News

Infection, Not Vaccination, May Be Culprit in Post-H1N1 Narcolepsy

View on the News

Findings at Odds With Previous Studies

The possibility that narcolepsy could be a rare side effect of H1N1 flu vaccination was first reported by the Swedish and Finnish medical product agencies in August 2010, with a potential link to Pandemrix vaccination containing the adjuvant ASO3 and squalene/alpha-tocopherol.

Last year, within three major world centers of reference for narcolepsy (Montpellier, France; Montreal; and Stanford [Calif.] University), we reported an unusual increase in abrupt-onset narcolepsy-cataplexy diagnosed within a few months of H1N1 onset. Cases were reported with a clear temporal link between vaccination and disease onset (mean, 8 weeks), with occasionally an unusual clinical presentation with rapid development and severity of both excessive daytime somnolence and cataplexy.


Dr. Yves Dauvilliers

Findings by the World Health Organization indicated a ninefold increased risk of narcolepsy in children and adolescents aged 4-19 years following vaccination with Pandemrix, and findings of the Swedish Medical Products Agency showed that the relative risk of narcolepsy was 6.6 times higher in vaccinated vs. unvaccinated children and adolescents. All of these results contrast with the exciting findings of this study by Dr. Han and colleagues, in which the occurrence of narcolepsy onset was seasonal, significantly influenced by month and calendar year.

In contrast to our results and the Finnish-Swedish studies, this increased incidence cannot be explained by the H1N1 vaccination.

Narcolepsy onset, at least in China, seems highly correlated with seasonal and annual patterns of upper airway infections, including H1N1 influenza, a finding that could, indeed, be explained by the issues regarding the pathophysiology of narcolepsy with cataplexy mentioned by the authors. These issues include a specific immune-mimicry component to an H1N1-related antigen mediated through the presentation by HLA DQB1*06:02, and nonspecific factors, such as adjuvants, influenza, or streptococcus infections.

Yves Dauvilliers, M.D., Ph.D., is with the National Reference Network for Narcolepsy in the department of neurology at Hôpital Gui de Chauliac, Montpellier, France. Dr. Dauvilliers has consulted for UCB Pharma, Cephalon, Bioprojet, and Novartis.


 

FROM ANNALS OF NEUROLOGY

They also noted that if specific peptides of pandemic H1N1 are shown to interact with narcolepsy-associated genes, an understanding of the triggers of narcolepsy may begin to emerge, potentially leading to new approaches for prevention and treatment.

As for the emerging concerns about adjuvanted vaccine and narcolepsy risk, Dr. Hauser and Dr. Johnston noted that the findings of this study raise the possibility that narcolepsy following infection and vaccination might represent a common immune response to a similar antigenic challenge – a phenomenon seen with ADEM (acute disseminated encephalomyelitis) that can occur following both native infection with measles virus, or after administration of measles vaccine. In the case of ADEM, the risk is far greater with infection than with vaccination.

"Clearly we need to insure that all flu vaccines ... are as safe as possible; however, we need also to keep in mind that the risk of any adverse outcome related to vaccination must be balanced against the known risk of community-acquired infection," they wrote.

This study was supported by research grants from the National Science Foundation of China, the Sino-German Center for Research Promotion, the Beijing Municipal Science and Technology commission, and by the Veterans Administration Research Service. Dr. Emmanuel Mignot, one of the authors, reported serving as a consultant and/or providing expert testimony for Jazz Pharmaceuticals, Merck, Mead, and the Federal Trade Commission. Dr. Mignot also has been in discussion with GlaxoSmithKline, the maker of Pandemrix, regarding the funding of contractual research.

Pages

Recommended Reading

Cerebrovascular Pathologies May Underlie Parkinsonian Signs in Elderly
MDedge Internal Medicine
Cognitive Measures, Not Biomarkers, Predict MCI Conversion
MDedge Internal Medicine
Depression, Cognitive Impairment Often Complicate Multiple Sclerosis
MDedge Internal Medicine
Childhood Bacterial Meningitis Brings Hefty Late Sequelae
MDedge Internal Medicine
Keep It Simple With Your Spine Patients
MDedge Internal Medicine
Medical Therapy Beats Intracranial Stenting for Stroke
MDedge Internal Medicine
Poststroke Statins May Not Raise Hemorrhage Risk
MDedge Internal Medicine
SSRIs, Periodic Limb Movements of Sleep Linked in Children
MDedge Internal Medicine
Concussion Management Gains Ground With New Laws
MDedge Internal Medicine
Release of Glutamate From Gliomas Sparks Seizures
MDedge Internal Medicine