title: Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A.
abstract: BACKGROUND
  From October 2009 to January 2010, approximately 470,000 children and adolescents in Norway ages 4-19 years were vaccinated with Pandemrix® against influenza A (H1N1 subtype). The vaccination coverage in this age cohort was approximately 50%.
  
  
  OBJECTIVE
  Our study was performed to evaluate the possible association between Pandemrix® vaccination and narcolepsy in Norway.
  
  
  METHODS
  Children and adolescents with sudden onset of excessive daytime sleepiness (EDS) and cataplexy occurring after the 2009-2010 vaccination period were registered by the National Institute of Public Health in cooperation with the Norwegian Resource Center for AD/HD, Tourette Syndrome, and Narcolepsy.
  
  
  RESULTS
  Fifty-eight vaccinated children and adolescents (35 girls, 23 boys) ages 4-19 years (mean age, 10.5 years) were diagnosed as new cases of confirmed narcolepsy and were included in our study during 2010 and 2011. Forty-two children had onset of symptoms within 6 months after vaccination, with 12 of them having symptoms within the first 6 weeks. All had EDS, 46 had documented cataplexy, 47 had mean sleep latency less than 8 min, and 43 had two or more sleep-onset rapid eye movement sleep (SOREM) periods in multiple sleep latency tests (MSLT). Cerebrospinal fluid (CSF) hypocretin levels were measured in 41 patients, with low levels in all. Thirty seven patients that were analyzed had tissue type HLADQB1*0602. During the same period, 10 unvaccinated cases were reported (mean age, 12.5 years).
  
  
  CONCLUSIONS
  The data collected during 3 years following vaccination showed a significantly increased risk for narcolepsy with cataplexy (P<.0001) and reduced CSF hypocretin levels in vaccinated children ages 4-19 years the first year after Pandemrix® vaccination, with a minimum incidence of 10 of 100,000 individuals per year. The second year after vaccination, the incidence was 1.1 of 100,000 individuals per year, which was not significantly different from the incidence of 0.5-1 of 100,000 per year in unvaccinated children during the same period.
authors.affiliation: Norwegian Resource Center for AD/HD, Oslo University Hospital, Norway. msheier@online.no
authors.forename: M S
authors.initials: MS
authors.lastname: Heier
authors.forename: K M
authors.initials: KM
authors.lastname: Gautvik
authors.forename: E
authors.initials: E
authors.lastname: Wannag
authors.forename: K H
authors.initials: KH
authors.lastname: Bronder
authors.forename: E
authors.initials: E
authors.lastname: Midtlyng
authors.forename: Y
authors.initials: Y
authors.lastname: Kamaleri
authors.forename: J
authors.initials: J
authors.lastname: Storsaeter
mesh_terms: D000293:Adolescent; D002385:Cataplexy / Q000134:cerebrospinal fluid / Q000453:epidemiology / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D006970:Disorders of Excessive Somnolence / Q000134:cerebrospinal fluid / Q000453:epidemiology / Q000209:etiology; D005260:Female; D006801:Humans; D015994:Incidence; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid; D008297:Male; D009290:Narcolepsy / Q000134:cerebrospinal fluid / Q000453:epidemiology* / Q000209:etiology*; D009479:Neuropeptides / Q000134:cerebrospinal fluid; D009664:Norway / Q000453:epidemiology; D000068797:Orexins
chemical_list: D007252:Influenza Vaccines; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; C556153:pandemrix
keywords: Cataplexy; Children; EDS; Influenza; Narcolepsy; Vaccination