{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:35:13Z","timestamp":1787063713646,"version":"build-2736575974"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001665","name":"French National Research Agency","doi-asserted-by":"publisher","award":["ANR-24-INBS-0015"],"award-info":[{"award-number":["ANR-24-INBS-0015"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation pour la Recherche M\u00e9dicale"},{"name":"European Community","award":["ERARE18-052 NARCOMICS"],"award-info":[{"award-number":["ERARE18-052 NARCOMICS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Study Objectives<\/jats:title>\n                    <jats:p>Cerebrospinal fluid (CSF) hypocretin-1\/orexin-A quantification via radioimmunoassay (RIA) is used for diagnosing narcolepsy type 1(NT1), but its limitations require alternative methods. Using liquid chromatography\u2013mass spectrometry (LC\u2013MS), this study aimed to 1) fully characterize CSF orexin-A fragments detected by the gold standard RIA method, and 2) assess diagnostic relevance of measuring the most prevalent fragment, a 16-mer, in patients with NT1, narcolepsy type 2 (NT2), idiopathic hypersomnia (IH), and nonspecified hypersomnolence (NSH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CSF samples were analyzed using RIA and LC\u2013MS in patients with hypersomnolence disorders evaluated at the French Narcolepsy National Reference Center. Fractionation techniques isolated orexin-A and its fragments, which were identified via targeted MS. Statistical analysis compared LC\u2013MS performance against RIA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CSF samples from 115 patients (54.8% females, mean age 30.4\u2009\u00b1\u200915.8\u00a0years) including 52 with NT1, 6 NT2, 13 IH, and 44 NSH were analyzed by RIA and LC\u2013MS. A 16-mer orexin-A fragment was identified and quantified by LC\u2013MS, with lower levels in NT1. This fragment correlated strongly with RIA-measured orexin-A (r\u2009=\u20090.83, p &amp;lt; .0001) and demonstrated high sensitivity (98.1%) and specificity (85.7%) for diagnosis of NT1. Receiver operating characteristics analyses confirmed the high performance with an area under the curve of 0.975 and an optimal diagnostic cutoff of 10.67\u00a0pg\/mL for LC\u2013MS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The 16-mer orexin-A peptide represents a promising biomarker that could in the future help in the diagnosis of central hypersomnolence disorders. The transition from RIA to LC\u2013MS methods for the quantification of 16-mer orexin-A represents a critical advance toward improving diagnostic accuracy and understanding orexinergic dysfunction in sleep disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/sleep\/zsaf237","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T11:33:18Z","timestamp":1754998398000},"source":"Crossref","is-referenced-by-count":12,"title":["16-mer hypocretin-1\/orexin-A in cerebrospinal fluid to diagnose narcolepsy"],"prefix":"10.1093","volume":"48","author":[{"given":"Jerome","family":"Vialaret","sequence":"first","affiliation":[{"name":"LBPC-PPC, University of Montpellier, IRMB, CHU de Montpellier , Montpellier ,","place":["France"]},{"name":"Institute of Neurosciences of Montpellier (INM), INSERM , Montpellier 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