330 Chapter 11 A H1N1 influenza pandemic and association with Pandemrix vaccination [135, 174]. Our analyses incorporating preceding influenza season severity provided important supporting arguments for type A H1N1 influenza as a potential trigger for narcolepsy type 1 within Europe, something that was recently also proposed in China [60, 61, 162] and the United States [59]. Findings presented in Chapter 4 suggest that other non-type A H1N1 influenza-related infections should also be considered as potential triggers. Involvement of other potential triggers makes sense as type A H1N1 influenza was nearly absent its pandemic in 1918 until the reintroduction in 2009 [388]. An important commonality across chapters is the strong association with influenza in narcolepsy type 1. Besides the known association with type A H1N1 influenza infection and 2009-2010 influenza vaccination, we report a strong positive association between preceding type B Victoria influenza season severity and narcolepsy type 1 incidence rates in children in Chapter 3. As no reliable type B influenza severity data was available for other included countries than the Netherlands, this promising finding warrants external confirmation. This is possible to some extent with recently published Chinese narcolepsy type 1 incidence rates [162] and WHO-derived influenza season severity in China [165], which shows type B Victoria presence prior to the child-onset narcolepsy incidence peaks in 2010, 2012 and 2014. Most interestingly, type B Victoria and type A H1N1 influenza both predominate in children compared to type A H3N2 influenza which similarly affects all age groups [160, 389-392], the common age for development of narcolepsy type 1 [55]. This could explain the weaker associations we found in adults. Within their respective type A and type B strains, both type A H1N1 and type B Victoria strains became more dominant in recent decades [393]. It seems logical that other triggers must have been present prior to the reintroduction of the type A H1N1 influenza virus in 2009, and type B Victoria influenza should now be considered as a serious contender. Trigger-related pathophysiologies of narcolepsy type 2 and idiopathic hypersomnia? The incidence peaks in narcolepsy type 2 and idiopathic hypersomnia presented in Chapter 3 are surprising. We are among the first to provide supporting data for a possible immunological origin of these poorly understood disorders of hypersomnolence. This is further substantiated by our findings in Chapter 4 with frequent self-reported infections (and not vaccinations) close to onset of excessive daytime sleepiness. Environmental influences, including infections, may hereby also play a significant role in the onset of narcolepsy type 2 and idiopathic hypersomnia. Despite the small samples of narcolepsy type 2 and
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