Development and validation of the Epilepsy-Heart syndrome: a focus on ictal asystole and developing evidence-based national consensus guidelines

Description

An exciting new opportunity has arisen for a PhD student interested in cardiovascular science, neuroscience (or cardiology and neurology) and health data science to help us develop and validate a condition we believe exists: the Epilepsy-Heart syndrome. The main focus will be to help us gather the evidence needed to develop a national consensus guideline on the management of a rare cardiac complication of epilepsy, called ictal asystole. The student would also help put the guideline together alongside the Association of British Neurologists (ABN) and the British Cardiovascular Society (BCS).

Transient loss of consciousness (TLoC) affects around half of the UK population at least once during their lifetime and commonly presents to physicians at all levels. We need to be able to recognise and manage the various causes of TLoC appropriately.

Ictal asystole is a rare cause of TLoC that is not well known amongst physicians. It occurs when a seizure (abnormal electrical discharges in the brain) causes the heart to stop (absence of electrical discharges in the heart). Although ictal asystole is a treatable condition, the diagnosis is often delayed or missed, which may result in significant harm. There is also lack of consensus on how to treat ictal asystole. On the one hand, antiseizure medications can be used to try and prevent seizures. However, they do not necessarily stop all seizures, and patients remain at risk of seizures occurring despite antiseizure medication. When that happens, the seizures will still cause the heart to stop. On the other hand, we have the option of inserting pacemakers – small electrical devices inserted into the chest cavity that kick in to restart the heart if it stops. This is not without complications, including infections and risk of needing to remove the pacemakers and insert new ones when batteries run out. Cardiologists do not normally wish to put in pacemakers in everybody, especially when they are young and would need the pacemakers in and replaced over many years.

The challenges for managing ictal asystole, are, therefore, the following:

• Is it acceptable to manage ictal asystole with antiseizure medications alone?
• Must you use antiseizure medications and a pacemaker
• If both, would you treat simultaneously or sequentially? And using what thresholds for progressing to the next step

These are questions that plague both neurologists and cardiologists, who have differing opinions on these questions. As a result, there remains substantial heterogeneity in practice on this nationally, and patients are coming to harm as a result.

The aim of this project is as follows: 

• Systematically review all of the literature on ictal asystole: which is generally case reports, case series, and narrative reviews;
• Use this to develop a prospective study in collaboration with a national network of neurologists and cardiologists, seeking information on cases of ictal asystole they have come across and asking them about how they were managed (antiseizure medications alone? Antiseizure medications + pacemaker?) and what the outcomes were (did the patients do well? What were the issues raised?).
• Use information from 1) + 2) to provide evidence to underpin the development of a national guideline with the ABN and BCS on how ictal asystole should be managed, based on published literature and experience from colleagues around the country.
• The student would also be expected to develop a broader understanding of Epilepsy-Heart syndrome, reviewing literature on cardiac complications in epilepsy more generally and working within TriNetX to generate hypotheses around Epilepsy-Heart syndrome. There may also be opportunities to harness and analyse local health data on the cardiac complications of epilepsy and clinical pathways taken between neurology and cardiology in people with Epilepsy-Heart syndrome within Cheshire and Merseyside (C&M) via the award-winning Combined Intelligence for Population Health Action (CIPHA) platform, in collaboration with Civic Health Innovations Lab (CHIL). 

This PhD project will provide a fantastic training framework for the successful applicant to develop their skills in cardiovascular science, neuroscience,  and health data science. It will also allow them to develop something from their PhD project that has real clinical meaning and impact for patients around the country. There will be ample opportunity for high-impact journal publications for the successful applicant through this project, and it will be an invaluable platform for them to become a future leader in research.

The student will work with an experienced team at University of Liverpool (where the project is based), including:

• Dr Gashirai Mbizvo (primary supervisor): NIHR Academic Clinical Lecturer in Neurology with a specialist interest in epilepsy;
• Professor Gregory Lip (co-supervisor): a consultant cardiologist who leads global research in cardiovascular epidemiology and risk using health data and created the highly impactful CHA₂DS₂-VASc score, the most widely used predictive tool for stroke following atrial fibrillation globally;
• Professor Tony Marson (co-supervisor): a consultant neurologist with a specialist interest in epilepsy, leader of the largest pragmatic randomised controlled trials in epilepsy SANAD 1 and 2, both published The Lancet;
• Professor Iain Buchan (co-supervisor): a public health physician and data scientist working to harness data and technologies for patients and population, director of the Director of CHIL. 

Applicant Suitability

This PhD would suite either a clinical or non-clinical candidate with any of the following skills or experiences:

• Cardiovascular science or cardiology
• Neuroscience or neurology
• Health Data Science
• Statistics
• Mathematics
• Health Informatics
• R or Python

Application Process

Application is via CV and cover letter (including details of any skills or experience in one or more of the items in Applicant Suitability) to the Project Supervisor email (Gashirai.Mbizvo@liverpool.ac.uk). Informal enquires can also be made to the same email address prior to making a decision to apply. Include “Epilepsy-Heart syndrome PhD” in the subject line of application submission or informal enquires. 

Application deadline is 02/12/2024 (although may close sooner if enough suitable candidates apply prior to that).

Interviews will be held over the subsequent weeks virtually, with a view to commencing the PhD around January 2025 (exact start dates are flexible). This is a full-time or part-time post.