{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T08:18:33Z","timestamp":1770884313802,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:00:00Z","timestamp":1672272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>In multiple sclerosis (MS), the transition from relapsing-remitting to the secondary-progressive phase is characterized by a progression independent of relapse activity (PIRA), resulting in physical disability accumulation and invisible symptoms, i.e., fatigue and cognitive impairment (CI). These symptoms are related to neurodegenerative processes and have been correlated with MRI measures of brain atrophy only at a group level; however, the application in clinical practice of atrophy-based measurements for single-patient evaluation is yet to be fully investigated. In the present study, we aimed to evaluate the association between brain atrophy, measured with easy-to-use automatic software, and the \u201cinvisible\u201d MS symptoms of cognition and fatigue. A total of 69 MS patients were included in the study; cognitive impairment and fatigue (FSS) (in addition to neurological disability, EDSS) were assessed and correlated with brain volumes calculated using the automated software QyScore\u00ae which is validated for single-patient use in the clinical setting. Results showed that the cognitive status was accurately reflected by measures of atrophy, with a sensitivity of up to 90%. CI patients showed a lower volume compared to cognitively normal patients in the whole brain (p = 0.017), gray matter (p = 0.042), insula (p = 0.035), cerebellum (p = 0.008), and limbic lobe (p = 0.049). FSS was associated with temporal lobe (r = \u22120.37, p = 0.013) and insular (r = \u22120.36, p = 0.019) volumes. The volumes of the same regions were also associated with EDSS. The global\/regional atrophy results, assessed with automatic and easy-to-use software, correlated with cognitive and fatigue symptoms, thus supporting the clinical application in routine patient management.<\/jats:p>","DOI":"10.3390\/bioengineering10010041","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T02:54:42Z","timestamp":1672282482000},"page":"41","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Making Visible the Invisible: Automatically Measured Global and Regional Brain Volume Is Associated with Cognitive Impairment and Fatigue in Multiple Sclerosis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0426-7223","authenticated-orcid":false,"given":"Stefano","family":"Ziccardi","sequence":"first","affiliation":[{"name":"Neurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca Benedetta","family":"Pizzini","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2341-9253","authenticated-orcid":false,"given":"Maddalena","family":"Guandalini","sequence":"additional","affiliation":[{"name":"Neurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnese","family":"Tamanti","sequence":"additional","affiliation":[{"name":"Neurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Cristofori","sequence":"additional","affiliation":[{"name":"Neurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3362-7403","authenticated-orcid":false,"given":"Massimiliano","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Neurology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1212\/WNL.0000000000000768","article-title":"Atlas of Multiple Sclerosis 2013: A growing global problem with widespread inequity","volume":"83","author":"Browne","year":"2014","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/ni0901-762","article-title":"Multiple sclerosis: A two-stage disease","volume":"2","author":"Steinman","year":"2001","journal-title":"Nat. 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