{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:51:20Z","timestamp":1791341480740,"version":"4.3.1"},"reference-count":84,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000894","name":"Spinal Muscular Atrophy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000894","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012070","name":"Anatomical Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020940","name":"National Institutes of Health, Pakistan","doi-asserted-by":"publisher","award":["R35NS122306"],"award-info":[{"award-number":["R35NS122306"]}],"id":[{"id":"10.13039\/100020940","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Spinal muscular atrophy (SMA) is a life\u2010limiting paediatric motor neuron disease characterised by lower motor neuron loss, skeletal muscle atrophy and respiratory failure, if untreated. Revolutionary treatments now extend patient survival. However, a limited understanding of the foundational neuropathology challenges the evaluation of therapeutic success. As opportunities to study treatment\u2010na\u00efve tissue decrease, we have characterised spinal cord pathology in severe infantile SMA using gold\u2010standard techniques, providing a baseline to measure treatment success and therapeutic limitations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Detailed histological analysis, stereology and transmission electron microscopy were applied to post\u2010mortem spinal cord from severe infantile SMA patients to estimate neuron number at the end of life; characterise the morphology of ventral horn, lateral horn and Clarke's column neuron populations; assess cross\u2010sectional spinal cord area; and observe myelinated white matter tracts in the clinically relevant thoracic spinal cord.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ventral horn neuron loss was substantial in all patients, even the youngest cases. The remaining ventral horn neurons were small with abnormal, occasionally chromatolytic morphology, indicating cellular damage. In addition to ventral horn pathology, Clarke's column sensory\u2013associated neurons displayed morphological features of cellular injury, in contrast to the preserved sympathetic lateral horn neurons. Cellular changes were associated with aberrant development of grey and white matter structures that affected the overall dimensions of the spinal cord.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We provide robust quantification of the neuronal deficit found at the end of life in SMA spinal cord. We question long\u2010accepted dogmas of SMA pathogenesis and shed new light on SMA neuropathology out with the ventral horn, which must be considered in future therapeutic design.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.13013","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T02:26:21Z","timestamp":1729823181000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A reassessment of spinal cord pathology in severe infantile spinal muscular atrophy"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6967-4706","authenticated-orcid":false,"given":"Hazel","family":"Allardyce","sequence":"first","affiliation":[{"name":"Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition University of Aberdeen  Aberdeen Scotland UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin D.","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition University of Aberdeen  Aberdeen Scotland UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas O.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Neurology and Pediatrics Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte J.","family":"Sumner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neuroscience, and Genetic Medicine Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8848-8738","authenticated-orcid":false,"given":"Simon H.","family":"Parson","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition University of Aberdeen  Aberdeen Scotland UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(08)60921\u20106"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u201012\u2010803685\u20103.00014\u20108"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u2010510X(97)00161\u20105"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01776636"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010008\u20100411\u20101"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01669211"},{"key":"e_1_2_13_8_1","unstructured":"Jing C. 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