Huge Seizure Reduction Through DBS (in LGS) - Linda Dalic, Austin Health, Australia

Learn of the huge reduction in seizures amongst adults with the epilepsy Lennox-Gastaut Syndrome - as the result of DBS! With Linda Dalic.

Reported by Torie Robinson | Edited and produced by Carrot Cruncher Media.

Podcast

• Transcription

  00:00 Linda Dalic
  ”That’s Deep Brain Stimulation. So, what you'll do is you'll stimulate through these electrodes that go into the hypothalamus (in our case) and there's a little pacemaker box that's inserted just below the collarbone in the chest and that really drives, you can do all your programming through there and it will deliver electrical signals through those electrodes in the brain.”

  00:21 Torie Robinson
  Fellow homo sapiens! Welcome back to Epilepsy Sparks Insights. My name is Torie and I’m here to help bridge the gaps in communication between clinicians, scientists, researchers, and those of us affected by and/or interested in the epilepsies! Do make sure that you like, comment, and subscribe to the channel to help spread awareness and understanding of the epilepsies around the world!
  Now, DBS or Deep Brain Stimulation is a type of neuromodulation that can be a cool tool to help improve the lives of some people with a refractory epilepsy. Well, this week we hear from neurologist Linda Dalic from Austin Health and the University of Melbourne, Australia, who tells us about her Randomised control trial using Direct Brain Stimulation as a treatment for people with the rare genetic epilepsy Lennox-Gastaut Syndrome (or LGS) - and the results are promising!
  So, onto our star of the week, Linda Dalic

  01:16 Linda Dalic
  I am a neurologist, mainly, specialising in epilepsy, but I've also now embarked upon the journey of becoming a scientist! So, I do a bit of research as well, on the side. So, mainly looking at what we call neuromodulation research, which is basically a way in which we can alter brain networks that are driving seizures to try and, you know, quell seizures. So, that's been my passion and my drive for the last five to eight years, five to six years whilst I completed my Ph.D..

  01:47 Torie Robinson
  What was the title of your Ph.D.?

  01:49 Linda Dalic
  So, I looked at neuromodulation, mainly in the form of Deep Brain Stimulation in patients that have a quite a severe type of epilepsy called Lennox-Gastaut Syndrome, which some of your listeners are probably familiar with. So, it's predominantly a childhood-onset epilepsy, but we studied young adults and we implanted a Deep Brain Stimulator device in their brains - in 20 young adults - and we performed what we call a randomised control trial - so we tested the device or the treatment with a half of the patients and then the other half of the patients - they were “blinded” (so they didn't know whether they were on or off (and they were in the “off” group)). And we compared whether the treatment was or wasn't successful. And we actually did show that there was a reduction in seizures, so we were very pleased with the result, but our research is still at the very early stages and we're ongoing with longer term follow-up stages.

  02:41 Torie Robinson
  You mentioned, of course, clearly the results when it comes to seizures. Do you look at other aspects of affecting quality of life when it comes to treatment for epilepsy?

  02:49 Linda Dalic
  100% and,you know, a lot of the times when people have this type of epilepsy, it is more than just the seizures. The parents in particular; they are quite concerned about patients quality of life. So, sleep, their ability to communicate, ability to mobilise, things like that. So in our cohort, the majority of our patients were on the quite severe end of intellectual disability. Where possible, we did try and test cognition and we did this using an iPad-based test called the NIH Toolbox, but, you know, as you can imagine, if people are non-verbal and have inability to use their hands, you know it's hard to use the NIH Toolbox. So, that was only capturing a small portion of our cohort that we tested, but we also looked at caregiver assessments. So, their disability of their epilepsy in something called the GAD score…

  03:49 Torie Robinson
  Yeah.

  03:50 Linda Dalic
  …the overall severity of epilepsy in the GACE, and also we did an ABAS [(Adaptive Behavior Assessment System)] assessment, which is measuring your adaptive skills. So, that's everything somebody needs in order to basically navigate their way through life. So, can they walk across the road? Can they feed themselves? Can they give themselves medication, things like that. So, we looked at all of those things and then in addition to looking at seizure diaries, which we know are notoriously fraught with... they're not the most accurate things(!), but nonetheless, every single drug and device that we have is based on seizure diaries. But we definitely used that, and that was what we looked at what we call our primary outcome.
  But in addition to that, we also looked at the seizures that were captured on an EEG, a 24-hour EEG. And actually, that was the most striking result; that the group that were in the stimulated group, they had 89%…89% of them had a 50% or more reduction in their seizures. So, I think we really just captured the tip of the iceberg when we looked at the recorded seizures in the diaries, but when we looked at the actual electrographic seizures, there was a lot more going on that we picked up. So, that was a really useful exercise to do - despite it being so laborious to count all those seizures.

  05:05 Torie Robinson
  Gosh, well there were that many and that's and that’s actually an interesting thing because some people will have squillions a day and often they don't know they have them right as well.

