Thank you for attending today's Ask the Expert webinar on Principles of Patient Selection and Outcomes for Laser Interstitial Thermal Therapy for Drug-Resistant Epilepsy. Please note that this webinar does offer continuing education credit after completing the evaluation. You will be taken to the evaluation immediately after the webinar. You will receive an email when the on-demand version is available. Before we get started, I would like to take a moment to acquaint you with a few features of this web event technology. At any time, you may adjust your audio using any computer volume settings that you may have. Should you encounter any audio issues, refer to the meeting information pod for further instruction. On the right-hand side of your screen, you will see the text Q&A window. There is a large window which holds all of your sent messages and a smaller text box at the bottom where you will type in your questions. To send a question, click in the text box and type your text. When finished, click the send button. All questions that you submit are only seen by today's presenters. Your questions will be responded to in the order in which they were received and will be addressed at the end of the presentation. I'd now like to introduce today's moderator, Dr. Jai Singh Singh, AES Online Education Committee member. Thank you. Thank you, Eric. So, let me reintroduce. I'm Jai Singh Singh. I'm an epileptologist and Assistant Professor of Neurology. I'm also a Co-Director of the Epilepsy Surgery Program at Ohio State University. It's my immense pleasure to welcome Dr. Lara Jai. She's a well-known name in the field of epilepsy surgery. She needs no introduction, but she's a Professor of Neurology. She's also a Chief Research Information Officer at Cleveland Clinic. So, with that, let's get started. Dr. Jai, thank you for accepting our invitation. If we go to the next slide, I'll let you disclose your – any disclosures, if you have. I have none. Thank you. So, to the audience who are joining online, this is a very open forum for discussion. As the title says, Ask the Expert. We will be presenting – Dr. Jai will be presenting some data on the topic. And at the end, we dedicated a significant amount of time for Q&A sessions. So, please feel free to log in, post your questions as they come, and then I'll be posting them. If there are some questions which are missed out, please do not hesitate to reach out to us via email. We'll be happy to get back to you. So, on that note, let me get started. Let me start today's webinar by presenting one of my case. Actually, a very interesting young guy. He was 32 years old when he came to my clinic for epilepsy surgery evaluation. And his seizures started around the age of 3 years after having an event of febrile seizures at the age of 18 months. And his seizures thereafter being focal seizures where he kind of has a behavioral arrest, has a repetitive oral chewing movement, and has a language impairment during the seizure and even after. And some of the seizures do evolve into bilateral tonic-clonic seizures, but the amount is largely the seizure burden is the behavioral arrest seizures. He underwent an EMU monitoring with us where we recorded a left perda and a frequent abluptogenic discharges over the left anterior temporal head chain, pointing towards more to the temporal pole and the base of the temporal lobe. He also recorded some seizures with rhythmic theta activity over the left anterior temporal chain. On his MRI brain, he has a classical mesial temporal lobe sclerosis with a flare signal change and a significant volume loss over the left hippocampal head region. That also was consistent with decreased hypermetabolism over the left mesial temporal lobe structures. And his neuropsych profile also was consistent with left hemispheric dysfunction. A very classical case of mesial temporal lobe epilepsy. And with that case, I'm going to hold on to this case and let Dr. Jai start the presentation and then we will circle back on this case to get her idea that what she would have done with this case would have been an ideal case to go directly to a laser or would any of the testing would have benefited him a lot. So with that, Dr. Jai, I'm going to take a pause and I'll hand over to you. Thank you, Dr. Singh, for the case and thank you for the invitation. It's a privilege to be sharing with you this forum for the American Epilepsy Society. And I'm particularly privileged because I'm looking at the list of the attendees, the folks who have joined the meeting, and I see in the names many who are experts in the field in laser. So I am really looking forward to the discussion that we will have afterwards and their input and their questions to what we're going to discuss. Next slide, please. So this is the poll to the audience. The expected rates of seizure freedom after LIT are, and you have the options there. So pick one. We'll give it a few seconds for the lines to stabilize, and then, okay, it seems like we've settled. So, let's