Mapping Brain Metabolites in Tuberous Sclerosis Complex: A 3T MR Spectroscopic Imaging Study.

BACKGROUND AND PURPOSE: Tuberous sclerosis complex (TSC) is a genetic disorder that affects multiple organs, particularly the brain, and is associated with neurologic impairments such as cognitive deficits and seizures. There are relatively few prior studies investigating brain metabolites in TSC. The aim of this study was to investigate neurochemical alterations in TSC, focusing on cortical/subcortical glioneuronal tubers as well as normal-appearing regions, and comparing them with matched healthy control subjects.

MATERIALS AND

METHODS

The study included 19 subjects with TSC (mean, 15.9 [SD, 9.5] years), and 33 age- and sex-matched healthy controls (mean, 19.7 [SD, 8.2] years). Multislice 2D-MR spectroscopic imaging was used for quantification of metabolites, including total N-acetylaspartate (tNAA), choline (tCho), creatine (tCr), glutamate and glutamine (Glx) and myo-inositol (mI) in both tubers and normal-appearing brain regions in individuals with TSC and comparing them with those in control subjects. Metabolite ratios were also examined for correlation with age.

RESULTS

mI/tCr was significantly elevated in TSC compared with controls in WM, GM, and tubers (P < .05 or better). In addition, both tNAA/tCr and tCho/tCr were decreased in tubers and in normal-appearing WM compared with controls (P < .001). Finally, Glx/tCr was elevated in tubers compared with controls (P < .05), and individuals with TSC did not exhibit age-related Glx/tCr decreases that were observed in controls in both GM and WM.

CONCLUSIONS

Subtle, but significant metabolic abnormalities were found for subjects with TSC compared with healthy controls, both in tubers and in normal-appearing brain regions. The variation of metabolite levels as a function of age also differed between TSC and controls. These findings may provide information on the underlying pathophysiology of TSC, and future work is needed to investigate the relationships of these findings to neurologic symptoms, including seizures and cognitive impairment.