Neurofilament light and tau as blood biomarkers for sports-related concussion

Pashtun Shahim, Yelverton Tegner, Niklas Marklund, Kaj Blennow, Henrik Zetterberg, Pashtun Shahim, Yelverton Tegner, Niklas Marklund, Kaj Blennow, Henrik Zetterberg

Abstract

Objective: To compare neurofilament light (NfL) and tau as blood-based biomarkers for acute sports-related concussion (SRC) and determine whether their concentrations at different time points after the injury are associated with prolonged time to return to play (RTP).

Methods: A total of 288 professional hockey players were followed longitudinally from September 1, 2012, to April 30, 2015. Data collection and biomarker analyses were conducted between 2015 and 2017. Associations were tested between blood concentrations of NfL and tau, and RTP time. Serum concentrations of S100B and neuron-specific enolase (NSE) were also measured for comparison.

Results: Of 288 players, 105 sustained an SRC. Of these, 87 underwent blood sampling 1, 12, 36, and 144 hours after SRC and at the RTP time point. Serum NfL concentrations 1, 12, 36, and 144 hours after SRC were related to prolonged RTP time, and could separate players with RTP >10 days from those with RTP ≤10 days (area under the receiver operating characteristic curve [AUROC] 0.82). Also, serum NfL 144 hours after SRC discriminated players who resigned from the game due to persistent postconcussion symptoms (PCS) from those who returned to play (AUROC 0.89). Plasma tau 1 hour after SRC was related to RTP but less strongly than NfL, while S100B and NSE showed no such associations.

Conclusion: Serum NfL outperformed tau, S100B, and NSE as a biomarker for SRC. From a clinical standpoint, serum NfL may be useful to identify individuals at risk of prolonged PCS, and may aid in biomarker-informed decisions with regard to when RTP should be considered.

Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Figures

Figure 1. Screening and enrollment of study…
Figure 1. Screening and enrollment of study participants
RTP = return to play.
Figure 2. Effect of age on the…
Figure 2. Effect of age on the blood-based biomarkers
(A–C) Correlation between age and blood-based biomarkers in concussed athletes and preseason sample controls (both healthy controls and gymnasts). The ρ and p value are from the Spearman rank correlation. NfL = neurofilament light; NSE = neuron-specific enolase; S100B = S100 calcium-binding protein.
Figure 3. Temporal profile of the blood…
Figure 3. Temporal profile of the blood biomarkers in concussed professional hockey players
(A–D) Dynamic of blood neurofilament light (NfL), tau, S100 calcium-binding protein B (S100B), and neuron-specific enolase (NSE) in concussed professional hockey players measured at 1, 12, 36, and 144 hours, and when the players returned to play. The black dotted lines in each plot show the median of the preseason samples.
Figure 4. Prognostic utility of the biomarkers…
Figure 4. Prognostic utility of the biomarkers at selected time points after sports-related concussion (SRC)
(A) Area under the receiver operating characteristic curve (AUROC) for the biomarkers at 1 hour after SRC in players with return to play (RTP) >10 days vs RTP ≤10 days. (B) AUROC for the biomarkers at 144 hours after SRC in players with persistent postconcussion symptoms who eventually resigned vs players who could RTP. NfL = neurofilament light; NSE = neuron-specific enolase; S100B = S100 calcium-binding protein B.