close it and display the results. So, I see that the majority of folks felt that the correct answer is 60% at three years. So, let's show now the real correct answer, and it is actually 40% at three years. So, I'll show you the data in this talk to support this conclusion, and it's great, because it's always good to start when we feel like there's something we can learn, right? If we already knew the answer, then what's in the rest 30 minutes or so? So, let's move to the next slide. I wanted to start with this, because as I was thinking for why, you know, how did we as a field in epilepsy get to the innovation that is laser interstitial thermoablation? Because it is an innovation. Right now, it's been, you know, a practice for close to a decade, so it's not as new as it was when it started, but how did we get here? And this is a quote that I think is helpful. I hate to start the talk with the word desperation, but it really describes how we were at the point when we were looking, right, and we still are looking for other options to treat our patients with drug-resistant epilepsy. If refective surgery was really the magic bullet that was giving us and our patients everything that we wanted, then we wouldn't have looked for other solutions, and the challenge that we've had and we continue to have with a traditional refective surgery approach is the inconvenience, cost, complications, and, of course, like any other field in medicine, surgeons like to innovate, thank God, and, you know, to find newer ways to deliver either the same level of care with lower risk or with lower cost or better care with higher cost or higher risk, but this, to me, is the starting point for how I think about how to fit LIT, LASER, into the larger, bigger picture of surgical therapy for drug-resistant epilepsy. Next slide. So, let's see now what evidence, what have we learned about 10 years into doing this and how robust, you know, is the evidence that we have for how effective this treatment is, and typically, if I was giving this talk for resection in epilepsy surgery, this would be the place where I would show the slide with the WIB trial, the randomized clinical trial for temporal lobe resection with, you know, what the outcomes were. So, how many randomized clinical trials do we have with LASER? We don't have any, so this slide was easy. None. There is nothing. Next slide. Then, I would show what prospective controlled observational studies do we have, so prospective controlled observational studies would be observational studies that are conducted prospectively where we are controlling for what variables we are collecting and how we are matching the patients or co-variants that we think might influence the outcome of interest. So, it is a, they're very complicated to conduct, and they're very costly, actually. So, do we have that with LASER? We don't. So, this slide was also easy. Next slide. What retrospective observational controlled studies do we have for either temporal lobe epilepsy or extratemporal lobe epilepsy with LASER? Again, here, retrospective observational controlled, the keyword there is controlled. Again, it is retrospective studies that are designed, in a way, to match for co-variants. So, you do these things with approaches like propensity matching or propensity weighting. We don't have that. Next slide. What we do have is the SLATE trial, so that's the first thing, you know, and the scale of evidence. I'm working the way down from the top level of evidence being randomized clinical studies and then working down from there. The highest level of evidence that we're looking at is the prospective single-arm observational study that is the SLATE trial for mesial temporal lobe epilepsy. So, this study is designed to look at safety and efficacy of MRI-guided LASER ablation for the treatment of temporal lobe epilepsy. It's looking to enroll up to 150 patients. The primary efficacy endpoint is seizure freedom, defined as an ANGEL score of 1 in the first 12 months following the procedure, so that's additional classification of success after surgical therapy. And it's also looking at primary safety endpoints. And the comparator group to this study is going to be a historical control, basically a historical value of both safety and efficacy following anterior temporal lobe resection. Next slide. So, what have we learned from SLATE so far? Well, one thing that is obvious is that even the single-arm prospective studies that's purely observational here, you know, we're not talking about any of the additional control criteria that I mentioned. Even doing something like that is expensive and is complicated. It's an observational study that includes 25 sites. This information that you see is what is available from the clinicaltrials.gov, the website that tracks all of clinical trials, and this is from, like, you know, when I had to prepare this talk just a month ago. And you can see that it started in December 2016, and it's expected to complete in 2025, so 10 