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 Heart Rhythm Society (BHRS).

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 (ASMs) 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 ASMs. 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 ASMs alone?

- Must you use ASMs and a pacemaker?

- If using both ASMs and a pacemaker, would you treat simultaneously or sequentially? Following what criteria? 

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:

i. Systematically review all of the literature on ictal asystole: which is generally case reports, case series, and narrative reviews; 

ii. Use this to inform and undertake a prospective observational study in collaboration with a national network of neurologists and cardiologists (including using the ABN’s rare disease reporting platform (RADR), seeking information on cases of ictal asystole members have come across and asking them about how they were managed (ASMS alone? ASMs and pacemaker early or late?) and what the outcomes were (Did the patients do well? What were the issues raised?);

iii. Use evidence generated from work packages i–ii around risk to inform a series of discrete choice experiments with physicians and people with epilepsy to understand the level of acceptable and unacceptable risk around these three management strategies;

iv. Use evidence generated from these three work packages to underpin the development of a national guideline with the ABN and BHRS on how ictal asystole should be managed, based on published literature and experience from colleagues around the country, taking patient and physician preferences into account.

v) 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 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 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 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 a public health physician and data scientist working to harness data and technologies for patients and population, director of the Director of CHIL

- Dr Adam Noble a Senior Lecturer in Health Services Research with a psychology background 

Applicant Suitability

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

-Cardiovascular science/cardiology

-Neuroscience /neurology

-Health Data Science

-Statistics

-Mathematics

-Health Informatics

-R or Python 

Application Process

Application is via CV and cover letter (including details of skills/experience in one or more of the Applicant Suitability items) to Project Supervisor email: Gashirai.Mbizvo@liverpool.ac.uk

Application deadline: 03/07/2025 (may close sooner if enough suitable candidates apply prior to that).

Interviews held over subsequent weeks virtually.

Start date around September 2025 (flexible). This is a full-time post.