sMater - Groundbreaking epilepsy study - Prof Aileen McGonigal

In this episode of sMater, Professor Aileen McGonigal, from Mater’s Epilepsy Unit, discusses the groundbreaking Australian Epilepsy Project—set to be the world’s largest epilepsy study. 

Discover how cutting-edge imaging, genetics, and AI are transforming diagnosis and treatment, and why GPs and clinicians across Australia should tune in.

To learn more about Mater, visit https://www.mater.org.au/

Transcript

Hello and welcome to this episode of SMater, a podcast by clinicians for clinicians,

brought to you by Mater, an Australian leader in health care for more than a

century. I'm your host, Jillian Whiting, coming to you from Meanjin, the land on

which this podcast is being recorded. And I'm Dr Maria Boulton, GP Specialist and

former President of AMA Queensland. Today, we are joined by Professor Aileen

McGonigal, Clinical Director Director of the Mater Epilepsy Unit based at South

Brisbane and Research Group Leader. We are Mater. We are Mater. We are Mater.

This is Mater.

Aileen, welcome to Mater. Thanks very much. I'm delighted to be here. Can you give

us a snapshot, firstly, of epilepsy in Australia today? How common is it and who

does it affect? Yeah, sure.

often can't work, can't drive. It really can affect anybody.

It affects the whole lifespan from infancy, childhood, right up to old age.

Epilepsy can occur at any time of the lifespan, although there is a peak in

children and a peak in older people. As a GP, I find navigating epilepsy diagnosis

and treatment a bit tricky, so I'm so pleased to be speaking with you today, what

drew you to epilepsy? Well that's a good question. So I did my studies in the UK

and in Glasgow in Scotland in neurology, so I'm qualified as a general neurologist,

of course treating stroke and multiple sclerosis and Parkinson's disease and all the

other conditions. I was particularly fascinated by epilepsy, partly because it's so

complex and so difficult, can affect people in lots of different ways with many,

many different manifestations which occur in short periods of time. I think I was

particularly interested in the ability to record the brainwave activity through

electroencephalography. So that's electrodes usually on the scallop which can record

the brainwaves during the seizure. So we can actually study in a lot of detail the

brain changes underlying all the manifestations of epilepsy, which, as you know, can

affect conscious level memory movements. People might be prone to fall,

might even have convulsions. One way that we can think about epileptic seizures is

like a brain arrhythmia. So we know about arrhythmias in the heart. The brain is

much more complex than the heart as a structure, and an epileptic seizure is like a

disorder of the brainwave rhythms, which occurs during seconds or minutes. And

depending on which part of the brain it affects, that will determine what the person

feels and what everyone can observe. - Now you've just launched the Australian

Epilepsy Project. It's the world's largest and most comprehensive epilepsy study.

What is it? And how is it different from other epilepsy studies? - Yeah, so this is

a great initiative. This is led by Professor Graham Jackson at the Flory Institute,

Melbourne. So we are collaborating with his group and many other teams around the

country are part of this exciting initiative. The goal is really to collect a very

large cohort of epilepsy by studying people with different forms of epilepsy and

basically inviting them to take part in a series of tests. So one of those is a

high level MRI magnetic resonance imaging brain scan, which goes beyond what is

usually done in the hospital setting in terms of being a high resolution scan. So

we see much more detail in any very subtle brain abnormalities that might be the

cause of the epilepsy. There's also some testing done during that scan of brain

function. So people in the scanner will be asked to do some test for language or

memory, and that really shows us which parts of the brain light up, and we can

understand if the brain function is perhaps being altered due to epilepsy. And then

there are also some tests on cognition, so memory, language and so on, which are

conducted over telehealth with expert neuropsychologists. So we really get a snapshot

of not just the seizures, which of course have the main impact on people with

epilepsy, but also all of the issues in the background, which are mental health and

cognition, which are actually related to the impaired quality of life.

