{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:41:17Z","timestamp":1790991677079,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T00:00:00Z","timestamp":1704240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005202","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":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>With potential therapies for many forms of Charcot\u2010Marie\u2010Tooth disease (CMT), responsive outcome measures are urgently needed for clinical trials. Quantitative lower limb MRI demonstrated progressive calf intramuscular fat accumulation in the commonest form, CMT1A with large responsiveness. In this study, we evaluated the responsiveness and validity in the three other common forms, due to variants in GJB1 (CMTX1), MPZ (CMT1B) and MFN2 (CMT2A).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>22 CMTX1, 21 CMT1B and 21 CMT2A patients and matched controls were assessed at a 1\u2010year interval. Intramuscular fat fraction (FF) was evaluated using three\u2010point Dixon MRI at thigh and calf level along with clinical measures including CMT examination score, clinical strength assessment, CMT\u2010HI and plasma neurofilament light chain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All patient groups had elevated muscle fat fraction at thigh and calf levels, with highest thigh FF and atrophy in CMT2A. There was moderate correlation between calf muscle FF and clinical measures (CMTESv2 rho\u2009=\u20090.405;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001, ankle MRC strength rho\u2009=\u2009\u22120.481;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Significant annualised progression in calf muscle FF was seen in all patient groups (CMTX1 2.0\u2009\u00b1\u20092.0%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001, CMT1B 1.6\u2009\u00b1\u20092.1%\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004 and CMT2A 1.6\u2009\u00b1\u20092.1%\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). Greatest increase was seen in patients with 10\u201370% FF at baseline (calf 2.7\u2009\u00b1\u20092.3%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001 and thigh 1.7\u2009\u00b1\u20092.1%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Our results confirm that calf muscle FF is highly responsive over 12\u2009months in three additional common forms of CMT which together with CMT1A account for 90% of genetically confirmed cases. Calf muscle MRI FF should be a valuable outcome measure in upcoming CMT clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.51979","type":"journal-article","created":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T01:44:04Z","timestamp":1704332644000},"page":"607-617","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Lower limb muscle\n                    <scp>MRI<\/scp>\n                    fat fraction is a responsive outcome measure in\n                    <scp>CMT X1<\/scp>\n                    ,\n                    <scp>1B<\/scp>\n                    and\n                    <scp>2A<\/scp>"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0129-3573","authenticated-orcid":false,"given":"Carolynne M.","family":"Doherty","sequence":"first","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6879-8539","authenticated-orcid":false,"given":"Jasper M.","family":"Morrow","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Zuccarino","sequence":"additional","affiliation":[{"name":"Roy and Lucille Carver College of Medicine University of Iowa  Iowa City Iowa USA"},{"name":"Fondazione Serena Onlus, Centro Clinico NeMO Trento  Pergine Valsugana Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Howard","sequence":"additional","affiliation":[{"name":"Roy and Lucille Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Wastling","sequence":"additional","affiliation":[{"name":"Lysholm Department of Radiology National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menelaos","family":"Pipis","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Zafeiropoulos","sequence":"additional","affiliation":[{"name":"Lysholm Department of Radiology National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Roy and Lucille Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Grider","sequence":"additional","affiliation":[{"name":"Roy and Lucille Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawna M. E.","family":"Feely","sequence":"additional","affiliation":[{"name":"Seattle Children's Hospital University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Nopoulous","sequence":"additional","affiliation":[{"name":"Roy and Lucille Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariola","family":"Skorupinska","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelin","family":"Milev","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Nicolaisen","sequence":"additional","affiliation":[{"name":"Roy and Lucille Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Dudzeic","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"McDowell","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London UK"},{"name":"Lysholm Department of Radiology National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuran","family":"Dilek","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Muntoni","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4648-2896","authenticated-orcid":false,"given":"Alexander M.","family":"Rossor","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachit","family":"Shah","sequence":"additional","affiliation":[{"name":"Lysholm Department of Radiology National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Laura","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek A.","family":"Yousry","sequence":"additional","affiliation":[{"name":"Lysholm Department of Radiology National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Thedens","sequence":"additional","affiliation":[{"name":"Roy and Lucille Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Thornton","sequence":"additional","affiliation":[{"name":"Lysholm Department of Radiology National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8460-6971","authenticated-orcid":false,"given":"Michael E.","family":"Shy","sequence":"additional","affiliation":[{"name":"Roy and Lucille Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Reilly","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90613-4"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0960-8966(91)90055-W"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2011.00324.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-308826"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004296"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2011.00332.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh048"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv241"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/brv.12378"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.026"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12013"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-302451"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22166"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2020.07.006"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000474"},{"issue":"1","key":"e_1_2_10_17_1","first-page":"139","article-title":"Recent advances in the genetic neuropathies","volume":"4","author":"Rossor AM","year":"2016","journal-title":"Curr Opin Neurol"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2021.1935242"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.5607\/en20004"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(99)00206-1"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26633"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005650-199007000-00008"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000156517.00615.A3"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.3178"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70025-4"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2011.00350.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns.12084"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23572"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy280"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009035"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26518"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa323"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00242-2"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006214"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-320198"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2008.05.012"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910180211"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.01.015"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200757"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51979","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T23:14:20Z","timestamp":1711408460000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.51979"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,3]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/acn3.51979"],"URL":"https:\/\/doi.org\/10.1002\/acn3.51979","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,3]]},"assertion":[{"value":"2023-11-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}