years after it started, despite having the 25 study sites. And this is just a very humbling observation that I do want to communicate to folks on the call, where in the big scheme of things, collecting evidence, you know, there's a reason why my initial slides had none, none, none in there, because getting that information is very tricky. It's very difficult to get proper data on surgical therapy in epilepsy, particularly for us, because if you take the randomized clinical trial, for example, observation, that we don't have any, it will be very difficult for us to get a randomized clinical trial that looks at laser therapy versus resection for the treatment of temporal lobe epilepsy. We could have that debate after the call, you know, I finish the conversation, I guess, but if you put yourself in the shoes of the patient who's on the receiving end of this, and you're having a conversation with your doctor, and they're telling you that it's the one option with laser, where you are in and out of the hospital within a day, where you will not need to have a resection, you know, a craniotomy, and, you know, you'll get a treatment, and versus the option where we have to cut your, open your skull, do a procedure, you are not going to have equipoise, you're not going to be comfortable, at least I won't be comfortable with somebody flipping a coin, and I'm equally comfortable with both of those things. You're going to pick one, decide on one, and then go for it, and then you're not randomized anymore. So, the, that's why that is a none, and then here in this case, even the observational piece of it is taking this long, and at the end of it, still the findings of Slate will inform us on how to, you know, how does laser perform in the specific selection group that, of patients who are recruited for this study, who are people who have an MRI visible lesion, very consistent semiology with mesial temporal lobe epilepsy, no contralateral EEG abnormalities, and no prior surgery. So, it's sort of like exactly the case that Jay showed us at the beginning, but those of us who work in epilepsy surgery programs know that these people are like unicorns now, you know, the patients that are this clean and this selected, so we are still left with all the other cases that we see, and what do we do with them. Next slide. So, prospect, now if we look, so this is the other people that we see, those who have extra temporal lobe epilepsy, right now we don't have, as far as I know, you know, correct me if I'm wrong, at the end, a prospective single-arm observational study that's registered in clinicaltrials.gov that is looking at LITs in this particular population. Next slide. But we have many case theories out there, and there are meta-analyses that have looked at learning, you know, as much as we can, basically milking the knowledge that we can get from these case theories that are available. So, what have we learned there? Next slide. I picked this review because I felt it was the most comprehensive review. It was just published in Epilepsia about a year ago, and it looked, it was comprehensive because it included, you know, the bigger picture of minimally invasive procedures, so beyond LIT. They also included radiofrequency ablation, compared to refractive procedures, so with temporal lobectomy and with selective amygdalo-hippocampectomy. So, all in all, they had 43 studies total that they included. Next slide. And this table summarizes, really, the main findings of that meta-analysis. You have the MRI-guided LIT procedures, the radiofrequency ablation, temporal lobectomies, and selective amygdalo-hippocampectomy. And then the columns are the seizure outcome, the major complications, and the neuropsychological outcome. You see the raw numbers for each one of those categories, and then in the bottom row, the comparison, that's really the main, like, you know, the takeaway. So, the seizure freedom rates were the same, essentially, with temporal lobectomies and selective amygdalo-hippocampectomy. The seizure outcomes of LIT and radiofrequency ablation was also the same. As groups, the temporal lobe resections and the amygdalo-hippocampectomy had a higher rate of seizure freedom relative to the LIT and the RFA. And that superiority with regards to seizure outcomes was mostly visible with longer follow-up. So, in patients where there was more than 60 months of follow-up available, that was the group where there was the biggest split, and with higher rates of seizure freedom in those that had the resective procedures. The differences in the major complications were not statistically significant. As far as the neuropsych outcomes, all procedures correlated with memory deficit. So, there was none that was, like, you know, safe. You get no change in your memory afterwards. The memory deficit is always there, but it is less with laser and or selective amygdalo-hippocampectomy. And there was less lateral temporal deficits in naming with these more selective procedures. Next slide. So, when