58 Chapter 2 Switzerland. The significant increases in 2010 are seen in more countries, such as the Netherlands, Germany, Spain, and Czech Republic. This was not found in some of these countries in previous studies (i.e. the Netherlands and Spain [57, 140]). We also replicate the insignificances already reported in Italy [57] and Switzerland [139] in 2010, and find confirmative data supporting an age-specific temporal evolution of NT1 in children versus adults as previously reported in Germany [148]. Some important differences between the increases in 2010 and 2013 should be explicitly mentioned: 1. The countries showing increased number of NT1 cases in 2010 and 2013 are not identical. Only France and the Netherlands show an increase in both years, whereas in Italy and Switzerland it is just present in 2013. 2. The increased NT1 onset in 2013 is age-specific for children and show a typical subacute disease onset as previously described in immunemediated narcolepsy. In 2010, the increase is found in both adults and children patients in most countries. These results suggest the exposures in 2010 and 2013 are likely to be different. 3. About 50% of new patients in 2010 develop symptoms in winter, while in 2013 the onset mainly (72.2%) occurs in spring. Both of our findings, the 2013 and the 2010 data provide several arguments to further elucidate the potential association between narcolepsy and exposure to a vaccine or an infectious agent. The 2013 incidence peak supports an epidemiological event in 2012–2013 triggering de novo cases in childhood narcolepsy. The majority of these children cases (64%) developed cataplexy within 6 months after EDS, consistent with the clinical descriptions of rapid symptom progression in immune-mediated narcolepsy in 2009–2010 [133, 135]. Also the age of the 2010 and the 2013 children/adolescent cases are remarkably similar. It is less likely that Pandemrix vaccination, which was no longer used after 2009–2010 pH1N1, is responsible for the NT1 increase in 2013. A role for H1N1 virus in 2013 can still not be excluded as it has recirculated in the years after the pandemic of 2009, but involvement of other/new viruses or other environmental factors is similar possible. In the countries with the 2013 NT1 increase, the 2012–2013 influenza season was severe compared to other years with circulation of different influenza types [149-153]. Type B influenza virus may be a candidate as it more often impacts children [154, 155] and its peak circulation in affected countries in 2013 was in late February/early March [149153] which was a few months before the peak number of de novo NT1 occurred
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