The Nocturnal Brain: Nightmares, Neuroscience, and the Secret World of Sleep

by Guy Leschziner

It was within a year of the vaccination campaign, however, that researchers noticed something rather unusual. Several cases of narcolepsy appeared to be related to one of the H1N1 vaccines used in Europe, called Pandemrix. The numbers of cases of narcolepsy rose dramatically in countries where this vaccine was used, particularly in children, but a similar increase in numbers was not seen in the USA, which used a different vaccine. In later years, the numbers of new cases dropped down to levels prior to this vaccination programme. It was not only the vaccination that was associated with onset of narcolepsy, though. In China, cases of narcolepsy were found to be related to the H1N1 influenza virus itself. Interestingly, in mice bred without intact immune systems, the H1N1 virus has been shown to migrate to the hypothalamus and brainstem, causing sleep disruption directly. Expression of high levels of viral components in these areas of the brain may make them particularly vulnerable to autoimmune damage, if the immune system is intact. So, it is not just the Pandemrix vaccine that appears to trigger narcolepsy, but the flu virus strain itself.

Subsequent studies, including our own, have demonstrated this strong association between Pandemrix and narcolepsy. The vaccine has been associated with a two-to twentyfold increased risk of developing narcolepsy. But this marked increase in cases has not been seen with the other commonly used H1N1 vaccine. The reason for this is not entirely understood, although there are subtle differences between the two vaccines, in the nature and quantities of the viral fragments contained. Studies have shown that the chemical structure of fragments of the H1N1 virus are very similar to bits of the hypocretin receptor, implying that the immune system, in particular circumstances, may mount an immune response against the virus or vaccine that also erroneously targets aspects of the hypocretin system. The hypocretin-producing cells are ‘collateral damage’.

This concept of collateral damage of the immune system is not a new one in the world of neurology. There are many neurological conditions that have a similar basis. Guillain—Barré syndrome, a devastating and life-threatening destruction of peripheral nerves, has long been known to be triggered by Campylobacter, a bacterium that causes food poisoning, and post-infection and post-vaccination damage to the brain or peripheral nerves is well recognised. Infectious agents will often use ‘molecular mimicry’ — appearing structurally similar to the body’s own molecules — to outsmart the immune system. But if your immune system is configured in a particular way, it is liable to recognise these ‘mimics’, destroying the infectious agent but also aspects of your body that look chemically identical. For narcolepsy, it appears that Pandemrix is somehow better at triggering this response than natural infection or the other vaccine widely used, if you carry the H...