14800-DvRappard

117 Quantitative MR spectroscopic imaging in metachromatic leukodystrophy 7 Using MRSI in juvenile and adult MLD, WM metabolite concentrations at diagnosis correlate well with outcome, with NAA as main explanatory variable. This is underlined by the strong association between baseline NAA concentrations and motor function at follow-up in our cohort, but also in late-infantile MLD, 25 indicating that preserved neuroaxonal function is a prerequisite for good or moderate clinical outcome. The same conclusion was drawn in an MRS study on outcome after HCT in patients with X-linked adrenoleukodystrophy. 26 Patients with poor outcome had severely reduced concentrations of NAA, Glu and Glx, and increased Lac and Ins. In patients with moderate outcome, most metabolite concentrations were closer to normal. Compared with controls, Cho was increased only in patients with good outcome, possibly reflecting signs of active demyelination and/ or increased glial density. This latter explanation is supported by the observation of increased Cr and Glx in patients with good outcome compared to controls. Because concentrations of NAA and Glu are similar in patients with good outcome and controls, it can be assumed that axonal density is preserved in an early disease stage. The increased Glx must be due to a higher concentration of Gln, which together with Cr suggest a higher glial density in this disease stage. 27 It should be noted that these results were obtained from metabolite concentrations in overall WM using a combined analysis of tissue segmentation and 2D MRSI. However, since lesions in MLD start to develop in periventricular WM, it can be assumed that single voxel MRS in a periventricular WM region will give comparable results. Longitudinal evolution Even in some patients with good outcome, metabolic and imagingmarkers deteriorated in the first follow-up scan six months after transplantation, indicating ongoing disease activity and delayed treatment effect. Partial normalization of the Cho/NAA ratio in subsequent examinations in successfully treated patients implies reduction of demyelinating activity and some axonal tissue recovery. In several patients, Cho/NAA improvement indeed coincided with a reduction of MRI score and lesion volume, supporting our interpretation of tissue repair. However, in a few patients we could not observe a concomitant decrease of MRI score or lesion volume. This may be partly explained by the fact that the MRI score reflects WM damage at the level of the MRSI slab as well as WM involvements in other regions and atrophy of both supra- and infratentorial structures.