SINGLE-VOXEL H1 MR SPECTROSCOPY OF NORMAL APPEARING WHITE MATTER IN PATIENTS WITH TUBEROUS SCLEROSIS

Objectives: Tuberous Sclerosis Complex (TSC) is a congenital disease transmitted by autosomal dominant inheritance, with variable expression in multiple organs. CNS lesions include cortical tubers, subependymal nodules, subependymal giant cell astrocytomas, and heterotopic neurons in the white matter (WM). Although microscopic lesions of WM are not depicted by conventional MR imaging, statistically significant changes of normal appearing white matter (NAWM) have been demonstrated by diffusion MRI. The present study was designed to determine the spectroscopic features of NAWM and to test the hypothesis that MR proton spectra of NAWM is abnormal, because of clusters of dysplastic cells invariably present in the white matter of TSC patients.

Methods: 10 patients with TSC and 10 age-matched control subjects underwent proton MR spectroscopy (MRS) with a single-voxel point-resolved spectroscopy pulse sequence. Voxels (8 cm3) were placed in the NAWM of the centrum semiovale bilaterally. N-acetylaspartate (NA)/creatine (Cr) and choline (Cho)/Cr ratios were assessed.

Results: compared with control subjects, TSC patients showed statistically increased NA/Cr (1.87 vs. 2.23) and NA/(Cho+Cr) ratios (0.94 vs. 1.03) in the NAWM. An increase in the Cho/Cr ratio was also observed between the controls and TSC group (0.98 vs. 1.16).

Conclusion: in TSC proton MRS depicted abnormalities in the NA/Cr and NA/Cho ratios in the normal-appearing white matter suggesting that brain alterations may be more diffuse than expected. MRS may play a role in the estimation of white matter disorganization in TSC. Further studies are needed to determine if abnormalities detected by proton MRS might represent a neuroimaging marker to understand the phenotypic variation in TSC patients and to assess the functional outcome.