Serum neurofilament measurement improves clinical risk scores for outcome prediction after cardiac arrest: results of a prospective study

Abstract

Background A recent study found serum neurofilament light chain (NfL) levels to be strongly associated with poor neurological outcome in patients after cardiac arrest. Our aim was to confirm these findings in an independent validation study and to investigate whether NfL improves the prognostic value of two cardiac arrest-specific risk scores. Methods This prospective, single-center study included 164 consecutive adult after out-of-hospital cardiac arrest (OHCA) patients upon intensive care unit admission. We calculated two clinical risk scores (OHCA, CAHP) and measured NfL on admission within the first 24 h using the single molecule array NF-light® assay. The primary endpoint was neurological outcome at hospital discharge assessed with the cerebral performance category (CPC) score. Results Poor neurological outcome (CPC > 3) was found in 60% (98/164) of patients, with 55% (91/164) dying within 30 days of hospitalization. Compared to patients with favorable outcome, NfL was 14-times higher in patients with poor neurological outcome (685 ± 1787 vs. 49 ± 111 pg/mL), with an adjusted odds ratio of 3.4 (95% CI 2.1 to 5.6, p < 0.001) and an area under the curve (AUC) of 0.82. Adding NfL to the clinical risk scores significantly improved discrimination of both the OHCA score (from AUC 0.82 to 0.89, p < 0.001) and CAHP score (from AUC 0.89 to 0.92, p < 0.05). Adding NfL to both scores also resulted in significant improvement in reclassification statistics with a Net Reclassification Index (NRI) of 0.58 (p < 0.001) for OHCA and 0.83 (p < 0.001) for CAHP. Conclusions Admission NfL was a strong outcome predictor and significantly improved two clinical risk scores regarding prognostication of neurological outcome in patients after cardiac arrest. When confirmed in future outcome studies, admission NfL should be considered as a standard laboratory measures in the evaluation of OHCA patients.

Absolute serum neurofilament light chain levels and its early kinetics predict brain injury after out-of-hospital cardiac arrest

“…These findings have independently been confirmed in recent studies: in a post-hoc analysis of another study involving 120 patients and assessment in blood taken at 48 h of admission, median NFL concentrations in plasma were found higher in patients with poor outcome compared to those with good outcome (2343 vs. 19 pg/ml), with the outcome assessed at month 6 of admission [10]. In a singlecenter study including 164 OHCA patients, NFL was measured already within 24 h of admission, and the median NFL values were higher in patients with poor outcome compared to those with good outcome (116 vs. 27 pg/mL) [11]. The three key studies mentioned allow the conclusion that NFL should be further evaluated for the purpose of neuroprognostication of OHCA patients in clinical routine.…”

Brain injury after cardiac arrest: pathophysiology, treatment, and prognosis

“…Neurofilament light chain (NFL) is a cytoskeletal component of large, myelinated axons of the central and peripheral nervous system and increased blood levels correlate with severity of several neurologic disorders including stroke, amyotrophic lateral sclerosis, and dementia. A limited number of studies, using the highly sensitive SIMOA-technology, indicate that NFL has superior prognostic performance compared to the other biomarkers [ 107 – 109 ] and also to other available methods [ 108 ]. In a recent study [ 110 ] investigating the ability of six biomarkers to predict good neurological outcome after arrest, NFL was the most consistent predictor, having the second best sensitivity and specificity.…”

Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest

“…The aim of the current study was to examine whether normal levels of brain injury markers predict good neurological outcome after CA. We focused on neuron-specific enolase (NSE), the only marker recommended by guidelines [ 4 ], and on neurofilament light chain protein (NFL), a neuroaxonal marker which has previously demonstrated high prognostic accuracies [ 22 , 26 , 27 ]. In addition, we report results for the neuroaxonal marker total tau, the neuronal cell body marker ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and the astrocytic markers S100B and glial fibrillary acidic protein (GFAP).…”