{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:07:37Z","timestamp":1787944057436,"version":"build-2784847793"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Evolving evidence suggests that measurement of cerebrospinal fluid (CSF) kappa free light chain (KFLC) synthesis has high diagnostic sensitivity and specificity for multiple sclerosis (MS), but its prognostic ability is less investigated. The usefulness of KFLC in predicting cognitive impairment (CI) is still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a monocentric longitudinal retrospecitve cohort study, KFLC-index ([CSF KFLC\/serum KFLC]\/[CSF albumin\/serum albumin]) measured by latex-enhanced immunonephelometry was prospectively determined as part of the diagnostic workup in patients with early relapsing-remitting MS (RRMS, n=77). The ability of KFLC-index to predict information processing speed (IPS) worsening as assessed with the symbol digit modalities test (SDMT) was investigated in univariable and multivariable models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In patients with KFLC-index&amp;gt;100 (n=31), 11 subjects (35.5%) showed reduced SDMT scores by \u22658 points at follow-up (mean follow-up time 7.3 \u00b1 2.6 years), compared with their baseline scores (p=0.01). Baseline KFLC-index&amp;gt;100 was strongly associated with a higher hazard of SDMT score reduction at follow-up (adjusted hazard ratio 10.5, 95% confidence interval 2.2-50.8, p=0.003; median time to SDMT reduction 7 years).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Intrathecal KFLC synthesis has become an attractive diagnostic tool for MS. We show for the first time that in a real-world setting of early RRMS, KFLC-index predicted cognitive decline. Whether this predictive ability of KFLC-index also concerns other cognitive domains than IPS, warrants further investigations.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1106028","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T12:38:50Z","timestamp":1674218330000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["High levels of kappa free light chain synthesis predict cognitive decline in relapsing-remitting multiple sclerosis"],"prefix":"10.3389","volume":"14","author":[{"given":"Igal","family":"Rosenstein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Axelsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"Novakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Rasch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lycke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/ene.13819","article-title":"Multiple sclerosis - a review","volume":"26","author":"Dobson","year":"2019","journal-title":"Eur J Neurol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000000560","article-title":"Defining the clinical course of multiple sclerosis: The 2013 revisions","volume":"83","author":"Lublin","year":"2014","journal-title":"Neurology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12715","article-title":"Cognitive impairment in a population-based study of patients with multiple sclerosis: Differences between late relapsing-remitting, secondary progressive and primary progressive multiple sclerosis","volume":"23","author":"Planche","year":"2016","journal-title":"Eur J Neurol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(14)70256-x","article-title":"Pathological mechanisms in progressive multiple sclerosis","volume":"14","author":"Mahad","year":"2015","journal-title":"Lancet Neurol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.168","article-title":"Progressive multiple sclerosis: Pathology and pathogenesis","volume":"8","author":"Lassmann","year":"2012","journal-title":"Nat Rev Neurol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1017\/s1355617717000959","article-title":"Neuropsychology of multiple sclerosis: Looking back and moving forward","volume":"23","author":"Benedict","year":"2017","journal-title":"J Int Neuropsychol Society: JINS"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1177\/1352458507077943","article-title":"Cognitive dysfunction in patients with clinically isolated syndromes or newly diagnosed multiple sclerosis","volume":"13","author":"Glanz","year":"2007","journal-title":"Mult Scler"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.41.5.685","article-title":"Cognitive dysfunction in multiple sclerosis","volume":"41","author":"Rao","year":"1991","journal-title":"I. 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