phosphocreatine and Adrenoleukodystrophy

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.. 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.. Spectroscopic imaging acquisition mode (MRSI, 16 x 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.

Topics: Adolescent; Adrenoleukodystrophy; Adult; Age Factors; Brain; Child; Choline; Data Interpretation, Statistical; Demyelinating Diseases; Female; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phenotype; Phosphocreatine; Prognosis; Sensitivity and Specificity

We have performed localised proton magnetic resonance spectroscopy (MRS) of the brain on four patients with X-linked adrenoleukodystrophy (X-ALD). The spectrum is characterised at the beginning of the disease by a decrease in N-acetylaspartate and phosphocreatine-creatine content. Choline is strongly increased, and lactate can be detected in some cases. A proton signal from the CH2 groups borne by free intracellular very long chain fatty acids can also be observed. Later in the disease, the levels of all metabolites, in particular NAA, decrease significantly. The progression of neurometabolism documented by MRS correlates well with MRI and clinical progression on follow-up study. In one case, the metabolic profile recorded by proton MRS was abnormal before any change occurred on MRI. Proton MRS of the brain might be the method of choice for monitoring patients with X-ALD, to screen presumed cases and to study the effects of treatment.

Topics: Adolescent; Adrenoleukodystrophy; Adult; Aspartic Acid; Brain; Child; Creatine; Demyelinating Diseases; Fatty Acids; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Phosphocreatine; Sex Chromosome Aberrations; X Chromosome

Multislice proton magnetic resonance spectroscopic imaging permits metabolic analysis of brain tissue in vivo by data acquisition in four oblique axial slices, each 15-mm thick and divided into 0.8-ml single-volume elements. We applied this technique to the systematic study of 25 patients with adrenoleukodystrophy: 3 with the severe childhood or adult cerebral form of the disease, 5 with adrenomyeloneuropathy, 12 with no demonstrable neurological involvement, and 5 women heterozygous for adrenoleukodystrophy who had some degree of neurological disability. Abnormalities on magnetic resonance spectroscopic imaging included a reduction in N-acetyl aspartate, an increase in choline-containing compounds, and at times, an increase in lactate. Five patients showed abnormalities in the presence of normal-appearing magnetic resonance images, and in 8 other patients the alterations on spectroscopic images were more severe than those demonstrable by magnetic resonance imaging. Correlation with clinical course suggests that an increase in the choline-containing compounds is associated with an active demyelinative process, whereas such compounds are not elevated in lesions that are stable. We conclude that magnetic resonance spectroscopic imaging is a more sensitive indicator of early neurological involvement than is magnetic resonance imaging, and that the character of abnormalities detected by the former technique may serve as a gauge of the degree of activity of the demyelinating process and as a guide to the selection and evaluation of therapeutic approaches.

Topics: Adolescent; Adrenoleukodystrophy; Adult; Aged; Aspartic Acid; Brain Diseases; Child; Child, Preschool; Choline; Creatine; Female; Genetic Linkage; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phenotype; Phosphocreatine; X Chromosome