Quantitative analysis of neurometabolites in adolescents with persistent symptoms following concussion using magnetic resonance spectroscopy

Abstract

There is great interest in developing physiologic markers of persistent concussion symptoms (PCS) that can occur following mild traumatic brain injury (mTBI). Magnetic resonance spectroscopy (MRS) can non-invasively measure changes in brain metabolism and is directly translatable to clinical application. Previous studies have shown that mTBI is associated with decreases in N-acetylaspartate (NAA), though most prior work has focused on adults. In this pilot project, we hypothesized that adolescents with PCS would have decreased NAA in frontal white matter (FWM) and the anterior cingulate cortex (ACC) relative to adolescents without PCS. Twenty-two patients (14–18 years old) with persistent symptoms following sport or recreation-related concussion (PCS+) were recruited from a concussion clinic and assessed at least 4-week post-injury. Twenty-one adolescents with varying concussion history but without PCS served as controls (PCS−). Exclusion criteria included current or prior moderate/severe TBI, neurodevelopmental disorder, or psychiatric disorder unrelated to current injury. Participants completed a clinical assessment battery that included self-reported concussion and psychiatric symptoms and neurocognitive testing. MRS was performed in the ACC and right FWM using a PRESS sequence on a GE 3T scanner. Spectra were analyzed using LCModel to calculate metabolite levels. Independent samples t -tests were used to compare groups, with apriori analyses focused on NAA, NAA plus N-acetylaspartylglutamic acid (total NAA), and combined glutamate and glutamine (Glx). PCS+ showed significant elevations in concussion and psychiatric symptoms as well as decreased neurocognitive performance compared to controls ( p = 0.05). In addition, PCS+ had a significant decrease in total NAA ( p = 0.012) and a non-significant decrease in NAA ( p = 0.057) in the FWM when compared to PCS−. No differences between groups were seen in the ACC ( p = 0.1). Our results suggest a relationship between PCS in adolescents and decreased total NAA in frontal white matter. Additional analyses investigating the relationship between neuro metabolites and clinical measures are underway.