{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:51:32Z","timestamp":1791204692622,"version":"4.2.0"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["441409627"],"award-info":[{"award-number":["441409627"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spasticity represents a core clinical feature of Autosomal Recessive Spastic Ataxia of Charlevoix\u2010Saguenay (ARSACS) patients. Nonetheless, its pathophysiological substrate is poorly investigated. We assessed the microstructural integrity of the corticospinal tract (CST) using diffusion MRI (dMRI) via profilometry analysis to understand its possible role in the development of spasticity in ARSACS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>In this multi\u2010center prospective study, data of 37 ARSACS (M\/F\u2009=\u200921\/16; 33.4\u2009\u00b1\u200912.4\u2009years) and 29 controls (M\/F\u2009=\u200913\/16; 42.1\u2009\u00b1\u200917.2\u2009years) acquired within the PROSPAX consortium were collected from January 2021 to October 2022 and analyzed. Differences in terms of global CST microstructural integrity were probed, as well as a possible spatial distribution of the damage along the tract via profilometry analysis. Possible correlations between clinical severity, including the Spastic Paraplegia Rating Scale (SPRS), were also tested.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A significant global involvement of the CST was found in ARSACS compared to controls (all tests with\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), with a spatially defined pattern of more pronounced microstructural integrity loss occurring right below and above the pons, a structure that was also confirmed to be thickened in these patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). A bilateral negative correlation emerged between the microstructural integrity of the CST and clinical indices of spasticity expressed via SPRS (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02 for both CSTs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A clinically meaningful microstructural involvement of CST is present in ARSACS patients, with a spatially defined pattern of damage occurring right below and above a thickened pons. An evaluation of the microstructure of this bundle might serve as a possible biomarker in this condition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70128","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T04:40:38Z","timestamp":1745815238000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An Investigation of Corticospinal Tract Microstructural Integrity in ARSACS Using a Profilometry MRI Analysis: Results From the PROSPAX Study"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6375-5783","authenticated-orcid":false,"given":"Alessandra","family":"Scaravilli","sequence":"first","affiliation":[{"name":"Department of Advanced Biomedical Sciences University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Mari","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Diffusion Imaging and Connectivity Estimation (DICE) lab University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Gabusi","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Diffusion Imaging and Connectivity Estimation (DICE) lab University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Battocchio","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Diffusion Imaging and Connectivity Estimation (DICE) lab University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bosticardo","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Diffusion Imaging and Connectivity Estimation (DICE) lab University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Schiavi","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Diffusion Imaging and Connectivity Estimation (DICE) lab University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Bender","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Neuroradiology University of T\u00fcbingen  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kessler","sequence":"additional","affiliation":[{"name":"Center for Neurology and Hertie Institute for Clinical Brain Research University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4207-5065","authenticated-orcid":false,"given":"Roberta","family":"La Piana","sequence":"additional","affiliation":[{"name":"Department of Neurology &amp; Neurosurgery Montreal Neurological Institute, McGill University  Montreal Canada"},{"name":"Department of Diagnostic Radiology McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart P.","family":"van de Warrenburg","sequence":"additional","affiliation":[{"name":"Department of Neurology Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirco","family":"Cosottini","sequence":"additional","affiliation":[{"name":"Department of Translational Research on New Technologies in Medicine and Surgery University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Timmann","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center for Translational Neuro\u2010 and Behavioral Sciences (C\u2010TNBS) Essen University Hospital  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"PROSPAX Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Daducci","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Diffusion Imaging and Connectivity Estimation (DICE) lab University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Sch\u00fcle","sequence":"additional","affiliation":[{"name":"Center for Neurology and Hertie Institute for Clinical Brain Research University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE)  T\u00fcbingen Germany"},{"name":"Division of Neurodegenerative Diseases, Department of Neurology Heidelberg University Hospital and Faculty of Medicine  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2280-7273","authenticated-orcid":false,"given":"Matthis","family":"Synofzik","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE)  T\u00fcbingen Germany"},{"name":"Division Translational Genomics of Neurodegenerative Diseases Center for Neurology and Hertie Institute for Clinical Brain Research, University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1359-9062","authenticated-orcid":false,"given":"Filippo Maria","family":"Santorelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine IRCCS Stella Maris Foundation  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0300-5160","authenticated-orcid":false,"given":"Sirio","family":"Cocozza","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/72769"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f4d86c"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(07)70054\u20106"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2011.03.005"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048\u2010008\u20100131\u20107"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/354906"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2010.00149"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031\u2010007\u20100029\u20100"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2011.05.011"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A3488"},{"key":"e_1_2_10_12_1","unstructured":"\u201cPROSPAX\u2014An Integrated Multimodal Progression Chart in Spastic Ataxias. 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