Serum Neurofilament Light Chain for Prognosis of Outcome after Cardiac Arrest

Marion Moseby-Knappe; Niklas Mattsson; Niklas Nielsen; Henrik Zetterberg; Kaj Blennow; Josef Dankiewicz; Irina Dragancea; Hans Friberg; Gisela Lilja; Philip S. Insel; Christian Rylander; Erik Westhall; Jesper Kjaergaard; Matt P. Wise; Christian Hassager; Michael A. Kuiper; Pascal Stammet; Michael C. Jaeger Wanscher; Jørn Wetterslev; David Erlinge; Janneke Horn; Tommaso Pellis; Tobias Cronberg

doi:10.1001/jamaneurol.2018.3223

Serum Neurofilament Light Chain for Prognosis of Outcome after Cardiac Arrest

Marion Moseby-Knappe^*, Niklas Mattsson, Niklas Nielsen, Henrik Zetterberg, Kaj Blennow, Josef Dankiewicz, Irina Dragancea, Hans Friberg, Gisela Lilja, Philip S. Insel, Christian Rylander, Erik Westhall, Jesper Kjaergaard, Matt P. Wise, Christian Hassager, Michael A. Kuiper, Pascal Stammet, Michael C. Jaeger Wanscher, Jørn Wetterslev, David ErlingeJanneke Horn, Tommaso Pellis, Tobias Cronberg

^*Corresponding author for this work

Department of Clinical Medicine

56 Citations (Scopus)

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.

Original language	English
Journal	JAMA Neurology
Volume	76
Issue number	1
Pages (from-to)	64-71
Number of pages	8
ISSN	2168-6149
DOIs	https://doi.org/10.1001/jamaneurol.2018.3223
Publication status	Published - 2019

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Moseby-Knappe, M., Mattsson, N., Nielsen, N., Zetterberg, H., Blennow, K., Dankiewicz, J., Dragancea, I., Friberg, H., Lilja, G., Insel, P. S., Rylander, C., Westhall, E., Kjaergaard, J., Wise, M. P., Hassager, C., Kuiper, M. A., Stammet, P., Wanscher, M. C. J., Wetterslev, J., ... Cronberg, T. (2019). Serum Neurofilament Light Chain for Prognosis of Outcome after Cardiac Arrest. JAMA Neurology, 76(1), 64-71. https://doi.org/10.1001/jamaneurol.2018.3223

Moseby-Knappe, M, Mattsson, N, Nielsen, N, Zetterberg, H, Blennow, K, Dankiewicz, J, Dragancea, I, Friberg, H, Lilja, G, Insel, PS, Rylander, C, Westhall, E, Kjaergaard, J, Wise, MP, Hassager, C, Kuiper, MA, Stammet, P, Wanscher, MCJ, Wetterslev, J, Erlinge, D, Horn, J, Pellis, T & Cronberg, T 2019, 'Serum Neurofilament Light Chain for Prognosis of Outcome after Cardiac Arrest', JAMA Neurology, vol. 76, no. 1, pp. 64-71. https://doi.org/10.1001/jamaneurol.2018.3223

@article{41cdb33eafbc4fa98f467b5f5068b7ed,

title = "Serum Neurofilament Light Chain for Prognosis of Outcome after Cardiac Arrest",

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.",

author = "Marion Moseby-Knappe and Niklas Mattsson and Niklas Nielsen and Henrik Zetterberg and Kaj Blennow and Josef Dankiewicz and Irina Dragancea and Hans Friberg and Gisela Lilja and Insel, {Philip S.} and Christian Rylander and Erik Westhall and Jesper Kjaergaard and Wise, {Matt P.} and Christian Hassager and Kuiper, {Michael A.} and Pascal Stammet and Wanscher, {Michael C. Jaeger} and J{\o}rn Wetterslev and David Erlinge and Janneke Horn and Tommaso Pellis and Tobias Cronberg",

year = "2019",

doi = "10.1001/jamaneurol.2018.3223",

language = "English",

volume = "76",

pages = "64--71",

journal = "JAMA Neurology",

issn = "2168-6149",

publisher = "The JAMA Network",

number = "1",

}

TY - JOUR

T1 - Serum Neurofilament Light Chain for Prognosis of Outcome after Cardiac Arrest

AU - Moseby-Knappe, Marion

AU - Mattsson, Niklas

AU - Nielsen, Niklas

AU - Zetterberg, Henrik

AU - Blennow, Kaj

AU - Dankiewicz, Josef

AU - Dragancea, Irina

AU - Friberg, Hans

AU - Lilja, Gisela

AU - Insel, Philip S.

AU - Rylander, Christian

AU - Westhall, Erik

AU - Kjaergaard, Jesper

AU - Wise, Matt P.

AU - Hassager, Christian

AU - Kuiper, Michael A.

AU - Stammet, Pascal

AU - Wanscher, Michael C. Jaeger

AU - Wetterslev, Jørn

AU - Erlinge, David

AU - Horn, Janneke

AU - Pellis, Tommaso

AU - Cronberg, Tobias

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1001/jamaneurol.2018.3223

DO - 10.1001/jamaneurol.2018.3223

M3 - Journal article

C2 - 30383090

AN - SCOPUS:85055856966

SN - 2168-6149

VL - 76

SP - 64

EP - 71

JO - JAMA Neurology

JF - JAMA Neurology

IS - 1

ER -

Serum Neurofilament Light Chain for Prognosis of Outcome after Cardiac Arrest

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