SEEG in Epilepsy Surgery: Current & Future Role

Podcast Transcript

Neuro Pathways Podcast Series

Release Date: December 1, 2024

Expiration Date: December 1, 2025

Estimated Time of Completion: 31 minutes

SEEG in Epilepsy Surgery: Current & Future Role

Demitre Serletis, MD, PhD

Description

Each podcast in the Neurological Institute series provides a brief, review of management strategies related to the topic.

Learning Objectives

• Review up to date and clinically pertinent topics related to neurological disease
• Discuss advances in the field of neurological diseases
• Describe options for the treatment and care of various neurological disease

Target Audience

Physicians and Advanced Practice providers in Family Practice, Internal Medicine & Subspecialties, Neurology, Nursing, Pediatrics, Psychology/Psychiatry, Radiology as well as Professors, Researchers, and Students.

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• American Medical Association (AMA)
  Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
  
  Participants claiming CME credit from this activity may submit the credit hours to the American Osteopathic Association for Category 2 credit.

• American Nurses Credentialing Center (ANCC)
  Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 ANCC contact hours.

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  A certificate of participation will be provided to other health care professionals for requesting credits in accordance with their professional boards and/or associations.

• American Board of Surgery (ABS)
  Successful completion of this CME activity enables the learner to earn credit toward the CME requirements of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.

Credit will be reported within 30 days of claiming credit.

Podcast Series Director

Imad Najm, MD
Epilepsy Center

Additional Planner/Reviewer

Cindy Willis, DNP

Faculty

Demitre Serletis, MD, PhD
Epilepsy Center

Host

Glen Stevens, DO, PhD
Cleveland Clinic Brain Tumor and Neuro-Oncology Center

Agenda

SEEG in Epilepsy Surgery: Current and Future Role

Demitre Serletis, MD, PhD

Disclosures

In accordance with the Standards for Integrity and Independence issued by the Accreditation Council for Continuing Medical Education (ACCME), The Cleveland Clinic Center for Continuing Education mitigates all relevant conflicts of interest to ensure CME activities are free of commercial bias.

The following faculty have indicated that they may have a relationship, which in the context of their presentation(s), could be perceived as a potential conflict of interest:

Imad Najm, MD	Eisai Advisor or review panel participant NIH Other activities from which remuneration is received or expected: Research Funding LivaNova, PLC Advisor or review panel participant SK Life Science Inc Advisor or review panel participant Teaching and Speaking
Glen Stevens, DO, PhD	DynaMed Consulting

The following faculty have indicated they have no relationship which, in the context of their presentation(s), could be perceived as a potential conflict of interest: Cindy Willis, DNP, Demitre Serletis, MD, PhD.

CME Disclaimer

The information in this educational activity is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient's medical condition. The viewpoints expressed in this CME activity are those of the authors/faculty. They do not represent an endorsement by The Cleveland Clinic Foundation. In no event will The Cleveland Clinic Foundation be liable for any decision made or action taken in reliance upon the information provided through this CME activity.

HOW TO OBTAIN AMA PRA Category 1 Credits™, ANCC Contact Hours, OR CERTIFICATE OF PARTICIPATION:

Go to: Neuro Pathways Podcast December 1, 2024 to log into myCME and begin the activity evaluation and print your certificate If you need assistance, contact the CME office at myCME@ccf.org

Copyright © 2024 The Cleveland Clinic Foundation. All Rights Reserved.

Introduction: Neuro Pathways, a Cleveland Clinic podcast exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neurorehab and psychiatry.

Glen Stevens, DO, PhD: Stereo electroencephalography, or SEEG, involves a surgical placement of intracranial electrodes to record brain activity and has revolutionized the way we localize seizure foci and plan resective surgery. In today's episode of Neuro Pathways, we're discussing the current role of SEEG in epilepsy surgery and exploring how more than 1,000 cases are evolving the use of this technology by Cleveland Clinic epilepsy surgeons. I'm your host, Glen Stevens neurologist/neuro-oncologist in Cleveland Clinic's Neurological Institute. I'm very happy to once again be joined by Dr. Demitre Serletis. Dr. Serletis is a neurosurgeon and neuroengineer in Cleveland Clinic's Epilepsy Center, he also directs the Brain Dynectome Lab which serves as a signal processing hub for SEEG data analysis. Demitre, welcome to Neuro Pathways.