And then the last part of the testing of the Australian epilepsy project is a

genetics test, which is done at home with a mouse swab for a saliva sample for

testing for DNA. So the goal is to really offer this very high -level testing to

people all around the country. So, of course, someone with epilepsy who lives in the

city centre, perhaps in Melbourne, where there's very big academic hospitals, can be

quite easy to access these types of tests in a routine way, almost,

whereas people living in more distant regions, especially here in Queensland, where we

have a lot less in the way of epilepsy services compared to some other parts of

Australia, they're often disadvantaged by not being able to access the high -level

technology and the high -level specialist expertise. So this project really kind of

highlights that gap and makes it accessible for people to have the best quality

imaging looked at by very specialist neurologists and then to have the high -level

psychology. And the best thing about it for the patients who take part is that The

results are then transmitted back to the referring clinician who has to be a

neurologist and we can share those results with the patient and it often then

affects their treatment in real time. And then in the background we're collecting

this huge data set which will lead to new knowledge about different forms of

epilepsy and lead to hopefully better diagnosis and treatment in the future. It is

huge, clearly very important. How many people? What's the duration? Is there any more

you can tell us about the project. Yeah, so the goal is to enrol 4000 people

around Australia. So here in Queensland, our kind of target is to enrol 1000. So

we're key partners in this study, which we're very proud to be, and it's really

thanks to the amazing support from Ata Research that this has been made possible.

And we're so far, I think, up to about 500 recruitment, so we're already halfway

there, which is really great. So the goal is to, as I said, enrol this large

population. The study organisers are keen to have a sample of healthy volunteers in

there so that we can also have some brain scans of people without epilepsy or

neuropsychology and so on to compare the differences of brain function between people

with epilepsy and people without epilepsy.

According to the Epilepsy Foundation people over the age of 60 are now the largest

group of Australians living with epilepsy. One in 200 Australian children live with

epilepsy as do one in four people with a profound disability.

How do you think the findings will potentially change the way that epilepsy is

diagnosed and treated? Yeah that's a good question because I think it's got actually

quite fire -reaching impact for people in Australia, but also I think other countries

around the world will look to this study and learn from it. So I think to go back

to what I said about the kind of access and equity of being able to have the high

level testing, the goal of this study is actually to show that if we do make high

level testing available, especially early in the condition, ideally as soon as

possible after the first seizure, actually, then we can have a chance to affect

outcomes. So that, for example, some people with epilepsy have epilepsy due to a

cause that could be treated surgically. Most people with epilepsy, to take a step

back, are treated with medication. So as you know, and the listeners will know, the

mainstay of treatment is anti seizure medications of which we now have more than 20

different molecules in the market which are taken every day and their role is to

stabilize the brain rhythms and avoid the risk of these arrhythmias which are causing

the epileptic seizures. So it's really a preventative treatment to stop the seizures

but of course it doesn't tackle the cause of the epilepsy. Epilepsy can be caused

by many many different conditions And in some people, it's fairly straightforward to

work out why they have epilepsy. They might develop seizures after a stroke, or they

might have a first seizure, and then they have a scan, and it turns out to be a

brain tumor or something else like that. Structural lesion that we can see, other

people might have a genetic cause for epilepsy. The brain scan might look normal,

but we might know that they've had a family history of epilepsy, and that might

point towards a genetics cause. But really half of people don't have a clear -cut

cause like that that we can really put our finger on. And yet, as the imaging,

the neuroimaging becomes advanced, we're starting to see more and more very subtle

brain abnormalities, which are actually the cause of the epilepsy. And many of those

are congenital, meaning that there's been a development problem in the brain before

birth. The commonest of these is called focal cortical dysplasia. This is where a

few of the brain cells during development migrate into the wrong place. They connect

up in an abnormal way and that kind of connection leads to electrical instability

which can predispose towards epileptic seizures. So going back to what the study can

tell us, as we do these higher -level imaging testing, we're starting to see more

and more of these subtle abnormalities which cause epilepsy. And that's important

because when, apart from the importance for a person with epilepsy and their family

to know why it's happened, that's very important psychologically of course, but it

might also open up new treatment options because when we've tried medications, the

GPs listening will know that many people who don't have good control of seizures

despite medications, in fact up to a third of people of what we call drug resistant

epilepsy, meaning that despite adequate medications, and we define that as being

failure of two medications, once someone has tried two appropriately chosen,

appropriately dozed medications for seizures and their seizures are not well

controlled, at that point they should be referred for specialist evaluation because

there might be other treatment options, including surgery for some people that could

bring about seizure control. You mentioned genetics. What role does genetics play in

epilepsy?

