Although mild traumatic brain injury (mTBI), or concussion, is not typically associated with abnormalities on computed tomography (CT), it nevertheless causes persistent cognitive dysfunction for many patients. Consequently, new prognostic methods for mTBI are needed to identify at risk cases, especially at an early and potentially treatable stage. Here, we quantified plasma levels of the neurodegeneration biomarker calpain-cleaved αII-spectrin N-terminal fragment (SNTF) from 38 participants with CT-negative mTBI, orthopedic injury (OI), and normal uninjured controls (UCs) (age range 12–30 years), and compared them with findings from diffusion tensor imaging (DTI) and long-term cognitive assessment. SNTF levels were at least twice the lower limit of detection in 7 of 17 mTBI cases and in 3 of 13 OI cases, but in none of the UCs. An elevation in plasma SNTF corresponded with significant differences in fractional anisotropy and the apparent diffusion coefficient in the corpus callosum and uncinate fasciculus measured by DTI. Furthermore, increased plasma SNTF on the day of injury correlated significantly with cognitive impairment that persisted for at least 3 months, both across all study participants and also among the mTBI cases by themselves. The elevation in plasma SNTF in the subset of OI cases, accompanied by corresponding white matter and cognitive abnormalities, raises the possibility of identifying undiagnosed cases of mTBI. These data suggest that the blood level of SNTF on the day of a CT-negative mTBI may identify a subset of patients at risk of white matter damage and persistent disability. SNTF could have prognostic and diagnostic utilities in the assessment and treatment of mTBI.
Keywords: surrogate marker, concussion, calpain, DTI, spectrin, diffuse axonal injury, prognostic marker, cognitive impairment
Citation: Siman R, Giovannone N, Hanten G, Wilde EA, McCauley SR, Hunter JV, Li X, Levin HS and Smith DH (2013) Evidence that the blood biomarker SNTF predicts brain imaging changes and persistent cognitive dysfunction in mild TBI patients. Front. Neurol. 4:190. doi: 10.3389/fneur.2013.00190
Received: 02 October 2013; Paper pending published: 27 October 2013;
Accepted: 04 November 2013; Published online: 18 November 2013.
Edited by:Firas H. Kobeissy, University of Florida, USA
Reviewed by:Deborah Shear, Walter Reed Army Institute of Research, USA
Copyright: © 2013 Siman, Giovannone, Hanten, Wilde, McCauley, Hunter, Li, Levin and Smith. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Robert Siman, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 502 Stemmler Hall, 36th and Hamilton Walk, Philadelphia, PA 19104, USA e-mail: email@example.com