Demitre Serletis, MD, PhD: Thank you so much, grateful to be here.

Glen Stevens, DO, PhD: So, Demitre, I know we discussed this a little bit when you were here before but, for those who haven't met you previously, tell us a little bit about yourself, how you came to the Cleveland Clinic.

Demitre Serletis, MD, PhD: Yes, thank you very much. I'm a Canadian, if you recall from last time, and was trained in the great white north at the University of Toronto. I was fortunate during residency to complete a PhD at that time and my travels brought me to Cleveland Clinic in 2012 specifically to study an epilepsy surgery with the great minds of Dr. Bingaman, Dr. Najm and the whole team here at the Epilepsy Center. From there, my travels took me to Little Rock, Arkansas, a very random place for a Canadian to go and, after three years there, I moved back to Winnipeg, Canada for six years and now I've been here for three years and counting and really just thrilled to be here.

Glen Stevens, DO, PhD: Well, we're thrilled to have you here. So, I'll just set the table a little bit. I think just short of 3.5 million individuals in the United States have epilepsy and about one-third of those have refractory epilepsy. Now, not all those will be necessarily drug-resistant epilepsy but they'll be refractory so, clearly, we need to do a better job. And I find it interesting, we're at the hundred-year anniversary this year from when Hans Berger recorded the first EEG.

Demitre Serletis, MD, PhD: That's right.

Glen Stevens, DO, PhD: So, we've been at it for a hundred years so you're going to tell us the new and updated EEG with this SEEG. So, if you can, tell us a little bit what SEEG is and how we can use it in the field of this intractable epilepsy problem that we have.

Demitre Serletis, MD, PhD: Yes, absolutely. So, SEEG stands for stereoelectroencephalography or stereo EEG. This is a method that was pioneered by and Dr. Talairach and Dr. Bancaud in France in the '60s and has since caught on its spread from France to Italy and many European centers and made its way to Canada and the United States several decades ago. In the meantime, this is a method that allows us to implant electrodes safely, accurately and precisely into the brain of patients with intractable epilepsy. These are patients who have failed medical therapy and they go on to have an extensive workup through the Epilepsy Center here, for example, and we implant electrodes in a meticulous fashion using the knowledge of the anatomy, the electrophysiology and the workup the patient has had up to that point.

In other words, it's not a shotgun approach to firing electrodes into the brain and we meet as a team and we decide on a selective implantation to investigate further. None of the tests up to that point, video EEG, an MRI, nuclear medicine testing and so on, captures information from the depths of the brain and this makes the difference. And we're at the point now where at least half of our patients who are referred for surgery end up starting with the stereo EEG evaluation which then gives us some data to guide decision-making in surgery.

Glen Stevens, DO, PhD: So, when I trained, we used to do depth electrodes.

Demitre Serletis, MD, PhD: Yes.

Glen Stevens, DO, PhD: How is it different?

Demitre Serletis, MD, PhD: It's a little bit different. Depth electrodes refers to a small number in combination oftentimes with a grid, an electrocorticographic grid that we would use and apply on the surface and you sample one or two shorter electrodes into the cortical space. Stereo EEG is much more meticulous in that we're targeting, not just deep structures in the brain, but also the trajectory is very important. It gives us access to areas that subdural grids or even depth electrodes couldn't reach before and we're talking about structures like the cingulate gyrus, the insula, the posterior orbital frontal region, even the depths of sulci, to be honest. It takes a little bit of planning to arrange these procedures, we plan for about four or five hours before we get to surgery and I tell my residents and fellows this is half of the surgery is the careful planning that goes into it but the information we get is much more detailed in this way.

