2010 and 2013 incidence peaks in narcolepsy and idiopathic hypersomnia linked to type A H1N1 and type B Victoria influenza strains

Abstract

AbstractIntroductionIncreased narcolepsy type 1 (NT1) incidence rates have been reported globally in 2010, and were linked to the type A H1N1 2009-2010 influenza pandemic and Pandemrix vaccination. A European child-specific NT1 incidence peak was additionally observed in 2013 post the H1N1 pandemic. Thus, the relationship between NT1 and influenza infection remains unclear. Whether other influenza viruses may also trigger NT1 or other central disorders of hypersomnolence (CDH), is unknown. This study investigated annual European incidence patterns of all CDH in complete samples from multiple European centers, in relation to the severity of individual flu strains in preceding influenza seasons.MethodsIncidence rates of NT1 (N=981) and the combined group of narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) (N=545) from eight European countries were temporally analysed to identify possible incidence peaks from 1995 to 2019. Linear mixed models and spearman correlations were conducted between hypersomnolence disorder incidence rates and the number of influenza infections of preceding influenza season, split for types A H1N1 and H3N2, and in the Netherlands also types B Victoria and Yamagata influenza.Results2010 and 2013 incidence peaks were present in NT1, and a 2010 children peak was unexpectedly found in the combined group of NT2 and IH. Both hypersomnolence groups exhibited a significantly positive relationship with preceding H1N1 influenza season severity and a negative relationship with H3N2 influenza. NT1 was additionally significantly positively correlated with influenza type B Victoria in the Netherlands and showed highest correlation in children.ConclusionsBesides H1N1 influenza, the temporal association and severity correlation suggest that influenza type B Victoria may be a novel potential trigger for NT1 that requires further investigation. We additionally provide insights into possible immune-related pathophysiologies of NT2 and IH associated with the 2009-2010 H1N1 influenza pandemic. Further immunological investigations are warranted to unravel the complexities of these relationships and their implications for CDH.