JOURNAL OF NEUROTRAUMA Volume 21, Number 11, 2004 © Mary Ann Liebert, Inc. Pp. 1539–1552 Proton MR Spectroscopy Detected Glutamate/Glutamine Is Increased in Children with Traumatic Brain Injury S. ASHWAL, 1 B. HOLSHOUSER, 2 K. TONG, 2 T. SERNA, 1 R. OSTERDOCK, 3 M. GROSS, 1 and D. KIDO 3 ABSTRACT Adults with traumatic brain injury (TBI) have been shown by invasive methods to have increased levels of the excitatory neurotransmitter glutamate. It is unclear whether glutamate release con- tributes to primary or secondary injury and whether its protracted elevation is predictive of a poor outcome. Preliminary studies at our institution in adults found that early increases in magnetic res- onance spectroscopy (MRS)–detected glutamate/glutamine (Glx) were associated with poor out- comes. We therefore studied 38 children (mean age, 11 years; range, 1.6–17 years) who had TBI with quantitative short-echo time (STEAM, TE  20 msec) proton MRS, a mean of 7  4 (range, 1–17) days after injury in order to determine if their occipital or parietal Glx levels correlated with the severity of injury or outcome. Occipital Glx was significantly increased in children with TBI compared to controls (13.5  2.4 vs. 10.7  1.8; p  0.002), but there was no difference between children with good compared to poor outcomes as determined by the Pediatric Cerebral Perfor- mance Category Scale score at 6–12 months after injury. We also did not find a correlation between the amount of Glx and the initial Glasgow Coma Scale score, duration of coma, nor with changes in spectral metabolites, including N-acetyl aspartate, choline, and myoinositol. In part, this may have occurred because, in this study, most patients with poor outcomes were studied later than patients with good outcomes, potentially beyond the time frame for peak elevation of Glx after injury. Ad- ditional early and late studies of patients with varying degrees of injury are required to assess the importance to the pathophysiology of TBI of this excitatory neurotransmitter. Key words: children; glutamate; infants; spectroscopy; traumatic brain injury 1539 Departments of 1 Pediatrics, 2 Radiology, and 3 Neurosurgery, Loma Linda University School of Medicine, Loma Linda, Cali- fornia. INTRODUCTION S ECONDARY INJURY after traumatic brain injury (TBI) is mediated by many mechanisms including the re- lease of excitatory amino acids (EAAs) such as glutamate and aspartate (Meldrum, 2001). Numerous studies in adults and one study in children have shown that ven- tricular cerebrospinal fluid (CSF) or brain extracellular fluid (ECF) glutamate levels are increased after TBI (Gopinath et al., 2000; Bullock et al., 1998; Ruppel et al., 2001). EAAs can cause cerebral edema with cell swelling, vacuolization, and neuronal death (Bullock et