Glen Stevens, DO, PhD: And it goes without saying that this is really a technology for focal epilepsies not generalized epilepsies unless we thought someone had a focal leading to a secondary generalized, right?

Demitre Serletis, MD, PhD: That's right. And in fact, as we speak, this field is evolving. It was the case that it started out more of an exploration for focal epilepsies. We still believe that, even if we don't see a lesion on the MRI scan, for example, like a subtle cortical dysplasia, these are still patients who benefit from stereo EEG because it allows us to make an electrical map of the architecture and the evolution of the seizure in its onset and spread even if these are non-lesional cases. But now, we're at the point people are implanting deeper structures like the thalamus in select patients with generalized epilepsy because the information from the SEEG is being used to guide the implantation and management with neuromodulation which is even being applied now to patients with Lennox-Gastaut and other generalized epilepsies too. So, it's an exciting time and, in fact, the SEEG is unlocking more doors than we anticipated maybe 10 years ago.

Glen Stevens, DO, PhD: So, is there still a role for subdural grids?

Demitre Serletis, MD, PhD: Yes, I would say there is and it's very important for trainees who train with us to learn these methods. The grid, the subdural grid, when applied on the surface, allows us to map extensively and much more closely an eloquent part of the cortex so language is a nice example of that. And we have some patients where, yes, we can do an awake craniotomy if they'll tolerate it, but sometimes you have patients who will not tolerate an awake procedure, we can implant a grid and put them in the epilepsy unit for a few days to allow a much more precise language mapping. Stereo EEG is more like an exploration of important networks so they're not quite so densely put together as they are on a grid, for example, the contacts.

Glen Stevens, DO, PhD: And before we get into a lot of the details, what percentage of your patients would require or you feel would benefit from SEEG versus just surface electrodes?

Demitre Serletis, MD, PhD: Yeah, I would say now we're at the point where a patient who's reviewed at patient conference, it used to be the case that 25 may be up to 50% would be referred for stereo EEG. Now, it's over 50% that are benefiting and being referred for stereo EEG to inform next steps. It's also a reflection that we have much more complex epilepsy patients coming to our clinic now. These are patients who may have had procedures elsewhere, they may have tried a resection or a laser ablation or have a current indwelling device, like a deep brain stimulator or a NeuroPace device, which hasn't quite hit the mark and helped the way that the clinicians thought it would and they're coming back for an exploration with stereo EEG. So, it allows us to open up another path for them which is nice.

Glen Stevens, DO, PhD: Good. Well, that's the benefit also of a multidisciplinary conference where you discuss these cases.

Demitre Serletis, MD, PhD: That's right, absolutely. This is a team sport, this is not just one person and we're thrilled, when we can tell patients, it gives them reassurance to know that there are 20 or 30 colleagues who have vetted their file and we've either agreed or perhaps disagreed, but it's important for them to know some recommendations coming out of the group.

Glen Stevens, DO, PhD: So, I'm a patient that comes and sees you and I have focal epilepsy and it's refractory. So, a few questions, do you have to shave my head?

Demitre Serletis, MD, PhD: That's a great question and one that we talk about every single time. We tend to shave the head at our center and, from personal experience, having had a few patients treated elsewhere with stereo EEG, they've come in with some infections and so on and I've had to open up and there's literally hair in the brain so we recommend really highly to shave the head. It keeps it sterile, it allows for us to clean it well and so on and manage the electrodes but also it keeps patients cool under the head wrap because they're admitted for a week or two weeks, the average is two weeks at a time, and I think every little bit helps, so we tend to shave the head.

Glen Stevens, DO, PhD: When you place the electrodes, and maybe you were going to get into this later, but when you place the electrodes, are you using, for your stereo localization, are you using a frame, do you use a robot with AI, what do you use?

