Concussion Acutely Decreases Plasma Glycerophospholipids in Adolescent Male Athletes

Concussions are frequent in sports and can contribute to significant and long-lasting neurological disability. Adolescents are particularly susceptible to concussions, with accurate determination of the injury challenging. Our previous study demonstrated that concussion diagnoses could be aided by metabolomics profiling and machine learning, with particular weighting on changes in plasma glycerophospholipids (PCs). Here, our aim was to report directional change of PCs after concussion and develop a diagnostic concussion panel utilizing a minimum number of plasma PCs. To this end, we enrolled 12 concussed male athletes at our academic Sport Medicine Concussion Clinic, as well as 17 sex-, age-, and activity-matched healthy controls. Blood was drawn and 71 plasma PCs were measured for statistically significant changes within 72 h of injury, and individual PCs were further analyzed with receiver operating characteristic (ROC) curves. Our data demonstrated that 26 of 71 PCs measured were significantly decreased after sports-related concussion (p < 0.01). None of the PCs increased in plasma after concussion. ROC curve analyses identified the top four PCs with areas under the curve (AUCs) ≥0.86 for concussion diagnosis: PCaeC36:0 (0.92; p < 0.001); PCaaC42:6 (0.90; p < 0.001); PCaeC36:2 (0.86; p = 0.001), and PCaaC32:0 (0.86; p = 0.001). Cut-off values in μM were ≤0.31, 0.22, 5.07, and 4.63, respectively. Importantly, combining these four PCs produced an AUC of 0.96 for concussion diagnoses (p < 0.001; 95% confidence interval, 0.89, 1.00). Our data suggest that as few as four circulating PCs may provide excellent diagnostic potential for adolescent concussion. External validation is required in larger cohorts.