Sleeping Sickness: A W5 investigation into the sudden rise in childhood narcolepsy
It's a medical mystery. Why are children all around the world developing severe narcolepsy -- a rare sleeping disorder with no known cure?
It is a question that Christine and Ian pondered after their perfectly healthy daughter developed symptoms, shortly after being hospitalized with a flu like infection in 2011.
Makenna was once an alert and active young girl but now she falls asleep without warning.
Her parents took Makenna off her medication temporarily to show W5 the effects of the disorder. As they play a board game in the kitchen, her head starts to bob and then Makenna face hits the table.
Then there is a bizarre related symptom called cataplexy, which also affects her. Makenna suddenly loses muscle control and collapses when she laughs or feels strong emotions, something that happens to the eight-year-old several times a day.
When her mother hugs her, Makenna simply drops. She's awake but paralyzed. Her parents make it safe for her to have these symptoms at home, but out in the world, it's a different matter.
"We do a lot to keep her safe, but I worry about her when she is on her own," said her mother, Christine, who asked W5 not to reveal their last name or home town to preserve their privacy.
"We had to take her out of swimming, if she had an episode she would quickly drown. All of those things you do every day, walking down the stars, what if she loses her legs and just goes limp?" said her father Ian.
Makenna is now on several medications to keep her alert during the day, so she can take part in school and gymnastics. But this bright articulate girl wonders what lies ahead.
“What kind of job am I going get? And if I am going to be able to drive or not, and how will I handle a baby, if I can even have one,” said Makenna.
In Alberta, 11 year-old Matthew also suffers from bouts of extreme sleepiness and cataplexy. His symptoms suddenly emerged a year ago.
“As a parent our hearts kind of dropped to our stomach we were not prepared for something like that,” said his father Jeff, who did not want the family’s last name used.
“As we started to understand the diagnosis a bit more we started to realize that it wasn’t just something you could cure overnight, it was a lifelong challenge for Matthew and it was going to involve a lot of structure in his life.”
Matthew now takes five pills a day to help control his narcolepsy and cataplexy and must nap at school to stay alert. His parents still wonder what caused his condition to appear so suddenly.
“We are curious and we wonder why it happened and we like to know where it originated from” said Jeff.
His mother Sherri added, “It would be nice to know how so it can help others from getting it.”
So what caused the illness that has stricken these two children?
Blood tests suggest those who develop narcolepsy have a genetic susceptibility. But doctors know that narcolepsy needs an environmental trigger -- a virus or infection that destroys cells that regulate the wake sleep cycle.
Makenna's parents now wonder about two events in her childhood. She was vaccinated against the H1N1 virus during the pandemic flu outbreak in 2009. Over a year later she developed a severe flu-like infection. Her symptoms began four weeks later.
"We thought okay, we'll something happened there and this appears to be a fallout from that," said Ian.
Pediatric sleep medicine specialist Dr. Manisha Witmans told W5 she has seen a baffling spike in cases among patients at her clinic, the Synergy Wellness Centre in Edmonton. Narcolepsy is a rare condition, and Witmans usually treats only two cases annually. In the last year and a half, however, she has diagnosed 10 pediatric cases, with four to five more awaiting definitive tests.
"I was shocked," said Witmans. "I noticed that the cases were more severe and in that most of the children that I see now have cataplexy and that can be unusual in children."
Witmans told W5 that she's not alone in seeing a sudden surge, as colleagues in Toronto, Seattle, Washington and Philadelphia are reporting similar increases in this rare brain disorder. She is now collecting data and hopes to make her report public in the coming months.
The H1N1 Link
The spike in narcolepsy, particularly among children, has also been reported outside North America, with cases in China and across Europe. The symptoms, like Makenna’s began abruptly and are often severe.
“I was swamped," said Dr. Catherine Crowe, a sleep specialist at the Mater hospital in Dublin.
"There were so many patients coming, normally I would see a few patients a year. And here I was having young narcoleptic patients every week," she told W5. "I was just amazed. Nothing like it obviously, this was terrible seeing all these little children like this."
"For me it has all the elements of a detective story," said Dr. Emmanuel Mignot, director of the Stanford Center for Sleep Sciences and Medicine, and one of the world’s leading experts on narcolepsy.
Dr. Mignot is on the hunt to understand the cause of the phenomenon, collecting blood samples from children with the disorder from around the globe. In China he reviewed narcolepsy cases following the 2009 H1N1 pandemic. He discovered that China had a threefold increase in the sleep disorder. The majority were children.
His theory is that in some cases, the H1N1 virus itself triggered the immune system to destroy hypocretin cells in the brain that run the sleep-wake cycle, research he published in the Annals of Neurology in 2011.
"Before H1N1 we were getting closer but we could not really find (the trigger)," he said. “And then with H1N1 it was clear that the flu had to be involved at least for this outbreak.”
His research is also showing most of the children affected by the outbreak -- had a genetic predisposition to narcolepsy.
Dr. Mignot hopes to turn this insight into a new diagnostic tests and possibly new treatments for a long neglected disorder. He hopes to publish his research next year.
But the swine flu virus appears to be only one part of the puzzle.