Demitre Serletis, MD, PhD: Yeah, these are great questions. So, technology has taken us from the days of the French in the '60s although it's a remarkable story. They started out with a frame and Dr. Talairach built the frame at that time for this purpose. We've evolved, we can use a Leksell frame for example and now we use the Leksell head holder, the frame piece just to secure the head. We take advantage though of a very nice robotic technology, there's many systems in fact and there are new ones that are coming out in the near future as well which allow us to plan carefully on the robotic platform and take the map that we make together as a group and plan those electrodes safely. And it serves as a navigation tool, the surgeon is still doing the work, using the drill, a couple of tools to open up the dura and make a tract and then safely put the electrode.

Glen Stevens, DO, PhD: And I'm sure it varies a lot depending on where you're going in the brain, but on average, how many electrodes are being placed?

Demitre Serletis, MD, PhD: I would say, on average, we're somewhere between 15 to 20 on a given side. It very much depends on the hypothesis going in and that's what we meet as a group to decide that. It has gone up in numbers, if you look at the old literature in the '60s, '70s, they started out putting six and maybe two on the other side. We've certainly increased those numbers over time, there is a sweet spot. But beyond that 20 mark or so, we don't know exactly, but let's say 25, 30, putting more electrodes at that level also reflects that maybe we don't quite understand the epilepsy or the hypothesis. And we certainly don't want to give the impression that this is what we call a fishing expedition, it has to be justified by the pre-invasive work up to that point.

Glen Stevens, DO, PhD: And do the electrodes have to be a set distance from each other? They can't be too far, is there some distance?

Demitre Serletis, MD, PhD: There's a practicality to putting an electrode immediately next to another one, we use a small bolt to secure them in place but, apart from that, they can get quite close and sometimes we have to rely on that. Areas like the amygdala and hippocampus are very close to one another, the insula, depending on how densely we want to sample the insula, the electrodes can get quite close at times but we have some tricks that we can use to get them in there. And sometimes we have to implant with an oblique trajectory as well. Most of these are coming from the side in an orthogonal fashion and that's important because that's how our epileptologists read these signals studying the propagation of waves of seizure onset and spread. But the insula, the posterior orbital frontal region are some examples where we come at it from above, more of a parasagittal approach and it's a longer trajectory down but a very safe one as well.

Glen Stevens, DO, PhD: And these patients are all under general anesthesia?

Demitre Serletis, MD, PhD: For the procedure, yes.

Glen Stevens, DO, PhD: For the procedure?

Demitre Serletis, MD, PhD: That's right.

Glen Stevens, DO, PhD: And what's the average length of time for placement?

Demitre Serletis, MD, PhD: The surgical part takes about two and a half hours but, with anesthesia and the robot and all these other steps, we also check the electrodes, it ends up being about four or five hours on average.

Glen Stevens, DO, PhD: So, I come see you, you shave my head, you put me under, you do a couple hours of placement, I've got the electrodes in-

Demitre Serletis, MD, PhD: That's right.

Glen Stevens, DO, PhD: ... I take it I go to the epilepsy unit?

Demitre Serletis, MD, PhD: That's right, yes.

Glen Stevens, DO, PhD: And I could stay there for up to two weeks did you say?

Demitre Serletis, MD, PhD: The average is two weeks.

Glen Stevens, DO, PhD: Okay.

Demitre Serletis, MD, PhD: Some patients it's much quicker and sometimes we have a period of a week or two where the patient doesn't have a seizure and we've gone the length of putting electrodes and our epileptologist, during this time, they're weaning some of the medicines, they have some options in terms of sleep depriving patients as well or even getting out a little exercise machine for them, sometimes these activities bring on the seizures. By three weeks, four weeks at the latest, most patients have had some activity that we can use and there becomes an infection risk too. Patients are on antibiotics the whole time but, past that mark that I mentioned, we aim towards taking them out.

Glen Stevens, DO, PhD: And I know that we do ambulatory EEGs but this is not something that you can go home with it, is that correct?

Demitre Serletis, MD, PhD: No, that's a great question and I wish it were the case that we had wireless technologies. Patients have to be hooked up to a computer, lifetime, so they're typically in bed or very close to the bed sitting at a chair, they can get to the restroom, we give them breaks but, again, we want to record the seizure events themselves and it might be a few fleeting events during that two-week period. Every little bit of data counts.

