Tuberous Sclerosis Australia Reach Out Magazine October 2016

Information
Information
New approach to treating
epilepsy in babies with TSC
shows promising early results
From an interview with Dr Kate Riney, paediatric
neurologist and TSC clinic lead at Lady Cilento
Children’s Hospital, Brisbane
Lachlan, QLD
Can you describe this new approach to treating infants
with tuberous sclerosis?
The new approach is to look at the electroencephalogram (EEG)
of babies with TSC before they’ve had a clinical seizure. A clinical
seizure is one we can recognise just by looking at the baby. Some
babies are diagnosed with TSC after the discovery of cardiac
rhabdomyomas (a growth in the heart associated with TSC) in
the baby during pregnancy but before they have clinical seizures.
In these babies, we’ve had the opportunity to study changes on
EEG that occur before a clinical seizure occurs. We’ve recognised
that there is a clear pattern of abnormality appearing on the
EEG approximately two months before the onset of clinical
seizures. This gives us an opportunity to treat these infants earlier
than would otherwise have occurred, and we know that earlier
treatment of some seizure types is better. In some infants we
have found from looking at their EEGs prior to clinical seizures
appearing, that they are actually having seizures on the EEG
that are just incredibly difficult to recognise in a small baby as
they don’t cause very obvious movement or behaviour change.
Identifying this has been important so that these can be treated.
In short, we’ve learnt that the EEG can be incredibly informative
when it is done regularly from birth for babies with TSC, even
though they have not yet been seen to have a clinical seizure. The
hope is now that with obtaining this information on all babies
with TSC from early life, that earlier treatment might improve the
development of clinical seizures or epilepsy and that it might even
improve development.
What type of seizures do you normally see in babies
with TSC? What treatment do you use for these
seizures?
The most common seizures in small babies with TSC that we now
pick up with EEG testing are focal seizures, these are seizures that
stay localized in one part of the brain, arising from a tuber. They
can have little visible effect on babies. Sometimes there is just a
minor cessation in feeding, or a brief quietening in behaviour.
When these have been occurring for a period of time, the seizures
develop the capacity to spread wider around the brain and a more
widespread seizure then appears. This is typically a seizure type
called an epileptic spasm. The best first treatment for any type
of seizures in an infant with TSC is a medicine called vigabatrin
(Sabril). If seizures cannot be controlled by this medicine then
there are a few other medications that can be trialled but the best
curative approach may be removing the tuber causing the seizures.
This is called epilepsy surgery.
Matilda, VIC
What research has been published on this new
approach to treating infants with tuberous sclerosis?
The original research[1] came from TSC clinics in Europe. It
was initially in a very small group of babies that were followed
with EEG before onset of clinical seizures. This showed that
there was a potentially important role for EEG monitoring
and possibly a role for treating the EEG to improve seizure and
developmental outcomes.
After this, larger studies are rolling out and these are active at
the moment. Some data from these studies have been presented
at international conferences, both at TSC and general epilepsy
meetings. Some data is being prepared for publications in academic
journals.
In addition, studies have already been published recently
that demonstrate that EEG is a valuable predictive tool [2-4].
They show that if you follow EEG changes in babies with TSC
before the onset of clinical seizures and you don’t treat that
EEG that there is a timeframe of about two months where the
EEG becomes abnormal and these babies will develop clinical
seizures. This provides us with extra confidence in making the
decision to treat an abnormal EEG before the babies have had
clinical seizures.
What research is your team at Lady Cilento Children’s
Hospital involved in?
Our TSC Clinic is collaborating as an Australian site in a
multi-centre research project running across European Union
countries. This work is looking at early predictors of epilepsy
in infants with TSC and determining whether earlier treatment
when there are purely EEG abnormalities, but before clinical
seizures appear, may improve outcomes. We are looking at both
epilepsy outcomes as well as outcomes related to development
and cognition.
What else do we know about this new approach?
As various clinicians become familiar with doing EEGs as a
regular monitoring activity in small babies with TSC who have
not yet had clinical seizures, there has been greater opportunity to
see how EEG changes correlate with how the baby is progressing
in their level of interaction and development. Through this time,
clinical knowledge is being acquired about the baby and their EEG
patterns. This allows clinicians to have the capacity to predict what
will happen next and to have plans considered for treatment and
intervention that can then be implemented more rapidly than if
this knowledge was not already there.
The EEG still gives you additional
information over what families, parents
or even doctors looking at the child can
actually tell.
It’s often a cause of worry and anxiety for parents and
carers that they are not recognising subtle seizures
in their babies. This worry can continue even after
medication is started. What role does regular EEGs
have for babies who have not had TSC diagnosed
before they present with clinical seizures?
I also see babies presenting for the first time with the onset of
clinical seizures and TSC diagnosis at that time. I think the
same principles still apply. The EEG still gives you additional
information over what families, parents or even doctors looking
at the child can actually tell. For this reason, I generally apply the
same monitoring to any infant after the onset of clinical seizures
as I would to the infant who is on the preventive surveillance
EEG regime. I do think this helps to make sure that you’ve better
control of the seizures over what is guessed clinically. And regular
EEGs even after onset of a clinical seizure can still predict seizures
breaking through later. I think the EEG surveillance, even in
these infants, offers us the maximum information about the early
developing brain to allow us to make the best decisions to improve
the potential outcome.
How frequent are these EEGs?
This can vary from team to team. We follow the protocol that
other researchers in Europe are following. For me, this is our
minimum frequency:
• For babies up to 6 months of age, once every four weeks;
• For babies between 6 and 12 months of age, once every
six weeks;
• For babies between 12 and 24 months, once every
eight weeks.
In practice, if there is an abnormal pattern on EEG or a very active
EEG, I might do EEGs every two weeks as I change medications to
try to get better control.
We’ve discovered there are some specific windows of time in
the life of a TSC baby when they are more susceptible to having
seizures. These are the times in which we tend to see more abnormal
EEGs, so we’re often doing more EEGs in those time windows.
For some babies, they are born with lots of sub-clinical seizures on
their very early EEGs just after birth. We then have a group of babies
that will develop EEG patterns that suggest a risk of developing
epileptic spasms at around 6 months of age. And then there seems
to be another risky period at about 18-20 months of age when some
breakthrough seizures can occur, often with viral illnesses, but
after that last risk period, things tend to be more smooth sailing.
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OCTOBER 2016 ISSUE 104
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