A New Panel of Blood Biomarkers for the Diagnosis of Mild Traumatic Brain Injury/Concussion in Adults

No routine tests currently exist to objectively diagnose mild traumatic brain injury (mTBI)/concussion. Previously reported biomarkers for mTBI represented proteins released from damaged neurons or glia. However, low levels of these proteins, and/or the complexity of assays used for their detection, limits implementation of these biomarkers in routine practice. Here, we sought to identify proteins whose synthesis is altered post-mTBI and whose blood levels could be measured using standard immunoassays. Adult patients sustaining a concussion within the past 24h were enrolled. Controls were uninjured subjects and patients with orthopedic injury (OI). Four candidate biomarkers were identified: copeptin; galectin 3 (LGALS3); matrix metalloproteinase 9 (MMP9); and occludin (OCLN). A 3.4-fold decrease (p<0.0001) in plasma concentration of copeptin was found in mTBI patients within 8h after accident, compared to uninjured controls. Plasma levels of LGALS3, MMP9, and OCLN increased 3.6- to 4.5-fold (p<0.0001) within the same time frame postinjury. Levels of at least two biomarkers were altered beyond their respective cut-off values in 90% of mTBI patients, whereas in none of uninjured controls were levels of two biomarkers simultaneously changed. A positive correlation (r=0.681; p<0.001) between plasma levels of LGALS3 and OCLN was also found in mTBI patients, whereas in OI patients or uninjured subjects, these variables did not correlate. This panel of biomarkers discerns, with high accuracy, patients with isolated concussion from uninjured individuals within the first 8h after accident. These biomarkers can also aid in diagnosing concussion in the presence of OI.