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latest research papers

Please find below a selection of the latest research papers from researchers at Epilepsy Society. The full versions of some papers may only be available through subscription. Where this is the case, the link will take you through to the abstract (summary) of the paper.

Predicting epilepsy after head injury or stroke

Attempts have been made to identify drugs that might prevent epilepsy developing after a head injury or stroke. In most cases, epilepsy starts slowly and takes a long time to develop, for example over 20 years after a head injury.

It is, however, difficult to identify which people are at highest risk of developing epilepsy, so that specific drugs, such as anti-inflammatory drugs, can be tried.

We looked at the evidence for inflammation in the brain causing epilepsy, and how the development of inflammation in the brain might be seen in life with novel brain scans, and be used to direct treatment.

In order to test such novel treatments, we need to be able to predict who is at greatest risk of developing epilepsy.  To do this, we developed and tested in over 2000 patients from four areas, the SeLECT predictive score, to identify those patients at highest risk of developing epilepsy after stroke, so that they might be offered a treatment  designed to prevent epilepsy from developing.  This score was shown to be a good predictor of the risk of seizures and is freely available as a smartphone app. It is a step towards more personalised medicine.

Prediction of late seizures after ischaemic stroke with a novel prognostic model (the SeLECT score): a multivariable prediction model development and validation study
February 2018

Neuroinflammation imaging markers for epileptogenesis
July 2017

The help of biomarkers in the prevention of epilepsy
July 2016

 

Computers to read our brains

Finding an abnormality in one part of the brain is vitally important when considering brain surgery to try to cure epilepsy that has not been controlled with medication. 

If a small abnormality in the brain can be seen with brain scanning the chances of surgery being effective are much greater than if no abnormality can be seen.

In a quarter of people with epileptic seizures, brain scans do not show the cause. We have developed powerful computing methods to analyse brain scans that appear normal to the naked eye, to compare each individual patient’s brain scan with a bank of scans from people with and without epilepsy. 

This method can identify abnormalities in some increasing the chances of curative brain surgery.

Voxel-based magnetic resonance image postprocessing in epilepsy
September 2017

 

Measuring the hippocampus in the brain

The part of brain called the hippocampus (aka the seahorse) is commonly the site in the brain where epileptic seizures start and so removing an abnormal hippocampus has a high chance of stopping epilepsy. It may be hard to decide if a hippocampus is normal or not and in this situation, taking detailed measurements can answer this vital question.

We have developed automated ways of making these measurements quickly and accurately, so that we can precisely and diagnose this key finding.

Automated T2 relaxometry of the hippocampus for temporal lobe epilepsy
September 2017

 

Predicting which is the best epilepsy drug for each person

MRI has revolutionised the way we treat people with epilepsy by offering people who did not respond to medication the chance of seizure-freedom by surgically removing parts of the brain.

Structural MRI scanning helps us to identify and predict who will benefit from surgery, and functional MRI (fMRI) tells us who is at risk of developing cognitive problems following surgery.

However, only a small minority of people benefit from surgical procedures, about 1,000 patients out of over 10,000 patients followed up annually at our clinics. For the others, we continue to rely on medical treatment with trial and error, as to whether a drug might help or cause side-effects.

At the Chalfont Centre, we have developed an MRI method called pharmaco-fMRI to determine the effects of anti-epileptic drugs on how the brain works, particularly effects on speech and memory.  Our aim is that we will be able to use these imaging techniques, after a test dose of an epilepsy drug, to predict how an individual patient will respond to that drug in the long-term, so that we can avoid side-effects.

Imaging biomarkers of anti-epileptic drug action: insights from magnetic resonance imaging
August 2017

Effect of topiramate and zonisamide on fMRI cognitive networks
March 2017

Determining the functional anatomy of the effects of medication
October 2016

 

Do seizures  result in progressive brain damage?

It has long been unclear whether people with epilepsy experience cumulative loss of brain tissue over the years.

We analysed all previous MRI brain scans research, on more than 1000 people with the most common difficult-to-treat epilepsy - temporal lobe epilepsy - over the past 20 years.

Longer duration of epilepsy and a higher frequency of seizures were associated with widespread loss of brain tissue, both close to and distant from the site where seizures started.

Future investigations need to track changes in individual subjects over the years, to identify the effects of epilepsy on top of changes caused by normal ageing.

This study highlights the need to improve seizure control and to consider surgical treatment, to minimise the chance of progressive brain damage in epilepsy.

A meta-analysis on progressive atrophy in intractable temporal lobe epilepsy: Time is brain?
August 2017

 

Navigating the brain

This series of papers describes our work to create an image-guided pathway for brain surgery. Brain surgery is considered if epilepsy comes from one part of the brain and if medication does not control seizures.

