Association Between EEG Patterns and Serum Neurofilament Light After Cardiac Arrest

Abstract

Background and objectives:Electroencephalography (EEG) is widely used for prediction of neurological outcome after cardiac arrest. To better understand the relationship between EEG and neuronal injury, we explore the association between EEG and neurofilament light (NFL) as a marker of neuroaxonal injury. We evaluate whether highly malignant EEG patterns are reflected by high NFL levels. Additionally, we explore the association of EEG backgrounds and EEG discharges with NFL.Methods:Post-hoc analysis of the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Routine EEGs were prospectively performed after the temperature intervention ≥36 hours post-arrest. Patients who awoke or died prior to 36 hours post-arrest were excluded. EEG-experts blinded to clinical information classified EEG background, amount of discharges and highly malignant EEG patterns according to the standardized American Clinical Neurophysiology Society terminology. Prospectively collected serum samples were analyzed for NFL after trial completion. The highest available concentration at 48 or 72-hours post-arrest was used.Results:262/939 patients with EEG and NFL data were included. Patients with highly malignant EEG patterns had 2.9 times higher NFL levels than patients with malignant patterns and NFL levels were 13 times higher in patients with malignant patterns than those with benign patterns (95% CI: 1.4-6.1 and 6.5-26.2 respectively, effect size 0.47, p<0.001). Both background and the amount of discharges were independently strongly associated with NFL levels (p<0.001). The EEG background had a stronger association with NFL levels than EEG discharges (R2=0.30 and R2=0.10, respectively). NFL levels in patients with a continuous background were lower than for any other background (95% CI for discontinuous, burst-suppression and suppression, respectively: 2.26-18.06, 3.91-41.71 and 5.74-41.74, effect size 0.30 and p<0.001 for all). NFL levels did not differ between suppression and burst-suppression. Superimposed discharges were only associated with higher NFL levels if the EEG background was continuous.Discussion:Benign, malignant, and highly malignant EEG patterns reflect the extent of brain injury as measured by NFL in serum. The extent of brain injury is more strongly related to the EEG background than superimposed discharges. Combining EEG and NFL may be useful to better identify patients misclassified by single methods.Clinical Trials Registration Number:clinicaltrials.gov, NCT01020916

Aberrant brain-heart coupling is associated with the severity and prognosis of hypoxic-ischemic brain injury after cardiac arrest

“…We thus show that both directions of the brain-heart interplay are impaired in CA survivors with a dose-effect relationship with the severity of HIBI, as assessed by EEG background patterns, results of N20 on SSEP, and serum NSE levels. This multimodal approach to patients’ prognosis with concordant findings from different complementary prognostic markers 47 and the dose-effect relationship considerably strengthens the validity of our findings and suggests that the degree of ANS dysfunction is probably related to the burden of anoxo-ischemic lesions 48 which are not uniformly distributed within the brain 1,49 . Unfortunately, brain-imaging or pupillometry data were not available in this cohort to precisely document the regions involved in this aberrant coupling.…”

Longitudinal serum neurofilament light kinetics in post‐anoxic encephalopathy

“…Although EEG were only performed in a minority of patients, we confirmed that malignant EEG patterns reflect the extent of brain injury as measured by sNfL. 10 While sNfL levels were comparable in survivors and non-survivors at admission, non-survivors showed up to 1000-fold sNfL increase at 24 h, reaching higher concentrations than those observed in other conditions affecting the central nervous system (including most neurodegenerative diseases). 11 Notably, sNfL concentrations remained high for up to 10 days after CA.…”

“…Higher sNfL levels were associated with age, suggesting that age‐related brain susceptibility to the anoxic insult can contribute to neuronal death. Although EEG were only performed in a minority of patients, we confirmed that malignant EEG patterns reflect the extent of brain injury as measured by sNfL 10 …”

Neurofilaments contribution in clinic: state of the art

“…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 ).…”