Neurofilament light chain as an early and sensitive predictor of long-term neurological outcome in patients after cardiac arrest

Abstract

Background

Neurofilament light chain (NF-L) is the major intermediate filament specifically expressed in neurons and their axons. No data are available concerning serum levels of NF-L after global cerebral ischemia due to cardiac arrest. To find a specific neuronal marker of long-term neurological outcome, we examined serum levels of NF-L in patients after cardiac arrest.

Methods

A prospective observational cohort study was conducted. Blood samples for the measurement of NF-L were analyzed from 85 patients within 2 h after admission, as well as on 2nd, 3rd, 5th, and 7th day. Neurological outcome was assessed 6 months after cardiac arrest by employing the Modified Glasgow Outcome Score (MGOS).

Results

The serum course of NF-L in patients with poor neurological outcome (MGOS 1 + 2) was significantly augmented compared to patients with good neurological outcome (MGOS 3 + 4 + 5) (on admission (pg/ml): good: 125 ± 11.7 vs. poor: 884.4 ± 86.2 pg/ml; 3rd day: good: 153.1 ± 13.2 vs. poor: 854.4 ± 119.1; 7th day: good: 112.5 ± 10.4 vs. poor: 1011.8 ± 100.8; P < 0.001). Intermediate NF-L serum values were found in patients with MGOS 0, which represents a mixture of patients who died with and without certified brain damage (on admission (pg/dl): 433.7 ± 49.8; 3rd day: 598.3 ± 86.6; 7th day: 474 ± 77.4). A prediction power of 0.93 (c-statistic, 95%-CI 0.87–0.99) on 1st, 0.85 (0.81–0.95) on 2nd, 0.92 (0.85–0.99) on 3rd, 0.97 (0.92–1) on 5th and 0.99 (0.98–1) on 7th day was achieved for NF-L predicting poor neurological outcome.

Conclusions

The present data suggest that within 7 days after cardiac arrest serum NF-L is a valuable marker of long-term neurological outcome.

Introduction

Out-of-hospital cardiac arrest (CA) is the leading cause of death in the USA and Europe affecting about 750,000 people annually [1]. In clinical routine, it is desirable to rely on early and specific biochemical markers to predict final neurological outcome, to plan further therapeutic strategies after successful cardiopulmonary resuscitation (CPR) and to avoid futile medical capabilities.

Serum levels of neuron-specific enolase (NSE) and S-100B protein are considered to be promising candidate marker proteins for the prediction of neurological status in patients in which spontaneous circulation after CPR has been restored [2], [3], [4], [5]. However, previous studies on these two markers have yielded contradictory results [6], [7], [8]. Importantly, both markers are not solely expressed in neuronal structures, e.g. NSE is expressed in red blood cells and platelets and S-100B is present in adipose and other tissue [9], [10], [11], [12], [13]. This makes changes specifically those associated with brain injury in serum levels difficult to evaluate.

Neurofilaments (NF) are major structural elements of the neuronal cytoskeleton. The neurofilament light chain protein (NF-L) comprises the major component of the neurofilament core and is the major intermediate filament protein in neurons and axons [14], [15]. There is some evidence that levels of NF-L in the cerebrospinal fluid are highly predictive for poor neurological outcome in patients after CA [16]. However, assessment of biochemical markers in the cerebrospinal fluid is less practicable because of awareness of various complications during and after lumbar puncture especially in ventilated patients. No data are available concerning serum levels of NF-L after global cerebral ischemia from CA in humans. In an attempt to find a reliable and specific neuronal marker for long-term neurological outcome, we performed a prospective observational cohort study to investigate serum levels of NF-L in patients after CA.