108 Chapter 4 similar pathophysiological mechanisms in narcolepsy type 2 as observed in narcolepsy type 1 which should be further studied. The limited group sizes of narcolepsy type 2 and idiopathic hypersomnia preclude statistical subgroup comparisons but both diagnoses contributed similarly to the reported EBV, and other respiratory and non-respiratory infections. Flu was less frequently reported compared to narcolepsy type 1 which contrasts the hypothesis of similar underlying pathophysiologies. Molecular mimicry studies in narcolepsy type 2 and idiopathic hypersomnia between pathogens underlying the reported infections and hypocretin-1 neurons and other neuron systems involved in sleep-wake regulation should be performed. These studies could provide important new pathophysiological insights in the relationship between infections and onset of narcolepsy type 2 and idiopathic hypersomnia. Previous reports described that some people positive for HLA-DQB1*0602 are initially diagnosed with narcolepsy type 2 and, because of occult or still evolving hypocretin-1 deficiency, at a later stage develop cataplexy [27, 192, 193]. HLADQB1*0602 positivity was surprisingly common (80%) in our sample of people with narcolepsy type 2. The underlying pathophysiology of the transition to narcolepsy type 1 remains unknown but it could align with the multiple-hit hypothesis [4]. In our study we identified six people (all positive for HLADQB1*0602) who had EDS and reported an infection just before developing cataplexy. These individuals would have first been classified as narcolepsy type 2 or idiopathic hypersomnia because of the initial absence of cataplexy if hypocretin-1 levels were not measured at first presentation. This suggests that secondary immunological triggers could play an important role in this transitioning process of people diagnosed as narcolepsy type 2. Our small sample of people with narcolepsy type 2 does not allow for direct statistical comparisons with the narcolepsy type 1 group on potential trigger distributions. Future studies should include larger samples of people with narcolepsy type 2 with longer follow-up to test whether those who later develop cataplexy initially report similar potential triggers to those directly diagnosed with narcolepsy type 1. The different potential trigger distribution suggests differences in potential triggers between narcolepsy type 1 and narcolepsy type 2 and idiopathic hypersomnia. EBV was particularly commonly reported in narcolepsy type 2 and idiopathic hypersomnia. One small study found positive EBV serology in people with idiopathic hypersomnia [187], but no direct link has yet been reported on symptomatic EBV infection before the onset of a central disorder of hypersomnolence. Multiple subjects across all central hypersomnolence disorders reported having symptomatic EBV infection just before onset of
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