The disorder, the virus and the vaccine
In 2009, new vaccines had been introduced at the height of H1N1 pandemic when world health officials feared that the swine virus could sicken and kill millions. By 2010, researchers from Sweden and Finland were reporting a link between narcolepsy and a H1N1 flu vaccine named Pandemrix – a vaccine manufactured by GlaxoSmithKline and used in 47 countries.
By 2013, there were 800 children with narcolepsy who had been linked to vaccination against the flu across Europe, with doctors reporting more cases emerging in adults. The Scandinavian studies were supported by research from France, Norway, Ireland and the UK with some scientists reporting a seven to 13-times higher risk of narcolepsy after vaccination.
Pandremix contained a deactivated part of H1N1 virus. But it also had a novel adjuvant, or booster, called ASO3 that could induce a powerful immune reaction. The advantage is that adjuvants allow vaccine doses to be made quickly and with a worldwide pandemic threatened the World Health Organization had asked for speeded up delivery.
Mignot believes the combination may have created a perfect storm -- a virus that could trigger narcolepsy, children with a genetic predisposition to the disorder and a vaccine containing a potent adjuvant that may have made those children all the more susceptible.
"What happened is the adjuvant really does its job. It is something that is supposed to boost the immune response and together with the H1N1 it just produced a too strong immune response and then it increased the risk of developing narcolepsy," said Mignot.
Other researchers are also investigating the sudden increase and the possible vaccine link. Dr. Jeff Kwong, a scientist with the University of Toronto and the Institute for Clinical and Evaluative Studies there, is examining records of children aged four to 19 vaccinated in Ontario during 2009 and 2010 to see if there is an increase in narcolepsy cases.
Glaxo SmithKline is investigating the link between its vaccine and narcolepsy. But they believe there is insufficient evidence to draw any conclusions.
In an e-mailed statement to W5 they wrote: “Epidemiological data currently available to GSK suggest an increased risk of narcolepsy following vaccination with Pandemrix (H1N1).
"Further research is needed to determine whether the observed risk is related to the vaccine, environmental effects, genetic factors, other factors or a combination of them."
In Europe, parents of children affected have formed support groups to demand answers and compensation.
W5 traveled to Dublin to meet members of Sufferers of Unique Narcolepsy Disorder (SOUND), a group representing 60 children struggling with narcolepsy and cataplexy.
"Jenna was a perfectly healthy before she ever had her vaccine, and overnight she turned around and slept 75 per cent of her life away," said Mark Haide, whose daughter was three when she was vaccinated.
Tom Matthews' 16-year-old daughter Ellen began having symptoms just weeks after she got vaccinated.
"I would say in our case, the incidence of a healthy child becoming a sick child, the main event was the vaccination. There was no other measure that took place, said Matthews.
Ray Donovan's eight-year-old son Alex has the sleep disorder. He now suffers from depression and said he "wishes he was never born".
In Canada there many questions remain. What is the total number of new pediatric narcolepsy cases since the swine flu? Are they linked to the virus or the vaccine?
Documents reviewed by W5 reveal that eleven million doses of a Glaxo SmithKline vaccine called Arepanrix – were used in 2009 and 2010 during massive public health inoculation programs. Arepanrix contained a similar ASO3 adjuvant to that is being studied in Europe.
So far five cases of childhood narcolepsy following vaccination have been officially reported to the Public Health Agency of Canada, which concluded that the data so far "does not suggest a vaccine safety concern." Furthermore, the vaccine is no longer in use now that the pandemic is over, confirmed by Glaxo SmithKline.
Researchers in Quebec have reported a four-times increased risk of narcolepsy after vaccination, compared to those who did not receive the vaccine. In that province GlaxoSmithKline is supporting. According to Dr. Philippe de Wals, an epidemiologist at the Université Laval, it amounts to one case of narcolepsy for every one million doses of vaccine, a very remote risk. He said the data also suggests that some of the cases are only linked to infection with the H1N1 virus.
"Further research is needed to evaluate the potential association between GSK's adjuvanted H1N1 pandemic flu vaccine and narcolepsy in a country where a similar vaccine to Pandemrix™ (H1N1) was used," the company said in its e-mailed statement.
The preliminary results of this study are anticipated to be published by early 2014. But doctors interviewed by W5 predicted that this story is just beginning.
Whitmans said some of her patients in Alberta developed narcolepsy symptoms after the vaccination with Arepanrix. Others recently diagnosed were never inoculated and may have only been exposed to the flu virus. Many took months to get a proper diagnosis. Ultimately, she believes there may be many children who are suffering from narcolepsy but have not yet been formally diagnosed.
"I think there are a lot more kids out there that are affected that are out there that we don’t know," said Witmans. “We need to work together so we can identify these individuals and learn from them and figure out what are the factors that made them vulnerable and how to help them.”
That's why Makenna's family came forward with their story hoping to connect with other affected Meantime, Dr. Mignot wants the public to understand that the increase in narcolepsy cases seems to be the result of a perfect medical storm -- a powerful flu virus, narcolepsy and a vaccine that set out to protect millions around the world, but which may have produced collateral damage.
Dr. Mignot worries the cases may raise unfounded fears about all vaccines. He remains a staunch supporter of childhood vaccines for whooping cough, measles and mumps as well as the annual flu vaccination which he stresses save lives and remain very safe.
- Having sleep problems? You’re not alone… If you are having problems with sleep – get more information from the Canadian Sleep Society