14800-DvRappard

19 General introduction 1 spectra in chapter 7 . Diffusion tensor imaging (DTI) is a MRI technique that quantifies the direction and magnitude of water diffusion in the brain. 36 There are different diffusion parameters describing different degrees of displacement of water molecules. Fractional anisotropy (FA) and mean diffusivity (MD) are a combined measure of axial diffusivity (AD) and radial diffusivity (RD). Since the displacement of water molecules is impeded by cellular microstructures surrounding it, pathological processes such as demyelination, loss of axonal integrity and inflammatory processes can modulate the direction of diffusion. In chapter 8 , we study DTI parameters in MLD patients in order to gain insight into the organization and structure of brain tissue and how this is affected by the disease. TREATMENT Enzyme replacement therapy Animal models of intrathecal continuous infusion of ASA showed reversal of sulfatide storage, suggesting that this may be efficacious for the treatment of MLD. 37 However, the rapid demyelination that occurs in the early onset forms is unlikely to be sufficiently halted by ERT. Intravenous administration of the enzyme has been found not to be effective due to the inability to cross the blood brain barrier. Currently, the IDEAMLD phase I/II clinical trial (NCT01510028) uses multiple intrathecal infusions with recombinant ASA for patients with the late-infantile subtype. The trial has been completed in January 2017, preliminary results are expected soon . Hematopoietic Cell Transplantation The theory behind hematopoietic cell transplantation (HCT) is that monocytic cells of bone marrow or umbilical cord blood cells (from a donor) cross the blood brain barrier and differentiate into macrophages, which start producing ASA to cross-correct the enzyme deficiency. Still, its exact mechanism is not yet fully understood. Prior to the transfusion of donor cells, patients undergo myeloablative chemotherapy which makes it a complicated procedure with the risk of infections and post-transplant complications such as graft versus host disease (GvHD). Treatment related mortality was estimated to be 10-15%, but is nowadays, with less toxic induction protocols, considerably lower, at least in children. 38 PNS involvement does not seem to be influenced by HCT, which hampers motor function in a substantial part of transplanted patients. 12,39 Another important issue is the time it takes for the donor cells to replace resident tissue. This can take 6 to 12 months, whilst disease progression continues. Unfortunately, this makes HCT ineffective for patients with the late-infantile form, because disease progression