ANNALS OF NEUROLOGY | OCTOBER 5, 2017

Niklas Mattsson MD, PhD, Henrik Zetterberg MD, PhD, Niklas Nielsen MD, PhD, Kaj Blennow MD, PhD, Josef Dankiewicz MD, Hans Friberg MD, PhD, Gisela Lilja PhD, Philip S. Insel, Christian Rylander MD, PhD, Pascal Stammet MD, Anders Aneman MD, PhD, Christian Hassager MD, Jesper Kjaergaard MD, Michael Kuiper MD, PhD, Tommaso Pellis MD, PhD, Jørn Wetterslev MD, PhD, Matthew Wise MD, PhD, Tobias Cronberg MD, PhD
Annals of Neurology
DOI: 10.1002/ana.25067

Abstract

Objective: To test serum tau as a predictor of neurological outcome after cardiac arrest.

Methods: We measured the neuronal protein tau in serum at 24, 48, and 72 h 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 Category 3-5 at 6 months.

Results: Increased tau was associated with poor outcome at 6 months after cardiac arrest (median 38.5 [IQR 5.7-245] ng/L in poor versus 1.5 [0.7-2.4] ng/L in good outcome, for tau at 72 h, p<0.0001). Tau improved prediction of poor outcome compared to using clinical information (p<0.0001). Tau cut-offs had low false positive rates (FPR) for good outcome while retaining high sensitivity for poor outcome. For example, tau at 72 h had FPR 2% (95% CI 1-4%) with sensitivity 66% (95% CI 61-70%). Tau had higher accuracy than serum NSE (the area under the receiver operating characteristic curve was 0.91 for tau versus 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 to predict outcome by serum tau was equally high for patients randomized to 33°C and 36°C targeted temperature after cardiac arrest.

Interpretation: Serum 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. This article is protected by copyright. All rights reserved.