Sleep, Biological Rhythms & Headache

Student thesis: Doctoral ThesisDoctor of Philosophy


While the potential relationships between sleep, biological rhythmicity and headache have long been postulated, they remain largely speculative, and under-utilised therapeutically. These interactions are thought to feature prominently in several primary headache disorders, most notably cluster headache, hypnic headache and migraine, in which attacks can arise from, be modulated by, and associated with sleep, as well as probabilistically being more likely to occur at certain times during the 24-hour period. By way of introduction, aspects of the clinical and therapeutic relationships between sleep, biological rhythmicity and these disorders, are first critically reviewed, together with an appraisal of the impact their treatment may have on sleep and biological rhythms, and potential mechanistic levels of anatomical, physiological and pharmacological interactions.

Chapters 2 and 4 then describe the development and application of a rigorous laboratory protocol designed to experimentally probe these relationships. This work reports, for the first time, a physiological data set examining sleep homeostasis, in response to a 40-hour period of extended wakefulness, as a quantitative function of sleep- electroencephalographic (EEG) slow wave activity, and ultradian rhythmicity within the cranial autonomic system, in the form of the ‘nasal cycle’, documented continuously over a 40-hour constant routine protocol, in patient volunteers with cluster headache. These data are used to form the basis of novel ideas relating sleep and biological rhythmicity to the temporal organisation of cluster headache attacks, providing a framework for further investigation.

Chapter 4 continues to examine cluster headache, in an open-label cohort study of a new treatment modality, non-invasive vagus nerve stimulation, which has led to further randomised controlled trials of the technology, and wide-spread therapeutic approval of the device. Conventional vagus nerve stimulation is associated with the development of sleep-disordered breathing as a side-effect, but this non-invasive, on-demand use of it mitigates this risk. This study provides the context for a small pilot investigation assessing the effects of this intervention on local sleep.

Chapters 5 and 6 concern themselves with novel clinical observations, which serve as paradigms from which to build a broader appreciation of the complexities of the relationship between sleep and headache. Chapter 5 characterises a case-series of patients with episodic hypersomnia (Kleine-Levin syndrome), clinical phenotypic markers of which are studied to propose that the disorder may be a variant of, or highly analogous to, migraine with brainstem aura. In Chapter 6, the overnight sleep studies of patients with the parasomnia Exploding Head Syndrome, thought to be more prevalent in people with coexistent migraine, are examined to describe trait-like characteristics in the power spectra of their sleep EEG.

The final section draws together the various themes examined within this thesis, and openly reflects upon their conclusions, as well as lessons learnt, both practically and scientifically, from them. It uses this to provide informed suggestions as to how our understanding of the relationships between sleep, biological rhythmicity and headache might be better understood in future, by outlining further novel experimental approaches to consider.
Date of Award1 Nov 2020
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorPeter Goadsby (Supervisor), Ivana Rosenzweig (Supervisor) & Derk-Jan Dijk (Supervisor)

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