{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T21:56:53Z","timestamp":1784930213268,"version":"3.55.0"},"reference-count":33,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To explore whether proxies of premorbid structural reserve\u2014intracranial volume (ICV) and spinal cervical canal area (SCCA)\u2014influence long-term disability accumulation in multiple sclerosis (MS), specifically through progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We included 253 patients with relapsing-onset MS, \u2a7e5-year follow-up from first demyelinating event (FDE), and available 3D T1-weighted magnetic resonance imaging (MRI) scan enabling estimation of ICV and SCCA. To account for PIRA and RAW co-occurrence in the same individuals, we used negative binomial regression to estimate adjusted event rate ratios (adj.-ERRs) and competing risk models to derive subdistribution hazard ratios (SHRs) for PIRA and RAW events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Over a median 17-year follow-up, higher SCCA was associated with fewer PIRA events (adj.-ERR\u2009=\u20090.74,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.014) and delayed PIRA onset (SHR\u2009=\u20090.50,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.05), while larger ICV was associated with fewer RAW events (adj.-ERR\u2009=\u20090.70,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.033) and both later occurrence (SHR\u2009=\u20090.41,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.02) and older age at RAW (SHR\u2009=\u20090.30,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.002). Patients with high combined reserve (both larger ICV and SCCA) reached EDSS\u2009\u2a7e\u20096.0 later (hazard ratio (HR)\u2009=\u20090.33,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.025) and at older age (HR\u2009=\u20090.37,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.045) than those with low reserve.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Pre-morbid structural reserve mitigates the MS-related disability accrual, supporting the integration of ICV and SCCA into prognostic models as markers of neuroanatomical resilience.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585251372440","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T09:33:35Z","timestamp":1759916015000},"page":"1472-1482","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["How premorbid structural reserve affects disability accrual in multiple sclerosis"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0450-7699","authenticated-orcid":false,"given":"Elena","family":"Barbuti","sequence":"first","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, Rome, Italy"},{"name":"MS Centre, S. Andrea Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3237-6267","authenticated-orcid":false,"given":"Luca","family":"Prosperini","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, S. Camillo-Forlanini Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Ruggieri","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, S. Camillo-Forlanini Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalom","family":"Haggiag","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, S. Camillo-Forlanini Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Stasolla","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, S. Camillo-Forlanini Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Pozzilli","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, Rome, Italy"},{"name":"MS Centre, S. Andrea Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3959-4067","authenticated-orcid":false,"given":"Claudio","family":"Gasperini","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, S. Camillo-Forlanini Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9037-7300","authenticated-orcid":false,"given":"Carla","family":"Tortorella","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, S. Camillo-Forlanini Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9429-2769","authenticated-orcid":false,"given":"Maria","family":"Petracca","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.3331"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26913"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.03.022"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000433"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002702"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjno-2024-000670"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2022-330613"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000210136"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/13524585241272046"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2025.0495"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01475-y"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318296e98b"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A7899"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1177\/13524585241266180"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.2453"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30076-5"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.3238"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207936"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac016"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/122.12.2279"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02408-y"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207768"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200388"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200399"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2023-331799"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26281"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2017.01.007"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh721"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000213744"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-025-13221-x"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.33"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-018-0408-5"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26776"}],"container-title":["Multiple Sclerosis Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585251372440","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13524585251372440","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585251372440","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:19:30Z","timestamp":1777695570000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13524585251372440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":33,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1177\/13524585251372440"],"URL":"https:\/\/doi.org\/10.1177\/13524585251372440","relation":{},"ISSN":["1352-4585","1477-0970"],"issn-type":[{"value":"1352-4585","type":"print"},{"value":"1477-0970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]}}}