45 Narcolepsy Type 1 2013 Incidence Peak Introduction Narcolepsy type 1 (NT1) is a rare brain disorder (prevalence: 0.02%–0.05% [4, 132]) characterized by the presence of excessive daytime sleepiness (EDS) and cataplexy, and/or a selective loss or dysfunction of orexin neurons. NT1 may arise from the complex interactions of genetic and environmental factors that trigger immune-mediated responses targeting orexin neurons [4, 68, 133]. The increased incidence rates (IRs) of NT1 after Pandemrix (GlaxoSmithKline Biologicals, Wavre, Belgium), a pandemic H1N1 (pH1N1) influenza vaccine, have been repeatedly reported in European countries including Finland, Sweden, France, England, Ireland, and Norway in both children and adults [56, 57, 134, 135] after the 2009–2010 pH1N1, leading to a suspicion of the association between Pandemrix and the development of NT1. However, the increased IRs of NT1 have also been reported in East Asia regions not widely using Pandemrix such as in mainland China [60, 136], Taiwan [58], and South Korea [137]. Thus, Pandemrix or the virus itself as potential environmental factor induces NT1, is still not completely understood. One reason for the unclear association between NT1 and the exposures (vaccine or virus) is the lack of the data collected following the 2009 pH1N1 that can contribute to clarify the confounding between the exposures. Narcolepsy is a clinical syndrome with either severe/abrupt symptom onset or a progressive development [22]. Patients presenting EDS in 2009–2010 could be diagnosed a few years later due to the progressive development. The delayed diagnosis can cause a bias when investigating the temporal association between vaccination/ virus and NT1 [135]. If increased NT1 incidence in influenza seasons after 2010 would be identified, it could indicate that the influenza virus, some other agents circulating after 2010 or a combination of different immunological triggers (e.g. a viral infection combined with a streptococcal infection [138]) may serve as other hits triggering NT1 (i.e. the so-called multiple-hit hypothesis [4, 68, 132, 133]), in addition to Pandemrix as it was not available after 2010 [135]. Currently, only limited data after 2010 were available [136, 139, 140]. Decreased incidence of childhood NT1 was reported 2 years after 2009 pH1N1 in China [136] and after Pandemrix vaccination in Finland [141], suggesting that the increased NT1 was unique in 2009–2010 winter [136]. No long-term follow-up data after 2012 were available until now. The European narcolepsy network (EU-NN), an association of leading European sleep centres, launched the European narcolepsy database allowing collection of patients’ data in a standardized, comprehensive, and systematic way [22]. It includes data of 994 NT1 patients diagnosed from 1980s to 2018. 2
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