For this to be successful the parts of the brain that give rise to seizures needs to be pinpointed and removed, with great care taken not to damage any parts of the brain that carry out important functions such as speech, control arms and legs, sensation and vision.

In some patients it is necessary to place recording wires into the depths of the  brain to pick up the abnormal electrical signals of seizures.

Placing wires in the brain and carrying out surgery requires careful planning and millimetre accuracy. 

To enable this the surgeon benefits from having a 3D map of the brain that shows all the structures, and blood vessels,  areas of abnormality and critical areas that carry out vital functions and the connections between important parts of the brain.

We have developed the EpiNav programme that enables the 3D-display of the brain, its blood supply and normal structures, including vital connections, and the overlying skull,  so that precise planning can be made.

We have developed a computer-assisted programme that automatically guides the placement of recording wires into the brain and minimizing the risk of causing injury.

The software that we have created to place the wires safely can be used to control a small robot that assists the accurate placement of the wires in the brain and we are just starting a trial with this robot.

Our aim is that these advances will make epilepsy surgery more accurate and precise, quicker, safer and simpler, so that this potentially curative treatment can be offered to more individuals, sooner. 

Resection planning in extratemporal epilepsy surgery using 3D multimodality imaging and intraoperative MRI (full text available)
August 2017

Anatomy-driven multiple trajectory planning (ADMTP) of intracranial electrodes for epilepsy surgery (full text available)
June 2017

Accuracy of intracranial electrode placement for stereoencephalography: a systematic review and meta-analysis
June 2017

 Automated multiple trajectory planning algorithm for the placement of stereo-electroencephalography (SEEG) electrodes in epilepsy treatment (full text available)
January 2017

A pipeline for 3D multimodality image integration and iomputer-assisted planning in epilepsy surgery (full text available)
May 2016

Brain Imaging in the assessment for epilepsy surgery
February 2016

 

Is there a brake in the brain?

Seizures often happen at random times and almost always are self-terminating. We partly understand how they start but much less is known about how they stop. 

After a seizure, people are often unconscious or confused, as probably the brain is less active and this can be extreme after a convulsive seizure.

Extreme suppression of the brain activity (post-ictal generalized EEG suppression) was previously linked to an increased risk of SUDEP. It is currently unknown why the brain activity is suppressed after a seizure.

To understand this, we first created a computer model that simulated epileptic seizures and how they stop. This model provided hypotheses that were tested in EEG recordings of people with epilepsy at the time of seizures.

This showed that the duration of brain activity suppression can be predicted from the rhythmical movements during a seizure: the slower the rhythmical movements become at the end of a seizure, the longer the brain activity is suppressed after the seizure.

There may thus be a "brake" in the brain, which ensures that an epileptic attack stops by reducing the brain activity. Future research is needed to determine what this brake is and how it works and should allow for the study of potential triggers for SUDEP in computer models and as such is great improvement in previous methodology. This study shows how innovative computer models can help to identify crucial mechanisms that play a role in epilepsy.

Dynamics of convulsive seizure termination and post-ictal generalised EEG suppression
(Bauer et al., Brain, 2017) January 2017

 

Genetic tests show it's a question of diet

Epilepsy commonly presents in childhood as part of a syndrome, and some children may reach adult services without an underlying syndromic diagnosis.

For adult neurologists taking over their care, it is often unclear how hard to search for an underlying diagnosis. The diagnostic yield may be small and such a diagnosis may not change management.

Young adults with learning difficulties are also challenging to investigate, as they may not tolerate standard epilepsy tests. This research presents a case in which simple tests identified a unifying diagnosis confirmed by genetics testing, which identified a mutation in the CCDS gene.

A diagnosis of guanidinoacetate methyltransferase (GAMT) deficiency was made, and the patient and a sibling started treatment with creatinine, a food supplement which had a significant impact on seizures and quality of life. 

Guanidinoacetate methyltransferase (GAMT) deficiency: a rare but treatable epilepsy
January 2017

 

How study of brains of people with epilepsy is helping us understand causes of dementia

People with epilepsy are at risk of developing dementia, and people with dementia are at risk of developing epilepsy. 

We showed how the study of brains from people with epilepsy can help to understand causes of dementia.

In fact, epilepsy is unique, as epilepsy surgery allows us to look under the microscope at parts of brains, which are important for memory functions, like the hippocampus, from people who are still alive. We can basically travel back in time and compare the ability of a person to memorise things with how his brain lookede 10 or 20 years ago.

This is important for the study of Alzheimer’s disease, as we know that some changes in the brain of Alzheimer patients can be detected many years before the onset of dementia.

We looked at the role of a particular protein, called tau, for the development of memory problems in individuals with epilepsy. Tau is seen in the brain in those with Alzheimer’s disease, and we found large amounts of this protein in individuals with epilepsy.

