14800-DvRappard

32 Chapter 2 DIAGNOSIS Magnetic Resonance Imaging An important tool in establishing the diagnosis of MLD is MRI, which shows characteristic brain abnormalities. Demyelination in MLD leads to bilateral symmetric abnormal T2 signal hyperintensity starting in the corpus callosum and then involving the periventricular white matter. In the infantile form, the disease usually starts in the splenium of the corpus callosum and the parietooccipital white matter, in the adult form, in the rostrum and frontal white matter (figure 2). The subcortical fibers are usually spared. 13 In severe disease there is often involvement of the projection fibers, cerebellar white matter, basal ganglia and thalami which have a decreased signal intensity on T2- weighted images, probably as a result of accumulation of metal or other breakdown products in the brain. 14 Typical for MLD is a pattern of radiating stripes with bands of normal signal intensity within the abnormal white matter, 15 the so called “tigroid- pattern”. This is also seen in globoid cell leukodystrophy (Krabbe’s disease) and infantile GM1 gangliosidosis. Histopathological techniques confirmed that the stripes are related to perivascular preservation of myelin. 15 Eichler et al 14 developed a scoring system for the MRI abnormalities in MLD which can, when combined with clinical parameters, be used as a measure of disease severity. It takes into account extent and severity of abnormal white matter signal, involvement of projection fibers and basal ganglia and atrophy. 14 Staging (mild, moderate or severe) is based on the total amount of points. The amount of demyelinated white matter can also be quantified as demyelination load and is correlated with disease duration and deterioration of gross motor function. 16 Proton magnetic resonance spectroscopy ( 1 H-MRS) can be used to gain insight into chemical information in addition to the anatomic information provided by MRI. 17 In MLD, 1 H-MRS is characterized by a low N- acetylasparate (NAA) level and elevated myo-inositol (figure 3). 17 The low NAA level can be explained by the diffuse neuronal loss that is seen inMLD. The highmyo-inositol level has been attributed to reactive gliosis, characteristic for MLD. 18 Assadi et al 18 furthermore found an increased lactate to creatine ratio, which is likely due to oligodendrocyte injury limiting lactate transport into axons. Biochemical and genetic diagnosis Diagnosing MLD consists of a combination of biochemical procedures and genetic analysis. 1 The biochemical procedure consists of measuring ASA enzymatic activity in leucocytes from whole blood. 19 Sulfatide excretion in urine can be measured when the levels of ASA enzymatic activity are normal in a child with typical clinical presentation and MRI and also when there is doubt about pseudodeficiency.