Brain creatine concentrations are associated with sex and symptom severity after concussion: a cross-sectional MR-spectroscopy investigation of adolescents with concussion

Post-concussion brain energy is important for recovery, and measuring energy markers with individual characteristics may clarify recovery mechanisms. To examine the association between magnetic resonance spectroscopy (MRS)-based brain energy measures (creatine concentration) with sex and patient-reported outcomes after concussion. We evaluated adolescents with a concussion ≤3 weeks post-injury. Participants underwent 3T short-echo single-voxel MRS using a 32-channel head coil. Point-resolved spectroscopy (TR = 2000 ms, TE = 30 ms, voxel size = 20 × 20 × 20 mm3, 128 averages) quantified posterior cingulate gyrus (PCG) creatine concentration. Participants completed Post-Concussion Symptom Inventory and PROMIS Pediatric Global 25 mobility, fatigue, and pain-interference domains. N = 27 adolescents (N = 15 female, age = 15.8 ± 1.2 years, 11.5 ± 4.4 days after concussion; N = 12 male, age = 15.8 ± 1.5 years, 11.9 ± 4.0 days after concussion) participated. Male participants had greater PCG creatine concentrations than female participants (12.9 ± 0.41 vs. 12.3 ± 0.71 mmol; p = 0.01; d = 1.07). Creatine concentrations were correlated with concussion symptom severity (r = −0.61; p < 0.001), mobility impairments (r = −0.57; p = 0.003), and pain interference (r = −0.40; p = 0.02). Post-concussion sex differences in creatine concentrations were detected, as higher creatine levels moderately correlated with patient-reported outcomes. Creatine may reflect altered energy dynamics in the brain. The absence of a non-injured control group limits determination of whether these differences are concussion-specific or reflective of baseline physiology.