{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:50:58Z","timestamp":1791337858226,"version":"4.3.1"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,9,17]],"date-time":"2018-09-17T00:00:00Z","timestamp":1537142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Narcolepsy is a sleep disorder characterized in humans by excessive daytime sleepiness and cataplexy. Greater than fifty percent of narcoleptic patients have an onset of symptoms prior to the age of 18. Current general agreement considers the loss of hypothalamic hypocretin (orexin) neurons as the direct cause of narcolepsy notably cataplexy. To assess whether brain histamine (HA) is also involved, we quantified the cerebrospinal fluid (CSF) levels of HA and <jats:italic>tele<\/jats:italic>\u2010methylhistamine (<jats:italic>t<\/jats:italic>\u2010MeHA), the direct metabolite of HA between children with orexin\u2010deficient narcolepsy type 1 (NT1) and controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included 24 children with NT1 (12.3\u00a0\u00b1\u00a03.6\u00a0years, 11 boys, 83% cataplexy, 100% HLA DQB1*06:02) and 21 control children (11.2\u00a0\u00b1\u00a04.2\u00a0years, 10 boys). CSF HA and <jats:italic>t<\/jats:italic>\u2010MeHA were measured in all subjects using a highly sensitive liquid chromatographic\u2010electrospray\/tandem mass spectrometric assay. CSF hypocretin\u20101 values were determined in the narcoleptic patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with the controls, NT1 children had higher CSF HA levels (771 vs 234\u00a0pmol\/L, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), lower <jats:italic>t<\/jats:italic>\u2010MeHA levels (879 vs 1924\u00a0pmol\/L, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), and lower <jats:italic>t<\/jats:italic>\u2010MeHA\/HA ratios (1.1 vs 8.2, <jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.001). NT1 patients had higher BMI <jats:italic>z<\/jats:italic>\u2010scores (2.7\u00a0\u00b1\u00a01.6 vs 1.0\u00a0\u00b1\u00a02.3, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.006) and were more often obese (58% vs 29%, <jats:italic>P\u00a0=\u00a0<\/jats:italic>0.05) than the controls. Multivariable analyses including age, gender, and BMI <jats:italic>z<\/jats:italic>\u2010score showed a significant decrease in CSF HA levels when the BMI <jats:italic>z<\/jats:italic>\u2010score increased in patients (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.007) but not in the controls. No association was found between CSF HA, <jats:italic>t<\/jats:italic>\u2010MeHA, disease duration, age at disease onset, the presence of cataplexy, lumbar puncture timing, and CSF hypocretin levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Narcolepsy type 1 children had a higher CSF HA level together with a lower <jats:italic>t<\/jats:italic>\u2010MeHA level leading to a significant decrease in the <jats:italic>t\u2010<\/jats:italic>MeHA\/HA ratios. These results suggest a decreased HA turnover and an impairment of histaminergic neurotransmission in narcoleptic children and support the use of a histaminergic therapy in the treatment against narcolepsy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13057","type":"journal-article","created":{"date-parts":[[2018,9,18]],"date-time":"2018-09-18T04:48:21Z","timestamp":1537246101000},"page":"386-395","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Impaired histaminergic neurotransmission in children with narcolepsy type 1"],"prefix":"10.1111","volume":"25","author":[{"given":"Patricia","family":"Franco","sequence":"first","affiliation":[{"name":"Integrative Physiology of the Brain Arousal System, CRNL, INSERM\u2010U1028, CNRS UMR5292 University Lyon1 Lyon France"},{"name":"National Reference Centre for Orphan Diseases Narcolepsy, Idiopathic hypersomnia and Kleine\u2010Levin Syndrome (CNR narcolepsie\u2010hypersomnie) Bron France"},{"name":"Pediatric Sleep Unit, Mother\u2010 Children Hospital, Hospices Civils de Lyon University Lyon1 Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Dauvilliers","sequence":"additional","affiliation":[{"name":"National Reference Centre for Orphan Diseases Narcolepsy, Idiopathic hypersomnia and Kleine\u2010Levin Syndrome (CNR narcolepsie\u2010hypersomnie) Bron France"},{"name":"Sleep Unit, Department of Neurology, Gui de Chauliac Hospital CHU Montpellier Montpellier France"},{"name":"Inserm, U1061 Univ Montpellier 1 Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara Odilia","family":"Inocente","sequence":"additional","affiliation":[{"name":"Integrative Physiology of the Brain Arousal System, CRNL, INSERM\u2010U1028, CNRS UMR5292 University Lyon1 Lyon 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