News - The
relevance of basic research and patients
4 November 2004
The Epilepsy Research Foundation's first
research seminar to be aimed specifically
at a lay audience was held in conjunction
with this year's AGM on 23 September 2004.
The theme was 'From Bench to Bedside:
The Relevance of Basic Research to Patients'.
Basic research is fundamental research,
looking for basic principles of knowledge.
It aims to seek knowledge for knowledge's
sake. Basic research in epilepsy includes
trying to find out how the brain works,
what makes a brain likely to have seizures,
and what happens in brain cells during a
seizure. It includes studies at the molecular
level and at the cellular level. It might
involve studying computer models of brain
activity, animal tissue experiments, and
tests on human brain tissue. It also includes
genetic studies and the development of methods
of imaging or scanning.
Dr Mumford explained that basic research
has to be carried out before any clinical
research (that is, research involving patients)
can be done. Fifty-nine percent of the projects
funded to date by the Foundation have been
in basic research (including projects on
the genetics of epilepsy). This accounts
for 56% of the money we have allocated to
research projects.
A new imaging
method - electrical impedance tomography
Dr Holder has been working on electrical
impedance tomography (EIT) imaging in epilepsy
since 1986. Imaging methods in use today,
such as electroencephalography (EEG), functional
magnetic resonance imaging (fMRI) and positron
emission tomography (PET), have made possible
huge advances in our understanding of epilepsy.
However, they all have limitations. EEG,
though instrumental in the diagnosis of
epilepsy, records electrical activity from
the surface of the brain only; it cannot
measure exactly where the activity comes
from inside the brain. In contrast, fMRI
and PET can produce true images of activity
in the brain, but the scanners required
are bulky and complex, so these methods
are expensive.
Electrical impedance tomography is a new
imaging method. During a seizure, the activity
of brain cells increases dramatically, and
so does the flow of blood to these cells.
The electrical properties, or impedance,
of these areas therefore changes. In EIT,
tiny electrical signals (which are quite
safe and cannot be felt) are applied to
the head via EEG electrodes, and the equipment
measures the impedance of the brain tissue.
On the scan, areas of the brain with normal
activity and areas where a seizure is happening
therefore show up in different colours.
The images produced are quite fuzzy (not
as clear as fMRI or PET scans) but the equipment
required is small and safe, so EIT images
can be produced quickly and easily at the
patient's bedside.
Dr Holder explained that EIT has great
potential in epilepsy. It has previously
been used on other parts of the body, e.g.,
the chest (imaging the lungs) and breast
(to find cancerous lumps). Dr Holder and
his team (several members of which were
present in the audience) have pioneered
its use for imaging brain activity. The
patient wears a head-net of electrodes,
attached to a small box worn on a waistcoat,
and is able to walk around, while the equipment
takes a series of 'snapshots' of the electrical
impedance of the brain. The technique is
safe, fast and inexpensive.
Dr Holder showed a video recording of a
the onset of a complex partial seizure together
with an EEG scan and EIT images taken during
the same seizure. As the seizure began,
a small, clearly defined area of the brain
lit up in the EIT scan. This happened several
seconds before any epileptic activity was
visible on the EEG. This clearly showed
the potential of EIT to pinpoint the seizure-generating
areas of the brain, for example prior to
surgery. The technique might also be used
to evaluate the effectiveness of new drugs.
Current work (funded by the Foundation's
grant) includes testing of multi-frequency
and low-frequency EIT. This last is very
exciting as it is expected to allow imaging
over tens of milliseconds rather than tens
of seconds (much more frequent snapshots
of brain activity) - this should allow imaging
of the spread of electrical activity during
seizures.
Fast brain waves
and the start of seizures
Professor John Jefferys is studying what
happens in the brain at the very beginning
of seizures. He showed a sequence of EEG
images of seizures, and drew the audience's
attention to sudden localised bursts of
fast brain waves (much faster than brain
activity during a seizure) in specific areas,
that occurred before seizures began. His
theory is that these fast brain waves are
generated by groups of neurones functioning
as a group, called an aggregate. These aggregates
join up, and their rate of firing slows.
It is at present unknown whether these aggregates
develop into seizures or merely help seizures
to start.
In a non-epileptic brain, brain cells are
controlled by inhibitory cells such as basket
cells. Therefore, aggregates of overactive
cells cannot form, and if they do, they
cannot spread far. However in an epileptic
brain, this inhibition is absent or not
strong enough, so aggregates can form and
spread, and seizures can develop.
Professor Jefferys' research team is at
present studying the conditions which lead
to the formation of aggregates, and whether
the process of aggregation can be blocked.
If so, there is potential for the development
of new drugs which prevent the spread of
aggregates into a full seizure.
The seminar was a great success, with a
30-minute of question-and-answer session
following the final presentation. Judging
by feedback already received, it will no
doubt be the first of many such seminars
aimed at a lay audience to be organised
by the Foundation in the future.
