Grant winner 2016

Grant type: Pilot grant

Principal investigator: Professor Alexander Hammers

Institution: King’s College London

Amount: £30,000

Duration: 18 months

Scientific titleInflammation in tuberous sclerosis as a potential marker of epileptogenicity: a [11C]PK11195 and elastography PET-MR study

“We are really grateful to Epilepsy Research UK for offering us the possibility of exploring this exciting approach. If the new PET-MRI scanner methods help us find where these patients’ seizures come from, many more patients will be able to undergo surgery in the future.” Professor Alexander Hammers (pictured)

Background
Tuberous sclerosis, also known as tuberous sclerosis complex, is a rare genetic condition that causes growths known as ‘tubers’ to develop in different parts of the body. It is present from birth (although obvious problems may not be present immediately), and it is reported to affect approximately 1/6,000 newborns.

Due to the frequent involvement of the brain, most people with tuberous sclerosis also have epilepsy, and this is often drug-resistant, i.e. seizures continue despite medication. If a seizure-causing tuber is identified it can be removed surgically, but the process of finding the ‘culprit’ is complex and invasive. This limits the number of people who are put forward for surgery.

The study
Previous studies have shown that tubers removed during surgery have signs of long-standing inflammation. Through this grant, Professor Hammers and his colleagues want to find out if inflammation in tubers is in fact a marker that can be used to identify those that are epileptogenic (capable of inducing seizure activity). This would be a lot easier and less arduous for the patient than trying to find signs of epileptic activity in tubers directly.

Signs of long-standing inflammation in tubers are:

  • The presence of certain immune cells, which can be detected with a technique called positron emission tomography (PET) using a “dye” labelled with a tiny amount of radioactivity.
  • Inflammation may also increase stiffness of the tuber. Stiffness will be measured using a newly developed special form of magnetic resonance imaging (MRI).

The team will use a combination of PET and MRI to look for inflammation in the brain tubers. They will use a new scanner, only the second in the UK, that can take PET and MRI images at the same time. The team will scan 12 people with tuberous sclerosis and drug-resistant epilepsy, who are aged between 10 and 45 years. For each subject, tubers that show signs of inflammation will be carefully mapped, and information from detailed EEG scans (which record electrical activity in the brain) will be used to find out if the locations of the inflamed tubers correspond with the areas in which seizures are occurring.

Significance
If the results of this pilot grant suggest that inflammation in tubers is a reliable marker of epileptic activity, and these findings are confirmed in further studies, PET-MRI imaging could potentially give a lot more people with tuberous sclerosis the chance to benefit from surgical treatment. The impact of this funding could be seen in the next 3-5 years.

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