CN-01EVIDENCE FOR ACTIVE GLYCOLYSIS IN THE WHITE MATTER OF AN ADULT SURVIVOR OF A PEDIATRIC BRAIN TUMOR WITH LONG-TERM TREATMENT-RELATED BRAIN INJURY

BACKGROUND: Mitigating long-term treatment-related effects in survivors of pediatric brain tumors is hampered, in part, by a long clinical prodrome, ill-defined diagnostic criteria, and reliance on indirect observations of the brain. Recently, oxidative stress has been associated with several forms of brain injury. The brain's response to increased oxidative stress includes, in part, a shift from oxidative phosphorylation to glycolysis for its ATP production. We investigated if lactate, a product of glycolysis, was increased in the brain of a patient with treatment-related brain injury via magnetic resonance spectroscopy (MRS). METHODS: A 24 year-old patient treated for a mixed germ cell tumor at the age of 17 with a standard protocol including high-dose chemotherapy, hematopoietic progenitor cell rescue, and irradiation developed evidence of treatment-related brain injury 6 years later. MRS was performed on abnormal-appearing white matter before and serially over 100 minutes after oral administration of 13Carbon-labeled glucose. RESULTS: MRS of abnormal-appearing parietal white matter demonstrated inverted choline:creatine ratio, decreased levels of N-acetyl aspartate, and elevated levels of lactate when compared to historical age-matched controls. Subsequent spectra obtained over the course of 100 minutes following administration of 13Carbon-labeled glucose demonstrated a linear decrease in the concentration of native 12Carbon lactate (slope = -0.003, R2 = 0.51, p = 0.006). CONCLUSIONS: The metabolite profile of the abnormal white matter was not consistent with a non-metabolically active pool or necrosis. The real-time decrease of observed 12Carbon lactate indicated the active production of 13Carbon lactate following oral 13Carbon-labeled glucose administration. To our knowledge, this is the most direct evidence of active glycolysis in the abnormal-appearing white matter in a survivor of a pediatric brain tumor with treatment-related brain injury. Thus, the detection of active glycolysis by increased concentrations of lactate may indicate a compensatory mechanism of neurons under increased oxidative stress and serve as a potential biomarker for this injury.