Quesolinic acid in cerebrosplnal fluid of children after traumatic brain injury: a preliminary report

Introduction: Quinolinic acid (QUIN) is a tryptophan-denved N'MDA agonist produced by macrophages during CNS infection and injury'. QUIN progressively increases in cerebrospinal fluid (CSF) in adults after traumatic brain injury (TBI) and is associated with mortality2. This is the first report of CSF QUIN concentration in children after TBI. Methods: Samples of ventricular CSF were obtained from 17 children (age 2 mo16 y) after severe TBI (GCS < 8). QUIN was measured on admission and then daily for up to 7 d after TBI by gas chromatography and mass spectroscopy Univahate and muta'variate analyses were performed to assess CSF QUIN and clinical variables including time, mortality and age. Results: The normal range for CSF QUIN in children is 5-25 nM. There were 5 non-survivors and 12 survivors. There was progressive increase in CSF QUIN after injury (p = 0.03 for time effect, univariate analysis) and CSF QUIN was increased in non-survivors vs. survivors (mean ±SEM, 391.5 nM 199.7 vs. 66.8 nM ±16.2, p = 0.002, multivariate analysis). After admission, CSF QUIN was greater than tne upper limit of normal in all samples from non-survivors. CSF QUIN was not associated with age. Conclusions: A large and progressive increase in the inflammation-derived neurotoxin QUIN is seen following severe TBI in children. The increase is strongly associated with increased mortality. These data raise the possibility mat OLTN mav olav a role in secondary iniurv after TBI in children. 'Heves et al. 1992; 2 Sinz et al, 1997.