Grant round winners 2011

Status epilepticus can be either convulsive (CSE) or non-convulsive (NCSE) and is defined as a seizure lasting 30 minutes or more, or a series of seizures that occur in succession without consciousness being regained in between. CSE is a recognised medical emergency and is very easily detected, however NCSE is a lot rarer and more difficult to diagnose and treat. This is because, although NCSE produces a similar EEG pattern to that seen in CSE, there are usually very few visible signs of a seizure, meaning that it is often overlooked or incorrectly diagnosed. In addition it is not considered a medical emergency.

Non-convulsive status epilepticus (NCSE) usually occurs in children with complex, severe epilepsies, and can lead to a significant loss of ability. It needs to be treated promptly; however most existing therapies have sedative effects and increase the risk of complications such as chest infections. There is a clear need, therefore, for more research into NCSE and the development of better treatments.

 

The processes underlying seizure onset and termination are not entirely understood, however existing evidence suggests that brain pH plays a role in both processes. For example an increase in pH (alkalosis) has been shown by various researchers to trigger seizure seizures, whilst a decrease in pH (acidosis) has been shown to inhibit them. The mechanisms by which this occurs is not clear, but it is thought that certain ion channels that control the electrical current in neurons are sensitive to pH and only open when pH is at a particular level.

 

One way of decreasing brain pH is to breathe in air that contains slightly more carbon dioxide than normal. The carbon dioxide gas diffuses into the blood and dissolves in the blood plasma to form carbonic acid. An important effect of acidity in the blood is that it causes blood vessels to dilate.

Carbogen is a mixture of 95% oxygen and 5% carbon dioxide (the same percentages as those found in exhaled air). It is already used therapeutically for conditions such as arterial occlusion and certain cancers (in which an increased blood supply to a particular area is required). Evidence to date suggests that this treatment is safe and well tolerated, and that it has no sedative effect.

Previous studies have already shown that carbogen is effective in stopping seizures in animal and pilot human adult studies. Dr Rob Forsyth, at the University of Newcastle, and colleagues in Newcastle and Manchester, have now been awarded £24,767, over 24 months, to carry out a project entitled Phase 1 pilot study of use of 5% carbogen in treatment of paediatric non-convulsive status epilepticus, which will be the first study of carbogen in the treatment of children with epilepsy.

The team plans to recruit 30 inpatients (aged 3-12 yrs), with established epilepsy and confirmed NCSE, from two paediatric neurology centres. Each child will be asked to inhale carbogen through a hand-held mask for two minutes, whilst being monitored via EEG. The researchers will assess the effect of the carbogen on the children’s EEG, along with how safe and well-tolerated it is as a treatment.

Dr Forsyth hopes that if the results from this project are encouraging, the effects of carbogen in other types of seizure will be explored. He believes that carbogen could potentially represent a new direction for the acute treatment of seizures in the future.