Neuron-Specific Enolase as a Predictor of Death or Poor Neurological Outcome After Out-of-Hospital Cardiac Arrest and Targeted Temperature Management at 33°C and 36°C

Stammet, Pascal; Collignon, Olivier; Hassager, Christian; Wise, Matthew Peter; Hovdenes, Jan; Åneman, Anders; Horn, Janneke; Devaux, Yvan; Erlinge, David; Kjærgaard, Jesper; Gasche, Yvan; Wanscher, Michael; Cronberg, Tobias; Friberg, Hans; Wetterslev, Jørn; Pellis, Tommaso; Kuiper, Michael; Gilson, Georges; Nielsen, Niklas

doi:10.1016/j.jacc.2015.03.538

Cited by 253 publications

(245 citation statements)

References 34 publications

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“…We found no effects of hemolysis on tau, but as reported before,10 NSE was increased in samples with significant hemolysis ( p = 0.047). We therefore excluded samples with a positive hemolysis index (n = 21 from 18 participants in the original cohort with NSE data).…”

Section: Resultssupporting

confidence: 83%

“…This assay uses a monoclonal capture antibody that reacts with a linear epitope in the midregion of all tau isoforms, and a detection antibody that reacts with a linear epitope in the N‐terminal region of total tau. NSE was measured using a Cobas e601 instrument with an Electrochemiluminescent immunoassay (Roche Diagnostics, Rotkreuz, Switzerland), as described previously 10. Hemolysis was tested with the Cobas system.…”

Section: Methodsmentioning

confidence: 99%

“…Using an a priori assumption of an AUC of 0.85 for NSE,10 we had > 80 % power (with α = 0.05) to detect a significantly higher AUC of at least 0.90 for tau 23. We also tested combinations of tau, NSE, and clinical information to predict poor outcome, and we performed survival analyses for combinations of NSE and tau.…”

Section: Methodsmentioning

confidence: 99%

“…The most studied biochemical marker in cardiac arrest is serum neuron‐specific enolase (NSE),10 which is included in guidelines11, 12 and already used in clinical practice in some countries. However, NSE is susceptible to false‐positive values due to hemolysis 13.…”

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confidence: 99%

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Serum tau and neurological outcome in cardiac arrest

Mattsson

Zetterberg

Nielsen

et al. 2017

Annals of Neurology

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ObjectiveTo test serum tau as a predictor of neurological outcome after cardiac arrest.MethodsWe measured the neuronal protein tau in serum at 24, 48, and 72 hours after cardiac arrest in 689 patients in the prospective international Target Temperature Management trial. The main outcome was poor neurological outcome, defined as Cerebral Performance Categories 3–5 at 6 months.ResultsIncreased tau was associated with poor outcome at 6 months after cardiac arrest (median = 38.5, interquartile range [IQR] = 5.7–245ng/l in poor vs median = 1.5, IQR = 0.7–2.4ng/l in good outcome, for tau at 72 hours, p < 0.0001). Tau improved prediction of poor outcome compared to using clinical information (p < 0.0001). Tau cutoffs had low false‐positive rates (FPRs) for good outcome while retaining high sensitivity for poor outcome. For example, tau at 72 hours had FPR = 2% (95% CI = 1–4%) with sensitivity = 66% (95% CI = 61–70%). Tau had higher accuracy than serum neuron‐specific enolase (NSE; the area under the receiver operating characteristic curve was 0.91 for tau vs 0.86 for NSE at 72 hours, p = 0.00024). During follow‐up (up to 956 days), tau was significantly associated with overall survival. The accuracy in predicting outcome by serum tau was equally high for patients randomized to 33 °C and 36 °C targeted temperature after cardiac arrest.InterpretationSerum tau is a promising novel biomarker for prediction of neurological outcome in patients with cardiac arrest. It may be significantly better than serum NSE, which is recommended in guidelines and currently used in clinical practice in several countries to predict outcome after cardiac arrest. Ann Neurol 2017;82:665–675

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Section: Resultssupporting

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Serum tau and neurological outcome in cardiac arrest

Mattsson

Zetterberg

Nielsen

et al. 2017

Annals of Neurology

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“…In einer Sekundärana -lyse der TTM-Studie wurden die NSESerumkonzentrationen nach 24, 48 und 72 h bei 686 Patienten gemessen. Eine Erhöhung der NSE-Werte zwischen zwei beliebigen Zeitpunkten war mit einem schlechten neurologischen Ergebnis assoziiert [335].…”

Section: Neuronenspezifische Enolase (Nse)unclassified