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May 09, 2017; 88 (19) Article

Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports

Pashtun Shahim, Henrik Zetterberg, Yelverton Tegner, Kaj Blennow
First published April 12, 2017, DOI: https://doi.org/10.1212/WNL.0000000000003912
Pashtun Shahim
From the Institute of Neuroscience and Physiology (P.S., H.Z., K.B.), Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; and the Division of Medical Sciences (Y.T.), Department of Health Sciences, Luleå University of Technology, Sweden.
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Henrik Zetterberg
From the Institute of Neuroscience and Physiology (P.S., H.Z., K.B.), Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; and the Division of Medical Sciences (Y.T.), Department of Health Sciences, Luleå University of Technology, Sweden.
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Yelverton Tegner
From the Institute of Neuroscience and Physiology (P.S., H.Z., K.B.), Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; and the Division of Medical Sciences (Y.T.), Department of Health Sciences, Luleå University of Technology, Sweden.
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Kaj Blennow
From the Institute of Neuroscience and Physiology (P.S., H.Z., K.B.), Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK; and the Division of Medical Sciences (Y.T.), Department of Health Sciences, Luleå University of Technology, Sweden.
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Citation
Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports
Pashtun Shahim, Henrik Zetterberg, Yelverton Tegner, Kaj Blennow
Neurology May 2017, 88 (19) 1788-1794; DOI: 10.1212/WNL.0000000000003912

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Abstract

Objective: To evaluate whether the axonal protein neurofilament light (NFL) in serum is a sensitive biomarker to detect subtle brain injury or concussion in contact sports athletes.

Methods: Two prospective cohort studies involving (1) 14 Swedish amateur boxers who underwent fluid biomarker assessments at 7–10 days after bout and after 3 months of rest from boxing and (2) 35 Swedish professional hockey players who underwent blood biomarker assessment at 1, 12, 36, and 144 hours after concussion and when the players returned to play were performed. Fourteen healthy nonathletic controls and 12 athletic controls were also enrolled. Serum NFL was measured using ultrasensitive single molecule array technology.

Results: Serum NFL concentrations were increased in boxers 7–10 days after bout as compared to the levels after 3 months rest as well as compared with controls (p = 0.0007 and p < 0.0001, respectively). NFL decreased following 3 months of rest, but was still higher than in controls (p < 0.0001). Boxers who received many (>15) hits to the head or were groggy after bout had higher concentrations of serum NFL as compared to those who received fewer hits to the head (p = 0.0023). Serum NFL increased over time in hockey players, and the levels returned to normal at return to play. Importantly, serum NFL could separate players with rapidly resolving postconcussion symptoms (PCS) from those with prolonged PCS.

Conclusions: The results from these 2 independent cohort studies suggest that serum NFL is a highly sensitive biomarker for concussion.

GLOSSARY

AUC=
area under the receiver operating characteristic curve;
DTI=
diffusion tensor imaging;
IQR=
interquartile range;
LLOQ=
lower limit of quantification;
LOD=
limit of detection;
LP=
lumbar puncture;
mTBI=
mild traumatic brain injury;
NFL=
neurofilament light;
PCS=
postconcussion symptoms;
RTP=
return to play;
SHL=
Swedish Hockey League;
TBI=
traumatic brain injury

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Editorial, page 1780

  • Received September 16, 2016.
  • Accepted in final form December 21, 2016.
  • © 2017 American Academy of Neurology
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