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In our systematic investigation of the evolution of T2-hyperintensities in patients with the late-infantile form, we describe and characterize T2-pseudonormalization in the advanced stage of the natural disease course.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The volume of T2-hyperintensities was quantified in 34\u00a0MRIs of 27\u00a0children with late-infantile MLD (median age 2.25\u00a0years, range 0.5\u20135.2 years). In three children with the most advanced clinical course (age &gt;4\u00a0years) and for whom the T2-pseudonormalization was the most pronounced, WM microstructure was investigated using a\u00a0multimodal MRI protocol, including diffusion-weighted imaging, MR spectroscopy (MRS), myelin water fraction (MWF), magnetization transfer ratio (MTR), T1-mapping and quantitative susceptibility mapping.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>T2-hyperintensities in cerebral WM returned to normal in large areas of 3\u00a0patients in the advanced disease stage. Multimodal assessment of WM microstructure in areas with T2-pseudonormalization revealed highly decreased values for NAA, neurite density, isotropic water, mean and radial kurtosis, MWF and MTR, as well as increased radial diffusivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In late-infantile MLD patients, we found T2-pseudonormalization in WM tissue with highly abnormal microstructure characterizing the most advanced disease stage. Pathological hallmarks might be a\u00a0loss of myelin, but also neuronal loss as well as increased tissue density due to gliosis and accumulated storage material. These results suggest that a\u00a0multimodal MRI protocol using more specific microstructural parameters than T2-weighted sequences should be used when evaluating the effect of treatment trials in MLD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00062-020-00975-2","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T05:42:42Z","timestamp":1606110162000},"page":"969-980","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["T2-Pseudonormalization and Microstructural Characterization in Advanced Stages of Late-infantile Metachromatic Leukodystrophy"],"prefix":"10.1007","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0678-6417","authenticated-orcid":false,"given":"Pascal","family":"Martin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela E.","family":"Hagberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Schultz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Harzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Klose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Bender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"N\u00e4gele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Scheffler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingeborg","family":"Kr\u00e4geloh-Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Groeschel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"key":"975_CR1","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1002\/glia.23598","volume":"67","author":"CG Bergner","year":"2019","unstructured":"Bergner CG, van der Meer F, Winkler A, Wrzos C, T\u00fcrkmen M, Valizada E, Fitzner D, Hametner S, Hartmann C, Pfeifenbring S, Stoltenburg-Didinger G, Br\u00fcck W, Nessler S, Stadelmann C. 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S.\u00a0Groeschel received institutional research support from Shire\/Takeda, outside of the submitted work. He is advisor and co-investigator for trials in metachromatic leukodystrophy (Shire\/Takeda, Orchard, Bioclinica, Homology Medicine), but receives no personal payment related to this role. B.\u00a0Bender is co-founder and shareholder of AIRAmed GmbH (unrelated to the current work).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants or on human tissue were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the ethical committees of the University of T\u00fcbingen, Germany. Informed consent was obtained from the legal representatives of all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standards"}}]}}