Serum Neurofilament Light As a Biomarker for Mild Traumatic Brain Injury in Contact Sports

Overview

Journal Neurology

Specialty Neurology

Date 2017 Apr 14

PMID 28404801

Citations 156

Authors

Pashtun Shahim

Henrik Zetterberg

Yelverton Tegner

Kaj Blennow

Affiliations

Soon will be listed here.

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 ( = 0.0007 and < 0.0001, respectively). NFL decreased following 3 months of rest, but was still higher than in controls ( < 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 ( = 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.

Citing Articles

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References

Shitaka Y, Tran H, Bennett R, Sanchez L, Levy M, Dikranian K . Repetitive closed-skull traumatic brain injury in mice causes persistent multifocal axonal injury and microglial reactivity. J Neuropathol Exp Neurol. 2011; 70(7):551-67. PMC: 3118973. DOI: 10.1097/NEN.0b013e31821f891f. View

Zetterberg H, Smith D, Blennow K . Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood. Nat Rev Neurol. 2013; 9(4):201-10. PMC: 4513656. DOI: 10.1038/nrneurol.2013.9. View

Johnson V, Stewart W, Smith D . Axonal pathology in traumatic brain injury. Exp Neurol. 2012; 246:35-43. PMC: 3979341. DOI: 10.1016/j.expneurol.2012.01.013. View

Shahim P, Tegner Y, Wilson D, Randall J, Skillback T, Pazooki D . Blood biomarkers for brain injury in concussed professional ice hockey players. JAMA Neurol. 2014; 71(6):684-92. DOI: 10.1001/jamaneurol.2014.367. View

Shahim P, Gren M, Liman V, Andreasson U, Norgren N, Tegner Y . Serum neurofilament light protein predicts clinical outcome in traumatic brain injury. Sci Rep. 2016; 6:36791. PMC: 5098187. DOI: 10.1038/srep36791. View

Neselius S, Brisby H, Theodorsson A, Blennow K, Zetterberg H, Marcusson J . CSF-biomarkers in Olympic boxing: diagnosis and effects of repetitive head trauma. PLoS One. 2012; 7(4):e33606. PMC: 3319096. DOI: 10.1371/journal.pone.0033606. View

Gisslen M, Price R, Andreasson U, Norgren N, Nilsson S, Hagberg L . Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study. EBioMedicine. 2016; 3:135-140. PMC: 4739412. DOI: 10.1016/j.ebiom.2015.11.036. View

Zetterberg H, Hietala M, Jonsson M, Andreasen N, Styrud E, Karlsson I . Neurochemical aftermath of amateur boxing. Arch Neurol. 2006; 63(9):1277-80. DOI: 10.1001/archneur.63.9.1277. View

Norgren N, Rosengren L, Stigbrand T . Elevated neurofilament levels in neurological diseases. Brain Res. 2003; 987(1):25-31. DOI: 10.1016/s0006-8993(03)03219-0. View

10.

Rissin D, Kan C, Campbell T, Howes S, Fournier D, Song L . Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat Biotechnol. 2010; 28(6):595-9. PMC: 2919230. DOI: 10.1038/nbt.1641. View

11.

McCrory P, Meeuwisse W, Aubry M, Cantu B, Dvorak J, Echemendia R . Consensus statement on concussion in sport: the 4th International Conference on Concussion in Sport held in Zurich, November 2012. Br J Sports Med. 2013; 47(5):250-8. DOI: 10.1136/bjsports-2013-092313. View

12.

Williams W, Potter S, Ryland H . Mild traumatic brain injury and Postconcussion Syndrome: a neuropsychological perspective. J Neurol Neurosurg Psychiatry. 2010; 81(10):1116-22. DOI: 10.1136/jnnp.2008.171298. View

13.

Lu C, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N . Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis. Neurology. 2015; 84(22):2247-57. PMC: 4456658. DOI: 10.1212/WNL.0000000000001642. View

14.

Al Nimer F, Thelin E, Nystrom H, Dring A, Svenningsson A, Piehl F . Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light. PLoS One. 2015; 10(7):e0132177. PMC: 4489843. DOI: 10.1371/journal.pone.0132177. View

15.

Ellenbogen R, Berger M, Batjer H . The National Football League and concussion: leading a culture change in contact sports. World Neurosurg. 2011; 74(6):560-5. DOI: 10.1016/j.wneu.2010.11.016. View

16.

Ljungqvist J, Zetterberg H, Mitsis M, Blennow K, Skoglund T . Serum Neurofilament Light Protein as a Marker for Diffuse Axonal Injury: Results from a Case Series Study. J Neurotrauma. 2016; 34(5):1124-1127. DOI: 10.1089/neu.2016.4496. View

17.

Baugh C, Stamm J, Riley D, Gavett B, Shenton M, Lin A . Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging Behav. 2012; 6(2):244-54. DOI: 10.1007/s11682-012-9164-5. View

18.

Corsellis J, Bruton C . The aftermath of boxing. Psychol Med. 1973; 3(3):270-303. DOI: 10.1017/s0033291700049588. View

19.

Marmarou C, Walker S, Davis C, Povlishock J . Quantitative analysis of the relationship between intra- axonal neurofilament compaction and impaired axonal transport following diffuse traumatic brain injury. J Neurotrauma. 2005; 22(10):1066-80. DOI: 10.1089/neu.2005.22.1066. View

20.

Kuhle J, Barro C, Andreasson U, Derfuss T, Lindberg R, Sandelius A . Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa. Clin Chem Lab Med. 2016; 54(10):1655-61. DOI: 10.1515/cclm-2015-1195. View