Serum neurofilament light chain at time of diagnosis is an independent prognostic factor of survival in amyotrophic lateral sclerosis

Abstract

Background and purposeThe prognostic value of serum neurofilament light chain (sNfL), a biomarker of neurodegeneration, compared to other prognostic factors of amyotrophic lateral sclerosis (ALS) at the time of diagnosis, remains unclear.MethodsSera from ALS patients were prospectively collected at the first diagnostic visit in our centre. sNfL levels were determined by single molecule array in 207 ALS patients and in 21 healthy controls. The prognostic value of sNfL was compared with that of other known clinical prognostic factors using a Cox regression model and multivariate analysis.ResultsSerum neurofilament light chain levels were higher in ALS patients than in controls (P < 0.0001). Seven parameters were predictive of death in ALS: older age, bulbar onset, higher ALS Functional Rating Scale revised (ALSFRS‐R) score, greater weight loss, lower maximal inspiratory pressure, forced vital capacity and higher sNfL levels. A Cox regression model showed that sNfL (P < 0.0001), weight loss (P = 0.040) and site at onset (P = 0.048) were independent predictive factors of death. In a sub‐cohort restricted to 139 patients with complete spirometry data, sNfL level (P < 0.005) and forced vital capacity (P = 0.022) were independent factors predictive of death. In a subgroup of 142 patients in whom ALSFRS‐R score was available at several time points, sNfL levels positively correlated with ALSFRS‐R rate of decline (r = 0.571, P < 10−12).ConclusionsHigher sNfL concentration is a strong and independent prognostic factor of death in ALS as early as the time of diagnosis.

Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease

“…These findings suggest that pNfH levels in serum indicate the spreading and the global rate of CNS involvement and may offer a quick and simple measure to assess and predict neuronal damage in MND. Our results extend the previous findings that both neurofilament subunits and other wet biomarkers should be thoroughly assessed to be included in future prognostic models [18,22,36].…”

Neurofilaments in motor neuron disorders: towards promising diagnostic and prognostic biomarkers

“…At the moment, however, the apparent lack of change of NFs concentration with advancing stages of diseases would indicate that the first measured value of NF would be informative about the rate of disease progression along the entire course of MND. The observation that baseline NF levels, i.e., at the first diagnostic visit, mostly in CSF [67,70,84], but also in serum [71,83,90] inversely correlated with survival in regression models support this conclusion. In univariate regression models, NF levels retain a high hazard risk for death [57,70,81].…”

Validation of Serum Neurofilaments as Prognostic & Potential Pharmacodynamic Biomarkers for ALS

“…While much has been written about the prognostic and potential pharmacodynamic utility of neurofilaments in ALS 7,12,13,21,27 and reproducibility (lowest CV between technical replicates in both serum and CSF).…”