{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:14:19Z","timestamp":1782270859758,"version":"3.54.5"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T00:00:00Z","timestamp":1577145600000},"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"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000445"],"award-info":[{"award-number":["UL1TR000445"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01\u00a0NS097821"],"award-info":[{"award-number":["R01\u00a0NS097821"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01\u00a0NS066927"],"award-info":[{"award-number":["R01\u00a0NS066927"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","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":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Hereditary neuropathy with liability to pressure palsies (HNPP) is caused by heterozygous deletion of the<jats:italic>peripheral myelin protein 22 (PMP22)<\/jats:italic>gene. Patients with HNPP present multifocal, reversible sensory\/motor deficits due to increased susceptibility to mechanical pressure. Additionally, age\u2010dependent axonal degeneration is reported. We hypothesize that length\u2010dependent axonal loss can be revealed by MRI, irrespective of the\u00a0multifocal phenotype in HNPP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Nerve and muscle MRI data were acquired in the proximal and distal leg of patients with HNPP (<jats:italic>n<\/jats:italic>\u00a0=\u00a010) and matched controls (<jats:italic>n<\/jats:italic>\u00a0=\u00a07). More specifically, nerve magnetization transfer ratios (MTR) were evaluated to assay proximal\u2010to\u2010distal gradients in nerve degeneration, while intramuscular fat percentages (<jats:italic>F<\/jats:italic><jats:sub>per<\/jats:sub>) were evaluated to assay muscle fat replacement following denervation. Neurological disabilities were assessed via the Charcot\u2010Marie\u2010Tooth neuropathy score (CMTNS) for correlation with MRI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>F<\/jats:italic><jats:sub>per<\/jats:sub>values were elevated in HNPP proximal muscle (9.8\u00a0\u00b1\u00a02.2%,<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01) compared to controls (6.9\u00a0\u00b1\u00a01.0%). We observed this same elevation of HNPP distal muscles (10.5\u00a0\u00b1\u00a02.5%,<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) relative\u00a0to controls (6.3\u00a0\u00b1\u00a01.1%). Additionally, the amplitude of the\u00a0proximal\u2010to\u2010distal gradient in<jats:italic>F<\/jats:italic><jats:sub>per<\/jats:sub>was more significant in HNPP patients than controls (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), suggesting length\u2010dependent axonal loss. In contrast, nerve MTR values were similar between HNPP subjects (sciatic\/tibial nerves\u00a0=\u00a039.4\u00a0\u00b1\u00a02.0\/34.2\u00a0\u00b1\u00a02.5%) and controls (sciatic\/tibial nerves\u00a0=\u00a037.6\u00a0\u00b1\u00a03.8\/35.5\u00a0\u00b1\u00a01.2%). Proximal muscle<jats:italic>F<\/jats:italic><jats:sub>per<\/jats:sub>values were related to CMTNS (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.69,<jats:italic>P<\/jats:italic>\u00a0=\u00a00.03), while distal muscle<jats:italic>F<\/jats:italic><jats:sub>per<\/jats:sub>and sciatic\/tibial nerve MTR values were not related to disability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Despite the multifocal nature of the HNPP phenotype, muscle<jats:italic>F<\/jats:italic><jats:sub>per<\/jats:sub>measurements relate to disability and exhibit a proximal\u2010to\u2010distal gradient consistent with length\u2010dependent axonal loss, suggesting that<jats:italic>F<\/jats:italic><jats:sub>per<\/jats:sub>may be a viable biomarker of disease progression in HNPP.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.50953","type":"journal-article","created":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T12:40:47Z","timestamp":1577191247000},"page":"15-25","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Length\u2010dependent MRI of hereditary neuropathy with liability to pressure palsies"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9879-7147","authenticated-orcid":false,"given":"Michael","family":"Pridmore","sequence":"first","affiliation":[{"name":"Vanderbilt University Institute of Imaging Science Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Castoro","sequence":"additional","affiliation":[{"name":"Department of Neurology Division of Neuromuscular Medicine Wake Forest School of Medicine Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan Simmons","family":"McCollum","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakmook","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Vanderbilt University Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Wayne State University School of Medicine Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Dortch","sequence":"additional","affiliation":[{"name":"Vanderbilt University Institute of Imaging Science Vanderbilt University Medical Center Nashville Tennessee USA"},{"name":"Department of Biomedical Engineering Vanderbilt University Nashville Tennessee USA"},{"name":"Department of Radiology and Radiological Sciences Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-012-8370-x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.68.4.483"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000216104.34658.82"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.7.1516"},{"key":"e_1_2_8_6_1","unstructured":"BirdTD.Hereditary neuropathy with liability to pressure palsies clinical characteristics clinical description.2019:1\u201312."},{"key":"e_1_2_8_7_1","first-page":"473","article-title":"Perplexity about the use of the Charcot\u2010Marie\u2010Tooth neuropathy score in rehabilitation","volume":"44","author":"Vinci P","year":"2008","journal-title":"Eur J Phys Rehabil Med"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20202"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910290607"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2007.05.004"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000919"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00242-2"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2015.03.003"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3159"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910370426"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.12.1769"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24776"},{"key":"e_1_2_8_18_1","volume-title":"MATLAB\u00ae statistics and machine learning toolbox release 2017a"},{"key":"e_1_2_8_19_1","volume-title":"MATLAB\u00ae curve fitting toolbox release 2017a"},{"key":"e_1_2_8_20_1","unstructured":"SmithDS BerglundJ KullbergJ.Optimization of fat\u2010water separation algorithm selection and options using image\u2010based metrics with validation by.21st Annu. Sci. Meet. ISMRM Abstr. #2413.2013."},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006290"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0404.2003.00132.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.7.974"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1385\/NMM:8:1-2:3"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.5435\/00124635-200407000-00008"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-009-0202-z"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.3178"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.22431"},{"key":"e_1_2_8_29_1","first-page":"149","article-title":"Variability of muscle fat fraction quantification in MRI using the Dixon technique","volume":"22","author":"Ortega X","year":"2016","journal-title":"Im\u00e1genes Pedi\u00e1tricas"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2016.00069"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40520-016-0556-z"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-014-3145-6"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2008.05.012"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12603-010-0081-2"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.951"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1801788115"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.683"},{"key":"e_1_2_8_38_1","first-page":"1885","article-title":"A comparison of magnetization transfer ratio, magnetization transfer rate, and the native relaxation time of water protons related to relapsing\u2010remitting multiple sclerosis","volume":"21","author":"Ropele S","year":"2000","journal-title":"AJNR Am J Neuroradiol"},{"key":"e_1_2_8_39_1","doi-asserted-by":"crossref","first-page":"P1.453","DOI":"10.1212\/WNL.90.15_supplement.P1.453","article-title":"Quantitative MRI of nerve pathology in mouse models of CMT1A and HNPP (P1.453)","volume":"90","author":"Manzanera I","year":"2018","journal-title":"Neurology"},{"key":"e_1_2_8_40_1","first-page":"1","article-title":"MRI biomarkers of proximal nerve injury in CIDP","volume":"5","author":"Lichtenstein T","year":"2016","journal-title":"Ann Clin Transl Neurol"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLI.0000000000000455"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22552"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25068"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facn3.50953","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.50953","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.50953","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.50953","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T03:47:46Z","timestamp":1722224866000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.50953"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,24]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1002\/acn3.50953"],"URL":"https:\/\/doi.org\/10.1002\/acn3.50953","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,24]]},"assertion":[{"value":"2019-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}