59 Narcolepsy Type 1 2013 Incidence Peak in June (Figure 7). This hypothesis needs to be further tested. A new infection/ vaccination as trigger would also fit the multiple-hit hypothesis [4, 133] and would be compatible with a new peak in incidence in children/adolescents soon after the 2009–2010 peak. Additional arguments derived from our 2010 data are in favour for a virus infection rather than Pandemrix for triggering narcolepsy in countries where Pandemrix was rarely used (e.g. Germany). This is in contrast to countries with high coverage of Pandemrix vaccination in 2009–2010 (e.g. Finland). In Germany, the temporal evolution of narcolepsy is age-specific and different in children/adolescent versus adult cases. The maximum increase for children/ adolescent narcolepsy occurs in 2011 while it occurs in 2009 for adults (Figure 5). Previous studies from Germany show an increased narcolepsy IR in children post-pandemic (maximum in 2011) compared to pre-pandemic [148]. Although the authors fail to find an overall increase in the IR in 2009–2011 in German adult cases, their data show that the maximum IR for adults is in 2009 and decreases after 2010. The overall vaccination coverage in Germany during 2009–2010 pH1N1 is estimated to be 8% in children and adults [156]. This low vaccination coverage together with our finding of the maximum increase occurring in 2009 rather than in 2010 in German adult cases suggest that H1N1 virus itself could be a triggering factor of narcolepsy. In two other countries, Finland and France (Figure 5), the numbers of adult cases also start to significantly increase in 2009. Additionally, in the whole EU-NN database we could find that the number of adult patients in 2009 is already significantly increased compared to pre-pandemic, although the peak is in 2010 (Figure 4) which is mainly due to the increased cases in Finland, France and Germany (Figure 5). The 2010 peaks in adult cases in Finland and France are also consistent with the results of previous studies in these two countries [134, 135]. Limitations and perspective We could not directly explore the pathophysiology of influenza/vaccination associated narcolepsy as the EU-NN database was not designed as a surveillance study and does not include the influenza and vaccination histories of the patients. This will be further analysed in future studies, limiting to countries where vaccination registries and individual vaccination histories are available. Second, for many reasons, not all patients have been entered from all sleep centres in EU-NN database. We also lack information from some non-EU-NN member countries (e.g. Ireland, Norway, and Sweden) where an association between Pandemrix and NT1 has been observed. Although we assume that our sample gives a representative figure about the European narcolepsy patients, 2
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