{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T04:10:15Z","timestamp":1784520615993,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Radiologically isolated syndrome (RIS) is defined by MRI findings that are suggestive of multiple sclerosis (MS) in the absence of prior clinical demyelinating events. We aimed to compare the health-related quality of life (HRQoL) between RIS and relapsing\u2013remitting MS (RRMS) after adjusting for fatigue, cognition, and psychological distress, and to contextualize generic HRQoL, relative to healthy controls. Methods: In this cross-sectional analysis of the baseline data, 30 RIS, 29 RRMS, and 30 healthy controls were analyzed. MS-specific HRQoL (patients only) was assessed with the Functional Assessment of Multiple Sclerosis (FAMS), and generic HRQoL (all participants) was assessed with the EuroQol-5D (EQ-5D) visual analogue scale and utility index. Multi-variable linear regression models with robust (HC3) standard errors were used, adjusting for demographics, fatigue impact, cognitive performance, and psychological distress. Results: The FAMS totals were similar in RIS vs. RRMS (median 167.5 vs. 164.0; p = 0.694) and remained non-different after adjustment (\u03b2= \u22122.37, 95% CI \u221210.18 to 5.44; p = 0.544). EQ-5D outcomes showed an unadjusted gradient across groups, but adjusted differences relative to RIS were not statistically significant. Greater fatigue impact was associated with poorer HRQoL across all models (all p &lt; 0.001). Psychological distress was associated with lower FAMS (\u03b2 = \u221214.53; p &lt; 0.001) but not with EQ-5D outcomes. Conclusions: HRQoL in RIS was comparable to RRMS, and fatigue impact was the most consistent correlate of poorer HRQoL.<\/jats:p>","DOI":"10.3390\/jcm15062184","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:26:19Z","timestamp":1773390379000},"page":"2184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Health-Related Quality of Life in Radiologically Isolated Syndrome Resembles Relapsing\u2013Remitting Multiple Sclerosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1769-4809","authenticated-orcid":false,"given":"Juli\u00e1n","family":"Benito-Le\u00f3n","sequence":"first","affiliation":[{"name":"Department of Neurology, 12 de Octubre University Hospital, 28041 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"},{"name":"Department of Medicine, Faculty of Medicine, Complutense University, 28040 Madrid, Spain"},{"name":"Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6768-189X","authenticated-orcid":false,"given":"Mar\u00eda","family":"D\u00edez-Cirarda","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitario Cl\u00ednico San Carlos, Health Research Institute \u201cSan Carlos\u201d (IdISCC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9993-1865","authenticated-orcid":false,"given":"Mariano","family":"Ruiz-Ortiz","sequence":"additional","affiliation":[{"name":"Department of Neurology, 12 de Octubre University Hospital, 28041 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Aladro","sequence":"additional","affiliation":[{"name":"Department of Neurology, Getafe University Hospital, 28905 Getafe, Spain"},{"name":"Faculty of Biomedical and Health Sciences, European University of Madrid, 28670 Villaviciosa de Od\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9192-9971","authenticated-orcid":false,"given":"Constanza","family":"Cuevas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitario Cl\u00ednico San Carlos, Health Research Institute \u201cSan Carlos\u201d (IdISCC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngela","family":"Domingo-Santos","sequence":"additional","affiliation":[{"name":"Department of Neurology, 12 de Octubre University Hospital, 28041 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Gal\u00e1n S\u00e1nchez-Seco","sequence":"additional","affiliation":[{"name":"Department of Neurology, 12 de Octubre University Hospital, 28041 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Labiano-Fontcuberta","sequence":"additional","affiliation":[{"name":"Department of Neurology, 12 de Octubre University Hospital, 28041 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5063-439X","authenticated-orcid":false,"given":"Ana","family":"G\u00f3mez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Neurology, 12 de Octubre University Hospital, 28041 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9218-5206","authenticated-orcid":false,"given":"Paula","family":"Salgado-C\u00e1mara","sequence":"additional","affiliation":[{"name":"Department of Neurology, 12 de Octubre University Hospital, 28041 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6512-4413","authenticated-orcid":false,"given":"Lucienne","family":"Costa-Frossard","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ram\u00f3n y Cajal University Hospital, Red Espa\u00f1ola de Esclerosis M\u00faltiple (REEM), Red de Enfermedades Inflamatorias (REI), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3293-0125","authenticated-orcid":false,"given":"Enric","family":"Monreal","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ram\u00f3n y Cajal University Hospital, Red Espa\u00f1ola de Esclerosis M\u00faltiple (REEM), Red de Enfermedades Inflamatorias (REI), 28034 Madrid, Spain"},{"name":"Department of Medicine, Faculty of Medicine, Alcal\u00e1 de Henares University, 28805 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8605-0049","authenticated-orcid":false,"given":"Susana","family":"Sainz de la Maza","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ram\u00f3n y Cajal University Hospital, Red Espa\u00f1ola de Esclerosis M\u00faltiple (REEM), Red de Enfermedades Inflamatorias (REI), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8162-9043","authenticated-orcid":false,"given":"Jorge","family":"Mat\u00edas-Guiu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Complutense University, 28040 Madrid, Spain"},{"name":"Department of Neurology, Hospital Universitario Cl\u00ednico San Carlos, Health Research Institute \u201cSan Carlos\u201d (IdISCC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Montero-Escribano","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitario Cl\u00ednico San Carlos, Health Research Institute \u201cSan Carlos\u201d (IdISCC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Luisa","family":"Mart\u00ednez-Gin\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Neurology, Gregorio Mara\u00f1\u00f3n General University Hospital, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Ayuso-Peralta","sequence":"additional","affiliation":[{"name":"Department of Neurology, Pr\u00edncipe de Asturias University Hospital, 28805 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5520-2708","authenticated-orcid":false,"given":"Jordi A.","family":"Mat\u00edas-Guiu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Complutense University, 28040 Madrid, Spain"},{"name":"Department of Neurology, Hospital Universitario Cl\u00ednico San Carlos, Health Research Institute \u201cSan Carlos\u201d (IdISCC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1212\/01.wnl.0000335764.14513.1a","article-title":"Incidental MRI anomalies suggestive of multiple sclerosis: The radiologically isolated syndrome","volume":"72","author":"Okuda","year":"2009","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1212\/01.wnl.0000337255.89622.ce","article-title":"The radiologically isolated syndrome: Is it very early multiple sclerosis?","volume":"72","author":"Bourdette","year":"2009","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1177\/1352458512451943","article-title":"Radiologically isolated syndrome\u2014incidental magnetic resonance imaging findings suggestive of multiple sclerosis, a systematic 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