Epilepsy and the brain

What is epilepsy?

The word epilepsy derives from the Greek epilambanein, meaning ‘to seize’.

It is a condition characterised by seizures which involve episodic, abnormal activity in nerve cells in the brain.

50 million

people worldwide are affected by epilepsy

While epilepsy always involves seizures, it can sometimes take a long time to make an accurate diagnosis. People can have convulsive seizures, where the body stiffens and shakes. There are also more subtle seizures during which people may lose awareness for short periods of time.

Epilepsy is more common as we age, and is the third most common neurological disorder in people aged over 65, after stroke and dementia.

1 in 20

people will have a seizure at some point in their life. Around 1 in 130 people will develop epilepsy

Identifying underlying causes of epilepsy

There is an increasing understanding among researchers that the causes of epilepsy may have a genetic link.

Associate Professor Usha Kini from the Radcliffe Department of Medicine leads the Genseize project which aims to deliver patient benefit through enhanced diagnosis and improve understanding of the genetic basis of epilepsy, by offering sophisticated genetic testing to all patients with epilepsy.

The project is funded by NHS England via the Central and South Genomic Medicine Service Alliance.

Associate Professor Kini appeared on the Epilepsy Sparks Insights podcast to share her work on the Genseize project.

The Epilepsy Imaging Research Group, part of the Nuffield Department of Clinical Neurosciences, use state-of-the-art brain imaging methods, Functional Magnetic Resonance Imaging (fMRI) and Diffusion Tensor Imaging (DTI), to understand how functional networks in the brain respond and adapt to epilepsy and epilepsy-associated lesions.

Associate Professor Natalie Voets’ and Dr Jane Adcock’s research focuses on understanding how functional systems in the brain, particularly those involved in memory, respond and adapt to acute and chronic brain injury, opening up opportunities to observe epileptic brains. Their work aims to improve the selection of patients likely to benefit from surgical intervention while minimising risks to functions central to their quality of life.

Researchers from the Department of Paediatrics’ Paediatric Neuroimaging Group, the Department of Psychiatry and the Nuffield Department of Clinical Neurosciences were part of a collaborative study, led by the Sir Peter Mansfield Imaging Centre at the University of Nottingham, using a wearable ‘bike helmet’ style brain scanner, that allows natural movement during scanning, with young children for the first time.

The team, including Associate Professor Caroline Hartley, Professor Rebeccah Slater, Professor Charlotte Stagg and Professor Mark Woolrich, demonstrated how they enhanced the ground-breaking Magnetoencephalography (MEG) technology with a novel helmet design that they used to measure brain activity in young children engaging in natural activities. 

As well as providing a new way to measure healthy brain function across the lifespan, the study opened up the opportunity to study a range of neurological and mental health conditions in children, including epilepsy and autism.

The Oxford Epilepsy Research Group, part of the Nuffield Department of Clinical Neurosciences, brings together researchers and clinicians from across the University of Oxford and Oxford University Hospitals to focus on all aspects of clinical and experimental epileptology, with an emphasis on clinically relevant research.

Epileptology:

Specialising in the treatment of epilepsy

The group is led by Associate Professor Arjune Sen, also from the Nuffield Department of Clinical Neurosciences, and focuses on an individual and holistic approaches to advancing care for people with epilepsy, who often face addition cognitive, psychological and psychosocial difficulties.

Psychosocial:

Relating to the interrelation of social factors and individual thought and behaviour

The researchers capitalise on the clinical expertise available at the John Radcliffe Hospital and the wider basic scientific research performed within the University of Oxford, collaborating with academic colleagues from universities across the United Kingdom, Africa, Australia, Brazil, Europe, India and the United States of America.

The group’s Clinical Epileptology team run a busy epilepsy surgery centre and contribute to EpiCARE: a European Reference Network for people with rare and complex epilepsies. They also work closely with epilepsy charities, particularly SUDEP Action and Epilepsy Society, and are part of the Humanology Project.

Another key focus for the group is Autoimmune Epilepsy, a term that was coined in Oxford.

The group is a leading centre for research in this area, and investigates the role of LGI1, CASPR2, NMDA and GAD antibodies in epilepsy as part of the Autoimmune Neurology Group in the Nuffield Department of Clinical Neurosciences.

The Oxford Epilepsy Research Group is actively involved in the field of Epilepsy Genomics and was heavily involved in the 100,000 Genomes Project.

Researchers and participating patients from the John Radcliffe Hospital contributed to an improved understanding in conditions such as Otahara syndrome, a rare form of epilepsy, and brain malformations in people experiencing seizures, as well as paving the way for a new Genomic Medicine Service in the NHS.

Impact of COVID-19

Associate Professor Arjune Sen from the Oxford Epilepsy Research Group led the Epilepsy Risks and COVID-19 project in partnership with local charity SUDEP Action to investigate how COVID-19 impacted on people with epilepsy, their carers and health care workers. In particular, they were interested in assessing escalation and mitigation of risk.

Commencing in May 2020, the study has now become one of the largest global surveys in epileptology with nearly 4000 responses. The first paper to come out of this study found that COVID-19 had far-reaching consequences on people with epilepsy.

UK respondents reported changes in seizure frequency, mental health, and sleep, with the study showing the importance of delivering optimal care to mitigate risk.

70%

of epilepsy consultations during the pandemic were held remotely

In another study surveying UK healthcare workers involved in the care of people with epilepsy, Associate Professor Sen and Professor Charles Newton from the Department of Psychiatry, along with academic colleagues from institutions in the UK and The Netherlands, found that during the pandemic 70% of respondents held the majority of their consultations remotely.