Glen Stevens, DO, PhD: Can the recorder be a stimulator?

Demitre Serletis, MD, PhD: So, part of the recording aspect of the study itself involves the epileptologist, one of the neurophysiologists will come into the room and stimulate as you said. And they use a range of parameters, low and high frequency. One is to map out the structural connectivity from one electrode to the other, we call this cortico-cortical evoked potentials. The other aspect is to map out function. If we're getting interested in an area of the brain, for example, thinking perhaps of a resection, we also want to establish that there isn't any function there and they can do that very nicely with some stimulation tests.

Glen Stevens, DO, PhD: Do you do functional MRIs and diffuser tensor imaging MRIs on your patients beforehand or not?

Demitre Serletis, MD, PhD: We do, it's part of the protocol. Yes, exactly. And this information comes into play as we investigate networks of interest to implant.

Glen Stevens, DO, PhD: Do you like to record X number of seizures?

Demitre Serletis, MD, PhD: There is no one set number of seizures and we're not looking for the patient's most severe seizures either. As they wean off their medicines, we just need to capture some representative events, it may be as few as two or three, for example. And some patients, once these seizures start, they start the cluster and they can have quite a number of them and the epileptologists are very good about putting them back on their medicines then. It's very controlled and highly monitored.

Glen Stevens, DO, PhD: So, I've been in the hospital now for two weeks, you've recorded multiple events, you feel comfortable with-

Demitre Serletis, MD, PhD: A plan.

Glen Stevens, DO, PhD: ... where my epilepsy's coming from. Now what? Back to the OR, take everything out?

Demitre Serletis, MD, PhD: Back to the OR. Yes, it's a nice controlled way to remove these electrodes. As you can imagine, there's a bit of tugging and pulling at the electrode site, very rarely do we have something that might be bent, a bolt, for example, that secures the electrode and rarely I've seen an electrode broken. So, there, we just take a few steps to open up just a small burr hole at the site enough to see the electrode and pull it out. It's a single stitch at every entry site and we wrap the patient's head, we get a CAT scan and most of them go home the next day.

Glen Stevens, DO, PhD: And sorry, the average number of electrodes is?

Demitre Serletis, MD, PhD: We said somewhere between 15 to 20 on a given side. Sometimes patients have bilateral implantations and that can be quite a number. Again, we don't just double that number but we do keep in mind, because one thing's very important with this procedure, there's a risk profile to it as well and the risk is about 1% for a significant hemorrhage.

Glen Stevens, DO, PhD: Yeah, that's what I was going to ask next is what's the risk?

Demitre Serletis, MD, PhD: Yeah, yeah.

Glen Stevens, DO, PhD: So, pretty low but very low.

Demitre Serletis, MD, PhD: It's not zero and 1% sounds like a lot. So, the way I tell patients there's a risk for infection, we have them on antibiotics, there's a risk for bleeding, of course. Twenty to 30% of the time, when we get a CAT scan right after the procedure, there's a little bit of blood product but not something that is causing any symptoms for the patient, nothing of concern and it makes sense. If you put a little probe in the body, you're going to get some bruising, something that you see on the scan. Two to 3% of the time, there may be a transient change, a deficit that recovers with time. That could be a little bit of a droop in the face, some weakness in the contralateral side, some speech-language effects that improve. 1% really refers to the risk of stroke or hemorrhage needing intervention meaning, unfortunately, having to open up and abort the SEEG to put out the fire.

Thankfully, knock on wood, that does not happen often and I'm very humbled and proud to say we're below the 1% mark. Back in fellowship, we quantified it by electrode, it was 0.04% per electrode and it sounds a little better that way.

The goal is safety though.

Glen Stevens, DO, PhD: So, you've completed my evaluation, you've successfully removed everything but let just go back one second. If I'm on a blood thinner... what happens there? Let's say I'm taking aspirin, Plavix or even Eliquis, warfarin?

