{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:00:51Z","timestamp":1793368851900,"version":"4.5.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Blood-cerebrospinal fluid (CSF) barrier dysfunction is pivotal for diagnosing immune-mediated neuropathies, especially in spinal nerve root inflammation. Typically, either total CSF protein or the CSF to serum albumin ratio (Q<jats:sub>Alb<\/jats:sub>) is measured. Total CSF protein measurements have limitations, notably its fixed reference value regardless of age, in contrast to the age-dependent reference for Q<jats:sub>Alb<\/jats:sub>. Our goal was to evaluate both markers in patients with immune-mediated neuropathies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In our multicenter research, we collected retrospective CSF data from patients suffering from immune-mediated neuropathies across four German research centers. These parameters were analyzed in relation to their clinical characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Out of 419 samples, 36 (8.6%) displayed a notable variation between total CSF protein and Q<jats:sub>Alb<\/jats:sub> values. A detailed analysis revealed that patients displaying elevated Q<jats:sub>Alb<\/jats:sub> but normal total CSF protein levels were significantly younger at disease onset (<jats:italic>p<\/jats:italic>\u2009=\u20090.01), at the time of diagnosis (<jats:italic>p<\/jats:italic>\u2009=\u20090.005), and when undergoing lumbar puncture (<jats:italic>p<\/jats:italic>\u2009=\u20090.001) compared to patients with elevated CSF protein and normal Q<jats:sub>Alb<\/jats:sub> levels. These effects were especially evident for the subgroup of samples derived by female patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our work confirms the crucial role of Q<jats:sub>Alb<\/jats:sub> in diagnosing immune-mediated neuropathies and particularly its efficacy as a marker for evaluating the blood-CSF barrier in patients with an earlier disease onset. Considering the significance of the albumin quotient, its assessment is especially advisable in younger patients of female sex to avoid missing a potential barrier dysfunction that might be falsely negative when using total protein.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2023.1330484","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T04:39:57Z","timestamp":1704775197000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Comparative analysis of albumin quotient and total CSF protein in immune-mediated neuropathies: a multicenter study on diagnostic implications"],"prefix":"10.3389","volume":"14","author":[{"given":"Tabea","family":"Seeliger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Gingele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunus Emre","family":"G\u00fczeloglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Heitmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"L\u00fcling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Kohle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Pre\u00dfler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Stascheit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremias","family":"Motte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Lena","family":"Fisse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gr\u00fcter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalliopi","family":"Pitarokoili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Skripuletz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e0228679","DOI":"10.1371\/JOURNAL.PONE.0228679","article-title":"Patients with chronic autoimmune demyelinating polyneuropathies exhibit cognitive deficits which might be associated with CSF evidence of blood-brain barrier disturbance","volume":"15","author":"Yalachkov","year":"2020","journal-title":"PloS One"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1136\/jnnp-2020-325868","article-title":"Oligoclonal IgG bands in chronic inflammatory polyradiculoneuropathies","volume":"92","author":"Ruiz","year":"2021","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1111\/JNS.12455\/SUPINFO","article-title":"European academy of neurology\/peripheral nerve society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force\u2014second revision","volume":"26","author":"Van den Bergh","year":"2021","journal-title":"J Peripher Nerv Syst"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/J.1529-8027.2010.00290.X","article-title":"European Federation of Neurological Societies\/peripheral nerve society guideline on management of multifocal motor neuropathy. 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Neurol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/S1474-4422(17)30378-2","article-title":"Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"17","author":"van Schaik","year":"2018","journal-title":"Lancet Neurol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1002\/mus.880141111","article-title":"Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barr\u00e9 syndrome","volume":"14","author":"Kleyweg","year":"1991","journal-title":"Muscle Nerve"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1177\/135245859800400302","article-title":"Cerebrospinal fluid--physiology, analysis and interpretation of protein patterns for diagnosis of neurological 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