Abstract
Cluster headache is a severe primary headache condition that affects approximately 0.1% of the population. It is characterised by recurrent unilateral attacks of pain in the trigeminal region, with ipsilateral cranial autonomic symptoms and restlessness. The pathophysiology involves the hypothalamus, trigeminovascular pathway and trigeminal autonomic reflex; however, there are still significant unknowns regarding the cluster headache attack. Spontaneous cluster headache attacks are episodic and often unpredictable; a human experimental model using nitroglycerin was employed to trigger attacks in a standardised and measured way.This PhD aimed to further our understanding of cluster headache biology through its clinical phenotyping of attacks and with the use of neuroimaging techniques. Study one (Chapter 5) addressed the first aim by systematically phenotyping nitroglycerin triggered cluster headache attacks. This study allowed observation of the evolution of cluster headache attacks and recognition of non-headache symptoms before the onset of pain.
The second aim was addressed by studies using arterial spin labelling (Chapter 7) to investigate regional cerebral blood flow changes and using functional connectivity (Chapter 8) to explore interactions during nitroglycerin triggered attacks. The imaging studies utilised a novel technique in cluster headache research by normalising data to a symmetric template before flipping to overlap attacks sides and analysed as if they stemmed from the same hemisphere. Regional cerebral blood flow changes were observed, with increases in ipsilateral pain anticipation and pain processing, with decreases in the contralateral default brain network as attention is shifted due to the severe pain experienced by patients. This is consistent with the functional connectivity findings, where there is a shift of emphasis away from contralateral networks not active or required during attacks to areas involved in pain processing. The functional connectivity changes involved the amygdala and hippocampus and perhaps as a reflection of the coping mechanism developed by cluster headache patients from experiencing repeated attacks.
| Date of Award | 1 Dec 2022 |
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| Original language | English |
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| Supervisor | Fernando Zelaya (Supervisor) & Peter Goadsby (Supervisor) |