111 Potential Immunological Triggers for Central Disorders of Hypersomnolence of possible infections were also more often seen in narcolepsy type 2 and idiopathic hypersomnia (57.4%) compared to narcolepsy type 1 (46.5%). To overcome this issue, we have also included analyses on the distribution of reported immunological events to identify whether different types of potential triggers were relatively more prevalent in both groups. Study limitations The absence of a control group of healthy individuals makes it difficult to conclude whether infection and influenza vaccination rates were higher than expected from similarly aged controls or people with other (neurological) disorders. In a large French study [134], the overall incidence rates of EBV, streptococcal, upper respiratory tract and gastrointestinal infections, and non-H1N1 influenza vaccinations were similar in people with narcolepsy with cataplexy and controls. The study reported that infectious episodes were common in both groups but did not provide data on the timing of these infections concerning the onset of narcolepsy symptoms. Our goal was not to identify whether infections or influenza vaccinations were more common in people with a hypersomnolence disorder. Instead, we performed detailed analyses on the timing of reported potential triggers concerning the onset of the central disorder of hypersomnolence. We additionally identified the diversity in immunological events that people reported before developing their hypersomnolence disorder and tested whether this distribution differed between narcolepsy type 1 and non-hypocretin-1 deficient diagnoses. An important limitation of our study is the substantial percentage of individuals with missing infection/influenza vaccination histories. This has impacted our sample sizes. Especially in narcolepsy type 2 and idiopathic hypersomnia the limited sample size hindered us to further compare reported immunological events between these non-hypocretin-1 deficient groups. Future international collaborations are necessary to replicate our findings in larger samples of narcolepsy type 2 and idiopathic hypersomnia, and advance our comprehension of these elusive conditions. Unnoticed infections due to no or mild symptoms are very common, and this could have resulted in underestimations of the absolute prevalences of infectious triggers. We however believe that unnoticed infections have introduced limited bias in our results as there is no reason to expect that one of the groups has a higher or lower chance to develop unnoticed infections. We also compared distributions of potential trigger types between the hypersomnolence groups (and not absolute prevalences). Many of the reported infections in our study may be triggered by multiple bacteria and viruses, and the exact pathogens 4
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