72 Chapter 3 Per country analyses in the largest datasets revealed that the 2010 NT1 incidence peak was significantly present in children in the Netherlands, France and Italy, and in adults in the Netherlands and France. The peak in 2013 was significantly present in children in the Netherlands, France and Italy, and in adults in the Netherlands and Italy (Appendix A, Supplementary Figures 1-4). Similar results were also found in NT1 excluding those with clinical diagnoses that had clear central disorder of hypersomnolence phenotype but did not strictly adhere to the ICSD-3 criteria (Appendix B, Supplementary Figure 7 and Figures 9-12). The 2010 and 2013 NT2/IH incidence peaks Similar significant incidence increases were found in 2010 and 2013 for NT2/ IH (Figure 2). The peak in 2010 was driven by child-onset cases compared to the 2013 peak that was driven by adults. Post-hoc exploratory analyses showed similar contributions of NT2 and IH to the 2010 and 2013 incidence peaks (Appendix A, Supplementary Figures 5-6). Figure 2. Narcolepsy type 2 and idiopathic hypersomnia incidence rates. The changes in narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) in all individuals (A), children (B) and adults (C). The predicted incidence rates and their 95% predictive confidence intervals are marked as green circles/lines and the actual values are in black circles with in red the relative significant increase in incidence rates with 95% predictive confidence intervals. EDS = excessive daytime sleepiness. The 2010 and 2013 incidence peaks in NT2/IH persisted when excluding individuals that were HLA DQB1*06:02 positive (Figure 3). Permutation testing with 10,000 random subsamples of 90% of the children with NT2/IH resulted in consistent replication of the significant 2010 incidence peak in NT2/IH (96.4% of iterations with P-value < 0.05). The significant 2013 incidence peak in adults
RkJQdWJsaXNoZXIy MjY0ODMw