{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:14:28Z","timestamp":1790720068300,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T00:00:00Z","timestamp":1667606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004807","name":"DFG","doi-asserted-by":"publisher","award":["GR4688\/2\u20101"],"award-info":[{"award-number":["GR4688\/2\u20101"]}],"id":[{"id":"10.13039\/100004807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Metachromatic leukodystrophy (MLD) has characteristic white matter (WM) changes on brain MRI, which often trigger biochemical and genetic confirmation of the diagnosis. In early or pre\u2010symptomatic disease stages, these typical MRI changes might be absent, hampering early diagnosis. This study aims to describe the characteristics of MRI WM abnormalities at diagnosis, related to clinical presentation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively reviewed brain MRIs of MLD patients followed in 2 centers at the time of diagnosis regarding MLD MRI score and presence of tigroid pattern. In addition, MLD subtype, symptom status, CNS\/PNS phenotype, motor\/cognitive\/mixed phenotype, and the presence of CNS symptoms were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included 104 brain MRIs from patients with late\u2010infantile (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u200943), early\u2010juvenile (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u200924), late\u2010juvenile (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u200920) and adult (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u200917) onset. Involvement of the corpus callosum was a characteristic early MRI sign and was present in 71% of the symptomatic late\u2010infantile patients, 94% of the symptomatic early\u2010juvenile patients and 100% of the symptomatic late\u2010juvenile and adult patients. Symptomatic early\u2010juvenile, late\u2010juvenile and adult patients generally had WM abnormalities on MRI suggestive of MLD. By contrast, 47% of the early\u2010symptomatic late\u2010infantile patients had no or only mild WM abnormalities on MRI, even in the presence of CNS symptoms including pyramidal signs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Patients with late\u2010infantile MLD may have no or only mild, nonspecific abnormalities at brain MRI, partly suggestive of \u2018delayed myelination\u2019, even with clear clinical symptoms. This may lead to significant diagnostic delay. Knowledge of these early MRI signs (or their absence) is important for fast diagnosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.51692","type":"journal-article","created":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T11:55:20Z","timestamp":1667649320000},"page":"1999-2009","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Recognizing early\n                    <scp>MRI<\/scp>\n                    signs (or their absence) is crucial in diagnosing metachromatic leukodystrophy"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1601-7379","authenticated-orcid":false,"given":"Daphne H.","family":"Schoenmakers","sequence":"first","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center Amsterdam UMC location Vrije Universiteit Amsterdam, Emma's Children's Hospital  Boelelaan 1117 Amsterdam The Netherlands"},{"name":"Amsterdam Neuroscience, Cellular &amp; Molecular Mechanisms  Amsterdam The Netherlands"},{"name":"Department of Endocrinology and Metabolism Amsterdam UMC location University of Amsterdam  Meibergdreef 9 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 Amsterdam UMC location Vrije Universiteit Amsterdam, Emma's Children's Hospital  Boelelaan 1117 Amsterdam The Netherlands"},{"name":"Amsterdam Neuroscience, Cellular &amp; Molecular Mechanisms  Amsterdam The Netherlands"},{"name":"Center for Translational Immunology University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Pediatric Transplant Center Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingeborg","family":"Kr\u00e4geloh\u2010Mann","sequence":"additional","affiliation":[{"name":"Department of Child Neurology and Developmental Medicine University Children's Hospital T\u00fcbingen  Hoppe\u2010Seyler\u2010Stra\u00dfe 1 72076 T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Elg\u00fcn","sequence":"additional","affiliation":[{"name":"Department of Child Neurology and Developmental Medicine University Children's Hospital T\u00fcbingen  Hoppe\u2010Seyler\u2010Stra\u00dfe 1 72076 T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Bender","sequence":"additional","affiliation":[{"name":"Diagnostic and Interventional Neuroradiology, Department of Radiology University Hospital T\u00fcbingen  Hoppe\u2010Seyler\u2010Stra\u00dfe 3 72076 T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo S.","family":"van der Knaap","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center Amsterdam UMC location Vrije Universiteit Amsterdam, Emma's Children's Hospital  Boelelaan 1117 Amsterdam The Netherlands"},{"name":"Amsterdam Neuroscience, Cellular &amp; Molecular Mechanisms  Amsterdam The Netherlands"},{"name":"Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1721-0728","authenticated-orcid":false,"given":"Nicole I.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center Amsterdam UMC location Vrije Universiteit Amsterdam, Emma's Children's Hospital  Boelelaan 1117 Amsterdam The Netherlands"},{"name":"Amsterdam Neuroscience, Cellular &amp; Molecular Mechanisms  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Groeschel","sequence":"additional","affiliation":[{"name":"Department of Child Neurology and Developmental Medicine University Children's Hospital T\u00fcbingen  Hoppe\u2010Seyler\u2010Stra\u00dfe 1 72076 T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,5]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"Metachromatic leukodystrophy. 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