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Original Investigation
January 2019

Serum Neurofilament Light Chain for Prognosis of Outcome After Cardiac Arrest

Author Affiliations
  • 1Department of Clinical Sciences Lund, Neurology, Lund University, Skåne University Hospital, Lund, Sweden
  • 2Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden
  • 3Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University, Helsingborg Hospital, Lund, Sweden
  • 4Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
  • 5Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
  • 6Department of Molecular Neuroscience, University College of London Institute of Neurology, London, United Kingdom
  • 7United Kingdom Dementia Research Institute, London, United Kingdom
  • 8Department of Clinical Sciences Lund, Cardiology, Lund University, Skåne University Hospital, Lund, Sweden
  • 9Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University, Skåne University Hospital, Lund, Sweden
  • 10Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  • 11Department of Clinical Sciences Lund, Clinical Neurophysiology, Skåne University Hospital, Lund, Sweden
  • 12Departments of Cardiology, Rigshospitalet and Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
  • 13Adult Critical Care, University Hospital of Wales, Cardiff, United Kingdom
  • 14Department of Intensive Care, Medical Center Leeuwarden, Leeuwarden, the Netherlands
  • 15National Rescue Services, Luxembourg City, Luxembourg
  • 16Department of Cardiothoracic Anaesthesia, The Heart Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
  • 17Copenhagen Trial Unit, Centre for Clinical Intervention Research Department, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
  • 18Department of Intensive Care, Academic Medical Center, Amsterdam, the Netherlands
  • 19Anesthesia and Intensive Care, Card. G. Panico Hospital Agency, Tricase, Italy
JAMA Neurol. 2019;76(1):64-71. doi:10.1001/jamaneurol.2018.3223
Key Points

Question  What is the value of serum neurofilament light chain measurement for prognosis of outcome after cardiac arrest?

Findings  In this analysis of biobank data from 717 patients at 29 sites, serum neurofilament light chain levels measured at 24 to 72 hours after cardiac arrest were a highly sensitive and specific marker for poor neurologic outcome 6 months later. The prognostic performance of serum neurofilament light is greater than for established serum biomarkers, head computed tomography, somatosensory-evoked potentials, electroencephalogram, and bedside clinical tests.

Meaning  Measurement of serum neurofilament light levels may improve management of care for patients with cardiac arrest.


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.