title: Temporal Changes in the Cerebrospinal Fluid Level of Hypocretin-1 and Histamine in Narcolepsy.
abstract: To follow the temporal changes of cerebrospinal fluid (CSF) biomarker levels in narcoleptic patients with unexpected hypocretin level at referral.
  
  
  
  From 2007 to 2015, 170 human leukocyte antigen (HLA) DQB1*06:02-positive patients with primary narcolepsy and definite (n = 155, 95 males, 60 females, 36 children) or atypical cataplexy (n = 15, 4 males, 3 children) were referred to our center. Cerebrospinal hypocretin deficiency was found in 95.5% and 20% of patients with definitive and atypical cataplexy, respectively. CSF hypocretin-1 (n = 6) and histamine/tele-methylhistamine (n = 5) levels were assessed twice (median interval: 14.4 months) in four patients with definite and in two with atypical cataplexy and hypocretin level greater than 100 pg/mL at baseline.
  
  
  
  CSF hypocretin levels decreased from normal/intermediate to undetectable levels in three of the four patients with definite cataplexy and remained stable in the other (>250 pg/mL). Hypocretin level decreased from 106 to 27 pg/mL in one patient with atypical cataplexy, and remained stable in the other (101 and 106 pg/mL). CSF histamine and tele-methylhistamine levels remained stable, but for one patient showing increased frequency of cataplexy and a strong decrease (-72.5%) of tele-methylhistamine levels several years after disease onset. No significant association was found between relative or absolute change in hypocretin level and demographic/clinical features.
  
  
  
  These findings show that in few patients with narcolepsy with cataplexy, symptoms and CSF marker levels can change over time. In these rare patients with cataplexy without baseline hypocretin deficiency, CSF markers should be monitored over time with potential for immune therapies in early stages to try limiting hypocretin neuron loss.
authors.affiliation: Unité des Troubles du Sommeil Service de Neurologie, Centre National de Référence Narcolepsie Hypersomnies, Hôpital Gui-de-Chauliac, Montpellier F-34000, France.|Inserm U1061, Montpellier F-34000, France.|Université de Montpellier, Montpellier F-34000, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Lopez
authors.affiliation: Unité des Troubles du Sommeil Service de Neurologie, Centre National de Référence Narcolepsie Hypersomnies, Hôpital Gui-de-Chauliac, Montpellier F-34000, France.|Université de Montpellier, Montpellier F-34000, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Barateau
authors.affiliation: Unité des Troubles du Sommeil Service de Neurologie, Centre National de Référence Narcolepsie Hypersomnies, Hôpital Gui-de-Chauliac, Montpellier F-34000, France.|Université de Montpellier, Montpellier F-34000, France.
authors.forename: Elisa
authors.initials: E
authors.lastname: Evangelista
authors.affiliation: Unité des Troubles du Sommeil Service de Neurologie, Centre National de Référence Narcolepsie Hypersomnies, Hôpital Gui-de-Chauliac, Montpellier F-34000, France.|Université de Montpellier, Montpellier F-34000, France.
authors.forename: Sofiene
authors.initials: S
authors.lastname: Chenini
authors.affiliation: Bioprojet-Biotech, Saint Grégoire F-35760, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Robert
authors.affiliation: Inserm U1061, Montpellier F-34000, France.|Université de Montpellier, Montpellier F-34000, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Jaussent
authors.affiliation: Unité des Troubles du Sommeil Service de Neurologie, Centre National de Référence Narcolepsie Hypersomnies, Hôpital Gui-de-Chauliac, Montpellier F-34000, France.|Inserm U1061, Montpellier F-34000, France.|Université de Montpellier, Montpellier F-34000, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Dauvilliers
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002385:Cataplexy / Q000134:cerebrospinal fluid; D002648:Child; D005260:Female; D059866:HLA-DQ beta-Chains / Q000276:immunology; D006632:Histamine / Q000134:cerebrospinal fluid*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008761:Methylhistamines / Q000134:cerebrospinal fluid; D008875:Middle Aged; D009290:Narcolepsy / Q000134:cerebrospinal fluid*; D000068797:Orexins / Q000134:cerebrospinal fluid* / Q000172:deficiency; D013997:Time Factors
chemical_list: D015415:Biomarkers; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D008761:Methylhistamines; D000068797:Orexins; D006632:Histamine; C020404:tele-methylhistamine
keywords: cataplexy; histamine.; hypocretin/orexin; narcolepsy