lower under disease-modifying treatment (β = 0.818, p = 0.003). Patients with sNfL levels above the 80th, 90th, 95th, 97.5th, and 99th HC-based percentiles had higher risk of relapses (97.5th percentile: incidence rate ratio = 1.94, 95% confidence interval [CI] = 1.21-3.10, p = 0.006) and EDSS worsening (97.5th percentile: OR = 2.41, 95% CI = 1.07-5.42, p = 0.034). INTERPRETATION: These results support the value of sNfL as a sensitive and clinically meaningful blood biomarker to monitor tissue damage and the effects of therapies in MS. Ann Neurol 2017;81:857-870.
The authors' abstract, as published at the source. Annals of Neurology, 2017 · DOI ↗
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Field: Pathology and Forensic Medicine
Pathology and Forensic MedicineMedicine