14800-DvRappard

126 Chapter 8 The precise pathomechanisms involved in MLD, such as importance of inflammation or how accumulated sulfatides lead to demyelination, are not completely understood. DTI is, taking into account its recognized limitations, a valuable tool to gain more insight into changes in tissue properties in MLD. We therefore compared diffusion measures (FA and the three diffusivities) between patients who were eligible for HCT, patients not eligible at time of diagnosis, and controls. HCT-eligible patients are typically in an early disease stage, while patients not eligible for HCT have more advanced disease with extensive demyelination of the WM. We also studied the longitudinal behavior of diffusion measures of both treated and untreated patients METHODS Patients and control subjects All 28MLD patients (4 late-infantile, 16 juvenile, and 8 adult onset), visiting the Center for Childhood White Matter Disorders, who underwent a quantitative MRI protocol at time of diagnosis between January 2007 and April 2017 were included in this retrospective study, in addition to 47 control subjects in the same age range (Table 1), after informed consent. Table 1. Subjects demographics Controls All MLD patients Eligible for HCT Not eligible for HCT Contrasts p Number of subjects 47 28 13 15 Male / female 23 / 24 9 / 19 6 / 7 3 / 12 (NS) Age at first scan (mean , SD, y) 10.5 (5.3) 14.5 (9.5) 16.9(10.6) 12.4(8.3) 0.017 a Late-infantile /juvenile / adult 4 / 16 / 8 2 / 5 / 6 2 / 11 / 2 (NS) a Post-hoc Dunnett’s T3 revealed no significant pairwise group differences The study was approved by the institutional review board. Diagnosis of MLD was established by brain MRI, ASA activity and ARSA mutation analysis.(4) Motor function was scored by the MLD Gross Motor Function (MLD-GMF) at baseline and at latest clinical follow up. 19 Cognitive function was evaluated through neuropsychological examination. Eligibility for HCT was based on patients’ neurological examination (no major abnormalities and able to walk independently) and cognitive function (IQ>75). Treatment with HCT was performed as described before. 4 Characteristics of individual patients are described in Table 2. Thirteen patients were considered eligible for HCT, and