Abstract
Axonal white matter injury is believed to be a major determinant of adverse outcomes following traumatic brain injury (TBI). We hypothesized that measurement of neurofilament light protein (NF-L), a protein found in long white-matter axons, in blood samples, may serve as a suitable biomarker for neuronal damage in TBI patients. To test our hypotheses, we designed a study in two parts: i) we developed an immunoassay based on Single molecule array technology for quantification of NF-L in blood, and ii) in a proof-of-concept study, we tested our newly developed method on serial serum samples from severe TBI (sTBI) patients (n = 72) and controls (n = 35). We also compared the diagnostic and prognostic utility of NF-L with the established blood biomarker S100B. NF-L levels were markedly increased in sTBI patients compared with controls. NF-L at admission yielded an AUC of 0.99 to detect TBI versus controls (AUC 0.96 for S100B), and increased to 1.00 at day 12 (0.65 for S100B). Importantly, initial NF-L levels predicted poor 12-month clinical outcome. In contrast, S100B was not related to outcome. Taken together, our data suggests that measurement of serum NF-L may be useful to assess the severity of neuronal injury following sTBI.
Highlights
Axonal protein in plasma using Single molecule array (Simoa) technology, which is up to 1000-fold more sensitive than conventional ELISA, and showed that tau measured 1 hour after concussion were significantly elevated in concussed athletes[12]
To test our specific hypotheses, we designed a study in 2 parts: i) we developed an ultrasensitive ELISA based on Simoa technology[18], for quantification of NF-L in serum, and ii) in a proof-of-concept study, we applied our newly developed assay on serial blood samples of severe TBI (sTBI) patients (n = 72), as well as neurologically healthy controls (n = 35)
We found increased serum levels of both NF-L and S100B in patients with sTBI compared with controls, but the dynamics were different; whilst NF-L concentrations were increased at admission to NICU, and continued to rise over the first 12 days post-injury, S100B concentrations fell over time after an initial peak the first day after trauma
Summary
Axonal protein in plasma using Single molecule array (Simoa) technology, which is up to 1000-fold more sensitive than conventional ELISA, and showed that tau measured 1 hour after concussion were significantly elevated in concussed athletes[12]. We assessed the univariate relationship between early (24 hours) NF-L levels and clinical outcome, and found higher levels of NF-L in patients with lower GOS score at 12 months after injury (r =−0.34, p = 0.010) (Fig. 4b).
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