So genetics probably plays a huge role in epilepsy beyond what we know nowadays. We

certainly know that some forms of epilepsy are purely genetic, so there's no other

explanation. And in the testing that we can do nowadays, we can find a gene that's

caused the epilepsy. So there's a certain number of genes that they call those

monogenic epilepsy, so a single gene abnormality causes the epilepsy. Then there are

all of the kind of less well understood genetic abnormalities which contribute to a

tendency to epilepsy that might not necessarily express, but in some people it will

do.

And in fact, we think that as technology advances, as we have better access to

genetic testing for more people will probably start to find more and more genetic

abnormalities. In the Australian epilepsy project, the testing that's done is called a

chromosomal microarray. So it's a fairly low -level genetic screening test. There are

then much more high -level genetic testing that can be done if we find any

abnormality on the first -level testing. You mentioned we need a thousand Queenslanders

at least for the study that you're hoping to recruit. What are the eligibility

criteria and how can GPs help particularly thinking about candidates from outside of

Metro? Yes, that's a good question. So there are three groups of patients who can

be enrolled into an Australian epilepsy project. The first group, which our team has

to the most of are called focal drug -resistant epilepsy. So as I mentioned, drug

-resistant means a diagnosis of epilepsy where medications are not sufficiently

controlling seizures. Focal means that seizures are coming from one hemisphere.

So one part of one hemisphere, they're usually coming from a localized region in the

brain. And defining that usually needs a neurologist to diagnose that. So the best

thing a GP could do if they think they have patients in their practice who might

be eligible, would be to refer that patient to a neurologist. It doesn't need to be

an epilepsy specialist. Our team here at MATTER are epilepsy specialist neurologists,

but any neurologist can refer a patient to Australian epilepsy projects. So refer to

a neurologist if you think your patient might have local drug resistant epilepsy. The

other two categories are really about the idea of trying to fine -tune as much

diagnostic information as possible early in the condition. So we can include patients

with a recent diagnosis of epilepsy within the first six months after diagnosis of

any form of epilepsy. And then the last group is patients with a first seizure. And

even when we're not 100 % sure whether it's an epileptic seizure, as we know often,

it's not that clear -cut in the first instance. But those groups of people are

important to understand whether perhaps if we were able to offer high level testing

early rather than wait for years, perhaps we can improve outcomes for those people.

- How important is diversity in this study? So different ages, different backgrounds,

all those kind of things. - Yeah, so the study is enrolling adults with epilepsy.

So the age range is 18 to 70. Of course that's in the context of this research

study, but in clinical practice we look after people with all different ages.

We work closely with the Queensland Children's Hospital who have an excellent epilepsy

team and we really endeavour to have a smooth transition of care between the

pediatric age group and the adult age group. So for example our team at Matter will

have meetings with the Queensland Children's Hospital team discussing complex cases,

especially those who might be surgical candidates who have the drug -resistant epilepsy

form, which is what our team at Matter particularly looks after, and really try to

smooth that passage, which is often occurring in the teenage years. Often a difficult

time for anybody, never mind a young person living with a complex condition like

epilepsy, which is impacting their social life, perhaps their schooling, their work

options, their ability to drive and so on. So we try to provide a transition with

psychological support and education, as well as the standard clinical care for those

young patients. - Would it be useful for GPs to flag that a patient might be a

candidate for the study? Just considering sometimes we are faced with waiting lists,

or would it be more useful for the GPs, particularly in rural and remote, to refer

straight to the Martyr Epilepsy Clinic? - So I think that a GP,

so you're quite right, waiting lists are a problem. I mean, they're a problem for

everybody. As I said, any neurologist can refer to this study.

