348 Chapter 11 1, future studies have yet to investigate fluid dynamics across central disorders of hypersomnolence and during different sleep stages. Section C – The Future: Improving Diagnostic Classification and Identifying New Treatment Options This final Sector C focussed on the future of central disorders of hypersomnolence. We performed unsupervised machine learning analyses to identify more reliable diagnostic subgrouping across central disorders of hypersomnolence, and investigated opioids as a promising new treatment option for individuals with narcolepsy type 1. Chapter 9 presents blinded unsupervised clustering of 1078 unmedicated individuals with narcolepsy type 1, type 2 and idiopathic hypersomnia from the EU-NN database. Seven clusters were identified. Four clusters were dominated by individuals with cataplexy and reflected one female and three disease severity subgroups. The two most distinct clusters consisted predominantly of subjects without cataplexy, and among other variables, significantly differed in presence of sleep drunkenness, subjective difficulty awakening, and weekendweek sleep length difference. Individuals formally diagnosed as narcolepsy type 2 and idiopathic hypersomnia were evenly mixed in these two clusters. The final cluster was small, evenly mixed individuals with and without cataplexy and presented limited differentiating variables. Especially the two clusters without cataplexy reflected distinct subgroups that were reproducible with our resampling analyses. Our results contest inclusion of SOREMPs in diagnostic criteria for people without cataplexy and we instead provide promising new variables for reliable diagnostic categories that better resemble underlying phenotypes. Chapter 10 shows a combined literature review, questionnaire and semi-structured interview study on the potential of opioids for treatment of narcolepsy type 1. Recent studies have suggested opioid use increases the number of hypocretin-producing neurons. Consistent with this observation, the systematic literature review mainly showed improvements in narcolepsy type 1 symptom severity. Recent opioid use was reported in 16/100 respondents with 20 instances of opioid use in total. Mainly oxycodone and, to a lesser extent, codeine were associated with self-reported narcolepsy symptom severity improvements in 11/20. Surprisingly, the majority of improvements were observed in disturbed nocturnal sleep rather than in cataplexy, which contradicts previous studies’ suggestions [125, 126]. Opioids were relatively
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