{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:21:53Z","timestamp":1791397313333,"version":"4.3.3"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Metachromatic leukodystrophy is a lysosomal storage disease caused by deficient arylsulfatase A. It is characterized by progressive demyelination and thus mainly affects the white matter. Hematopoietic stem cell transplantation may stabilize and improve white matter damage, yet some patients deteriorate despite successfully treated leukodystrophy. We hypothesized that post\u2010treatment decline in metachromatic leukodystrophy might be caused by gray matter pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three metachromatic leukodystrophy patients treated with hematopoietic stem cell transplantation with a progressive clinical course despite stable white matter pathology were clinically and radiologically analyzed. Longitudinal volumetric MRI was used to quantify atrophy. We also examined histopathology in three other patients deceased after treatment and compared them with six untreated patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The three clinically progressive patients developed cognitive and motor deterioration after transplantation, despite stable mild white matter abnormalities on MRI. Volumetric MRI identified cerebral and thalamus atrophy in these patients, and cerebellar atrophy in two. Histopathology showed that in brain tissue of transplanted patients, arylsulfatase A expressing macrophages were clearly present in the white matter, but absent in the cortex. Arylsulfatase A expression within patient thalamic neurons was lower than in controls, the same was found in transplanted patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Neurological deterioration may occur after hematopoietic stem cell transplantation in metachromatic leukodystrophy despite successfully treated leukodystrophy. MRI shows gray matter atrophy, and histological data demonstrate absence of donor cells in gray matter structures. These findings point to a clinically relevant gray matter component of metachromatic leukodystrophy, which does not seem sufficiently affected by transplantation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51796","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T10:11:20Z","timestamp":1684750280000},"page":"1146-1159","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Neurodegenerative disease after hematopoietic stem cell transplantation in metachromatic leukodystrophy"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8246-8963","authenticated-orcid":false,"given":"Murtadha","family":"Al\u2010Saady","sequence":"first","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, and Amsterdam Neuroscience, Cellular &amp; Molecular Mechanisms Vrije Universiteit  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2945-6784","authenticated-orcid":false,"given":"Shanice","family":"Beerepoot","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, and Amsterdam Neuroscience, Cellular &amp; Molecular Mechanisms Vrije Universiteit  Amsterdam the Netherlands"},{"name":"Center for Translational Immunology University Medical Center Utrecht  Utrecht the Netherlands"},{"name":"Nierkens and Lindemans Group Princess M\u00e1xima Center for Pediatric Oncology  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie C.","family":"Plug","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, and Amsterdam Neuroscience, Cellular &amp; Molecular Mechanisms Vrije Universiteit  Amsterdam the Netherlands"},{"name":"Department of Pathology, Amsterdam Leukodystrophy Center, Amsterdam University Medical Centers VU University and Neuroscience Campus Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein","family":"Breur","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, and Amsterdam Neuroscience, Cellular &amp; Molecular Mechanisms Vrije Universiteit  Amsterdam the Netherlands"},{"name":"Department of Pathology, Amsterdam Leukodystrophy Center, Amsterdam University Medical Centers VU University and Neuroscience Campus Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hristina","family":"Galabova","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, Amsterdam University Medical Centers VU university  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra J. W.","family":"Pouwels","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, Amsterdam University Medical Centers VU university  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap\u2010Jan","family":"Boelens","sequence":"additional","affiliation":[{"name":"Stem Cell Transplantation and Cellular Therapies Program, Department of Pediatrics Memorial Sloan Kettering Cancer Center  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Lindemans","sequence":"additional","affiliation":[{"name":"Stem Cell Transplantation and Cellular Therapies Program, Department of Pediatrics Memorial Sloan Kettering Cancer Center  New York NY USA"},{"name":"Pediatric Blood and Bone Marrow Transplantation, Princess M\u00e1xima Center for Pediatric Oncology  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"van Hasselt","sequence":"additional","affiliation":[{"name":"Stem Cell Transplantation and Cellular Therapies Program, Department of Pediatrics Memorial Sloan Kettering Cancer Center  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Matzner","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, Medical Faculty Rheinische Friedrich\u2010Wilhelm University  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Vanderver","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Bugiani","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, and Amsterdam Neuroscience, Cellular &amp; 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