The findings, which will be published online Aug. 22 in Annals of Neurology, a journal of the American Neurological Association and Child Neurology Society, show that a peak in narcolepsy cases occurred five to seven months after a peak in flu/cold or H1N1 infections in the country.
"Together with recent findings, these results strongly suggest that winter airway infections such as influenza A (including H1N1), and/or Streptococcus pyogenes are triggers for narcolepsy," Mignot, a professor of psychiatry and behavioral sciences, and his colleagues wrote in the paper.
The study follows recent reports that a particular H1N1 vaccine, not one used in the United States or China, seemed to lead to narcolepsy. This new paper, however, found no correlation between vaccination and narcolepsy among the patients studied in China. "The new finding of an association with infection, and not vaccination, is important as it suggests that limiting vaccination because of a fear of narcolepsy could actually increase overall risk," the authors wrote.
Approximately 3 million people worldwide suffer from narcolepsy, a neurological disease that is characterized by daytime drowsiness, irregular sleep at night and cataplexy — a sudden loss of muscle tone and strength. In 2009 Mignot and colleagues confirmed scientists' long-held suspicion that narcolepsy is an autoimmune disease, caused when patients' immune systems kill the neurons that produce the protein hypocretin.
Experts believe that a person has a genetic predisposition to the disease, and some environmental factor kicks his or her immune system into action leading to narcolepsy. As noted in the paper, past studies have shown that Streptococcus pyogenes infections, such as strep throat, have preceded the onset of narcolepsy in Caucasians, suggesting a role for upper airway infections in triggering the disease, Mignot said.
Last year, several European countries reported new cases of narcolepsy in children who had been vaccinated for the H1N1 strain of influenza; children who received the Pandemrix H1N1 vaccine in Finland, for example, faced a ninefold increased risk of narcolepsy. The World Health Organization led an investigation and determined that something about this particular vaccine acted in a "joint effort" with "some other, still unknown factor" to increase risk in those already genetically predisposed. (Pandemrix contains two adjuvants to invoke a stronger immune response; these additives are not included in the H1N1 vaccines used in the United States and China.)
For the new study, the researchers looked at the data of 906 patients who were diagnosed with narcolepsy in Beijing between September 1998 and February 2011, and determined the patients' month of onset of cataplexy and sleepiness. They conducted brief phone interviews with 154 patients whose narcolepsy appeared after October 2009, the date of the first H1N1 vaccination administered in China. The researchers also queried the patients about their history of seasonal flu, H1N1 vaccinations and other diseases.
Mignot's group found that the occurrence of narcolepsy onset was seasonal and significantly influenced by month. Onset was least frequent in November and most frequent in April; there was a five- to seven-month delay between the seasonal peak in flu/cold or H1N1 infections and the peak in narcolepsy onset occurrences.
The paper doesn't show cause and effect, but it does show a strong correlation between narcolepsy onset and this seasonal pattern.
The team also found a threefold increase in disease onset following the 2009-10 H1N1 winter flu pandemic compared with other years.
Only a small amount — 5.6 percent — of the patients interviewed recalled receiving an H1N1 vaccine. The onset, the researchers concluded, is unlikely to be explained by vaccinations. Instead, as they wrote in the paper, these winter infections appear to "initiate or reactivate an immune response that leads to hypocretin cell loss and narcolepsy in genetically susceptible individuals."
Mignot said the work is exciting because it provides insight on how the disease is triggered. "We're much closer to understanding what's happening in the autoimmune destruction of hypocretin cells," he explained.
From a public-health standpoint, Mignot said the work suggests that getting vaccinated and avoiding influenza may provide a protective benefit to patients. He said, "It's very possible that being vaccinated with a mild vaccine, one without the adjuvants in question, blocks you from getting a big infection that could increase your risk of narcolepsy."
As for the differences between the findings of the study and what has been observed in Europe, Mignot said it's possible that the strong immune response prompted by the Pandemrix vaccine increases the risk of narcolepsy. He emphasized, however, that more study is needed and that people shouldn't avoid getting vaccinated.
"Even with Pandemrix, it's still a very small risk — and there's a bigger risk from dying of an infection if you don't get vaccinated," he said.
Fang Han, MD, with the Beijing University People's Hospital, is the first author of the study. Mignot's Stanford co-authors include research associate Ling Lin, MD, PhD; postdoctoral scholar Simon Warby, PhD; and senior research scientist Juliette Faraco, PhD.
This study was funded by the National Natural Science Foundation of China, the Sino-German Center for Research Promotion, the Beijing Municipal Science & Technology Commission and the National Institutes of Health. Information about Stanford's Department of Psychiatry and Behavioral Sciences, which also supported this study, is available at http://psychiatry.stanford.edu/.
Mignot is now in discussion with GlaxoSmithKline, the maker of Pandemrix, about funding new research on the vaccine.
The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.
Michelle Brandt | EurekAlert!
WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf
First form of therapy for childhood dementia CLN2 developed
25.04.2018 | Universitätsklinikum Hamburg-Eppendorf
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
24.05.2018 | Ecology, The Environment and Conservation
24.05.2018 | Medical Engineering
24.05.2018 | Physics and Astronomy