Increased incidence rates of narcolepsy type-1 (NT1) have been reported worldwide after the 2009-2010 H1N1 influenza pandemic (pH1N1). While some European countries found an association between the... Show moreIncreased incidence rates of narcolepsy type-1 (NT1) have been reported worldwide after the 2009-2010 H1N1 influenza pandemic (pH1N1). While some European countries found an association between the NT1 incidence increase and the H1N1 vaccination Pandemrix, reports from Asian countries suggested the H1N1 virus itself to be linked to the increased NT1 incidence. Using robust data-driven modeling approaches, that is, locally estimated scatterplot smoothing methods, we analyzed the number of de novo NT1 cases (n = 508) in the last two decades using the European Narcolepsy Network database. We confirmed the peak of NT1 incidence in 2010, that is, 2.54-fold (95% confidence interval [CI]: [2.11, 3.19]) increase in NT1 onset following 2009-2010 pH1N1. This peak in 2010 was found in both childhood NT1 (2.75-fold increase, 95% CI: [1.95, 4.69]) and adulthood NT1 (2.43-fold increase, 95% CI: [2.05, 2.97]). In addition, we identified a new peak in 2013 that is age-specific for children/adolescents (i.e. 2.09-fold increase, 95% CI: [1.52, 3.32]). Most of these children/adolescents were HLA DQB1*06:02 positive and showed a subacute disease onset consistent with an immune-mediated type of narcolepsy. The new 2013 incidence peak is likely not related to Pandemrix as it was not used after 2010. Our results suggest that the increased NT1 incidence after 2009-2010 pH1N1 is not unique and our study provides an opportunity to develop new hypotheses, for example, considering other (influenza) viruses or epidemiological events to further investigate the pathophysiology of immune-mediated narcolepsy. Show less