So, the best thing a GP could do would be to refer the patient to their local

neurologist. The local neurologist may or may not be in the habit of referring

patients to the Matter Epilepsy team. In fact, they don't need to do that for the

purpose of the study. The neurologist in Townsville, for example, could then enrol

the patient via the website, and our team at matter would then deal with the

referral and work out the logistics of having the patient come to Brisbane for the

scan, for example. Are there any risks, or burdens or costs for patients who want

to be involved in the study? So definitely no costs. Everything's provided pre -of

-charge. And as I said, this is a very high level set of investigations which they

wouldn't normally have access to. So it's really an added value to take part in the

study. I would see it like that. And most of the patients and families have been

really delighted with being able to take part in that. I guess the main burden is

going through extra tests, so of course people with epilepsy often have had a number

of tests in the hospital, an MRI scan, an EEG scan. So they may say, "Well, why

do I need another MRI?" I think the answer to that is that in the study so far,

although we have good level imaging here in Australia and Queensland and elsewhere.

In fact, because of this more detailed research protocol that's being done on these

MRI scans, we've actually found that 10 % of people participating have had something,

an abnormality detected on the scan that wasn't recognised in the previous hospital

scan. So that's quite a high level. And it's even led,

as I said, to changes in practice. we had a young patient who's 20 years old,

who's just undergone epilepsy surgery up in the hospital just last week. And he was

originally considered to have a negative MRI scan, almost imaging, so we didn't know

why he had epilepsy. And we were preparing all kinds of invasive tests to try to

understand that better. Then in fact, when he went through the Australian Epilepsy

Project, we found out two very important things for him. One was that we found a

lesion on the scan called an encephalocial. It's like a tiny bulge of brain at the

very front of the temporal lobe, which is operable. And then the second very

important thing is that he was found to have reversal of his language dominance in

the functional testing. He wasn't left hemisphere dominant. He was right hemisphere

dominant for language. And that meant that he could safely be operated on the left

hemisphere for this tiny encephalocial, have it removed with no deficits and no

invasive imaging, no invasive recording needed before surgery. So that's quite a

transformative set of investigations for that patient's care. And if we even find

that in a, you know, a smallish number of people, that is definitely worth going

through the study.

A 2025 study titled a 10 -year projection of adult epilepsy burden in Australia

reveals a significant and growing health challenge. Researchers estimate that between

2024 and 2033 over 82 ,000 adults will develop epilepsy adding to the existing

population of those already living with the condition. The projected impact includes

over 15 ,000 deaths, nearly 1 million quality adjusted life years lost and 14 .2

billion US dollars in health care costs, much of it driven by drug resistant

epilepsy.

Can you paint a picture for GPs of what the patient experience is like coming to

the MADR epilepsy unit? Sure. So the first thing is that our poor patient population

that we see at MADR epilepsy clinic are people with drug resistant seizures. So many

of my colleagues in general you also look after people with epilepsy, but we

especially in the matter, epilepsy clinic look after people whose seizures are not

well controlled on medications. And the reason for referring people to our team or

to other teams around the country, which are similarly specialist epilepsy teams, is

really to confirm the diagnosis. So as the GPs know often, it's not so clear what

are causing seizures. Sometimes people have epileptic seizures, but And epileptic

seizures, so functional psychogenic seizures, can also mimic epileptic seizures. People

might be treated for years with anti -seizure medications and it turns out not to be

the right treatment for them. Any doubt as to diagnosis, is it epilepsy or not,

should have a referral to the hospital. The people we see most often tend to have

epilepsy confirmed, but we're then trying to fine -tune the classification of which

type of epilepsy and the cause of epilepsy in order to explore treatment options

beyond the medications that the person's already tried unsuccessfully. And so we are

