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Comment & Response |

Tau, S-100 Calcium-Binding Protein B, and Neuron-Specific Enolase as Biomarkers of Concussion—Reply

Pashtun Shahim, MD1; Kaj Blennow, MD, PhD1; Henrik Zetterberg, MD, PhD1,2
[+] Author Affiliations
1Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden
2Reta Lila Weston Laboratories, Department of Molecular Neuroscience, University College London Institute of Neurology, London, England
JAMA Neurol. 2014;71(7):926-927. doi:10.1001/jamaneurol.2014.1160.
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In Reply We thank Bazarian and Merchant-Borna for their comment on our article,1 suggesting that we should have interpreted the S-100 calcium-binding protein B (S-100B) and neuron-specific enolase (NSE) data in our study more positively than we did. We wish to clarify that we maintain our conclusion about the limited diagnostic value of S-100B and NSE in the context of mild traumatic brain injury (mTBI) for the following reasons: (1) the magnitude of the biomarker changes following concussion was higher for T-tau than for S-100B and NSE, (2) the levels of S-100B and NSE, but not T-tau, increased after a friendly game without concussion compared with baseline samples from the same individuals, and (3) postconcussion T-tau levels were more strongly associated with concussion severity than S-100B and NSE. An additional drawback with S-100B and NSE is that both of these proteins are expressed in extracerebral tissues,2 which may explain the increases we observed after a friendly game. In agreement, several studies have found increased serum levels of S-100B in the absence of head injury in soccer players, marathon runners, and patients with peripheral trauma.35 Neuron-specific enolase is also released in the blood by hemolysis, which may be a serious source of error in some cases. Finally, only 5 of the 28 concussed ice hockey players had S-100B elevations above the cutpoint suggested by Undén et al6 in their consensus statement on guidelines for the initial management of mTBI.


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July 1, 2014
Jeffrey J. Bazarian, MD, MPH; Kian Merchant-Borna, MPH
1Department of Emergency Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York
JAMA Neurol. 2014;71(7):925-926. doi:10.1001/jamaneurol.2014.1082.
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