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Sleep
. 2020 Sep 10;zsaa172.
doi: 10.1093/sleep/zsaa172. Online ahead of print.
New 2013 incidence peak in childhood narcolepsy: more than vaccination?
Zhongxing Zhang 1 , Jari Gool 2 3 4 , Rolf Fronczek 2 3 , Yves Dauvilliers 5 , Claudio L A Bassetti 6 7 , Geert Mayer 8 , Giuseppe Plazzi 9 10 , Fabio Pizza 9 10 , Joan Santamaria 11 , Markku Partinen 12 , Sebastiaan Overeem 13 14 , Rosa Peraita-Adrados 15 , Antonio Martins da Silva 16 , Karel Sonka 17 , Rafael Del Rio-Villegas 18 , Raphael Heinzer 19 , Aleksandra Wierzbicka 20 , Peter Young 21 , Birgit H?gl 22 , Mauro Manconi 23 , Eva Feketeova 24 , Johannes Mathis 6 , Teresa Paiva 25 , Francesca Canellas 26 , Michel Lecendreux 27 28 , Christian R Baumann 29 , Gert Jan Lammers 2 3 , Ramin Khatami 1 6
Affiliations
- PMID: 32909046
- DOI: 10.1093/sleep/zsaa172
Abstract
Increased incidence rates of narcolepsy type-1 (NT1) have been reported world-wide 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 modelling approaches, i.e., 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, i.e., 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, e.g., considering other (influenza) viruses or epidemiological events to further investigate the pathophysiology of immune-mediated narcolepsy.
Keywords: Childhood narcolepsy; H1N1 influenza; Narcolepsy.