Patients with a history of mild (n = 134) or moderate-to-severe (n = 91) TBI were asked to complete the Neurobehavioral Symptom Inventory (NSI) and the Posttraumatic Stress Disorder Checklist. Consistent with prior research, significantly more postconcussion symptoms were endorsed by the mild group. After controlling for age, time since injury, and mechanism of injury, TBI severity continued to be significantly related to postconcussion complaints on the NSI. However, after controlling for these same variables, along with posttraumatic stress disorder symptom severity, there no longer were differences between the TBI severity groups. That is, patients with mild TBI did not endorse significantly more complaints (adjusted mean = 22.4) than the moderate-to-severe group (adjusted mean = 21.8). These findings suggest that much of the symptom complaints in mildly injured patients may be due to emotional distress.
IMPORTANCE Approximately one-third of military personnel who deploy for combat operations sustain 1 or more traumatic brain injuries (TBIs), which increases the risk for chronic symptoms of postconcussive disorder, posttraumatic stress disorder, and depression and for the development of chronic traumatic encephalopathy. Elevated concentrations of tau are observed in blood shortly following a TBI, but, to our knowledge, the role of tau elevations in blood in the onset and maintenance of chronic symptoms after TBI has not been investigated.OBJECTIVES To assess peripheral tau levels in military personnel exposed to TBI and to examine the relationship between chronic neurological symptoms and tau elevations.
DESIGN, SETTING, AND PARTICIPANTSObservational assessment from September 2012 to August 2014 of US military personnel at the Madigan Army Medical Center who had been deployed within the previous 18 months. Plasma total tau concentrations were measured using a novel ultrasensitive single-molecule enzyme-linked immunosorbent assay. Classification of participants with and without self-reported TBI was made using the Warrior Administered Retrospective Casualty Assessment Tool. Self-reported symptoms of postconcussive disorder, posttraumatic stress disorder, and depression were determined by the Neurobehavioral Symptom Inventory, the Posttraumatic Stress Disorder Checklist Military Version, and the Quick Inventory of Depressive Symptomatology, respectively. Group differences in tau concentrations were determined through analysis of variance models, and area under the receiver operating characteristic curve determined the sensitivity and specificity of tau concentrations in predicting TBI and chronic symptoms. Seventy participants with self-reported TBI on the Warrior Administered Retrospective Casualty Assessment Tool and 28 control participants with no TBI exposure were included.
MAIN OUTCOMES AND MEASURES Concentration of total tau in peripheral blood.RESULTS Concentrations of plasma tau were significantly elevated in the 70 participants with self-reported TBI compared with the 28 controls (mean [SD], 1.13 [0.78] vs 0.63 [0.48] pg/mL, respectively; F 1,97 = 4.97; P = .03). Within the self-reported TBI cases, plasma total tau concentrations were significantly associated with having a medical record of TBI compared with self-reported TBI only (mean [SD], 1.57 [0.92] vs 0.85 [0.52] pg/mL, respectively; F 1,69 = 6.15; P = .02) as well as reporting the occurrence of 3 of more TBIs during deployment compared with fewer than 3 TBIs (mean [SD], 1.52 [0.82] vs 0.82 [0.60] pg/mL, respectively; F 1,69 = 8.57; P = .008). The severity of total postconcussive symptoms correlated with total tau concentrations in the self-reported TBI group (r = 0.37; P = .003).
CONCLUSIONS AND RELEVANCEMilitary personnel who report multiple TBIs have long-term elevations in total tau concentration. The total tau concentration relates to symptoms of postconcussive disorder.
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