Elsevier

Sleep Medicine

Volume 14, Issue 9, September 2013, Pages 867-871
Sleep Medicine

Original Article
Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A

https://doi.org/10.1016/j.sleep.2013.03.020Get rights and content

Abstract

Background

From October 2009 to January 2010, approximately 470,000 children and adolescents in Norway ages 4–19 years were vaccinated with Pandemrix® against influenza A (H1N1 subtype). The vaccination coverage in this age cohort was approximately 50%.

Objectives

Our study was performed to evaluate the possible association between Pandemrix® vaccination and narcolepsy in Norway.

Methods

Children and adolescents with sudden onset of excessive daytime sleepiness (EDS) and cataplexy occurring after the 2009–2010 vaccination period were registered by the National Institute of Public Health in cooperation with the Norwegian Resource Center for AD/HD, Tourette Syndrome, and Narcolepsy.

Results

Fifty-eight vaccinated children and adolescents (35 girls, 23 boys) ages 4–19 years (mean age, 10.5 years) were diagnosed as new cases of confirmed narcolepsy and were included in our study during 2010 and 2011. Forty-two children had onset of symptoms within 6 months after vaccination, with 12 of them having symptoms within the first 6 weeks. All had EDS, 46 had documented cataplexy, 47 had mean sleep latency less than 8 min, and 43 had two or more sleep-onset rapid eye movement sleep (SOREM) periods in multiple sleep latency tests (MSLT). Cerebrospinal fluid (CSF) hypocretin levels were measured in 41 patients, with low levels in all. Thirty seven patients that were analyzed had tissue type HLADQB1*0602. During the same period, 10 unvaccinated cases were reported (mean age, 12.5 years).

Conclusion

The data collected during 3 years following vaccination showed a significantly increased risk for narcolepsy with cataplexy (P < .0001) and reduced CSF hypocretin levels in vaccinated children ages 4–19 years the first year after Pandemrix® vaccination, with a minimum incidence of 10 of 100,000 individuals per year. The second year after vaccination, the incidence was 1.1 of 100,000 individuals per year, which was not significantly different from the incidence of 0.5–1 of 100,000 per year in unvaccinated children during the same period.

Introduction

In 2009, a pandemic of influenza A (H1N1 subtype) was expected in Europe. As a result, Norwegian health authorities instituted a campaign for mass vaccination with the adjuvanted vaccine Pandemrix® from October 2009 to January 2010. The vaccination coverage was 45% in the total population of five million inhabitants, and in individuals ages 4–19 years approximately 50% were vaccinated. Most vaccinations were performed during November and December 2009 (Fig. 1).

In August 2010 there were alerting reports of a sudden and marked increase in new cases of narcolepsy in children and adolescents who had been vaccinated with Pandemrix® in Finland and Sweden. Therefore, an investigation of the situation was initiated in Norway.

Section snippets

Methods

Medical institutions and practitioners in the four Norwegian health regions were called upon to report all new cases of excessive daytime sleepiness (EDS) and possible narcolepsy occurring after the vaccination period. New cases were registered by the National Institute of Public Health in cooperation with the Norwegian Resource Center for AD/HD, Tourette Syndrome, and Narcolepsy. The data were collected during the following 120 weeks after the vaccination period. The date of symptom onset was

Results

470,000 children were vaccinated in the period from November 1st, 2009 to January 5th, 2010, comprizing approximately 50% in this age group. Fifty-eight children (23 boys, 35 girls) were reported with confirmed narcolepsy after vaccination. Age distribution was 4–19 years with a mean age 10.5 years (Fig. 2). In addition, two children were still under clinical investigation, and therefore were not included in the reported results.

The median latency from vaccination to onset of symptoms was 11 

Discussion

The incidence of narcolepsy in Norway before the vaccination period is unknown. A previous study from 2009 has shown a prevalence of 0.022%, which is comparable to other European countries [2], [3], [4], [5]. The incidence is therefore assumed to be similar to what has been found by other sleep centers in Europe and is estimated to be around 0.5–1 of 100,000 individuals per year [6]. This is in accordance with the recording of five children with confirmed narcolepsy and five children with

Conclusion

Fifty-eight children (mean age, 10.5 years) developed narcolepsy with cataplexy and hypocretin deficiency during the first 2 years following vaccination with Pandemrix®. The incidence in the first year was more than 10 per 100,000 individuals, with a marked cluster during the first 6 months. The incidence was reduced to 1.1 per 100,000 individuals the second year, which is not statistically different from the incidence of 0.5–1.0 per 100,000 individuals per year among the unvaccinated children

Conflict of interest

The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2013.03.020.

. ICMJE Form for Disclosure of Potential Conflicts of Interest form.

References (29)

  • G. Plazzi et al.

    Complex movement disorders at disease onset in childhood narcolepsy with cataplexy

    Brain

    (2011)
  • L. Serra et al.

    Cataplexy features in childhood narcolepsy

    Mov Disord

    (2008)
  • G. Plazzi et al.

    Narcolepsy–cataplexy associated with precocious puberty

    Neurology

    (2006)
  • F. Poli et al.

    High prevalence of precocious puberty and obesity in childhood narcolepsy with cataplexy

    Sleep

    (2013)
  • Cited by (0)

    View full text