Study shows that narcolepsy is an autoimmune disorder

A study claims that narcolepsy is actually an autoimmune disorder which has important impacts for treatment options.

A recent study confirms long-held suspicions that the sleep disorder narcolepsy -- a condition where a person feels uncontrollably sleepy during the daytime and can experience muscle weakness -- is actually an autoimmune disorder. The findings also help to explain why narcolepsy was linked to the Pandemrix H1N1 flu vaccine.

Nearly all people with narcolepsy have a specific genetic signature -- called the HLA signature, where HLA stands for human leukocyte antigens -- but not everyone with this genetic signature goes on to develop narcolepsy (20 percent of the general population is thought to possess this signature). A type of immune cell, called the CD4+ T cell, is associated with this HLA signature; immune cells, like this type of T cell, are responsible for recognizing and eradicating foreign invaders in the body.

Previously, researchers had found evidence to suggest that the immune system was responsible for narcolepsy by attacking neurons that produce a neurotransmitter called hypocretin, which promotes wakefulness. (People with narcolepsy are known to have low levels of hypocretin).

In the new study, published in December in the journal Science Translational Medicine, researchers found that only people with narcolepsy have these CD4+ T cells that react to portions of the hypocretin protein, while people without narcolepsy do not have these T cells. WebMD reported that this discovery was based on examinationof 39 people with narcolepsy, and 35 people without the sleep disorder.

However, Nature News also pointed out that the study did not prove that these T cells themselves kill neurons that produce hypocretin -- there could be something else that's going on causing the death of these neurons.

The researchers also found that CD4+ T cells react strongly to a portion of the H1N1 hemagglutinin protein because it strongly resembles that of two portions of hypocretin -- which could help to explain the link between narcolepsy and the H1N1 Pandemrix vaccine, which actually contained parts of viral protein.

Reuters reported that 900 cases of narcolepsy, if not more, were linked with the Pandemrix vaccine, which was administered in the 2009/2010 flu pandemic in Europe but not the United States. (It is no longer being administered in Europe.)

"The relationship between H1N1 infection, vaccination and narcolepsygave us some very interesting insight into possible causes of the condition," study researcher Dr. Emmanuel Mignot, M.D., Ph.D., a professor of psychiatry and behavioral sciences at Stanford University School of Medicine, as well as director of the Stanford Center for Sleep Sciences and Medicine, said in a statement. "In particular, it strongly suggested to us that T cells of the immune system primed to attack H1N1 can occasionally also cross-react with hypocretin and somehow cause the destruction of hypocretin-producing neurons."

The new findings mean that researchers now have a target to set their sights on -- finding ways to stop the loss of brain cells by the body's own immune system.

"By giving us a new way to think about how neurons in these patients die, it alsosuggests new therapeutic approaches that we would not have considered if we hadn’t learned that this is an autoimmune disease," study researcher Dr. Elizabeth Mellins, M.D., an immunology researcher at Stanford, said in the statement.

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Increased Risk of Narcolepsy in Children Who Received Vaccination for Swine Flu

A study from England shows there is an increased risk of children developing narcolepsy if they received the H1N1 swine flu vaccine.

A study finds an increased risk of narcolepsy in children and adolescents who received the A/H1N1 2009 influenza vaccine (Pandemrix) during the pandemic in England.

The results are consistent with previous studies from Finland and Sweden and indicate that the association is not confined to Scandinavian populations. However, the authors stress that the risk may still be overestimated, and they call for longer term monitoring of the cohort of children and adolescents exposed to Pandemrix to evaluate the exact level of risk.

In 2009, pandemic influenza A (H1N1) virus spread rapidly, resulting in millions of cases and over 18,000 deaths in over 200 countries. In England the vaccine Pandemrix was introduced in October 2009. By March 2010, around one in four (24%) of healthy children aged under 5 and just over a third (37%) aged 2-15 in a risk group had been vaccinated.

In August 2010 concerns were raised in Finland and Sweden about a possible association between narcolepsy and Pandemrix. And in 2012 a study from Finland reported a 13-fold increased risk in children and young people aged 4-19.

But a lack of reported cases in other countries led to speculation that any possible association might be restricted to these Scandinavian populations.

Narcolepsy is a chronic disorder of excessive daytime sleepiness, often accompanied by sudden muscle weakness triggered by strong emotion (known as cataplexy). To evaluate the risk after vaccination in England, a team of researchers reviewed case notes for 245 children and young people aged 4-18 from sleep centres and child neurology centres across England.

Of these, 75 had narcolepsy (56 with cataplexy) with onset after 1 January 2008. Eleven had been vaccinated before onset of symptoms; seven within six months.

After adjusting for clinical conditions, vaccination at any time was associated with a 14-fold increased risk of narcolepsy, whereas vaccination within six months before onset was associated with a 16-fold increased risk.

In absolute numbers, this means that one in 52,000 to 57,500 doses are associated with narcolepsy, say the authors.

