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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. This article was first published in the October 2016 issue of Reach Out, TSA’s twice-yearly magazine.

Editor’s note – This approach to treating epilepsy in TSC is available at many centres around Australia. The availability of EEG testing, particularly in regional areas, is one barrier to more widespread use of this intensive monitoring protocol. For help finding a neurologist with experience treating TSC you can contact the TSC Information Service by emailing [email protected] or calling 1300 733 435.

Can you describe this new approach to treating infants with tuberous sclerosis?

Dr Kate Riney receiving her award at the annual seminar day in Sydney in August 2013
Dr Kate Riney receiving her award at the annual seminar day in Sydney in August 2013

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.

What research has been published on this new approach to treating infants with tuberous sclerosis?

A gorgeous TSC baby having an EEG
A gorgeous TSC baby having an EEG

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.

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?

oliver-nsw-eegThis 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.

How does knowing about these higher risk periods of time help parents and carers?

For all the parents of small babies with TSC, I explain what a subtle seizure or epileptic spasm looks like. Around those periods of higher risk for the baby (see above) we go back through that information, particularly if the EEG is starting to show some signs of being abnormal. Parents capturing video of events of concern is the most important thing at that time. Videos can be sent to neurologists who can review them rapidly and provide reassurance or arrange rapid assessment if the events are confirmed to be a seizure. Obtaining this rapid support for events of concern is one of the most important things for infants with TSC in these risky time windows. While I understand the urge to put TSC in the background and get on with life, I think that being over-anxious is probably better than being under-anxious when it comes to these early seizures in the life of an infant with TSC as early action is important for the best outcome.

What are the challenges in rolling out this new approach to all infants with TSC?

High frequency EEGs in early life for infants with TSC who have not yet had clinical seizures is a very resource intensive process. I can be seeing some babies every week or fortnight for an EEG. A lot of centres would not have the ability to provide that service given funding for EEG services. However a long term view of this resourcing is important, as if we provide this resource intense service early, and see these babies early on frequently, we can potentially make an important difference to the frequency of long term seizures and to their developmental outcome and this means that once the infant is 3 years of age and older, that child will not be a frequent attender in complex epilepsy clinics and requiring heavy lifelong support from hospital and health and care services. The trend that is emerging at our centre is that I am seeing these babies very intensively up until the age of 2 to 3 years of age and then only seeing them yearly after that. We’ve only been doing this new approach of EEG surveillance since 2011 so we still have more to learn about the approach on whether there is a long term benefit and how great this is.

What are the implications of this approach for general epilepsy, outside of TSC?

That’s a good question. This idea of controlling the EEG is new to epilepsy in general. We’ve always focused on the clinical seizures. We increasingly realise that clinical seizures are just the worst manifestation of abnormal biology in the brain and it is this abnormal biology that has enormous impact on quality of life, development, behaviour and sleep. So this principle of ‘clinical seizures are not everything’ is very important for other epilepsies.

TSC has some characteristics that are unique from other causes of epilepsy that make this approach particularly suitable. We know that the majority of babies with TSC will have epilepsy; we know that the EEG will, fairly reliably, predict the onset of clinical seizures; and we have the potential to prevent the brain developing very complex and difficult to control epilepsy. This is in contrast to other groups at risk of seizures, such as babies that have had a stroke. For this group there is a smaller percentage of babies that will go on to develop seizures, and these seizures are much more likely to be controlled with a single medication.

General principles from other epilepsies are however relevant to understanding why early treatment of an active tuber, identified on EEG is important. There is a concept that is known from general epilepsy, that ‘seizures beget seizures’. We’ve known for some time that if you’ve got ongoing abnormal electricity in part of the brain that this recruits wider and wider areas and seizures then come from the whole brain or other areas of the brain. Once this whole brain recruitment has occurred, it is harder to wind seizures down again with anti-convulsant medications. The new approach of EEG surveillance for infants with TSC is a very clear model of managing this: essentially we are catch seizure-generating tubers on an EEG very early and treating before they start recruiting other areas of the brain so that there is better overall epilepsy control or remission of seizures.

What advice would you give to parents of a new baby with TSC?

From a medical perspective, I encourage people to ensure they have access to a paediatric neurologist with an interest in TSC. This could be their doctor, or someone their doctor can link in with when needed for support and advice.

There has been incredible progress in TSC in the last 20 years. We only discovered the genetic changes that cause TSC in the 1990s and the pathways that these influence not long after that. Our knowledge of ways that we can positively influence the condition is increasing rapidly. I usually highlight that most of the information on the internet is out of date and that this can be unnecessarily alarming. I always emphasise that TSC is a highly individual condition and that every individual with TSC is an individual.

I try to tell my new families balanced information about current data from our clinic, which reflects some of the newer treatments, early access to EEG surveillance (from 2011), early access to curative epilepsy surgery and access to mTOR inhibitors. I give information that is balanced about current rates of epilepsy and intellectual disability in our modern TSC cohort. I have teenagers in our clinic who are school captains and some have high IQs, and will transition to university. It has a very diverse impact but in our clinic at this time, the rate of intractable epilepsy is low (14% of our cohort currently) and this likely reflects better and more intense therapy in early life.  The best information is therefore obtained from people who are familiar with TSC and this often helps allay anxiety that can escalate when the internet is accessed.


  1. Jozwiak, S., et al., Antiepileptic treatment before the onset of seizures reduces epilepsy severity and risk of mental retardation in infants with tuberous sclerosis complex. Eur J Paediatr Neurol, 2011. 15(5): p. 424-31.
  2. Wu, J.Y., et al., Clinical Electroencephalographic Biomarker for Impending Epilepsy in Asymptomatic Tuberous Sclerosis Complex Infants. Pediatr Neurol, 2016. 54: p. 29-34.
  3. Muzykewicz, D.A., et al., Infantile spasms in tuberous sclerosis complex: prognostic utility of EEG. Epilepsia, 2009. 50(2): p. 290-6.
  4. Domanska-Pakiela, D., et al., EEG abnormalities preceding the epilepsy onset in tuberous sclerosis complex patients – a prospective study of 5 patients. Eur J Paediatr Neurol, 2014. 18(4): p. 458-68.


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