As people around the world mark Purple Day to raise awareness of epilepsy, we took a moment to catch up with our experts who are working to better understand the condition as well as researching new treatments.
Over 600,000 people in the UK have epilepsy.
Epilepsy is a common and serious neurological condition that affects the brain and nervous system. Seizures always start in the brain and are caused by many different underlying causes, including a person’s genetics, a structural change in the brain or from other underlying conditions.
Seeing inside – mapping epileptic activity
Seizures continue in around a third of patients with epilepsy despite the best available medication; in some, epilepsy surgery can stop seizures if brain areas causing seizures can be found.
Current brain scans aren’t always able to do this, meaning patients miss out on possible life-changing treatment.
In March 2020, Dr Khalid Hamandi, Cardiff & Vale UHB and Neuroscience Research Unit Lead within the BRAIN Unit, was awarded £165,000 by Epilepsy Research UK to undertake research entitled: Seeing inside: non-invasive brain mapping of epileptic activity (SINIMA)
Dr Hamandi explained: “We would like to investigate further the use of two advanced brain scanning methods, magnetoencephalography (MEG), and functional MRI (fMRI).”
Both these methods can identify abnormal brain areas causing seizures, but more research is needed. This project will use the latest technological advances, with very powerful 7T-MRI, and MEG, and new analysis methods.
“We will scan 30 patients who are due to undergo a special type of EEG (stereo-EEG) as part of their standard care, where electrodes are surgically placed into the brain to pinpoint where seizures come from.
The results of the scans will be compared – where they don’t need to ‘enter the brain’ and are considered non-invasive – with the results from the invasive stereo-EEG.
“We hope the results will show better and safer methods to locate epileptic brain areas that could be tested in future larger clinical trials. We expect the results to be applicable to patients in three to five years’ time.”
Visit Epilepsy Research UK to read more about pinpointing the source of seizures and non-invasive brain mapping of epileptic activity.
Understanding the relationship between seizures and signal pathways in the brain
Mr Dmitri Shastin is a Wellcome Trust-funded GW4 Clinical Academic Training fellow with a particular interest in neuroimaging and epilepsy.
His research is aimed at uncovering the relationship between seizure activity in patients with epilepsy and the pathways that transfer signals from one part of the brain to another.
Dr Shashtin said: “To do this, I am recruiting 20 patients with epilepsy caused by a type of lesion called focal cortical dysplasia.
“Using tools (MEG) to non-invasively record abnormal brain rhythms I will create simulations of seizure activity spreading through the brain.”
Dr Shashtin will use MRI scans to non-invasively map brain activity.
He will then examine how this activity is affected by variations in tissue properties measured with state-of-the-art MRI scans obtained from the same patients. His approach is further enhanced by a detailed study of the shorter pathways which may have a particular role to play but which do not often get studied enough.
“By teasing out which tissue properties have a greater role in seizures, we are hoping to better understand the mechanisms that drive epilepsy while at the same time identifying novel therapeutic strategies.”
Hope for people living with temporal lobe epilepsy
Mesial temporal lobe epilepsy (mTLE) is a common type of focal epilepsy, which primarily affects the hippocampus, a structure in the brain that plays key roles in the complex processes of learning, memory and emotion.
People affected by mTLE often suffer significant learning impairment and loss of memory, yet the underlying mechanisms involved are not understood and no effective treatment/preventative measures are currently available.
There is normally a constant generation of new nerves (neurogenesis) in the hippocampus throughout life, which is important for learning and memory; however, this is significantly reduced in mTLE and might explain, at least in part, the learning and memory problems frequently seen.
Dr Malik Zaben has been working with colleagues under the supervision of Professor William Gray, at Cardiff University on Developing targeted pharmaceutical strategies for restoring hippocampal learning in temporal lobe epilepsy.
With infrastructural funding from Health and Care Research Wales supporting the use of human brain tissue removed during neurosurgical operations, Dr Zaben and colleagues have used cultures of human epileptic brain tissue to identify inflammatory pathways that reduce neurogenesis in the adult human epileptic brain.
Dr Zaben explained: “Our work has shown that the pro-inflammatory cytokines HMGB1 and IL-1beta inhibit neurogenesis in hippocampal tissue generated from patients with mTLE.”
Critically, they have shown that blockage of these cytokines restores neurogenesis back to normal.
These findings are promising, as they identify key inflammatory receptors for developing specific drugs to target them, rather than less specific drugs that have many side-effects.
“Our group has previously shown that increasing neurogenesis using an antidepressant completely reversed learning deficits in animal models of chronic epilepsy, showing proof of concept that reduced neurogenesis is a cause of learning impairment.
“Our future work will focus on the assessment of the efficacy of these drugs in restoring learning in animal models.
