14800-DvRappard

18 Chapter 1 DIAGNOSIS Diagnosis of MLD is made through clinical presentation, brainMRI, measurement of ASA activity in leukocytes and sulfatides levels in urine, and ARSA mutation analysis. Brain abnormalities seen on MRI are bilateral symmetric abnormal hyperintense T2 signal changes starting in corpus callosum and subsequently involving the periventricular white matter. 28 Depending on the age of onset, the white matter abnormalities either start in the spleniumof the corpus callosumand the parieto-occipital whitematter (late- infantile form) or in the genu and the frontal white matter (adult form) (Figure 4A,C). A pattern of radially oriented stripes of low signal intensity throughout the diffuse high signal intensity on T2-weighted images is typical for MLD and represents a combination of storage material and better preserved myelin (Figure 4B,D). 29 As the disease progresses, the subcortical white matter (U-fibers) become involved as well. With disease progression, the entire white matter becomes affected, and cerebral atrophy occurs with enlargement of the ventricles, eventually also cerebellar atrophy and demyelination. 30 The basal ganglia, especially the pallidum, and thalami usually have a decreased T2 signal intensity in this late disease stage, probably as a result of sulfatide accumulation. 31 Gröschel and colleagues correlated regression of cognitive function to more pronounced involvement of frontal WM areas in juvenile MLD patients, sparing the central motor parts of theWM. In certain patients, they found frontal demyelination to appear independently without impairment of the central region, accompanied by a relatively preserved motor function. 32 Eichler et al developed an MRI scoring system specifically for MLD. 31 Brain abnormalities on MRI can be scored based on their extent and intensity of abnormal white matter signal. Cerebral and cerebellar atrophy is also taken into account. The total amount of points gives an estimation of disease severity; categorized as either mild, moderate or severe. QUANTITATIVE MRI Quantitative MRI techniques can provide additional information about the physiology and pathophysiology of brain tissue next to the anatomical information provided by MRI. MRS is a technique providing chemical information on certain metabolites in the brain. 33 In MLD, spectra are characterized by decreased NAA, elevated myo-inositol (Ins) and choline-containing compounds (Cho) in the abnormal whitematter. 34,35 We describe the relationship between clinical outcome of patients and their baseline white matter