Abstract:Objectives
To test if the early kinetics of neurofilament light (NFL) in blood adds to the absolute values of NFL in the prediction of outcome, and to evaluate if NFL can discriminate individuals with severe hypoxic–ischemic brain injury (sHIBI) from those with other causes of poor outcome after out-of-hospital cardiac arrest (OHCA).
Design and setting
Monocentric retrospective study involving individuals following non-traumatic OHCA between April 2014 and… Show more
“…In this study, the predictive performance of NfL on admission to intensive care was low, which is in line with previous studies [ 3 , 6 , 20 ]. In patients with poor outcome, NfL levels increase substantially as post-hypoxic brain injury develops and may reach a steady state between 48 and 72 h [ 2 , 3 , 21 ].…”
Section: Discussionsupporting
confidence: 92%
“…Additionally, low levels of NfL at 24–72 h have been reported to accurately identify patients with good outcome [ 3 , 5 ]. The prognostic value is low early after ICU admission and the earliest time point when NfL can provide reliable prognostic information is unknown [ 3 , 6 ]. Previous studies reporting the highest prognostic performance of NfL included only selected cohorts of OHCA [ 2 , 3 ].…”
Background
Previous studies have reported high prognostic accuracy of circulating neurofilament light (NfL) at 24–72 h after out-of-hospital cardiac arrest (OHCA), but performance at earlier time points and after in-hospital cardiac arrest (IHCA) is less investigated. We aimed to assess plasma NfL during the first 48 h after OHCA and IHCA to predict long-term outcomes.
Methods
Observational multicentre cohort study in adults admitted to intensive care after cardiac arrest. NfL was retrospectively analysed in plasma collected on admission to intensive care, 12 and 48 h after cardiac arrest. The outcome was assessed at two to six months using the Cerebral Performance Category (CPC) scale, where CPC 1–2 was considered a good outcome and CPC 3–5 a poor outcome. Predictive performance was measured with the area under the receiver operating characteristic curve (AUROC).
Results
Of 428 patients, 328 (77%) suffered OHCA and 100 (23%) IHCA. Poor outcome was found in 68% of OHCA and 55% of IHCA patients. The overall prognostic performance of NfL was excellent at 12 and 48 h after OHCA, with AUROCs of 0.93 and 0.97, respectively. The predictive ability was lower after IHCA than OHCA at 12 and 48 h, with AUROCs of 0.81 and 0.86 (p ≤ 0.03). AUROCs on admission were 0.77 and 0.67 after OHCA and IHCA, respectively. At 12 and 48 h after OHCA, high NfL levels predicted poor outcome at 95% specificity with 70 and 89% sensitivity, while low NfL levels predicted good outcome at 95% sensitivity with 71 and 74% specificity and negative predictive values of 86 and 88%.
Conclusions
The prognostic accuracy of NfL for predicting good and poor outcomes is excellent as early as 12 h after OHCA. NfL is less reliable for the prediction of outcome after IHCA.
“…In this study, the predictive performance of NfL on admission to intensive care was low, which is in line with previous studies [ 3 , 6 , 20 ]. In patients with poor outcome, NfL levels increase substantially as post-hypoxic brain injury develops and may reach a steady state between 48 and 72 h [ 2 , 3 , 21 ].…”
Section: Discussionsupporting
confidence: 92%
“…Additionally, low levels of NfL at 24–72 h have been reported to accurately identify patients with good outcome [ 3 , 5 ]. The prognostic value is low early after ICU admission and the earliest time point when NfL can provide reliable prognostic information is unknown [ 3 , 6 ]. Previous studies reporting the highest prognostic performance of NfL included only selected cohorts of OHCA [ 2 , 3 ].…”
Background
Previous studies have reported high prognostic accuracy of circulating neurofilament light (NfL) at 24–72 h after out-of-hospital cardiac arrest (OHCA), but performance at earlier time points and after in-hospital cardiac arrest (IHCA) is less investigated. We aimed to assess plasma NfL during the first 48 h after OHCA and IHCA to predict long-term outcomes.
Methods
Observational multicentre cohort study in adults admitted to intensive care after cardiac arrest. NfL was retrospectively analysed in plasma collected on admission to intensive care, 12 and 48 h after cardiac arrest. The outcome was assessed at two to six months using the Cerebral Performance Category (CPC) scale, where CPC 1–2 was considered a good outcome and CPC 3–5 a poor outcome. Predictive performance was measured with the area under the receiver operating characteristic curve (AUROC).
