MR spectroscopic imaging of normal-appearing white matter in adrenoleukodystrophy

Background. Adrenoleukodystrophy (ALD) is characterised by wide phenotypic variation, and there is no marker to predict the onset of cerebral demyelination. The indications for therapeutic approaches depend largely on the onset of cerebral demyelination.¶Objective. To evaluate the brain spectroscopic pattern in normal-appearing white matter (NAWM) in patients with various phenotypes of ALD to determine if these abnormalities could be of useful prognostic value.¶Materials and methods. Spectroscopic imaging acquisition mode (MRSI, 16 × 16 voxels) was performed in 20 patients with ALD, including 7 neurologically asymptomatic patients without detectable demyelination on MRI, 3 patients with early signs of cerebral demyelination, 8 patients with adrenomyeloneuropathy (AMN) and 2 patients with cerebral ALD who had previously undergone bone marrow transplantation. Controls were 22 healthy subjects. In all patients, four voxels entirely located in the juxtaventricular NAWM were studied. The ratios NAA/Cho, NAA/CPC and Cho/CPC for the four ROIs were measured in the patient population and compared with control values.¶Results. In spite of a large distribution of ratios, the statistical tests did not show any significant difference between the ratios within NAWM in the patient population compared with control values. Means of ratios in the left posterior (LP) voxel compared normal subjects were (a) in neurologically asymptomatic ALD patients (n = 7) 2.27 ± 0.63 for NAA/CPC, 2.21 ± 0.75 for NAA/Cho, 1.06 ± 0.28 for Cho/CPC, (b) in patients with early signs of demyelination (n = 3) 3.43 ± 0.85 for NAA/CPC, 2.47 ± 0.32 for NAA/Cho, 1.37 ± 0.16 for Cho/CPC and (c) in AMN patients (n = 8) 1.47 ± 0.53 for NAA/CPC, 2.17 ± 1.58 for NAA/Cho, 0.83 ± 0.32 for Cho/CPC.¶Conclusions. The study did not show significant differences in metabolite ratios between patients and controls. The large distribution of results precludes the possibility of detecting small variations. Part of this distribution can be due to the CSI method. Longitudinal spectroscopic studies, preferentially using monovoxel spectroscopy, are clearly needed.