“If this is successful, we will take this concept to clinical (human) trials. This could potentially have an enormous impact on the quality of life of people with temporal lobe epilepsy.”
Get involved
At BRAIN we believe that active involvement from members of the public leads to research that is more relevant, more reliable and more likely to be used to improve health and social care services. If you are interested in playing a role in shaping our work, you can become a member of our BRAIN Involve community.
- Read more about BRAIN Involve
Learn more
Drs Cynthia Sandor, who is supported by the Ser Cymru II programme which is part-funded by Cardiff University and the European Regional Development Fund through the Welsh Government, Kathryn Peall and Professor Caleb Webber have recently received funding from the Health and Care Research Wales Health PhD Studentship awards to investigate the role of inflammation in Parkinson’s disease, as part of the Dementia Research Institute and BRAIN Unit at Cardiff University.
Parkinson’s disease is the most common neurodegenerative movement disorder, estimated to affect ~8000 people in Wales. However, considerable phenotypic heterogeneity, both in presentation and symptom progression, is observed in clinical practice.
In order to better understand these differences, Dr Sandor has developed a computational model that allows integration of genetic and clinical information, from which she has identified symptom sub-groups that mirror those that are seen in clinical practice. As part of this work, those patients with a greater genetic risk towards Alzheimer’s disease tended towards developing a more severe form of Parkinson’s disease, as well as demonstrating a more rapid progression of their symptoms over time.
Alzheimer’s disease research has highlighted the potential contribution of multiple components of the neuroinflammatory system in disease mechanism. To date, the role of these immune components has not been investigated in Parkinson’s disease, in particular how they might contribute to the different symptoms and disease severity levels of disease severity.
This project plans to make use of already collected, highly detailed, clinical and genetic information involving the Michael J Fox funded Parkinson’s Progression Markers Initiative (PPMI) and Accelerating Medicines Partnership (AMP)-PD. UK based cohorts – the UK Tracking cohort and UK Discovery cohort – will also be used in the development of machine learning approaches that may enable earlier identification of patients with more severe forms of Parkinson’s disease, with this having the potential to better plan clinical care.
Dr Cynthia Sandor said “Our aim is to accelerate our understanding of how Parkinson’s disease varies across individual patients and to identify blood-based biomarkers that will aid the disease course prediction, aid care planning. An understanding of the immune system, how the body is reacting to the disease, is clearly important for Parkinson’s disease. This research offers molecular insights that could guide the development of therapeutics able to alter the progression and manifestation of an individual’s Parkinson’s disease. Disease modifying therapies are more readily clinically trialled than preventative therapies for neurodegenerative diseases and thus are more likely to have a quicker impact on patients and their families.”
This forms an exciting PhD opportunity, using cutting edge computational approaches. It also represents a new working partnership between bioinformatics (Dr Sandor and Prof Webber) and clinical (Dr Peall) teams, aiming to ensure directly relevant application of novel genetic data to clinical practice.
This is an exciting opportunity for an enthusiastic Clinical Research Fellow to work on a Health and Care Research Wales funded project at Cardiff University “BRAIN Unit” under the supervision of Professor Gray.
The post is available from February 2021 for 12 months.
This fellowship will optimize 3D human brain cultures for translational research in Neuro-Oncology and will involve both clinical and laboratory research. Professor Gray as Cardiff University’s Professor of Functional Neurosurgery is the academic lead in neurosurgery in Wales with principal interest in basic and clinical stem cell research related to patients with mesial temporal lobe epilepsy, cell based therapies for neurological disease, and Neuro-Oncology. This post will support the Neuro-Oncology research of a collaborative group, including Professor Gray(3D culture model), Dr. Siebzehnrubl (personalized medicine research in brain tumours) and Professor Parker (oncolytic viral therapies).
Closing date 17 January 2021.
An exciting opportunity has arisen for a research assistant within the Neurology research group at Swansea University Medical School. They are looking for individuals with skills and experience in the analysis of data (preferably in health or social care) and a background in epidemiology, statistics, computing, or a related discipline, to work on routinely-collected data research for neurology and neuroscience research projects.
Closing Date 12 December 2020.
Welcome to the new Brain Repair and Intracranial Neurotherapeutics (BRAIN) Unit website. The new site offers details about ongoing research projects, specific research highlights, upcoming events, relevant news and helpful resources.
At a time when we are relying heavily on digital resources, the team at BRAIN hope this website will help to bridge the gap where engagement events and more regular meetings and seminars would have taken place. The ‘Resources’ section of the site includes a helpful archive of all of our annual reports and other printed materials ordinarily distributed at engagement events.