Demitre Serletis, MD, PhD: Excellent question. We have to stop those. Because of the risk of those events I mentioned, even some of the anti-seizure medicines, like Depakote for example, can thin the blood. So, we have to ask patients to come off these medicines and help bridge that gap as best as we can.

Glen Stevens, DO, PhD: And then am I re-initiated on my medications while I'm in house before you take the electrodes out?

Demitre Serletis, MD, PhD: That's right.

Glen Stevens, DO, PhD: Should I just go back to what I was on or-

Demitre Serletis, MD, PhD: Yeah, they'll start-

Glen Stevens, DO, PhD: ... something more?

Demitre Serletis, MD, PhD: Yeah, exactly. The epileptologist will start those medicines. By the time a patient goes home, they will be back on their medication and they will know something about the outcome and a projected plan as well. We like to give some answers before they head home.

Glen Stevens, DO, PhD: And I assume then the case goes back to the epilepsy-

Demitre Serletis, MD, PhD: That's right, the epilepsy conference. And we hope for one of several outcomes. The best-case scenario, if you go by the literature, is the plan for resection. Still, in this era, resection probably offers the best chance at seizure freedom or at least an improvement. At the same time, there's a quality-of-life aspect to it and so sometimes we're lucky. And if the SEEG, using the data from this study, if it's so focal, we can put a laser and perform a small ablation there too. In some-

Glen Stevens, DO, PhD: Let me just go back to that. So, if you do an ablation, would you do that while they're in-house or no?

Demitre Serletis, MD, PhD: That has now just started up, so we are lagging behind the Europeans in this regard. With the SEEG for 20 or more years, the French and the Italians are able to hook some alligator clips on the SEEG and perform what we call a radiofrequency ablation. This is different than a laser ablation, but it allows you to offer a diagnostic step and, if the patient's seizure burden is improved even for a short while, it gives some confidence to the team that, hey, we're on the right track. We've now caught up, a year ago, we were able to publish a nice approach using the SEEG bolts, using a pallidotomy probe. There's no FDA-approved SEEG technology that would let us do this at the bedside. We now have a lifetime SEEG technology that offers thermal tracking, you can measure the temperature and perform SEEG right through the existing leads.

And so, so far, between Dr. Bingaman and I, we've done three such patients, they're doing very well and it's been very helpful, actually, as a diagnostic step. And funny enough, a couple of those patients have remained seizure-free for several months now.

Glen Stevens, DO, PhD: Well, it's a little bit like the focused ultrasound-

Demitre Serletis, MD, PhD: Very much so, minimally invasive.

Glen Stevens, DO, PhD: ... where they'll do a thermal ablation at a much lower level-

Demitre Serletis, MD, PhD: That's right.

Glen Stevens, DO, PhD: ... to see if they're getting any confidence that they're in the right area for the tremor. When they're confident, they will then give the thermal ablation that's required.

Demitre Serletis, MD, PhD: That's right.

Glen Stevens, DO, PhD: It's the same process, right?

Demitre Serletis, MD, PhD: That's correct. And if it's so focal, you could come back later with a laser ablation, for example, which is a little bit bigger. That's exactly right.

Glen Stevens, DO, PhD: So, maybe you don't have this data at this point but I'd be curious if the SEEG allows you to do smaller resections than we used to do because my recollection in the older days was remove a lot of tissue.

Demitre Serletis, MD, PhD: Right, yes.

Glen Stevens, DO, PhD: But does this allow you to remove less or that hasn't changed?

Demitre Serletis, MD, PhD: It does. It informs us because now we have a tailored map relying on the electrodes as we've implanted for a given patient and their anatomy but you can also refine or restrict the resection zone. Sometimes it's just the temporal pole and perhaps the amygdala, sparing the hippocampus and some of the other lateral cortical, neocortical structures as well. In this way, we're able to localize much better, for example, to the cingulate area and realize we don't have to take the whole frontal lobe out with it and maybe just put a small laser and burn it in there. And at this point, we've started now implanting into the thalamus and this is giving us some new information where we ... And thanks to my colleague Dr. Rammo who's the PI, we've started together recruiting patients for a research study into the implantation of SEEG in the thalamus.

