{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:08:12Z","timestamp":1789549692405,"version":"build-2803163510"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Study Objectives<\/jats:title>\n                  <jats:p>The most sensitive and specific investigative method for the diagnosis of narcolepsy type 1 (NT1) is the determination of hypocretin-1 (orexin-A) deficiency (\u2264110 pg\/mL) in cerebrospinal fluid using a radioimmunoassay (RIA). We aimed to assess the reliability of the Phoenix Pharmaceuticals hypocretin-1 RIA, by determining the lower limit of quantification (LLOQ), the variability around the cutoff of 110 pg\/mL, and the inter- and intra-assay variability.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Raw data of 80 consecutive hypocretin-1 RIAs were used to estimate the intra- and inter-assay coefficient of variation (CV). The LLOQ was established and defined as the lowest converted concentration with a CV &amp;lt;25%; the conversion is performed using a harmonization sample which is internationally used to minimize variation between RIAs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The mean intra-assay CV was 4.7%, while the unconverted inter-assay CV was 28.3% (18.5% excluding 2 outliers) and 7.5% when converted to international values. The LLOQ was determined as 27.9 pg\/mL. The intra-assay CV of RIAs with lower specific radioactive activity showed a median of 5.6% (n = 41, range 1.6%\u201317.0%), which was significantly higher than in RIAs with higher specific activity (n = 36; median 3.2%, range 0.4%\u201311.6%, p = .013). The CV around the 110 pg\/mL cutoff was &amp;lt;7%.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Hypocretin-1 RIAs should always be harmonized using standard reference material. The specific activity of an RIA has a significant impact on its reliability, because of the decay of 125I radioactivity. Values around the hypocretin-1 cut-off can reliably be measured. Hypocretin-1 concentrations below 28 pg\/mL should be reported as \u201cundetectable\u201d when measured with the Phoenix Pharmaceuticals RIA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trial Information<\/jats:title>\n                  <jats:p>This study is not registered in a clinical trial register, as it has a retrospective database design<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/sleep\/zsac103","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T22:34:56Z","timestamp":1651790096000},"source":"Crossref","is-referenced-by-count":12,"title":["Hypocretin-1 measurements in cerebrospinal fluid using radioimmunoassay: within and between assay reliability and limit of quantification"],"prefix":"10.1093","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3255-8506","authenticated-orcid":false,"given":"Adrienne Elisabeth","family":"van der Hoeven","sequence":"first","affiliation":[{"name":"Department of Neurology, Leiden University Medical Center , Leiden , the Netherlands"},{"name":"Sleep-Wake Center, Stichting Epilepsie Instellingen Nederland (SEIN) , Heemstede , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"van Waaij","sequence":"additional","affiliation":[{"name":"Department of Neurology, Leiden University Medical Center , Leiden , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5169-9830","authenticated-orcid":false,"given":"Denise","family":"Bijlenga","sequence":"additional","affiliation":[{"name":"Department of Neurology, Leiden University Medical Center , Leiden , the Netherlands"},{"name":"Sleep-Wake Center, Stichting Epilepsie Instellingen Nederland (SEIN) , Heemstede , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik Willem Cornelis","family":"Roelandse","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center , Leiden , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6445-9836","authenticated-orcid":false,"given":"Sebastiaan","family":"Overeem","sequence":"additional","affiliation":[{"name":"Sleep Medicine Center, Kempenhaeghe , Heeze , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2918-7361","authenticated-orcid":false,"given":"Jaap Adriaan","family":"Bakker","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center , Leiden , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1935-7603","authenticated-orcid":false,"given":"Rolf","family":"Fronczek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Leiden University Medical Center , Leiden , the Netherlands"},{"name":"Sleep-Wake Center, Stichting Epilepsie Instellingen Nederland (SEIN) , Heemstede , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert Jan","family":"Lammers","sequence":"additional","affiliation":[{"name":"Department of Neurology, Leiden University Medical Center , Leiden , the Netherlands"},{"name":"Sleep-Wake Center, Stichting Epilepsie Instellingen Nederland (SEIN) , Heemstede , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"issue":"1","key":"2022071109003970100_CIT0001","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/sleep\/30.1.13","article-title":"The epidemiology of narcolepsy","volume":"30","author":"Longstreth","year":"2007","journal-title":"Sleep."},{"issue":"3","key":"2022071109003970100_CIT0002","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1474-4422(14)70218-2","article-title":"Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy","volume":"14","author":"Liblau","year":"2015","journal-title":"Lancet Neurol."},{"issue":"12","key":"2022071109003970100_CIT0003","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1212\/WNL.57.12.2253","article-title":"CSF hypocretin\/orexin levels in narcolepsy and other neurological conditions","volume":"57","author":"Ripley","year":"2001","journal-title":"Neurology."},{"issue":"6","key":"2022071109003970100_CIT0004","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1212\/01.WNL.0000081049.14098.50","article-title":"CSF hypocretin levels in Guillain-Barr\u00e9 syndrome and other inflammatory neuropathies","volume":"61","author":"Nishino","year":"2003","journal-title":"Neurology."},{"key":"2022071109003970100_CIT0005","article-title":"International Classification of Sleep Disorders. 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