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.3- 5 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.
Shahim P, Blennow K, Zetterberg H. Tau, S-100 Calcium-Binding Protein B, and Neuron-Specific Enolase as Biomarkers of Concussion—Reply. JAMA Neurol. 2014;71(7):926-927. doi:10.1001/jamaneurol.2014.1160