Dr Emer O'Connor obtained her medical degree in Dublin in 2012 and cultivated an early passion for neurological research as a junior doctor. She first encountered patients with cluster headache when participating in outpatient headache clinics and was struck by the terrible impact of the disorder on the lives of those affected.
Emer was awarded a Brain Research UK PhD studentship in 2017 to enable her to pursue research in cluster headache.
Prior to the award of this studentship, she spent a year working as a clinical research fellow at UCL Institute of Neurology, one of the world’s leading training centres for neurology. During this time she assembled a large series of cluster headache patients, who were central to her PhD project.
Cluster headache is a rare headache disorder characterised by recurring bouts of excruciating headaches on one side of the head. It has been described as one of the most painful conditions known to man, with the intensity of the pain often reported to give rise to suicidal thoughts.
It is a condition that impacts very heavily on the lives of patients. The all-consuming pain and unpredictability of attacks can make it hard to carry on a normal life. There are a number of different treatments that aim either to stop the pain during an attack or to stop the onset of attacks during a cluster, but there is no cure.
Emer recalls her first experience with cluster headache:
I was called to the ward one night because a gentleman was having a cluster episode and I will never forget how horrific it was. I had never seen anyone in that much pain in all my life. It was just horrific to see someone suffering in that way - he was screaming and banging his head off the wall, and crying and crying.
They say that cluster headache is the worst pain that you can possibly experience, and I didn't quite believe it until I saw that. My heart just broke for him. And this was something this gentleman had been going through on a nightly basis for weeks and weeks and weeks, whilst trying to provide for his family, be a father, a husband, and just live a normal life.
And people don't understand, an awful lot of the time they think ‘You have a headache, what’s the big deal?’ They don't understand how debilitating this condition really is.
The causes of cluster headache are unknown. This severely limits our understanding of the disease and the development of effective treatments. In order to work towards a cure, we first need to understand what causes the disorder.
Whilst people with close relatives with cluster headache have an increased risk of developing it themselves, suggesting an underlying genetic cause, previous studies examining genes had not produced any conclusive results.
Prior to embarking on her PhD studies, Emer had spent a year working as a clinical research fellow at Queen Square. During this time she worked with colleagues and headache specialists locally and internationally to assemble a set of more than 100 families with cluster headache, creating a biobank of DNA for further analysis. She was also part of an international collaboration collecting DNA from patients worldwide.
Emer used this rich resource as the basis for her PhD research, to examine the heritability of cluster headache and to identify and examine the genes responsible.
She first reviewed the cohort of patients from Queen Square to ascertain family history, before combining her results with a systematic review and meta-analysis of other studies of the heredity of cluster headache, including 3,415 patients in total. This revealed a family history in 6% of cases - the most accurate estimation of familial cluster headache to date, and adding to the body of evidence regarding a familial link and the role of genetic variation in cluster headache.
Having established this familial link, the next step was to identify the specific genes responsible. Requiring a greater number of cases, this work was facilitated by the international collaboration and led to the identification of a number of genetic variants, which were subsequently replicated in two independent cohorts of Dutch and Swedish patients.
Subsequent functional analysis of these genetic variants suggested a role for neuroinflammation in the aetiology of cluster headache, a concept not widely considered but one that is now gaining traction.
This PhD studentship provided Emer with the personal financial support to take time out from her medical training and dedicate her time and attention to this research, as well as funding the research costs for this ambitious and large-scale project. Emer was awarded her PhD in 2021.
The studentship facilitated a number of key publications and the dissemination of her work at national and international conferences, enabling her to gain recognition in the field. She went on to rank 8th in the UK in interviews for neurology specialist training, and started work as a neurology trainee at Imperial College NHS Trust in 2022.
Her research has advanced knowledge of the genetic and clinical factors influencing the development of cluster headache and its clinical course. The genetic analyses and functional studies will aid the design of potential new therapies, helping to create a framework for future studies of the mechanisms of cluster headache and enabling the stratification of patients for future clinical trials.
These developments will ultimately lead to more effective management and an improved quality of life for people with cluster headache, with the collaborative framework built during the course of Emer’s PhD providing a foundation for ongoing research into this poorly-understood condition.
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