336 Chapter 11 peak was notably subdued in these nations. This suggests the existence of a “limited pool” of people predisposed to developing narcolepsy. Narcolepsy incidence rates similarly varied between 1990 and 2017 in mainland China, but Wang et al. questioned the validity of the “limited pool” hypothesis, as Chinese post-pandemic narcolepsy incidence rates did not revert to normal and generally remained elevated [162]. A similar post-pandemic generalized increase was observed within our European samples [159, 436] and in the United States [59], persisting for at least six years after the pandemic. Increased global awareness recently after the pandemic seems insufficient to be the sole explanation for this trend. The “limited pool” hypothesis warrants further investigation before dismissal. The multiple-hit hypothesis posits a genetic predisposition (implying a finite number of possibly susceptible individuals) combined with environmental triggers [4]. Besides the strong association with HLA-DQB1*0602 positivity, several other HLA types have been linked to narcolepsy type 1 with either protective or risk-inducing effects [51]. Taking into account the relatively large group of individuals positive for HLADQB1*0602 (between 5-38% of the general population) [51, 53], it is possible that the reintroduction of type A H1N1 influenza in 2009 rendered previously unsusceptible individuals vulnerable to narcolepsy type 1. This potential expansion of the “limited pool” could account for the sustained increase in narcolepsy type 1 incidence rates post-pandemic. Possible underlying mechanisms include relatively strong potency of type A H1N1 influenza to trigger narcolepsy type 1 in genetically susceptible individuals compared to other potential triggers, or inter-individual genetic variances among those affected by different triggers. Complex genotypic inter-individual differences have been identified among individuals with narcolepsy type 1 [51], potentially explaining variations in environmental triggers that could precipitate the condition. No significant pre- and post-pandemic prevalence differences were however found in singular HLA types associated with narcolepsy type 1 [52] but this study did not explore interactions between different HLA types. A complex interaction between genetics and environmental triggers seems likely and future narcolepsy type 1 incidence rates modelling studies would benefit from multifactorial designs incorporating multiple self-reported environmental triggers associated with onset of narcolepsy type 1. Possible immunological origin of narcolepsy type 2 and idiopathic hypersomnia without long sleep time? Currently little is known about the pathophysiologies of narcolepsy type 2 and idiopathic hypersomnia without long sleep time. The overlapping incidence
RkJQdWJsaXNoZXIy MjY0ODMw