Serum Neurofilament Light Chain for Prognosis of Outcome after Cardiac Arrest

Research output: Contribution to journalArticle

Abstract

Importance: Prognostication of neurologic outcome after cardiac arrest is an important but challenging aspect of patient therapy management in critical care units. Objective: To determine whether serum neurofilament light chain (NFL) levels can be used for prognostication of neurologic outcome after cardiac arrest. Design, Setting and Participants: Prospective clinical biobank study of data from the randomized Target Temperature Management After Cardiac Arrest trial, an international, multicenter study with 29 participating sites. Patients were included between November 11, 2010, and January 10, 2013. Serum NFL levels were analyzed between August 1 and August 23, 2017, after trial completion. A total of 782 unconscious patients with out-of-hospital cardiac arrest of presumed cardiac origin were eligible. Exposures: Serum NFL concentrations analyzed at 24, 48, and 72 hours after cardiac arrest with an ultrasensitive immunoassay. Main Outcomes and Measures: Poor neurologic outcome at 6-month follow-up, defined according to the Cerebral Performance Category Scale as cerebral performance category 3 (severe cerebral disability), 4 (coma), or 5 (brain death). Results: Of 782 eligible patients, 65 patients (8.3%) were excluded because of issues with aliquoting, missing sampling, missing outcome, or transport problems of samples. Of the 717 patients included (91.7%), 580 were men (80.9%) and median (interquartile range [IQR]) age was 65 (56-73) years. A total of 360 patients (50.2%) had poor neurologic outcome at 6 months. Median (IQR) serum NFL level was significantly increased in the patients with poor outcome vs good outcome at 24 hours (1426 [299-3577] vs 37 [20-70] pg/mL), 48 hours (3240 [623-8271] vs 46 [26-101] pg/mL), and 72 hours (3344 [845-7838] vs 54 [30-122] pg/mL) (P <.001 at all time points), with high overall performance (area under the curve, 0.94-0.95) and high sensitivities at high specificities (eg, 69% sensitivity with 98% specificity at 24 hours). Serum NFL levels had significantly greater performance than the other biochemical serum markers (ie, tau, neuron-specific enolase, and S100). At comparable specificities, serum NFL levels had greater sensitivity for poor outcome compared with routine electroencephalogram, somatosensory-evoked potentials, head computed tomography, and both pupillary and corneal reflexes (ranging from 29.2% to 49.0% greater for serum NFL level). Conclusions and Relevance: Findings from this study suggest that the serum NFL level is a highly predictive marker of long-term poor neurologic outcome at 24 hours after cardiac arrest and may be a useful complement to currently available neurologic prognostication methods.

Details

Authors
  • Henrik Zetterberg
  • Kaj Blennow
  • Christian Rylander
  • Jesper Kjaergaard
  • Matt P. Wise
  • Christian Hassager
  • Michael A. Kuiper
  • Pascal Stammet
  • Michael C.Jaeger Wanscher
  • Jørn Wetterslev
  • Janneke Horn
  • Tommaso Pellis
Organisations
External organisations
  • Skåne University Hospital
  • Helsingborg Hospital
  • Sahlgrenska Academy
  • Sahlgrenska University Hospital
  • University College London
  • University of Copenhagen
  • University Hospital of Wales
  • Medical Center Leeuwarden
  • Copenhagen University Hospital
  • Academic Medical Center
  • Luxembourg Rescue Services Agency
  • Azienda Ospedaliera G. Panico
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Anesthesiology and Intensive Care
  • Neurology
  • Cardiac and Cardiovascular Systems
Original languageEnglish
Pages (from-to)64
JournalJAMA Neurology
Volume76
Issue number1
Early online date2018
Publication statusPublished - 2019 Jan 1
Publication categoryResearch
Peer-reviewedYes