  05:13 Linda Dalic
  Exactly. They're very subtle sometimes, you know, not just in Lennox-Gastaut but in all different types of epilepsy and I think that there's, in general this misconception that, you know, people only have generalised tonic-clonic seizures. Well, no! We know that there are multiple different types of seizures and that's why having video EES - especially in a cohort that are often, you know, they're not able to say “I've had a seizure” or they're not able to be monitored 24-7 because, you know, that's life. So, that was, we found that very, very helpful.

  05:45 Torie Robinson
  So, tell us what we've been speaking about DBS, but what does it stand for? And how does it differ from say, I don't know, RNS or from a million other acronyms, tell us.

  05:55 Linda Dalic
  Yeah, sure, so there's full of acronyms so breaking it down: Deep Brain Stimulation or DBS: it's basically a surgically implanted device. So you do have to undergo neurosurgery to have it inserted and what there are, are often two electrodes that are implanted deep in the brain and where they are implanted very much depends on, sort of, the type of epilepsy that you have. So, a lot of the work in epilepsy focuses on implanting the electrodes in the thalamus. So that's quite deep in the brain, you've got two (one on each side). And within the thalamus, there are different nuclei. So, we implanted in a part called the CM or the centromedian nucleus, but there was a really big study over 10 years ago called the SANTÉ study, which looked at patients that had focal epilepsy that wasn't responding to drugs and that implant they implanted the ANT or the Anterior Thalamic Nucleus. People also implant in the hippocampus and there's been studies done in the cerebellar area… so you can really implant anywhere! And you really choose your target based on the network I guess that you're trying to target. And for us, our group in particular (before we did the study) we were doing a lot of network studies that really highlighted where the epileptic network of Lennox-Gastaut Syndrome was and we knew that the centromedian nucleus was involved in it and that's why we chose it. So that's Deep Brain Stimulation. So, what you'll do is you'll stimulate through these electrodes that go into the thalamus (in our case) and there's a little pacemaker box that's inserted just below the collarbone (in the chest) and that really drives…you can do all your programming through there and it will deliver electrical signals through those electrodes in the brain. And you can change the parameters! So, there's thousands of different parameters that you can choose! You can have it on all the time, you can have it on in a cycling fashion - so on for a certain amount, off for a certain amount - you can change the frequency, you know there's lots of different things and I think we're still very much at the early stage of trying to figure out what the optimum settings are in epilepsy. This is a technology that's been around for decades in Parkinson's disease with much success and I think we're really lagging behind where they're at but that's I guess the exciting stage and that's another area of our research. So that's Deep Brain Stimulation.
  There's also RNS that you mentioned or Responsive Neuro Stimulation and it's a US developed device and they basically, you know, you can use it in the same cohort of patients. So, this is a group of people that have epilepsy that the drugs don't work, so we call that drug resistant epilepsy and you can implant what you do is you still insert these stimulating electrodes (like we do in Deep Brain Stimulation) but the actual RNS system will pick up on epileptic activity and then deliver the stimulation in response to that, hence the name “responsive stimulation”. So, unlike Deep Brain Stimulation that is just constantly giving stimulation without, sort of, any, you know, feedback from the brain, responsive stimulation is constantly signalling, you know, picking up the signals in the brain and then that will deliver the stimulation to the patient.

  09:21 Torie’s Robinson
  So, just to provide a little bit of reassurance for people - and people [being] patients, families, and clinicians who aren't familiar with, you know, epilepsy surgeries and treatments in general - when you talk about putting electrodes into a brain, it's not like getting a big thick wire and stabbing it somewhere or other, is it? It's like a tiny, like borderline invisible, well-targeted, in-between the squishy bits to the right area type thing.

  09:45 Linda Dalic
  Correct, yeah, it's all highly planned beforehand. So, what we'll do is patients will typically have an MRI beforehand, and then what we'll do is we'll sit down at a special computer and we'll plan where we're going to put the electrodes. And often there's two tiny burr holes in the scalp (and so they're just little tiny holes that the surgeon will drill, under anaesthetic). And we'll…using a frame that makes it very accurate, we'll be able to guide those wires down so that they go exactly where we’ve planned. And then at the end of the surgery, those wires are connected underneath the skin - so, they're tunnelled through the collarbone chest area - and the whole system is then, you know, connected and ready to use. And the surgeon will just place a little cap on where the burr hole was so that the wires don't move. But, you know, things happen, so, if, for example there's an infection (which can happen: about 5% of people that undergo surgery will develop infection), or if there's a small bleed, or any other complication, or, if patients just decide they don't want it anymore, it's a reversible procedure. So, it's very easy then later on for the surgeon to remove that cap and to remove those wires if needed. But, we hope that it never gets to that stage.

  11:01 Torie Robinson
  It’s not like a resection where, you know, scoop out a clump of tissue. It’s just “sticking something in” so it's much more… I mean it's a big deal, but it's not as major if you like.