seeing people in our epilepsy clinic. We're a group of consultants. We work closely

with our epilepsy nurse. It's a very multidisciplinary team. We also have

neuropsychology, clinical psychology, neuropsychiatry, speech pathology because people

with epilepsy can have language issues as well. We work very closely with

neurosurgery, so we're a whole team and a lot of what we're doing is sharing all

the expertise from the different team members to try to understand and manage as

best as possible each person's epilepsy. It's a very individual condition, so it does

need quite a personalized approach. People are seen in the epilepsy clinic and we'll

be going through all of their history, trying to understand what the seizures are

like, their past history, any risk factors for epilepsy, understand their current

medications and treatments and what they've tried in the past. And we will then be

deciding, does this person need extra testing? So that might be enrolling them into

the Australian Epilepsy Project is what we're doing quite often at the moment.

Checking if they've had the appropriate MRI testing, looking at other brain scans

such as PET scan, which is positron emission tomography, which looks at brain

metabolism. And then a big part of our work is using electroencephalography, EEG

methods, to better understand that person's epilepsy. And that can be an outpatient

EEG, which takes 30 minutes or so in our outpatient department. Or we bring people

in to monitoring in our hospital unit, where people come in usually at the start of

the week, they stay for five days or so. And we continuously monitor the brainwaves

in a room with a video camera and we are often reducing medications in order to

capture seizures because that allows us to examine the patient during the seizures

and understand exactly what the symptoms and signs are because that gives us clues

as to which part of the brain is causing the seizures. And you mentioned before

that epilepsy is like arrhythmias for the brain and it sounds like you have halter

monitors for the brain as well, like we do for cardiac arrhythmias that people can

do in hospital or out of hospital. Correct, that's right. So we also use ambulatory

EEG, which is where the patient comes to a hospital, has the electrodes placed on

the head and then goes home with a portable setup and we can record for one night

or two nights and they come back to the hospital and we can then really study

what's happening, especially overnight where often it's difficult to know if people

might be having seizures or not. So these technologies are very, very useful for

people with epilepsy. What about AI and this kind of work? And what is the future

really whole for epilepsy study? Yeah, so AI, that's a great point, because I think

AI is coming. We all know that it's coming in medicine. It's used already in some

hospital settings. I think it's got great potential for the world of epilepsy. It's

being used in the Australian epilepsy project to analyse some of the MRI data. And

for example, when we get the report back for the Australian epilepsy project, we

have automated quantification of the size of the hippocampus, for example. It's a

structure in the brain which is often prone to become epileptic, and the AI can

help to measure the size of that, and we get that as part of our report. In terms

of EEG, we're using some AI methods in the matter. Epilepsy unit, we're using that

to help us, for example, quantify the number of epileptic spikes on the EEG that

patients have during long -term recordings. So I think it's got huge potential to

help with analysing this type of complex data, of course, complementing the

clinician's human perception of it. It's not going to take your job. I don't think

it'll take our jobs, I don't think so. What advice do you have for GPs as we

support patients and parents of patients who have epilepsy? I mean,

it's a big diagnosis and it has a huge psychological impact. Yes. Yeah,

I think the psychological impact is definitely huge. I think it's important to know

that people with epilepsy are much more prone to anxiety and depression than both

the general population, but also compared to people living with other long -term

conditions like diabetes. And it's thought nowadays that this predisposition to

psychological issues is actually part of the brain dysfunction, if you like. It's not

just a reaction to having to live with this terribly difficult diagnosis of not

knowing when I might have a seizure, will I fall down, will I be able to start a

new job, will I ever be able to drive, will I ever be able to get married? These

kind of really life -changing effects of seizures which are devastating if the

epilepsy can't be well controlled. So it's important for practitioners to understand

that the anxiety and depression are real components of the condition. And as I

mentioned earlier, we know from studies that those are a major contribution to poor