They write: "The increased risk of narcolepsy after vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine indicates a causal association, consistent with findings from Finland. Because of variable delay in diagnosis, however, the risk might be overestimated by more rapid referral of vaccinated children."

While further use of this vaccine for prevention of seasonal flu seems unlikely, they say their findings "have implications for the future licensure and use of AS03 adjuvanted pandemic vaccines containing different subtypes such H5 or H9."

And they conclude: "Further studies to assess the risk, if any, associated with the other A/H1N1 2009 vaccines used in the pandemic, including those with and without adjuvants, are also needed to inform the use of such vaccines in the event of a future pandemic."

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Reduced Risk of Preterm Birth for Pregnant Women who Received Flu Vaccination

Women who were vaccinated for H1N1 in 2009 were less likely to have their children pre-term.

Pregnant women who received the H1N1 influenza vaccine during the 2009 pandemic were less likely to have premature babies, and their babies weighed more on average.

Influenza infection during pregnancy is associated with adverse infant outcomes such as preterm birth. Emory researchers from the Rollins School of Public Health, in a joint study with Kaiser Permanente of Georgia and the Mid-Atlantic States, evaluated the effectiveness of the H1N1 influenza vaccine in pregnant women against adverse infant outcomes during the 2009 pandemic. They compared birth outcomes among pregnant women who received the vaccine to those among pregnant women who were not vaccinated.

The researchers used de-identified electronic medical records for 3,327 women enrolled in Kaiser Permanente managed care organization sites between April 2009 and April 2010. The study looked at whether women got the H1N1 influenza vaccine during pregnancy and their birth outcomes such as premature birth and birth weight. Overall findings showed that vaccinated mothers were less likely to deliver their babies prematurely. On average, infants of vaccinated mothers also weighed more at birth than infants born to unvaccinated mothers.

"Our findings confirm the importance of receiving the influenza vaccine during pregnancy in order to protect the infant's health," explains Jennifer Richards, MPH, first author of the study. "Previous studies have shown that seasonal influenza vaccination may prevent preterm birth. This study shows that moms who were vaccinated during the H1N1 pandemic were less likely to have premature babies."

Influenza infection is especially dangerous for pregnant women. It increases risk of adverse infant outcomes, and of complications such as hospitalization for flu. During the 2009 H1N1 influenza pandemic, pregnant women in the U.S. experienced higher influenza-associated morbidity and mortality in comparison to the general population. Getting the flu vaccine during pregnancy can not only help to prevent infection for the mother, but studies have shown that it also protects the fetus and infant after birth.

"There is always an understandable heightened sense of caution by pregnant women," explains senior study author Saad B. Omer, PhD, assistant professor of global health at Rollins and an affiliate investigator at Kaiser Permanente Georgia. "Getting vaccinated has proven to be the best protection. Our study supports the U.S. policy to prioritize pregnant moms to receive the influenza vaccine."

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Study: No Link Between Flu Vaccine and Epileptic Seizures

This article discusses how no link was found between the H1N1 Influenza vaccine and the development of epilepsy or seizures.

Epileptics are often encouraged to receive flu vaccines because the risk of seizure increases when a patient has the flu. With more focus recently on vaccine safety and side effects, many are wondering if this preventative measure could actually make conditions worse.

A recent study looked at the risk of epileptic seizures after receiving the vaccine for the H1N1 flu. The study found no evidence of patients having more seizures after vaccination.

Lisen Arnheim-Dahlstrom, PhD, and colleagues from the Karolinska Institute in Stockholm, Sweden examined 373,398 people who received a version of the H1N1 vaccine, Pandemrix, in three counties in Sweden.

Pandemrix was developed by GlaxoSmithKline and began being distributed for the H1N1 flu in October 2009. It was one of four authorized vaccines used during the 2009 flu pandemic known as the swine flu.

The safety of Pandemrix drew attention when cases of narcolepsy occurred in children and teenagers after receiving the vaccine. In addition, the European Medicines Agency (EMA) received reports of epileptic seizures occurring after vaccination.

These reports made further investigation of the drug necessary.

The researchers were able to access records for the 373,398 through the Swedish vaccination register, a database of all vaccinations in Sweden. The patient’s unique personal identification number was then used to look up histories of epilepsy andantiepileptic drugs in other registries.

Within the study population, 7,787 people were considered epileptic during the year before the study and 356,611 were not.

Dr. Arnheim-Dahlstrom and team determined how many of the total study population experienced at least one epileptic seizure during the time period of 90 days before vaccination to 90 days after vaccination. During this 180 day period surrounding the vaccination, 859 people experienced epileptic seizures.

For those previously diagnosed with epilepsy, there was no increase in risk of seizures during the first week after vaccination. During this week, there was an insignificant decrease in risk of seizure for people without epilepsy.

From day 8 to day 30 after the vaccination, there was no increase in risk of seizure for those diagnosed with epilepsy. There was an insignificant increased risk of seizures in people without epilepsy during this time period.

These results dismiss safety concerns with Pandemrix for those with epilepsy.

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