By: Alan Q. Thomas, MD
Narcolepsy is a chronic neurologic disease associated with severe hypersomnolence and the brain’s inability to regulate REM sleep-wake cycles. In humans it is caused by the loss of cells located in the posterior hypothalamus that secrete the stimulating neurotransmitter hypocretin. This destruction of hypocretin cells is thought to be mediated by autoimmune attack, based on specific HLA association and T-cell receptor polymorphisms. The disease has an incidence of 0.3-0.6 per 100,000 person-years. Onset is typically in the teens. It is an extremely debilitating disease although pharmacologic treatments have improved.
Recent evidence suggests that narcolepsy can be triggered by certain types of H1N1 vaccines. An increased risk of narcolepsy has been associated with vaccination with Pandemrix, a monovalent H1N1 influenza vaccine that was used by several European countries in 2009. The increased risk was first described after an outbreak of severe sudden onset narcolepsy in children that received Pandemrix in Finland. Scientists have confirmed these findings in other European countries including Sweden and England. All children affected in these studies received Pandemrix.
Pandemrix is a product of GlaxoSmithKline Europe. It was specifically engineered for the pandemic 2009 H1N1 season. It contains an oil-in-water emulsion adjuvant known as ASO3 which enhances the immune system’s antibody production. No adjuvanted influenza vaccines have been licensed or used in the US during the 2009 influenza pandemic or at any other time. Pandemrix has not been used in the US and its use was halted in Europe after 2009.
Research is ongoing to elucidate the mechanism of how adjuvanted H1N1 vaccination can lead to narcolepsy. Hypotheses include specific immune response to H1N1/ASO3 leading to autoimmune attack of hypocretin cells in the brain. This would suggest possible shared epitopes or molecular mimicry between the vaccine and the posterior hypothalamic hypcretin producing cells. Alternatively, ASO3 may lead to a generalized stimulation of the immune system. Intersetingly, an association between streptococcal infection and recent-onset narcolepsy has been described, in the absence of H1N1 vaccination or infection. Elevated ASO titers have been reported in European children with post-Pandemrix vaccination narcolepsy.
In response to the events in Europe, the CDC reviewed data from the US Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD). No association between US-licensed H1N1 or seasonal influenza vaccination and narcolepsy was found.
The CDC is currently sponsoring an international study on the associations between adjuvanted H1N1 vaccines and narcolepsy. It is expected to be complete in 2014.
The CDC continues to recommend influenza vaccination, including H1N1, to protect from influenza illness and severity.
· Miller et al. Risk of narcolepsy in children receiving an AS03 adjuvanted AH1N1 (2009) influenza vaccine in England. (2013). British Medical Journal. http://www.bmj.com/cgi/doi/10.1136/bmj.f794
· Partinen et al. Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland. PLoS One. 2012;7(3):e33723. Available online http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0033723
· Nohynek et al. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland. PLoS One. 2012;7(3):e33536. Available online: http://www.plosone.org/article/info:doi/10.1371/ journal.pone.0033536
· Eurosurveillance editorial team. Swedish Medical Products Agency publishes report from a case inventory study on Pandemrix vaccination and development of narcolepsy with cataplexy. Euro Surveill. 2011;16(26):pii=19904. Available online: http://www.eurosurveillance.org/ViewArticle.aspx? Article Id=19904
· ECDC Technical Report: Narcolepsy in association with pandemic influenza vaccination, a multi-country European epidemiological investigation [PDF - 8 MB]
· http://www.cdc.gov/vaccinesafety/Concerns/ h1n1_narcolepsy_pandemrix.html
Dr. Alan Thomas is in practice with Pulmonary Associates of the Southeast, PC, and is a member of the medical staff at Trinity Medical Center. Dr. Thomas specializes in Pulmonary Disease, Critical Care Medicine and Sleep Medicine. He is the medical director of the Trinity Sleep Disorders Center.