Results
Of 428 patients, 328 (77%) suffered OHCA and 100 (23%) IHCA. Poor outcome was found in 68% of OHCA and 55% of IHCA patients. The overall prognostic performance of NfL was excellent at 12 and 48 h after OHCA, with AUROCs of 0.93 and 0.97, respectively. The predictive ability was lower after IHCA than OHCA at 12 and 48 h, with AUROCs of 0.81 and 0.86 (p ≤ 0.03). AUROCs on admission were 0.77 and 0.67 after OHCA and IHCA, respectively. At 12 and 48 h after OHCA, high NfL levels predicted poor outcome at 95% specificity with 70 and 89% sensitivity, while low NfL levels predicted good outcome at 95% sensitivity with 71 and 74% specificity and negative predictive values of 86 and 88%.
Conclusions
The prognostic accuracy of NfL for predicting good and poor outcomes is excellent as early as 12 h after OHCA. NfL is less reliable for the prediction of outcome after IHCA.
“…Growing literature also highlights the predictive value of NfL concentrations in the intensive care setting, as it may be used to assess the risk of neurological events following either resuscitation (Fisse et al, 2021 ; Page et al, 2022 ) or cardiac arrest. Thus, high levels of blood NfL 48 h after cardiac arrest (>500 pg/ml) were described to predict neurological complications related to cerebral ischemia/hypoxia with high sensitivity (100%, 95%CI 70.0–100%) and specificity (91.7%, 95%CI 62.5–100%; Adler et al, 2022 ; Hoiland et al, 2022 ) and were correlated with EEG abnormalities, p < 0.001 (Grindegård et al, 2022 ).…”
Neurological biomarkers are particularly valuable to clinicians as they can be used for diagnosis, prognosis, or response to treatment. This field of neurology has evolved considerably in recent years with the improvement of analytical methods, allowing the detection of biomarkers not only in cerebrospinal fluid (CSF) but also in less invasive fluids like blood. These advances greatly facilitate the repeated quantification of biomarkers, including at asymptomatic stages of the disease. Among the various informative biomarkers of neurological disorders, neurofilaments (NfL) have proven to be of particular interest in many contexts, such as neurodegenerative diseases, traumatic brain injury, multiple sclerosis, stroke, and cancer. Here we discuss these different pathologies and the potential value of NfL assay in the management of these patients, both for diagnosis and prognosis. We also describe the added value of NfL compared to other biomarkers currently used to monitor the diseases described in this review.
“…Seven studies were excluded after a full-paper analysis. Finally, nine studies [ 15 – 23 ] were included for meta-analysis. Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Neurofilament light chain (NfL), an axonal structural protein, is an established biomarker for axonal damage [ 12 – 14 ]. Some studies have assessed the association between serum NfL and neurologic outcomes after cardiac arrest, but the results are inconclusive [ 15 – 23 ]. Therefore, this systematic review and meta-analysis aim to investigate the predictive value of serum NfL for neurologic outcomes after cardiac arrest.…”
Objective
Recently, an increasing number of studies have suggested using serum neurofilament light (NfL) chain to predict the neurologic outcome after cardiac arrest. However, the predictive ability of this approach remains inconclusive. Meta-analysis was performed on related studies to assess the ability of serum NfL to predict the neurologic outcome after cardiac arrest.
Materials and methods
PubMed, ScienceDirect and Embase were systematically searched from the date of their inception until June 2022. Data were extracted to calculate the area under the receiver operating characteristic curve (AUC), the sensitivity, the specificity and the publication bias to evaluate the predictive power of serum NfL using Stata 14.0.
Results
Nine studies were included in the present meta-analysis. Seven studies involving 1296 participants reported serum NfL 24 h post arrest for predicting the neurological outcome, and the AUC was 0.92 (77% sensitivity and 96% specificity). Seven studies involving 1020 participants reported serum NfL 48 h post arrest for predicting the neurological outcome, and the AUC was 0.94 (78% sensitivity and 98% specificity). Four studies involving 804 participants reported serum NfL 72 h post arrest for predicting the neurological outcome, and the AUC was 0.96 (90% sensitivity and 98% specificity). No significant publication bias was observed among the included studies.
Conclusion
The present meta-analysis results support the potential use of serum NfL as an early biomarker of neurologic outcome, especially 72 h post arrest.
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