{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:06:58Z","timestamp":1788430018204,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,5,16]],"date-time":"2017-05-16T00:00:00Z","timestamp":1494892800000},"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":[[2017,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to investigate whether the extent and topography of cerebral demyelination correlates with and predicts disease progression in patients with juvenile metachromatic leukodystrophy (<jats:styled-content style=\"fixed-case\">MLD<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 137 <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>s of 46 patients with juvenile <jats:styled-content style=\"fixed-case\">MLD<\/jats:styled-content> were analyzed. Demyelination load and brain volume were quantified using the previously developed Software \u201cclusterize.\u201d Clinical data were collected within the German Leukodystrophy Network and included full scale intelligence quotient (<jats:styled-content style=\"fixed-case\">FSIQ<\/jats:styled-content>) and gross motor function data. Voxel\u2010based lesion\u2010symptom mapping (<jats:styled-content style=\"fixed-case\">VLSM<\/jats:styled-content>) across the whole brain was performed to investigate the spatial relationship of cerebral demyelination with motor or cognitive function. The prognostic value of the demyelination load at disease onset was assessed to determine the severity of disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The demyelination load (corrected by the individual brain volume) correlated significantly with gross motor function (<jats:italic>r<\/jats:italic> = +0.55) and <jats:styled-content style=\"fixed-case\">FSIQ<\/jats:styled-content> (<jats:italic>r<\/jats:italic> = \u22120.55). Demyelination load at disease onset was associated with the severity of disease progression later on (<jats:italic>P<\/jats:italic> &lt; 0.01). <jats:styled-content style=\"fixed-case\">VLSM<\/jats:styled-content> results associated frontal lobe demyelination with loss in <jats:styled-content style=\"fixed-case\">FSIQ<\/jats:styled-content> and more central region demyelination with decline of motor function. Especially progression of demyelination within the motor area was associated with severe disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We were able to show for the first time in a large cohort of patients with juvenile <jats:styled-content style=\"fixed-case\">MLD<\/jats:styled-content> that the demyelination load correlates with motor and cognitive symptoms. Moreover, demyelination load at disease onset, especially the involvement of the central region, predicts severity of disease progression. Thus, demyelination load seems a functionally relevant <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> parameter.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.420","type":"journal-article","created":{"date-parts":[[2017,5,16]],"date-time":"2017-05-16T09:28:48Z","timestamp":1494926928000},"page":"403-410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Demyelination load as predictor for disease progression in juvenile metachromatic leukodystrophy"],"prefix":"10.1002","volume":"4","author":[{"given":"Manuel","family":"Str\u00f6lin","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology &amp; Developmental Medicine University Children's Hospital T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingeborg","family":"Kr\u00e4geloh\u2010Mann","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology &amp; Developmental Medicine University Children's Hospital T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Kehrer","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology &amp; Developmental Medicine University Children's Hospital T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Wilke","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology &amp; Developmental Medicine University Children's Hospital T\u00fcbingen Germany"},{"name":"Experimental Pediatric Neuroimaging University Children's Hospital T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Groeschel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology &amp; Developmental Medicine University Children's Hospital T\u00fcbingen Germany"},{"name":"Experimental Pediatric Neuroimaging University Children's Hospital T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,16]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"p. chapter 148","volume-title":"The online metabolic and molecular bases of inherited disease","author":"Gieselmann V","year":"2014"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1253412"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.193"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1739"},{"key":"e_1_2_7_6_1","first-page":"442","article-title":"Histopathologic correlates of radial stripes on MR images in lysosomal storage disorders","volume":"26","author":"Voorn JP","year":"2005","journal-title":"AJNR AmJNeuroradiol"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acra.2011.09.008"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31826e9ad2"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2012.155"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2011.04028.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-9-18"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9361-1"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.232"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000343049.00540.c8"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-27660-2"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30450-0"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.2067"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-015-0313-y"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2013.01.010"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-708479"},{"key":"e_1_2_7_21_1","first-page":"539","volume-title":"The metabolic basis of inherited disease","author":"Moser H","year":"1965"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2010.03821.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1050"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2014.09.034"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1162\/jocn.2007.19.7.1081"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2009.09.016"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2007.10.004"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01633-7"},{"key":"e_1_2_7_29_1","first-page":"C84","article-title":"Standardized description of rare diseases \u2010 the natural course and treatment of metachromatic leukodystrophy","volume":"48","author":"Groeschel S","year":"2014","journal-title":"Rev Neurol"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167274"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24194"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181feb217"},{"key":"e_1_2_7_33_1","first-page":"1929","article-title":"Serial MR after bone marrow transplantation in two patients with metachromatic leukodystrophy","volume":"15","author":"Stillman AE","year":"1994","journal-title":"AJNR Am J Neuroradiol"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.629"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.1037"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facn3.420","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.420","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T01:18:12Z","timestamp":1696641492000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,16]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1002\/acn3.420"],"URL":"https:\/\/doi.org\/10.1002\/acn3.420","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,16]]},"assertion":[{"value":"2017-03-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-04-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-05-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}