  11:11 Linda Dalic
  Correct, so typically there's no tissue removed, there's no damage done to the brain itself, the only thing that's sort of removed is a tiny bit of bone through the burr hole which is very, very small (if you could see my fingers now I'm just pointing very, very small!). But I guess that's one of the advantages versus doing resective surgery. But we know that Deep Brain Stimulation - it's not really something that we would offer to people if resective surgery was also on the cards. Because we know that resective surgery - by far - gives patients a better chance of becoming seizure free. We really consider Deep Brain Stimulation and Responsive Neurostimulation as what we call “palliative” procedures. So, although there are some people that are completely seizure free after they've had these procedures, it's definitely not the majority and that's something that I really try to emphasise to my patients if I'm counselling them for undergoing this: that, you know, whilst it'd be great if they could become seizure free, we're not always expecting it.

  12:11 Torie Robinson
  So, it benefits quality of life in ways other than seizure decrease.

  12:16 Linda Dalic
  We definitely hope for there to be seizure decrease and a lot of studies have shown decrease in seizures. It's just the seizure freedom that's the difficult part. And I think, you know, perhaps as we improve our parameters and our understanding of which targets for which type of epilepsy, then perhaps we might do better with obtaining seizure freedom. But at this stage, you know, it's not the majority of people. So, I think that there's still a lot of work to be done. And we know that with any form of neurostimulation, a lot of the studies have shown progressive benefits over time. So, I guess, as we do it more we'll have more long-term data to say well yes you might not be seizure free after the first year or two of having this procedure but, maybe… you know I don't know I'm just speculating.

  13:05 Torie Robinson
  Years later, right? Because it's almost like you tailor the technology to the patient, right? Is that correct?

  13:12 Linda Dalic
  Yes, yeah, we definitely try and do that. We definitely try and do that with the targeting and then hopefully as we sort of know more about the stimulation parameters to try and tailor that. And we've certainly been doing that with our cohort of patients that we studied with our Deep Brain Stimulation trial. We have tried different parameters now that the trial is over. And, you know, other studies have also looked at Deep Brain Stimulation using different parameters. So, it's also hard when there's so many different studies going on, all using different…not techniques but different parameters. It's trying to get some uniformity, but just going back to the long-term studies, you know, the SANTÉ study that I mentioned before, which was the focal epilepsy group, you know, they've now got data 10 years and there are more people there that are seizure-free than when they first did the trial. So, I think that there is some hope that we will perhaps get better results with neuromodulation as time goes on. That's literally what drives my research!

  14:10 Torie Robinson
  A huge thanks to Linda for sharing with us her exciting research results into treating LGS epilepsy using DBS or Deep Brain Stimulation!
  If you haven’t already, don’t forget to like, comment, and subscribe, and see you next time!

• Chapters

  00:00 Intro and DBS basics

  01:16 Meet Linda Dalic

  01:49 Deep Brain Stimulation (DBS) for Lennox-Gastaut Syndrome - study results

  02:41 Impact on sleep, communication, mobilisation, anxiety, adaptive behaviour etc.

  04:27 Massive reduction in seizures!

  05:45 What IS DBS?!

  08:26 What is Responsive Neurostimulation?

  09:45 The DBS surgical procedure

  11:32 DBS is palliative care

  13:05 Improving DBS going forward

  14:10 Conclusion and thanks

• About Linda

  Linda Dalic is a consultant neurologist an epileptologist, working as a consultant neurologist at Austin Health where she heads the Epilepsy Neuromodulation program and co-leads the Stereo-EEG program. She recently completed her PhD, through the University of Melbourne, investigating the role of neuromodulation in Lennox-Gastaut Syndrome - a severe childhood-onset form of epilepsy. As a result, she has expertise in the management of complex epilepsy and epilepsy neuromodulation. She has been published in both national and international journals.

  An accomplished specialist, Linda completed her initial undergraduate training at the University of Melbourne, where she graduated with a Bachelor of Biomedical Science and completed an Honours research project investigating epileptogenesis in temporal lobe epilepsy. Linda obtained a Bachelor of Medicine/Bachelor of Surgery from Queensland's Griffith University, before returning to Victoria - her home state - to begin physician and neurology training at Austin and St Vincent’s hospitals.

  She completed a two-year epilepsy fellowship at Austin Health, through the Bladin-Berkovic Comprehensive Epilepsy Program, and has presented her ground-breaking research findings at Australian and international medical conferences, as well as speaking publicly about them in the media.

  Linda consults, offering in-person and Telehealth appointments for:

  • Epilepsy diagnosis and management, including advanced surgical therapies such as stereo-EEG

  • Epilepsy neuromodulation - vagal nerve stimulation and deep brain stimulation

  • Headache disorders and treatment including Botulinum toxin therapy for chronic migraine

• Links to Linda

  X/Twitter: drlindadalic

  Website: drlindadalic.com.au

  Austin Health: nerve-brain-conditions/team

  The Neuro Group: dr-linda-dalic

  LGS Foundation: lgs-research-grant-recipients/linda-dalic

  VJ Neurology: dbs-for-lennox-gastaut-syndrome

  ResearchGate: Linda-Dalic

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