Introduction Increased 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.

Methods Incidence 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.

Results 2010 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.

Conclusions Besides 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.

The authors have declared no competing interest.

This study did not receive any funding

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

All sites are members of EUNN and they provided pseudonymised data with ethical approval from their local ethics committees and institutional review boards (i.e., the Netherlands: the Medical Ethical Committee of the VU Medical Center scrutinized the study as it consisted of an analysis of previously acquired clinical data posing no risk to included individuals [reference number: 2020.109]; Montpellier, France: Comité de Protection des Personnes France [reference number: 018-A00703-52]; Bologna, Italy: Comitato Etico di Area Vasta Emilia Centro [reference number: EM539-2022-17009-EM1-OSS-AUSLBO]; Prague, Czech Republic: Etická komise Všeobecné fakultní nemocnice v Praze [reference number: 115/21 S]; Warsaw, Poland: Instytut Psychiatrii I Neurologii Komisja Bioetyczna [reference number 21/2010]; Košice, Slovak Republic: Etická komisia Univerzitnej nemocnice L. Pasteura Košice [reference number 22.05.2014]; Innsbruck, Austria: Eithikkommission der Medizinischen Universität Innsbruck [reference number: AH3368 269/4.7 389/5.13(4311a)]; Madrid, Spain: Comité Ético de Investigación Clínica del Grupo Hospital de Madrid [reference number: 15.02.748-GHM]). The clinical experiments conformed to the principles outlined by the Declaration of Helsinki.

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All data produced in the present study are available upon reasonable request to the authors