At some centers, this is a gold standard, they're doing it already upfront without discussion. We wanted to prove to ourselves with a collection of a hundred patients, studying this at the end, that there was merit to doing so because this is going to guide things like deep brain stimulation or responsive neurostimulation with the NeuroPace device. And we're learning a lot even now about networks in the brain in this way so it's very exciting.

Glen Stevens, DO, PhD: Yeah, I think it's quite exciting that you can potentially do the thermal ablation-

Demitre Serletis, MD, PhD: Yes.

Glen Stevens, DO, PhD:... either using laser interstitial thermal therapy or radiofrequency.

Demitre Serletis, MD, PhD: That's right, yeah.

Glen Stevens, DO, PhD: At the time that you'd have the SEEG in is quite exciting, really.

Demitre Serletis, MD, PhD: It is. And we're at the point where, not only with the eye as we review with our electrophysiologist's help the data, but now we're evolving into quantitative tools to study stereo EEG as well. And we're studying the dynamics and that's part of the lab that I'm helping to direct with colleagues such as Dr. Bulacio and Dr. Krishnan, we have some students and post-docs and we're studying SEEG signals in a whole new light, studying the dynamics which is giving us even more information. Hoping to get to the point that, you have to understand, we're still limited by where these electrodes are and sometimes we have to infer between the lines or perhaps extrapolate and we need to develop some tools, some databases that will allow us to use machine learning, artificial intelligence to study these signals as well.

Glen Stevens, DO, PhD: How often do you see multiple foci of epileptogenicity?

Demitre Serletis, MD, PhD: It happens sometimes, there's no question. That's one reason, that's one indication for stereo EEG. In the days of grids, some patients would have to have a bilateral craniotomy, it's a huge procedure with a much higher risk profile than stereo EEG to investigate multi-onset or multifocal epilepsy. Sometimes we find that there's a clear propagation pattern that explains it, but when we don't find that, that's when we will turn to the more palliative methods like neuromodulation at this stage for treatment there.

Glen Stevens, DO, PhD: So, you mentioned a little bit with the neuromodulation but let's just go a little bit further on the response neuro stimulation, deep brain stimulation. How are you incorporating it or how do you see incorporating that into the SEEG?

Demitre Serletis, MD, PhD: Well, the SEEG is giving us the data to guide the surgical decision-making process. This is the point where we are at now, we can record seizure events, we can test function in brain areas and make a safe decision for a patient together about whether we may proceed to resect. If it's so discreet that we can perform a laser ablation or, if those won't work, if we're in an eloquent area, that's the decision then to look at the neuromodulation devices that are out there. And that includes also vagal nerve stimulation, too, which is outside the brain, of course, but then you have deep brain and responsive neurostimulation which are put into the brain. And you have to know where to implant them and that's where SEEG guides us.

Glen Stevens, DO, PhD: So, the future, we've talked about a little bit, very exciting stuff. Where else is this going because I'm sure it's just taking off?

Demitre Serletis, MD, PhD: So, one of the big things now with data-driven science, machine learning, neuroengineering, my humble background with a PhD in neuroengineering, we're studying these signals to get much more, to extract much more data content out of these signals than we previously were using. If we start to annotate this information in an organized database, we can start to classify seizures using biomarkers. So, if I use the example of genes in oncology, they're much further ahead, I would suggest, in this field where, if you have a tissue specimen, we now know the names of hundreds, maybe thousands of genes that we can test for. We don't have the names of genes to test for, I say genes in quotes, in signals. We need biomarkers so we're developing those types of biomarkers to study these signals and perhaps classify seizures by them and even perhaps decide how to control them with the neuromodulation devices.

I think the trend in surgery is becoming less invasive over time. We have these minimally invasive technologies that are gaining in popularity which is great from the patient's standpoint. And then there's the future of SEEG and what's next after SEEG. There are new technologies now looking at implanting electrodes through the vessels, endovascularly which will open up a whole new path towards studying these signals with, not only hundreds, but now thousands or maybe millions of electrode contacts. We have to approach the data problem and so we've started doing that.