The amount of tau we found in the hippocampi, which were surgically removed to treat patients with refractory epilepsy, partly explained the memory problems these individuals developed many years later: the more tau there was, the more memory difficulties they developed. 

This highlights the need to develop ways to visualise tau in the brain in life, with brain scans, and to develop treatments to target tau in the brain, to prevent the development of dementia.

Neurodegenerative processes in temporal lobe epilepsy with hippocampal sclerosis: clinical, pathological and neuroimaging evidence

December 2017

Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections

September 2016

 

Reducing risks in seizures

People with epilepsy may find it hard to think of words. We use the temporal lobe of the brain (at the side, in front of the ear) to think of words butd this part may not work well if epileptic seizures occur in this part of the brain. Most people use the temporal lobe on the left side of the brain to do this, but some may use the right-hand side, especially if the left side is damaged.

Also, brain surgery to try to cure the epilepsy, might make it harder to think of and to understand words if the operation damages the parts of the brain that are needed for speech.

At the Chalfont Centre, we have created ways of using the MRI scanner to identify the parts of the brain that are used to name objects, from written descriptions and from pictures.  This means that we can make detailed 3D maps of where language is going on in the brain. We can use this to see how the epilepsy is affecting speech and language and we can predict what effect an operation is likely to have.

This is really useful when deciding whether to do an operation. At this time, we are going on to see if it is possible to redesign how surgery is carried out so that these risks are reduced. 

Activations in temporal areas using visual and auditory naming stimuli: A language fMRI study in temporal lobe epilepsy
December 2016

 

Volume control

In a worldwide project of unprecedented scale (over 30,000 adults), we performed the largest ever meta-analysis of Genome Wide Association Studies (GWAS) of intracranial volume.

We discovered five previously unknown genetic loci (fixed positions on chromosomes) and confirmed two known signals, associated with intracranial volume.

We discovered evidence of a link between intracranial volume and other key traits such as height, cognitive function and Parkinson's disease.

This suggests that genes underlying brain development have far reaching effects that extend beyond the initial years of life. 

Novel genetic loci underlying human intracranial volume identified through genome wide association (full paper available)
October 2016

 

Adapting fMRI for Chinese languages

Chinese is one of the most commonly used languages in the world. One sixth (1.5 billion) of the world's population use Chinese as their mother tongue. Chinese characters differ from Western alphabet symbols. The relationship between Chinese spoken language and Chinese written language is very complex.

This means it is equally complex to use fMRI to investigate language networks in the brain for those using Chinese.

In this study we used Chinese language stimuli to explore activation patterns in Chinese people so as to investigate the potential of fMRI in Chinese patients considering temporal lobe surgery. The results can now be piloted in clinical trials. 

Mandarin functional MRI language paradigms (full text available)
August 2016

 

You can read more of our research papers below

Nestin-expressing cell types in the temporal lobe and hippocampus: Morphology, differentiation, and proliferative capacity.

Comparative effectiveness of antiepileptic drugs in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

Treatment of epileptic encephalopathies.

DNM1 encephalopathy: A new disease of vesicle fission.

Genome annotation for clinical genomic diagnostics: strengths and weaknesses.

Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy.

Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data.

Haploinsufficiency for ANKRD11-flanking genes makes the difference between KBG and 16q24.3 microdeletion syndromes: 12 new cases.

Familial childhood-onset progressive cerebellar syndrome associated with the ATP1A3 mutation.

Characterising subtypes of hippocampal sclerosis and reorganization: correlation with pre and postoperative memory deficit.

An examination of biochemical parameters and their association with response to ketogenic dietary therapies.

Impaired intracortical inhibition demonstrated in vivo in people with Dravet syndrome.

Photosensitive epilepsy is associated with reduced inhibition of alpha rhythm generating networks.

Neuropathology of SUDEP: Role of inflammation, blood-brain barrier impairment, and hypoxia.

Pharmacogenomics in epilepsy.

Current use of imaging and electromagnetic source localization procedures in epilepsy surgery centers across Europe.

From unwitnessed fatality to witnessed rescue: Nonpharmacologic interventions in sudden unexpected death in epilepsy.

Imaging Biomarkers of Anti-Epileptic Drug Action: Insights from Magnetic Resonance Imaging.

A meta-analysis on progressive atrophy in intractable temporal lobe epilepsy: Time is brain?

Neuroinflammation imaging markers for epileptogenesis.

Clinical studies and anti-inflammatory mechanisms of treatments.

Test-retest reproducibility of quantitative binding measures of [11C]Ro15-4513, a PET ligand for GABAA receptors containing alpha5 subunits.

Effect of topiramate and zonisamide on fMRI cognitive networks.

Seizure detection and neuromodulation: A summary of data presented at the XIII conference on new antiepileptic drug and devices (EILAT XIII).

WONOEP appraisal: Imaging biomarkers in epilepsy.