title: Epidemiology and Pathophysiology of Childhood Narcolepsy.
abstract: It is now recognized that there are two types of narcolepsy. Narcolepsy type I or Narcolepsy with cataplexy is caused by the loss of hypocretin or orexin neurons. Narcolepsy type II or narcolepsy without cataplexy has normal hypocretin and the etiology is unknown. Hypocretin is a neuropeptide produced by neurons in the lateral hypothalamus. Both genetic and environmental factors play a crucial role in the pathogenesis of narcolepsy. Most patients with narcolepsy type I and half of patients with narcolepsy type II carry HLA-DQB1*0602. HLA-DQB1*0602 forms a heterodimer with HLA-DQA1*0102 and may act as an antigen presenter to the T cell receptors, resulting in narcolepsy susceptibility. In addition, narcolepsy has been shown to be linked to polymorphisms in other non-HLA genes that may affect immune regulatory function, leading to speculation that autoimmune processes may play a crucial role in the loss of hypocretin neurons. Infections have been proposed as a potential trigger for the autoimmune-mediated mechanism. Several recent studies have shown increased cases of narcolepsy, especially in children and adolescents in relation with H1N1 influenza. The increased cases in Europe seems to be related to a specific type of H1N1 influenza vaccination (Pandemrix), while the increased cases in China are related to influenza infection. The data from the Pediatric Working Group of the Sleep Research Network have shown similar increases of early onset narcolepsy in the United States.
authors.affiliation: Sleep Center, Division of Pulmonary and Sleep Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45219, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Dye
authors.affiliation: Sleep Center, Division of Pulmonary and Sleep Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45219, USA.
authors.forename: Neepa
authors.initials: N
authors.lastname: Gurbani
authors.affiliation: Sleep Center, Division of Pulmonary and Sleep Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45219, USA. Electronic address: narong.simakajornboon@cchmc.org.
authors.forename: Narong
authors.initials: N
authors.lastname: Simakajornboon
mesh_terms: D015551:Autoimmunity; D059647:Gene-Environment Interaction; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000494:pharmacology; D007251:Influenza, Human / Q000150:complications*; D009290:Narcolepsy / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000276:immunology; D013290:Streptococcal Infections / Q000150:complications*
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007252:Influenza Vaccines
keywords: Autoimmune mechanism; Childhood narcolepsy; H1N1 pandemic; H1N1 vaccination; HLA; Narcolepsy; Narcolepsy epidemiology; Narcolepsy genetics; Narcolepsy pathogenesis; Narcolepsy with cataplexy; Streptococcal infection