Abstract
This thesis assesses the past (Section A), present (Section B) and future (Section C) of central disorders of hypersomnolence. Section A on the origin of central disorders targets the role of immunological triggers in developing central disorders of hypersomnolence. We studied annually fluctuating incidence rates of narcolepsy type 1 (Chapter 2) in the EU-NN database, annual incidence rates of all central disorders of hypersomnolence in relation to preceding flu season severity in multiple complete European centres (Chapter 3) and real-world insights on immunological events that people with a central disorder of hypersomnolence reported prior to disease onset (Chapter 4). The chapters on the present in Section B first focus on brain morphology of people with narcolepsy type 1 with DWI analyses on white matter morphology (Chapter 5) and human postmortem immunohistochemistry analyses on axonal density, orientation and myelin integrity (Chapter 6). This is followed by fMRI studies to investigate the behavioural and neural correlates of sustained attention (Chapter 7) and active sleep resistance (Chapter 8) in narcolepsy type 1. The final two chapters on the future of central disorders of hypersomnolence in Section C compose unsupervised machine learning analyses to identify more reliable subgrouping of people with a central disorder of hypersomnolence to potentially improve diagnostic classification (Chapter 9) and a combined literature review, questionnaire and semi-structured interview study to investigate the potential of opioids as a treatment option for narcolepsy type 1 (Chapter 10). The culmination of the thesis is presented in Chapter 11, a comprehensive discussion wherein the findings are summarized and contextualized in scientific discourse with proposed avenues for future research.
Original language | English |
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Qualification | PhD |
Awarding Institution |
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Supervisors/Advisors |
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Award date | 24 Jan 2025 |
Print ISBNs | 9789464736694 |
DOIs | |
Publication status | Published - 24 Jan 2025 |
Keywords
- Narcolepsy
- Idiopathic hypersomnia
- Cataplexy
- Hypocretin
- Orexin
- Infections
- Vaccinations
- Magnetic Resonance Imaging
- MRI
- Hypersomnolence