{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:43:28Z","timestamp":1792691008276,"version":"4.5.0"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jeroen Bosch Hospital Stipendium"},{"DOI":"10.13039\/501100014103","name":"Spoedeisende Geneeskunde Onderzoeksfonds","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014103","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dutch Organization for knowledge and innovation in health, healthcare and well-being","award":["10330022010010"],"award-info":[{"award-number":["10330022010010"]}]},{"name":"St. Jacobusstichting"},{"name":"Stichting Researchfonds Bronovo"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with isolated acute-onset continuous dizziness (iAOCD) are commonly seen at the emergency department (ED). Distinguishing peripheral vestibular disorders from central causes remains challenging. Existing diagnostic tools, including bedside examination and neuroimaging, have important limitations. Otolin-1, an inner ear\u2013specific glycoprotein, has been proposed as a biomarker of peripheral vestibular pathology. This study evaluated whether otolin-1 could serve as a diagnostic biomarker for this differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study analyzed samples from a prospective multicenter cohort of adult patients who were seen at the ED with acute onset, continuous dizziness without focal neurological deficits. Patients were included within 24 hours of symptom onset. Otolin-1 plasma concentrations were measured using an enzyme-linked immunosorbent assay. Final diagnoses (central versus peripheral) were determined by an expert panel based on clinical assessment, diffusion-weighted magnetic resonance imaging and 3-month follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We analyzed 245 patients (179 peripheral, 66 central). Median otolin-1 concentrations did not differ significantly between peripheral and central causes (517.6 [IQR 443.7\u2013592.8] pg\/mL vs 487.9 [424.9\u2013644.4] pg\/mL; p\u2009=\u20090.349). No significant differences were observed in hyperacute (&lt;4.5 hours after symptom onset) or acute (4.5\u201324 hours after symptom onset) subgroups. Similarly, otolin-1 concentrations did not differ between central iAOCD and specific peripheral diagnoses. Substantial overlap in concentration ranges was observed across all comparisons. Receiver operating characteristic analysis similarly showed no useful discrimination (AUC 0.539, 95% CI 0.455\u20130.623).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Otolin-1 does not differentiate between central and peripheral causes of iAOCD in the ED setting. Although biologically linked to inner ear pathology, otolin-1 lacks sufficient discriminatory value as a stand-alone diagnostic biomarker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0361036","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:24:14Z","timestamp":1792689854000},"page":"e0361036","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Otolin-1 for differentiating central and peripheral causes of acute continuous dizziness"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2566-1230","authenticated-orcid":true,"given":"Vincent W.","family":"Klokman","sequence":"first","affiliation":[{"name":"Jeroen Bosch Hospital","place":["\u2018s-Hertogenbosch, the Netherlands"],"department":["Department of Emergency Medicine"]},{"name":"University Medical Center Utrecht","place":["Utrecht, the Netherlands"],"department":["Department of Vascular Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0976-4181","authenticated-orcid":true,"given":"Merel J. J.","family":"Verhagen","sequence":"additional","affiliation":[{"name":"Haga Hospital","place":["The Hague, the Netherlands"],"department":["Department of Neurology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A. J.","family":"Ros","sequence":"additional","affiliation":[{"name":"Maasstad Hospital","place":["Rotterdam, the Netherlands"],"department":["Department of Neurology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlijn F.","family":"de Laat","sequence":"additional","affiliation":[{"name":"St. Antonius Hospital","place":["Nieuwegein, the Netherlands"],"department":["Department of Neurology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korn\u00e9","family":"Jellema","sequence":"additional","affiliation":[{"name":"Haaglanden Medical Center","place":["The Hague, the Netherlands"],"department":["Department of Neurology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique P. V.","family":"de Kleijn","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht","place":["Utrecht, the Netherlands"],"department":["Department of Vascular Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7661-5712","authenticated-orcid":true,"given":"Kim E.","family":"Jie","sequence":"additional","affiliation":[{"name":"Jeroen Bosch Hospital","place":["\u2018s-Hertogenbosch, the Netherlands"],"department":["Department of Emergency Medicine"]},{"name":"University Medical Center Utrecht","place":["Utrecht, the Netherlands"],"department":["Department of Vascular Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"pone.0361036.ref001","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/j.1553-2712.2008.00189.x","article-title":"Dizziness presentations in US emergency departments, 1995\u20132004","volume":"15","author":"KA Kerber","year":"2008","journal-title":"Acad Emerg Med"},{"key":"pone.0361036.ref002","doi-asserted-by":"crossref","first-page":"765","DOI":"10.4065\/83.7.765","article-title":"Spectrum of dizziness visits to US emergency departments","volume":"83","author":"DE Newman-Toker","year":"2008","journal-title":"Mayo Clin Proc"},{"key":"pone.0361036.ref003","doi-asserted-by":"crossref","DOI":"10.1503\/cmaj.100174","article-title":"Does my dizzy patient have a stroke?","volume":"183","author":"AA Tarnutzer","year":"2011","journal-title":"CMAJ"},{"issue":"11","key":"pone.0361036.ref004","doi-asserted-by":"crossref","first-page":"3504","DOI":"10.1161\/STROKEAHA.109.551234","article-title":"HINTS to Diagnose Stroke in the Acute Vestibular Syndrome","volume":"40","author":"JC Kattah","year":"2009","journal-title":"Stroke"},{"issue":"9","key":"pone.0361036.ref005","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1111\/acem.13960","article-title":"Can Emergency Physicians Accurately Rule Out a Central Cause of Vertigo Using the HINTS Examination? 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