Glen Stevens, DO, PhD: Mm-hmm. Well, fortunately, we have the IBM supercomputer here.

Demitre Serletis, MD, PhD: Yes, exactly, we do. The quantum machine and all of these wonderful technologies help but we also have to get organized as we annotate our data moving forwards and curate it. And as you build models to study these signals, we have to curate the data that's going in. There are fiber optic technologies that are coming out on the horizon, much smaller than the electrodes we currently use, there are subcutaneous implantable devices. And another new line of treatment that's opening up is gene therapy delivery also into the hippocampus as well. So, using methods like SEEG are helping us decide whether a patient may benefit from something like that. If it's very focal and restricted to a hippocampus, we may consider something like this.

Glen Stevens, DO, PhD: People generally vote with their feet and I'm just curious, across the globe, what's the state of SEEG?

Demitre Serletis, MD, PhD: Well, that's a great question, it's very timely because we celebrated our Epilepsy Summit for 2024 which was focused on SEEG and that was under Dr. Najm's amazing leadership and vision. So, the world came to Cleveland, in fact, and we were able to get a pulse on where SEEG is. We all sort of agree, we hope one day the future of SEEG may be no SEEG as our methods improve. For now, it's here to stay and I think there's a lot of technology and analytical workflow to support it with a lot of promise for patients who previously failed grids or attempts at surgery. We're thrilled to have had this kind of session, there's already another one in the books for a couple of years from now too, another big meeting, but it was a really great meeting of the minds, I would say. We really hashed out the excitement and the limitations of this method.

Glen Stevens, DO, PhD: Excellent. And you're the director of the Brain Dynectome Lab.

Demitre Serletis, MD, PhD: Right.

Glen Stevens, DO, PhD: This is a new word for me, I've never heard this word before, and I looked it up and I couldn't find it, so I think you're making words up.

Demitre Serletis, MD, PhD: Yes, that's right. We coined it.

Glen Stevens, DO, PhD: What does it mean in your mind?

Demitre Serletis, MD, PhD: Well, it's a fusion of dynamical and connectome. So, everyone talks about the connectome and, largely, it's used in a structural sense but these signals we're recording are the functional and the dynamical flow of information. So, we're not just looking at traffic restricted to roads, but traffic that uses air and ephaptic transmission and other pathways in the brain. The dynectome is meant to be a database that studies the dynamics of seizures. And finally, the ect in the middle is like the Greek word exo which means to remove and resect and ablate and so on. So, it had a little surgical theme to it, we thought it fit well with the lab.

Glen Stevens, DO, PhD: Well, it seems very clear to me that, if someone's sitting out there listening to this podcast and they have patients that have refractory epilepsy, sitting on the sidelines and just going through the 16th medication doesn't make sense.

Demitre Serletis, MD, PhD: I agree with you completely there, yeah.

Glen Stevens, DO, PhD: And I think it's very clear that we need to do a lot more surgical evaluation on patients with intractable epilepsy. So, appreciate all the work that you're doing.

Demitre Serletis, MD, PhD: No, thank you very much. Even just helping to get the word out about this method and the workflow, it can be very daunting and intimidating to some folks but, as they see the utility of the method, it can really open doors to treatment that they never had this option before.

Glen Stevens, DO, PhD: Well, you've made me a believer and it's been a great discussion on the future of epilepsy surgery and very proud of the fact that you had the big Epilepsy SEEG Summit here and I'm sure good things will come from it and appreciate your having spending some time with us again.

Demitre Serletis, MD, PhD: Thank you so much, I really appreciate it.

Closing: This concludes this episode of Neuro Pathways. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast, or subscribe to the podcast on iTunes, Google Play, Spotify, or wherever you get your podcasts. And don't forget, you can access real-time updates from experts in Cleveland Clinic's Neurological Institute on our Consult QD website. That's @CleClinicMD, all one word. And thank you for listening.