References

    1. Warden D. Military TBI during the Iraq and Afghanistan wars. J Head Trauma Rehabil 2006;21:398–402.
    1. Williams WH, Potter S, Ryland H. Mild traumatic brain injury and postconcussion syndrome: a neuropsychological perspective. J Neurol Neurosurg Psychiatry 2010;81:1116–1122.
    1. Shitaka Y, Tran HT, Bennett RE, et al. . Repetitive closed-skull traumatic brain injury in mice causes persistent multifocal axonal injury and microglial reactivity. J Neuropathol Exp Neurol 2011;70:551–567.
    1. Mouzon BC, Bachmeier C, Ferro A, et al. . Chronic neuropathological and neurobehavioral changes in a repetitive mild traumatic brain injury model. Ann Neurol 2014;75:241–254.
    1. Shahim P, Tegner Y, Gustafsson B, et al. . Neurochemical aftermath of repetitive mild traumatic brain injury. JAMA Neurol 2016;73:1308–1315.
    1. Blennow K, Hardy J, Zetterberg H. The neuropathology and neurobiology of traumatic brain injury. Neuron 2012;76:886–899.
    1. Kinnunen KM, Greenwood R, Powell JH, et al. . White matter damage and cognitive impairment after traumatic brain injury. Brain 2011;134:449–463.
    1. Zetterberg H, Hietala MA, Jonsson M, et al. . Neurochemical aftermath of amateur boxing. Arch Neurol 2006;63:1277–1280.
    1. Blennow K, Brody DL, Kochanek PM, et al. . Traumatic brain injuries. Nat Rev Dis Primers 2016;2:16084.
    1. Ost M, Nylen K, Csajbok L, et al. . Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injury. Neurology 2006;67:1600–1604.
    1. Shahim P, Gren M, Liman V, et al. . Serum neurofilament light protein predicts clinical outcome in traumatic brain injury. Scientific Rep 2016;6:36791.
    1. Kuhle J, Barro C, Andreasson U, et al. . 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;54:1655–1661.
    1. Rojas JC, Karydas A, Bang J, et al. . Plasma neurofilament light chain predicts progression in progressive supranuclear palsy. Ann Clin Transl Neurol 2016;3:216–225.
    1. Shahim P, Tegner Y, Wilson DH, et al. . Blood biomarkers for brain injury in concussed professional ice hockey players. JAMA Neurol 2014;71:684–692.
    1. Wiley CA, Bonneh-Barkay D, Dixon CE, et al. . Role for mammalian chitinase 3-like protein 1 in traumatic brain injury. Neuropathol 2015;35:95–106.
    1. Bonneh-Barkay D, Zagadailov P, Zou H, et al. . YKL-40 expression in traumatic brain injury: an initial analysis. J Neurotrauma 2010;27:1215–1223.
    1. Shahim P, Tegner Y, Marklund N, et al. . Astroglial activation and altered amyloid metabolism in human repetitive concussion. Neurology 2017;88:1400–1407.
    1. Cifu DX, Walker WC, West SL, et al. . Hyperbaric oxygen for blast-related post-concussion syndrome: 3-month outcomes. Ann Neurol 2013;75:277–286.
    1. McCrory P, Meeuwisse WH, Aubry M, et al. . Consensus statement on concussion in sport: the 4th International Conference on concussion in sport held in Zurich, November 2012. Br J Sports Med 2013;47:250–258.
    1. Rissin DM, Kan CW, Campbell TG, et al. . Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat Biotechnol 2010;28:595–599.
    1. Mac Donald CL, Johnson AM, Cooper D, et al. . Detection of blast-related traumatic brain injury in U.S. military personnel. New Engl J Med 2011;364:2091–2100.
    1. Mattsson N, Andreasson U, Zetterberg H, Blennow K, Alzheimer's Disease Neuroimaging Initiative. Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol 2017;74:557–566.
    1. Shahim P, Zetterberg H, Tegner Y, Blennow K. Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports. Neurology 2017;88:1788–1794.
    1. Gill J, Merchant-Borna K, Jeromin A, Livingston W, Bazarian J. Acute plasma tau relates to prolonged return to play after concussion. Neurology 2017;88:595–602.
    1. Alosco ML, Tripodis Y, Jarnagin J, et al. . Repetitive head impact exposure and later-life plasma total tau in former National Football League players. Alzheimer's Demen 2017;7:33–40.
    1. Zetterberg H, Smith DH, Blennow K. Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood. Nat Rev Neurol 2013;9:201–210.
    1. Olivera A, Lejbman N, Jeromin A, et al. . Peripheral total tau in military personnel who sustain traumatic brain injuries during deployment. JAMA Neurol 2015;72:1109–1116.
    1. Routsi C, Stamataki E, Nanas S, et al. . Increased levels of serum S100B protein in critically ill patients without brain injury. Shock 2006;26:20–24.
    1. Stalnacke BM, Ohlsson A, Tegner Y, Sojka P. Serum concentrations of two biochemical markers of brain tissue damage S-100B and neurone specific enolase are increased in elite female soccer players after a competitive game. Br J Sports Med 2006;40:313–316.
    1. Hasselblatt M, Mooren FC, von Ahsen N, et al. . Serum S100beta increases in marathon runners reflect extracranial release rather than glial damage. Neurology 2004;62:1634–1636.

Source: PubMed

3
S'abonner