Original ContributionSerum cleaved tau does not predict postconcussion syndrome after mild traumatic brain injury☆
Introduction
Annually, more than 1.2 million cases of mild traumatic brain injury (mTBI) are evaluated in US emergency departments (EDs) [1]. The prevalence of postconcussion syndrome (PCS) at 3 months post injury ranges from 24% to 84% [2]. Symptoms of PCS may be physical (headache and dizziness), cognitive (memory deficit and diminished concentration), or affective (anxiety and depression). Physicians currently have no readily available or reliable method for identifying those mTBI patients who will develop PCS. Early identification and treatment of PCS may be beneficial [3].
Several central nervous system (CNS) biomarkers have been studied as potential tools to predict PCS after mTBI with equivocal success. The most widely studied biomarker to date has been S-100B, which is localized to astroglial cells. Some studies have detected a relationship between serum levels of S-100B and patient outcome [4], [5], whereas others have not [1], [6], [7]. There are 2 published studies on acute serum levels of tau, a microtubule-associated structural protein localized to axons, after mTBI. There was no statistical difference between serum tau levels in mTBI patients compared to controls [8]. Serum tau levels after mTBI did not correlate with intracranial abnormalities on head computed tomography (CT) [8], [9].
Cleaved tau (C-tau) may represent a new biomarker for predicting PCS. Tau is proteolytically modified after axonal injury, and this cleavage product is known as C-tau. Serum C-tau levels may reflect CNS injury better than total tau levels. As axonal damage is also thought to underlie the neurologic dysfunction seen after mTBI, C-tau may have theoretical advantages over other CNS biomarkers. A previous report has shown that serum C-tau levels were predictive of intracranial injury and outcome after moderate and severe traumatic brain injury [10]. One small study of 35 mTBI patients did not find an association between serum C-tau levels and severity of 3-month PCS symptoms [1]. Our study extends their findings by considering 2 other clinically important outcomes, radiographically apparent intracranial injury and global health status. In addition to causing PCS symptoms, mTBI is known to adversely affect multiple health domains [11].
The objective of this preliminary study was to test our hypothesis that post-mTBI serum C-tau levels are elevated in those with radiographically apparent intracranial abnormalities, PCS, and worse health-related quality of life. If C-tau demonstrates acceptable sensitivity and specificity for intracranial injury, this assay may allow physicians to be more selective with use of intracranial imaging after mTBI. In addition, if serum C-tau can reliably predict PCS, early identification and treatment of patients at high risk for PCS may reduce morbidity.
Section snippets
Study design
We performed a prospective observational study of adults presenting to an urban level I trauma center after mTBI. The study was approved by the institutional review board.
Study setting and population
The study was conducted at an urban tertiary care hospital with an annual census of about 85 000 visits. The hospital is an American College of Surgeons level 1 trauma center.
A convenience sample of patients was enrolled between October 2003 and May 2004. Patients 18 years or older were included if they had recent mTBI, defined
Results
Fifty patients were enrolled. Age, race, sex, and mechanism of injury are described in Table 1, stratified by whether serum C-tau was detected. There were 15 patients with detectable levels of C-tau (30.0%; 95% CI, 18.3%-44.8%). Of these 15 patients, the mean serum C-tau concentration was 5.02 ng/mL (SD, 2.98 ng/mL). The time from injury to measurement of C-tau was similar between groups (Table 1).
Fourteen percent of patients with a GCS of 15 and 35.7% of patients with a GCS of 13 or 14 had at
Discussion
Despite an absolute difference of 19% between head CT abnormalities in patients with and without detectable C-tau, this result was not statistically significant. A larger sample size may better elucidate an association, if any. As tau is localized to axons, serum C-tau levels may correlate better with axonal injury, which is not readily detectable by CT. In our study, axonal injury was detected by CT in 1 patient who had a serum C-tau level of 4.98 ng/mL. White matter injury revealed by
Acknowledgment
The authors thank Robert Neumar, MD, PhD, for his insight in editing the manuscript.
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Research supported by National Institutes of Health grant R43-NS46822 (FPZ).
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Dr Ma was previously with the Department of Emergency Medicine, University of Cincinnati, Cincinnati, Ohio.