quality of life in people with epilepsy. And then the other issue which is often

tricky is the memory or cognitive issues that can also be part of the epilepsy

diagnosis, sometimes aggravated by some of the medications that we give that can

also, you know, increase of side effects on mood as well,

which can be negative. So I think it's important to try to look at the whole

picture and although our main goal is to try and treat the seizures we have to

kind of think about the whole person, think about support that we can offer which

might be referral for mental health plan to get some psychology input. We use our

psychology team very actively in our multi -disciplinary team setting because lots of

our patients need support with neuropsychiatry and neuropsychology. So much happening

in this area. What would you say to GPs who want to know a little bit more about

the AEP or any other advice, can you point them to any particular direction? Yeah,

sure. So the Australian Epilepsy Project has a great website, so it's very

comprehensive and designed for patients and their families to look at as well, so

that's very good and we can maybe put the details of that in the show notes. I

think two resources that we recommend a lot for patients would be Epilepsy

Queensland, so that's our local biggest.

the different types of epilepsy, treatment options, advice on driving that type of

thing. The Australian Epilepsy Project is a huge study with thousands of people.

How long are you going to be recruiting candidates for and when can we expect to

see the results? So the recruitment will definitely continue this year, next year. I

think hopefully by the end of next year the total number will have been achieved by

the end of 2026. Results are starting to come through all the time because of

course we have some interim analyses and the figure I mentioned of 10 % of

abnormalities on MRI is already a huge result actually so the study team are digging

into the different abnormalities that make up that 10 % and that will be getting

published quite soon. I think results will continue to come out because this data

set is very precious so I think With some of the more detailed analyses, we'll see

results that will impact Australian epilepsy care and also other parts of the world

over the coming five years or so. I think the real goal, though, is actually to

use the study and use the results to change current practice. I guess one thing

we'd like to do is to make it standard to have an excellent level MRI as early as

possible in the condition and make that accessible to everyone who has an epileptic

seizure. So the goal would be actually to make this the new normal that people with

epilepsy have high level investigations early in the condition rather than waiting for

10 years, 20 years when nothing really works.

They're huge results Eileen, congratulations on such amazing work and thank you for

joining us on SMater. Before you go though, a few back -to -basics questions from

Maria. - Sure. - You mentioned how important a high -level MRI is. As a GP, we like

to order those as the patient gets referred to an on -GP specialist. What should we

order? What should we write on that referral so that the patient gets the best MRI

possible? - Yeah, that's a great question. So the easy thing is to write MRI head,

epilepsy protocol, and the neurology, sorry, Neuro radiology teams will know what that

means. It essentially means that we have high -level scanning through the mesotemporal

regions, the hippocampus in particular, and that the scan goes far enough forward in

the brain to capture all of the temporal lobes, which are one part of the brain

that are most often epileptic. - In addition to that, what about blood tests? - So I

would say there are no routine blood tests needed. The most important thing actually

is the clinical history. is establishing what happened, the circumstances of the

seizure, what the patient could feel, what bystanders observed. That's actually the

most important information of all is clinical history, so that really is back to

basics. And back to the psychosocial effects of epilepsy. If you have a patient who

has epilepsy who needs medication for anxiety or depression, is it okay to use the

commonly used SSRIs or SNRIs? Are there any contraindications? Yes, definitely.

That question comes up a lot. So the SSRIs, SNRIs are safe to use in epilepsy.

There's often a misconception that antidepressant treatments could change the seizure

threshold. And sometimes we do see patients who've said, well, you know, no one

wanted to give me an antidepressant in case that affected my epilepsy. And that's

true only for the older generation antidepressants, like the tricyclics. We do, if

possible, avoid those ones, but the newer generation SSRIs definitely safe to use and

we definitely prescribe those a lot for our patients. That's excellent. Thank you so

much and that'll help for all our CPD as well. Thank you. Thank you. We've covered

so much ground today. Professor Aileen McGonagall, thanks again for joining us on

SMater. For our listeners at home or in the car or having a well -deserved break

between patients, thanks for tuning in. See you next time on SMater.