The incidence of hospital admissions with prolonged seizures and status epilepticus in England 1990-2015 Professor Matthew Walker, University College London Pilot grant of £11,275
THE HIPPOCAMPUS
‘Very prolonged seizures (status epilepticus) can have devastating consequences and can result in death. It is critical to understand how recent changes in the treatment of seizures and epilepsy have impacted upon status epilepticus. Funding from ERUK will enable us to determine how common status epilepticus is in the UK, how that has changed over time and what impact that has had on epilepsy deaths.’ Professor Matthew Walker Status epilepticus is a prolonged seizure (lasting more than five minutes) that requires urgent treatment and hospital admission. It is a significant cause of mortality in people with epilepsy, accounting for approximately 10% of epilepsy deaths. Since the 1990’s, a lot of work has been carried out to establish care pathways and protocols for status epilepticus/prolonged seizures, so that all hospitals in the United Kingdom have clear treatment regimens to manage them. Recent analyses suggest that the death rates for status epilepticus in England and Wales are falling, which may be due to improved/earlier treatment. However, it is impossible to know this for certain without knowing whether the frequency of status epilepticus has changed in the corresponding period (i.e. it could be that the fall in mortality rate is simply due to fewer cases of status epilepticus in that time). Currently there is no available data on the frequency of status epilepticus in England,
or indeed, whether the frequency of status epilepticus has changed over time. During this grant, Professor Walker and his colleagues hope to address this gap in knowledge. To achieve this, the team will obtain information about hospital admissions due to status epilepticus in England, for the period 1990-2015, from the Health and Social Care Information Centre (HSCIC). They will analyse the data to get an idea of the frequency of status epilepticus during this period, and find out if/how the frequency of status epilepticus changed. They will then see how their newly-acquired frequency data correlates with the mortality data that is already available. The findings of this study will help to establish why a fall in mortality rate due to status epilepticus has been seen in recent years, and whether the care pathways in hospitals are responsible for this decrease. This will allow for a more informed assessment of current treatment regimens and their effectiveness.
Modulation of glial signalling as a novel therapy for absence epilepsy Dr Mark Wall, University of Warwick Pilot grant of £29,300
‘Our work will hopefully identify a new therapeutic target to treat absence epilepsy and increase understanding of the disease.’ Dr Mark Wall
Background
The Study
Absence epilepsy is largely a childhood condition characterised by sudden, brief interruptions of consciousness. In severe cases there may be more than 200 of these episodes each day, and these can be accompanied by or develop into convulsive seizures. Many children with absence seizures don’t respond to existing antiepileptic medication, which can present numerous difficulties in daily life, particularly with schooling.
This grant focuses on brain cells called glial cells, which support neurons and are important for maintaining correct communication between them. More specifically, Dr Wall and Dr Ngomba (University of Lincoln) want to find out if a loss of glial cell function is responsible for the increased inhibition that leads to absence seizures.
On EEG, absence seizures show a specific pattern of brain activity that arises within a neuronal network called the thalamo-cortical network. The mechanisms that generate these episodes are still not fully understood, but evidence shows that enhancement of a particular type of inhibitory communication between neurons may be responsible. Attempts to develop treatments that directly reduce this inhibition have failed because of side effects, so a more targeted approach is required.
A CLOSER LOOK AT ... The hippocampus is a very important structure found deep within the temporal lobe of the brain. There are, in fact, two of them, one on each side of the brain, and they got their name because they are seahorse-shaped and hippocampus means seahorse. The hippocampi (plural of hippocampus) are involved in controlling our emotions and they are vital to our memory function. They are also one of the only regions where new nerve cells are created throughout adulthood. The hippocampus is mentioned a lot in epilepsy, because, particularly in people with temporal lobe epilepsy, it is frequently the place where seizures start. There is often damage to the hippocampus on the ‘affected’ side of the brain (and sometimes both hippocampi are involved), although it is still not clear whether this is the cause or result of seizures. Damage to the hippocampus causes loss of function and this is one of the reasons why many people with epilepsy experience memory problems. We have funded a number of grants aimed at understanding the role of the hippocampus in epilepsy (with a view to protecting it), and most recently we awarded Dr Stephanie Schorge, at University College London, a pilot grant to try and find out why the front end of the hippocampus is more likely to generate seizures than the back end. If successful, this research could help the development of exciting new epilepsy treatments that target the front part of the hippocampus with minimal side effects. You can read more about Dr Schorge’s research on p4.
The group will use a range of laboratory techniques to explore, in depth, how certain aspects of glial activity are altered in a rodent model of absence epilepsy. They also plan to investigate whether it is possible to reduce or even prevent absence seizures by enhancing glial cell activity.
Significance The findings from this project will give important new information about how absence seizures arise, and may reveal new targets for the development of more promising treatments.The methods used will also be useful for the screening process of anti-absence seizure drugs in the future.
transforming lives through research
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