Plasma Tumor Necrosis Factor Alpha Is a Predictor of Persisting Symptoms Post-Concussion in Children

Mild traumatic brain injury (mTBI)-associated blood proteomics have become an emerging focus in the past decade, with the U.S. Food and Drug Administration recently approving the use of a blood test to determine the necessity of a computed tomography scan after adult mTBI. We now also know that the blood proteome of children is different from that of adults, and new evidence suggests that children may take longer to recover from an mTBI. Despite this, comparatively fewer studies have analyzed changes in blood protein expression after pediatric mTBI. Concussions, an mTBI subset, often go underreported, despite the potential for post-concussive symptoms to last more than one month in up to 30% of children. In the current study, we used a multiplex immunoassay to measure blood protein expression of Apolipoprotein, enolase 2, glial fibrillary acidic protein, interleukin (IL)-1B, IL-6, IL-8, IL-10, S100 calcium-binding protein B, tau and tumor necrosis factor alpha (TNFα) at admission, one to four days, two weeks, and three months post-pediatric concussion, comparing patients with normal recovery (n = 9) with those with persisting symptoms (n = 9). We identified significant differences in IL-6 (p < 0.001) and tau (p = 0.048) protein expression across time post-injury irrespective of clinical outcome and in IL-8 protein expression (p = 0.041) across time post-injury specific to children with persisting symptoms. Significantly, we have identified an increase in TNFα protein expression at one to four days post-injury (p = 0.031) in children with persisting symptoms compared with normal recovery. To our knowledge, this is the first study to identify TNFα as a potential blood biomarker for persisting symptoms post-pediatric concussion.