Metabolic abnormalities in perituberous tissue: initial results of a proton MR spectroscopy study of pediatric Tuberous Sclerosis Complex

INTRODUCTION: Tuberous Sclerosis Complex (TSC), a genetic disorder with an incidence as high as 1/5000, leads to benign tumors in multiple organ systems. It causes epilepsy, autism, and neurocognitive delays. If antiepileptic medication is ineffective, seizures can be abolished with resection surgery if the onset region can be localized. Traditionally, the MRI-defined tuber has been the primary surgery target, but non-tuberous tissue, specifically surrounding an active tuber, may also be epileptogenic. Evidence for this includes: (i) patients with persisting epilepsy after tuber resection have improved outcome if perituberous tissue is subsequently removed; (ii) animal models and human cases of TSC in which epilepsy occurs in the absence of tubers (1). In this study, tubers and normal-appearing tissue were characterized with proton MR spectroscopy (H-MRS) to test the hypotheses that (i) diffuse or (MR-invisible) focal metabolic changes extend beyond the tuber border; (ii) the epileptogenic zone, as defined by electro-encephalography (EEG), can be characterized by a unique metabolic profile (biomarker). Since the H-MRS was acquired prior to electrode placement and seizure loci cannot be predicted by MRI alone, comprehensive brain coverage was required for retrospective identification of EEG-active regions. To this end, we used three-dimensional H-MRS to sample a large (480 cc) volume-of-interest (VOI) at a 1 cc spatial resolution to assess neuronal health, membrane turnover and glial status via their metabolic surrogates N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI).