Monitoring concussion in a knocked-out boxer by CSF biomarker analysis

Abstract

Concussion is common in many sports, and the incidence is increasing. The medical consequences after a sport-related concussion have received increased attention in recent years since it is known that concussions cause axonal and glial damage, which disturbs the cerebral physiology and makes the brain more vulnerable for additional concussions. This study reports on a knocked-out amateur boxer in whom cerebrospinal fluid (CSF) neurofilament light (NFL) protein, reflecting axonal damage, was used to identify and monitor brain damage. CSF NFL was markedly increased during 36 weeks, suggesting that neuronal injury persists longer than expected after a concussion. CSF biomarker analysis may be valuable in the medical counselling of concussed athletes and in return-to-play considerations.

Level of evidence IV

This is a preview of subscription content, access via your institution.

Fig. 1

References

  1. 1.

    Andreasen N, Minthon L, Vanmechelen E, Vanderstichele H, Davidsson P, Winblad B, Blennow K (1999) Cerebrospinal fluid tau and Abeta42 as predictors of development of Alzheimer’s disease in patients with mild cognitive impairment. Neurosci Lett 273(1):5–8

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Blennow K, Fredman P, Wallin A, Gottfries CG, Karlsson I, Langstrom G, Skoog I, Svennerholm L, Wikkelso C (1993) Protein analysis in cerebrospinal fluid. II. Reference values derived from healthy individuals 18–88 years of age. Eur Neurol 33(2):129–133

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Blennow K, Hardy J, Zetterberg H (2012) The neuropathology and neurobiology of traumatic brain injury. Neuron 76(5):886–899

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Blennow K, Wallin A, Agren H, Spenger C, Siegfried J, Vanmechelen E (1995) Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease? Mol Chem Neuropathol 26(3):231–245

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    DeKosky ST, Blennow K, Ikonomovic MD, Gandy S (2013) Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers. Nat Rev Neurol 9(4):192–200

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  6. 6.

    Guskiewicz KM, McCrea M, Marshall SW, Cantu RC, Randolph C, Barr W, Onate JA, Kelly JP (2003) Cumulative effects associated with recurrent concussion in collegiate football players: the NCAA Concussion Study. JAMA 290(19):2549–2555

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    McCrory P, Meeuwisse WH, Aubry M, Cantu B, Dvorak J, Echemendia RJ, Engebretsen L, Johnston K, Kutcher JS, Raftery M, Sills A, Benson BW, Davis GA, Ellenbogen RG, Guskiewicz K, Herring SA, Iverson GL, Jordan BD, Kissick J, McCrea M, McIntosh AS, Maddocks D, Makdissi M, Purcell L, Putukian M, Schneider K, Tator CH, Turner M (2013) Consensus statement on concussion in sport: the 4th International conference on concussion in sport held in Zurich, November 2012. Br J Sports Med 47(5):250–258

    Article  PubMed  Google Scholar 

  8. 8.

    Neselius S, Brisby H, Theodorsson A, Blennow K, Zetterberg H, Marcusson J (2012) CSF-biomarkers in Olympic boxing: diagnosis and effects of repetitive head trauma. PLoS ONE 7(4):e33606

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  9. 9.

    Neselius S, Zetterberg H, Blennow K, Marcusson J, Brisby H (2013) Increased CSF levels of phosphorylated neurofilament heavy protein following bout in amateur boxers. PLoS ONE 8(11):e81249

    PubMed Central  Article  PubMed  Google Scholar 

  10. 10.

    Norgren N, Rosengren L, Stigbrand T (2003) Elevated neurofilament levels in neurological diseases. Brain Res 987(1):25–31

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Petzold A, Michel P, Stock M, Schluep M (2008) Glial and axonal body fluid biomarkers are related to infarct volume, severity, and outcome. J Stroke Cerebrovasc Dis 17(4):196–203

    Article  PubMed  Google Scholar 

  12. 12.

    Rosengren LE, Ahlsen G, Belfrage M, Gillberg C, Haglid KG, Hamberger A (1992) A sensitive ELISA for glial fibrillary acidic protein: application in CSF of children. J Neurosci Methods 44(2–3):113–119

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Rosengren LE, Karlsson JE, Karlsson JO, Persson LI, Wikkelso C (1996) Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF. J Neurochem 67(5):2013–2018

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Shahani N, Brandt R (2002) Functions and malfunctions of the tau proteins. Cell Mol Life Sci 59(10):1668–1680

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Slobounov S, Slobounov E, Sebastianelli W, Cao C, Newell K (2007) Differential rate of recovery in athletes after first and second concussion episodes. Neurosurgery 61(2):338–344

    Article  PubMed  Google Scholar 

  16. 16.

    Vanmechelen E, Vanderstichele H, Davidsson P, Van Kerschaver E, Van Der Perre B, Sjogren M, Andreasen N, Blennow K (2000) Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization. Neurosci Lett 285(1):49–52

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Zetterberg H, Hietala MA, Jonsson M, Andreasen N, Styrud E, Karlsson I, Edman A, Popa C, Rasulzada A, Wahlund LO, Mehta PD, Rosengren L, Blennow K, Wallin A (2006) Neurochemical aftermath of amateur boxing. Arch Neurol 63(9):1277–1280

    Article  PubMed  Google Scholar 

  18. 18.

    Zetterberg H, Smith DH, Blennow K (2013) Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood. Nat Rev Neurol 9(4):201–210

    PubMed Central  CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study has been funded by Swedish Research Council, the Knut and Alice Wallenberg Foundation and Swedish State Support for Clinical Research.

Conflict of interest

The authors declare that there is no conflict of interest.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Sanna Neselius.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Neselius, S., Brisby, H., Granholm, F. et al. Monitoring concussion in a knocked-out boxer by CSF biomarker analysis. Knee Surg Sports Traumatol Arthrosc 23, 2536–2539 (2015). https://doi.org/10.1007/s00167-014-3066-6

Download citation

Keywords

  • Concussion
  • Traumatic brain injury (TBI)
  • Mild traumatic brain injury
  • Boxing