{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:47:02Z","timestamp":1775868422703,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,19]],"date-time":"2025-01-19T00:00:00Z","timestamp":1737244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The pathophysiology of cognitive impairment (CI) in multiple sclerosis (MS) remains unclear. Meningeal B cell aggregates may contribute to cortical grey matter pathology. Cerebrospinal fluid (CSF), kappa free light chains (KFLC), and KFLCs-Index (kappa-Index) are reliable quantitative markers of intrathecal synthesis, but few data have been presented exploring the association with CI, and no data are present for lambda FLC (LFLC) in MS. We evaluated cognition using the Brief International Cognitive Assessment for MS (BICAMS) battery and collected serum and CSF at diagnosis in newly diagnosed drug-na\u00efve MS patients. We observed that patients with impaired verbal memory and overall CI showed increased CSF KFLCs (respectively p: 0.0003 and p: 0.003) and kappa-Index (respectively p: 0.01 and p: 0.02) compared to those with normal verbal memory and no CI. Patients with CI also displayed lower CSF LFLCs (p: 0.04) and lambda-Index (p: 0.001); however, only CSF KFLC negatively correlated with normalized results of verbal memory (for age, sex, and educational levels), even after correction for EDSS (r: \u22120.27 p: 0.01). Finally, CSF FKLC and kappa-Index were significant predictors of verbal memory in a multivariate analysis. Our results, suggest that intrathecal B cell activity might contribute to CI development in MS patients.<\/jats:p>","DOI":"10.3390\/ijms26020826","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T06:53:32Z","timestamp":1737442412000},"page":"826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Biomarkers of Intrathecal Synthesis May Be Associated with Cognitive Impairment at MS Diagnosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0045-3806","authenticated-orcid":false,"given":"Eleonora","family":"Virgilio","sequence":"first","affiliation":[{"name":"Neurology Unit, Department of Clinical and Biological Sciences, University Hospital San Luigi Gonzaga, University of Turin, 10043 Turin, Italy"},{"name":"Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Ciampana","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Translational Medicine, University Hospital Maggiore della Carit\u00e0 di Novara, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0416-6687","authenticated-orcid":false,"given":"Chiara","family":"Puricelli","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry, University Hospital Maggiore della Carit\u00e0 di Novara, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Naldi","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Translational Medicine, University Hospital Maggiore della Carit\u00e0 di Novara, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6195-7357","authenticated-orcid":false,"given":"Angelo","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Translational Medicine, University Hospital Maggiore della Carit\u00e0 di Novara, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umberto","family":"Dianzani","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy"},{"name":"Clinical Biochemistry, University Hospital Maggiore della Carit\u00e0 di Novara, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5920-9210","authenticated-orcid":false,"given":"Domizia","family":"Vecchio","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy"},{"name":"Neurology Unit, Department of Translational Medicine, University Hospital Maggiore della Carit\u00e0 di Novara, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6862-9468","authenticated-orcid":false,"given":"Cristoforo","family":"Comi","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy"},{"name":"Neurology Unit, Department of Translational Medicine, University Hospital Maggiore della Carit\u00e0 di Novara, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/S1474-4422(20)30277-5","article-title":"Cognitive impairment in multiple sclerosis: Clinical management, MRI, and therapeutic avenues","volume":"19","author":"Benedict","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/s41583-018-0053-9","article-title":"Multiple sclerosis and cognition: Synaptic failure and network dysfunction","volume":"19","author":"Portaccio","year":"2018","journal-title":"Nat. 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