The survey also found that 43% of the health care workers surveyed reported an impact on their own mental health, and a fifth of respondents were significantly less confident in diagnosing epilepsy. Their findings concluded that remote delivery of care poses risks to the well-being of people with epilepsy and their clinicians.

55%

People who had COVID-19 were 55% more likely to develop epilepsy or seizures over the next six months than people who had influenza in an Oxford study

Associate Professor Sen, Dr Max Taquet and Professor Paul Harrison, both from the Department of Psychiatry, also investigated the risk of seizures and epilepsy in the 6 months following a COVID-19 diagnosis.

To try to definitively answer whether COVID-19 is associated with epilepsy or seizures, the researchers looked at health records of people who had been infected with COVID-19 and carefully matched them with a group of people who had been infected with influenza.

Each group consisted of 152,754 people, none of whom had previously been diagnosed with epilepsy or recurrent seizures.

The team compared the incidence of epilepsy and seizures between the two groups over a six month period following the initial infection, and found that the rate of new cases of epilepsy or seizures was 0.94% in the people who had COVID-19, compared with 0.6% in those who had influenza.

The results suggest that people who had COVID-19 were 55% more likely to develop epilepsy or seizures over the next six months than people who had influenza.

Treatments for epilepsy and its side effects

The Oxford Epilepsy Research Group is at the forefront of potentially ground-breaking work with patients who have drug-resistant epilepsy.

In August 2018, LivaNova PLC launched a global registry to evaluate the use of its Vagus Nerve Stimulation Therapy^® (VNS Therapy) System for patients with drug-resistant epilepsy. The system consists of two implantable components designed to stimulate the vagus nerve at regular intervals throughout the day.

Nearly 1 in 3

patients have drug-resistant epilepsy

Launched in 2019, the study will enrol up to 2,000 patients and follow them for five years. The analysis of the data from this large repository will help to evaluate the safety and effectiveness of this therapy, as well as clinical outcomes for patients. The Oxford Epilepsy Research Group enrolled the first patient in Europe to the trial.

Co-morbidities

The Oxford Epilepsy Research Group are developing research and clinical pathways to address co-morbidities associated with epilepsy, as well as aiming to improve our understanding of why seizures occur.

Their strong links with genomic research into epilepsy are developing many research projects to better evaluate co-morbidity in epilepsy, an area of epileptology that is often overlooked.

10 times more likely

People with epilepsy are 10 times more likely to die before their mid-fifties compared with the general population

A study led by researchers from the Department of Psychiatry examined links between mental illness and early death in people with epilepsy, the first study of its kind to look at the odds of premature death in people with epilepsy compared with their unaffected siblings.

Researchers, including Professor Seena Fazel and Professor Charles Newton, studied health data over 41 years for almost 70,000 people with epilepsy born in Sweden and compared data to participants’ unaffected siblings, finding a striking correlation between premature death and mental illness in these patients.

People with epilepsy were four times more likely to have received a psychiatric diagnosis compared with the general population.

The findings show they were four times more likely to die by suicide, and there was a strong correlation with mental illness and substance abuse, suggesting a need for treatment liaison between clinical epilepsy services and psychiatric and addiction services.

Investigating links between dementia and epilepsy

The Oxford Epilepsy Research Group is instrumental in investigating the interplay between conditions such as epilepsy, dementia and stroke. People with Alzheimer's disease may have seizures, as well as exhibiting abnormal brainwave activity without having obvious seizures.

Associate Professor Arjune Sen leads the ILiAD (Investigation of Levetiracetam in Alzheimer's Disease) trial, aiming to analyse the effect of the anti-epileptic drug Levetiracetam, which can reduce abnormal brainwave activity, on memory in Alzheimer's disease.

Funded by the by the MRC Confidence in Concept scheme, Associate Professor Sen’s team will allocate 30 patients with mild to moderate Alzheimer's disease with no history of a previous seizure to initially receive either Levetiracetam or a placebo, as well as a non-invasive test called an electroencephalogram (EEG) to look at their brainwave activity to see if it can be predicted which patients would benefit most from the drug.

Although curtailed by the pandemic, the trial demonstrated that Levetiracetam was well tolerated in this potentially vulnerable group.

Electroencephalogram (EEG):

A safe and convenient test to measure brain activity for research and clinical purposes

Building a better future for people with epilepsy

Over 85% of people with epilepsy live in low- and middle-income countries, where the increased risk from seizures contributes to much higher mortality. Underfunding, limited access to medical care, and stigma towards people with epilepsy means that in some places fewer than 20% of those who need anti-seizure medications receive them.

The Oxford Martin Programme on Global Epilepsy, at the Oxford Martin School, aims to find solutions to improve diagnosis, understand and mitigate the social impact of epilepsy, and begin to build a better future for people with the condition – especially those in resource-poor settings.

 70%

of people living with epilepsy could live seizure-free if properly diagnosed and treated

The programme is closely aligned with the EpInA project, and the interdisciplinary Oxford team includes Associate Professor Arjune Sen, Professor Charles Newton, Professor Timothy Denison, Associate Professor Sloan Mahone, Sonia Vallentin, Dr Gabriel Davis Jones, Dr Guillaume Pages, Ines Pont Sanchis and Lisa Aissaoui.  

The programme’s partner teams in Brazil, India, Kenya, South Africa and Zimbabwe connect researchers with communities and bring their own contextual expertise to the programme.