{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T07:25:28Z","timestamp":1764228328723,"version":"3.46.0"},"reference-count":12,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T00:00:00Z","timestamp":1755302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["5T32AR056993"],"award-info":[{"award-number":["5T32AR056993"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS087175","F32 NS095515"],"award-info":[{"award-number":["R01NS087175","F32 NS095515"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction\/Aims<\/jats:title>\n Giant axonal neuropathy (GAN) is a hereditary neurodegenerative disease due to the absence or loss of function of the gigaxonin gene. Pathologic findings in GAN are those of \u201cdying\u2010back\u201d axonal degeneration, in which the distal axon degenerates but the more proximal axon and neuronal cell body remain intact. Aims of this study were to (1) document imaging abnormalities that may occur in the spinal cords of GAN patients; and (2) assess histologically the spinal cords of GAN rodent models.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A clinical trial of intrathecal (\n IT<\/jats:styled-content>\n )\n scAAV9<\/jats:styled-content>\n \/\n JeT<\/jats:styled-content>\n \u2010\n \n GAN<\/jats:italic>\n <\/jats:styled-content>\n gene transfer provided a cohort of\n GAN<\/jats:styled-content>\n patients for study. We examined spinal magnetic resonance imaging (\n MRI<\/jats:styled-content>\n ) studies from a subset of pretreatment\n GAN<\/jats:styled-content>\n patients ages 6\u201314\u2009years. For radiologic\u2010pathologic correlation, we examined histologically spinal cords from\n GAN<\/jats:styled-content>\n rodent models with pathological features of human\n GAN<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 10\n GAN<\/jats:styled-content>\n \u2010patient spinal\n MRIs<\/jats:styled-content>\n , 7 showed cervical or diffuse cord atrophy. Five\n MRIs<\/jats:styled-content>\n additionally showed hyperintense,\n T2<\/jats:styled-content>\n \u2010signal abnormalities bilaterally in the cervical gracile tracts. Microscopy of\n GAN<\/jats:styled-content>\n \u2010rodent spinal cords revealed many actively degenerating axons in the cervical gracile tracts but few degenerating axons elsewhere in the cord.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n The localization of spinal T\u20102 signal abnormalities to the cervical gracile tracts in GAN patients mirrors the localization of active dying\u2010back axonal degeneration in GAN rodent models and suggests that these T2\u2010signal abnormalities may be used as a surrogate marker of active axonal degeneration in the long tracts of the spinal cord in GAN and possibly other dying\u2010back neurodegenerative diseases involving the spinal cord.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mus.70004","type":"journal-article","created":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T08:14:23Z","timestamp":1755332063000},"page":"1152-1155","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["T2<\/scp>\n Hyperintensities in Gracile Tracts of Cervical Spinal Cord in Giant Axonal Neuropathy (\n GAN<\/scp>\n )"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5540-5422","authenticated-orcid":false,"given":"Diane","family":"Armao","sequence":"first","affiliation":[{"name":"Department of Radiology University of North Carolina at Chapel Hill School of Medicine Chapel Hill North Carolina USA"},{"name":"Department of Pathology and Laboratory Medicine University of North Carolina at Chapel Hill School of Medicine Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas W.","family":"Bouldin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of North Carolina at Chapel Hill School of Medicine Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana X.","family":"Bharucha\u2010Goebel","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"},{"name":"Children's National Hospital Washington District of Columbia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terry S.","family":"Hartman","sequence":"additional","affiliation":[{"name":"North Carolina Translational and Clinical Sciences Institute, University of North Carolina at Chapel Hill School of Medicine Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven J.","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Texas Southwestern Medical Center Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel M.","family":"Bailey","sequence":"additional","affiliation":[{"name":"Center for Alzheimer's and Neurodegenerative Diseases University of Texas Southwestern Medical Center Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimah","family":"Saade","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Iowa Carver College of Medicine Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua J.","family":"Todd","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minal","family":"Jain","sequence":"additional","affiliation":[{"name":"National Institutes of Health, Clinical Research Center, Rehabilitation Medicine Department Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Waite","sequence":"additional","affiliation":[{"name":"National Institutes of Health, Clinical Research Center, Rehabilitation Medicine Department Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten G.","family":"B\u00f6nnemann","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Keith","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Radiology University of North Carolina at Chapel Hill School of Medicine Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073814542946"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab179"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410220118"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.21425"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2307952"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/13816810.2021"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1483"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.69.2.150"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70258-8"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389000500316"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00693779"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00691956"}],"container-title":["Muscle & Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.70004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T07:20:27Z","timestamp":1764228027000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.70004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,16]]},"references-count":12,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/mus.70004"],"URL":"https:\/\/doi.org\/10.1002\/mus.70004","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"type":"print","value":"0148-639X"},{"type":"electronic","value":"1097-4598"}],"subject":[],"published":{"date-parts":[[2025,8,16]]},"assertion":[{"value":"2024-12-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}