Another new element of the site is the rotating Research Highlights section, bringing attention to new and exciting developments within the Unit. The first highlight on the website features an exciting collaboration with Professor Alan Parker, focusing on oncolytic viral therapies research, obtaining the correct tissue from neurosurgical tumour operations and generating the additional cultures in the lab for testing.
The new site will also be supplemented with a newsletter, distributed quarterly, summarising research achievements and signposting events and job vacancies. To sign up for the newsletter please contact us to enquire.
In a year of change, the unit also oversaw the recruitment of a new manager, Jo Baker. Jo said;
“It has been incredibly inspiring seeing the hard work that continues to take place, keeping essential research going through the challenges of the pandemic and ensuring the safety of our patients is paramount to clinical trials restarting. As I settle into my role as BRAIN Unit manager, I am looking forward to engaging with our local and wider research community and supporting the translation of research into patient benefit.”
We have been adapting to the COVID-19 pandemic and have since been able to re-open our Neuroscience Research Unit at the University Hospital Wales and our Biobanking facility. Another core feature of our work on intracranial delivery of human fetal cell transplantation in the Huntington’s Disease trial TRIDENT. This is the only study of its kind globally at the current time; all permission is almost in place to resume activities.
Health and Care Research Wales (HCRW) hosted their first ever digital conference on 7 October 2020, centred around the theme ‘Making a difference: the impact of health and care research’. As part of the event, the team behind the DOMINO HD study (Multi Domain lifestyle targets for improving prognosis in Huntington’s disease) received the highly commended Public and Patient Involvement (PPI) award for their presentation.
Professor Monica Busse along with DOMINO team members Dr Cheney Drew and Dr Philippa Morgan-Jones and PPI representative Barry Mackintosh entered a virtual presentation titled ‘DOMINO HD: An example of successful, cross-cultural engagement with public and patient representatives to design a multi-national observational study.’
The presentation outlined how PPI was incorporated into all aspects of their research into Huntington’s Disease (HD), a neurodegenerative disorder for which there is currently no cure or effective treatment. However, there is growing evidence that environmental and genetic factors may have a part to play in determining the course of disease progression.
DOMINO-HD is a consortium study consisting of six European partners; the UK, Ireland, Spain, Switzerland, Germany and Poland. The overarching aim of the study is to identify the key environmental factors that may be responsive in targeted interventions with a view towards optimising disease management for individuals with HD. The study has 3 main parts; development of a digital platform and implementation framework involving the development of methods for collecting information about lifestyle factors; using remote monitoring technologies to measure aspects of lifestyle and; validation of commercially available monitoring technologies for measuring lifestyle factors in people with HD.
The project involves a twelve month observational study to investigate the interplay of lifestyle and genetic factors on HD symptom progression. This will take place across the five clinical sites in Europe, involving the recruitment of around four hundred and fifty participants. The team will collect data on disease symptoms, nutrition, physical activity, sleep and genetics at baseline and 12 months. Additionally, there will be continuous collection of data on physical activity and sleep across the cohort using Fitbit devices for the 12 months. All the information gathered will be used for predictive modelling of disease outcomes, the aim of which is to inform the design and development of a cross cultural, data and theory driven lifestyle intervention, aimed at improving the quality of life of people with HD. The intention is that this intervention will be co-designed with significant input from PPI representatives.
All this work is underpinned by public and patient involvement. The initial study concept was supported by input from a number of stakeholder events and PPI activities focusing on lifestyle and physical activity of people with HD; in partnership with the HD involving people group and BRAIN Involve. In long term studies of people with challenging conditions, particularly when asking participants to engage with unfamiliar technologies, successful delivery of the study is dependent on participant centric design, therefore this was a key focus from the outset.
Dr Cheney Drew said “As a team we are delighted with the recognition of the successful incorporation of PPI in DOMINO-HD, particularly for our PPI representatives who’s enthusiasm for the research and dedication to the study have made a significant contribution to the ongoing delivery of the project”
The multinational nature of the study requires cross cultural PPI input to ensure the relevance of the study in each partner country. As a result, a model was implemented featuring representatives from all five countries, acting as a conduit between the main research team and the wider PPI network within their own locale. This has helped to facilitate equal opportunities for involvement across all partner countries.
In an initial meeting, the team laid out their expectations of the PPI role which gave them an opportunity to identify any further training and support required for their representatives. This promoted confident and helpful input from the representatives, which proved pivotal in the co-development of participant friendly materials for gathering wider public and patient input.
One of the local representatives, Barry Mackintosh, provided his perspective as part of the presentation for HCRW. Barry said “I have been pleased and impressed by the efforts made by the project to include and engage with HD patients and family members. I know that our input has informed team decisions.”
To find out more about this study please visit the DOMINO-HD webpages here.
