Increased incidence of pediatric narcolepsy following the 2009 H1N1 pandemic: a report from the pediatric working group of the sleep research network

Abstract

This study was aimed to evaluate yearly incidence of pediatric narcolepsy prior to and following the 2009 H1N1 pandemic and to evaluate seasonal patterns of narcolepsy onset and associations with H1N1 influenza infection in the United States. This was a multi-center retrospective study with prospective follow-up. Participants were recruited from members of the Pediatric Working Group of the Sleep Research Network including 22 sites across the United States. The main outcomes were monthly and yearly incident cases of childhood narcolepsy in the United States, and relationship to historical H1N1 influenza data. 950 subjects were included in the analysis; 487 subjects were male (51.3%). The mean age at onset of excessive daytime sleepiness (EDS) was 9.6±3.9 years. Significant trend changes in pediatric narcolepsy incidence based on EDS onset (P<0.0001) occurred over the 1998-2016 period, peaking in 2010, reflecting a 1.6-fold increase in narcolepsy incidence. In addition, there was significant seasonal variation in narcolepsy incident cases, with increased cases in spring (P<0.05). Cross correlation analysis demonstrated significant correlation between monthly H1N1 infection and monthly narcolepsy incident cases (ρ=0.397, P<0.0001) with a lag time of 8 months. We conclude that there is a significant increase in pediatric narcolepsy incidence after the 2009 H1N1 pandemic in the United States. However, the magnitude of increase is lower than reported in European countries and in China. The temporal correlation between monthly H1N1 infection and monthly narcolepsy incidence, suggests that H1N1 infection may be a contributing factor to the increased pediatric narcolepsy incidence after the 2009 H1N1 pandemics.

Neurologic Complications With Vaccines

“…17 Initial studies in the United States, which did not use the Pandemrix vaccine, showed no association with H1N1 influenza vaccine and narcolepsy, 18 whereas later multicenter studies found increased incidences of narcolepsy associated with both H1N1 vaccines and H1N1 circulating virus. 19 This back and forth of associations highlights the complexity of associating a rare neurologic disease with vaccinations with the risk of false attributions to the vaccine resulting in damaging consequences. The SARS-CoV-2 vaccines pose a similar challenge.…”

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

“…In the United States and China, NT1 incidence rates were only weakly correlated to type A H1N1 influenza season severity 9,21 . This could be driven by geographic differences within these large countries in influenza season severity and strain dominance, or the influence of other, still unknown triggers.…”

“…Subsequent data from France suggested that the use of Pandemirix was associated with increased NT1 incidence rates in both children and adults 4 . Also in East Asia and the United States where Pandemrix was not used, incidence increases were noted, leading to the hypothesis that the type A H1N1 influenza virus itself may also trigger NT1 [5][6][7][8][9] . Later genetic evidence further supported this hypothesis 10 .…”