title: Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France.
abstract: An increased incidence of narcolepsy in children was detected in Scandinavian countries where pandemic H1N1 influenza ASO3-adjuvanted vaccine was used. A campaign of vaccination against pandemic H1N1 influenza was implemented in France using both ASO3-adjuvanted and non-adjuvanted vaccines. As part of a study considering all-type narcolepsy, we investigated the association between H1N1 vaccination and narcolepsy with cataplexy in children and adults compared with matched controls; and compared the phenotype of narcolepsy with cataplexy according to exposure to the H1N1 vaccination. Patients with narcolepsy-cataplexy were included from 14 expert centres in France. Date of diagnosis constituted the index date. Validation of cases was performed by independent experts using the Brighton collaboration criteria. Up to four controls were individually matched to cases according to age, gender and geographic location. A structured telephone interview was performed to collect information on medical history, past infections and vaccinations. Eighty-five cases with narcolepsy-cataplexy were included; 23 being further excluded regarding eligibility criteria. Of the 62 eligible cases, 59 (64% males, 57.6% children) could be matched with 135 control subjects. H1N1 vaccination was associated with narcolepsy-cataplexy with an odds ratio of 6.5 (2.1-19.9) in subjects aged<18 years, and 4.7 (1.6-13.9) in those aged 18 and over. Sensitivity analyses considering date of referral for diagnosis or the date of onset of symptoms as the index date gave similar results, as did analyses focusing only on exposure to ASO3-adjuvanted vaccine. Slight differences were found when comparing cases with narcolepsy-cataplexy exposed to H1N1 vaccination (n=32; mostly AS03-adjuvanted vaccine, n=28) to non-exposed cases (n=30), including shorter delay of diagnosis and a higher number of sleep onset rapid eye movement periods for exposed cases. No difference was found regarding history of infections. In this sub-analysis, H1N1 vaccination was strongly associated with an increased risk of narcolepsy-cataplexy in both children and adults in France. Even if, as in every observational study, the possibility that some biases participated in the association cannot be completely ruled out, the associations appeared robust to sensitivity analyses, and a specific analysis focusing on ASO3-adjuvanted vaccine found similar increase.
authors.affiliation: Sleep Disorder Centre, Neurology Department, Gui de Chauliac hospital, CHU Montpellier, INSERM, U1061, Montpellier, France. ydauvilliers@yahoo.fr
authors.forename: Yves
authors.initials: Y
authors.lastname: Dauvilliers
authors.forename: Isabelle
authors.initials: I
authors.lastname: Arnulf
authors.forename: Michel
authors.initials: M
authors.lastname: Lecendreux
authors.forename: Christelle
authors.initials: C
authors.lastname: Monaca Charley
authors.forename: Patricia
authors.initials: P
authors.lastname: Franco
authors.forename: Xavier
authors.initials: X
authors.lastname: Drouot
authors.forename: Marie-Pia
authors.initials: MP
authors.lastname: d'Ortho
authors.forename: Sandrine
authors.initials: S
authors.lastname: Launois
authors.forename: Séverine
authors.initials: S
authors.lastname: Lignot
authors.forename: Patrice
authors.initials: P
authors.lastname: Bourgin
authors.forename: Béatrice
authors.initials: B
authors.lastname: Nogues
authors.forename: Marc
authors.initials: M
authors.lastname: Rey
authors.forename: Sophie
authors.initials: S
authors.lastname: Bayard
authors.forename: Sabine
authors.initials: S
authors.lastname: Scholz
authors.forename: Sophie
authors.initials: S
authors.lastname: Lavault
authors.forename: Pascale
authors.initials: P
authors.lastname: Tubert-Bitter
authors.forename: Cristel
authors.initials: C
authors.lastname: Saussier
authors.forename: Antoine
authors.initials: A
authors.lastname: Pariente
mesh_terms: D000293:Adolescent; D000328:Adult; D002385:Cataplexy / Q000453:epidemiology* / Q000209:etiology; D002648:Child; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects*; D007251:Influenza, Human / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000453:epidemiology* / Q000209:etiology; D058873:Pandemics; D012306:Risk; D014611:Vaccination / Q000009:adverse effects*
chemical_list: D007252:Influenza Vaccines
keywords: H1N1; cataplexy; infection; narcolepsy; vaccine