Multimodal assessment of favorable neurological outcome using NSE levels and kinetics, EEG and SSEP in comatose patients after cardiac arrest

Abstract

Background: Prognostic markers of good neurological outcome after cardiac arrest (CA) remain limited. We aimed to evaluate the prognostic value of neuron-specific enolase (NSE), electroencephalogram (EEG) and somatosensory evoked potentials (SSEP) in predicting good outcome, assessed separately and in combination.

Methods: A retrospective study was conducted in a tertiary CA center, using a prospective registry. We included all patients comatose after discontinuation of sedation and with one EEG and NSE blood measurement at 24, 48 or/and 72 h after CA. The primary outcome was favorable neurological outcome at three months, a Cerebral Performance Categories (CPC) scale 1-2 defining a good outcome.

Results: Between January 2017 and April 2024, 215 patients were included. Participants were 63 years old (IQR [52-73]), and 73% were male. At 3 months, 54 patients (25.1%) had a good outcome. Compared to the poor outcome group, NSE blood levels were significantly lower in the good outcome group at 24 h (39 IQR[27-45] vs 54 IQR[37-82]µg/L, p < 0.001), 48 h (26 [18-43] vs 107 [54-227]µg/L, p < 0.001) and 72 h (20 µg/L IQR [15-30] vs 184 µg/l IQR [60-300], p < 0,001). Normal NSE (i.e., < 17 µg/L) at 24 h was highly predictive of good outcome, with a predictive positive value (PPV) of 71% despite a sensitivity (Se) of 9%. The best cut-off values for NSE at 24, 48 and 72 h were below 45.5, 51.5 and 41.5 µg/L, yielding PPV of 64%, 80% and 83% and sensitivities of 74%, 93% and 90%, respectively. A decreasing trend in NSE levels between 24 and 72 h was also highly predictive of good outcome (PPV 82%, Se 81%). A benign EEG pattern was more frequently observed in the good outcome group (87.1 vs 14.9%, p < 0.001) and predicted a good outcome with a PPV of 72% and a Se of 94%. Regarding SSEPs, a bilateral N20-baseline amplitude > 0.85 µV was predictive of good outcome (PPV 75%, Se 100%). The combination of NSE < 51.5 µg/l at 48 h, a decreasing NSE trend between 24 and 72 h and a benign EEG showed the best predictive value (PPV 96%, Se 76%).

Conclusion: In comatose patients after CA, a low NSE levels at 24, 48 h or 72 h, a decreasing trend in NSE over time, a benign EEG and a high N20 amplitude are robust markers of favorable outcome, reducing prognosis uncertainty.

Keywords: Cardiac arrest; Coma; EEG; Electroencephalography; NSE; Neuron-specific enolase; Neuroprognostication; SSEP; Somatosensory-evoked potentials.

Fig. 1

Prognosis performances of blood NSE at 24, 48 and 72 h after cardiac arrest. Abbreviations: AUC area under the curve; CI confidence interval; h hours; NSE neuron specific enolase