we think about this long-term, you know, this difference in seizure outcomes, that's why I started with the first question being, you know, the seizure freedom rates. It's important, as we, you know, when we think about how successful any procedure is, to think about it in terms of time. On day one, after any surgery, hopefully, 100% of our people are seizure-free. When we are throwing out numbers for proportion of seizure freedom, it's important that we know, well, so, when, like, when does that number apply? And this is another meta-analysis that looked at seizure freedom rates after LIT, and the LIT, and again, you see, you know, as time goes by, that proportion of seizure freedom falls. When all was said and done and everything was combined, the rates were about 65% at the one year, 47%, I think of it like, you know, two-thirds have two-thirds seizure-free at the one year, half seizure-free at the two years, and then about 40% seizure-free at the three-year mark. Of course, there will be variation between centers. Maybe some centers have, you know, better rates than others, but this is the meta-analysis of all data, all centers, you know, combined. Next slide. So, and this drop in seizure outcome, actually, with laser is not unique to laser. With resective surgery, we also get a drop in seizure freedom with time. Can we go back? I'm sorry. Can we go back to the previous slide? If we were looking at the plot of the seizure outcomes after resective surgery, it actually would have the same shape in that, you know, of course, there is a drop, and then afterwards, it stabilizes. The difference, though, is in, you know, the Y-axis, the rate. So, in resective surgery, as was shown in that meta-analysis with the superiority, it's about a 15% difference when you really get to the years out from surgery. With resection, typically, what you have is about 70%, 80% at the one year, about 66% or so at the, you know, at the five years, and then you get down to half, 50% to 55% seizure-free at the 10 years. With laser, it's sort of like, you know, squeezed into what you get with a resection in 10 years. That same drop happens with after laser within the first four to five years afterwards. Next slide. So, now let's dig into what drives, you know, what do we know about what drives that seizure outcome after laser? So, the first obvious question, same with, like, if you look at the literature with resection, we started, do people with hippocampus sclerosis do better, or people where we see a lesion? And here, actually, it's, I think it's, like, you know, you could believe whatever you want. So, there is one meta-analysis where, yes, patients with hippocampus sclerosis did do better after laser. But then, there's another multi-center study whose author is with us in the audience, I know. They found that, no, there was actually no difference in whether, in people who had hippocampus sclerosis versus not. So, one way, you know, at least my interpretation of how I reconcile it is seeing hippocampus sclerosis is in a way just a surrogate marker for the epilepsy is I know where it is and it is localized. So if I take it out whichever way, then that patient is going to do well. So if I'm in a place that can have the luxury of additional methods that can help localize the epilepsy and if that epilepsy is really very well localized without needing to have a lesion on the MRI and I laser it, yes, people will do well. So that, perhaps, is the reason why we have this difference in findings across the studies. So the key there is if you localize it, people will do well. Next slide. Does the extent of the ablation matter? Say, does the volume of this, how much we sex, does it matter? How much do we ablate, does it matter? And again, in individual studies, you may find answers that contradict. When you do, you pull together in a meta-analysis approach, the outcome was unrelated to the platform that's used for the stereotactic approach and it was unrelated to the total ablation volume. And my simple explanation of this is that anatomy trumps volume. Ablation trumps size, meaning if I take out, however, laser or otherwise, if I take out a big part of the brain but it is not really where the epilepsy is, that will have nothing to do with making people seizure-free. I might as well do a smaller surgery but if it is taking out the right localization, that is more important than how much brain I took. Big resection might do well in general just because the bigger you go, the more likely you are that you're going in all that sea that you removed, that you took out the part that was causing the seizures. But in and of itself, if it is not covering where the epilepsy is coming from, it's not enough to make people seizure-free. Next slide. And this, I think, is a nice, is a very elegant paper that really showed this distinction between anatomy and volume, you know, the location versus how much we ablate really well because you, so what's circled in green is the theoretical favorable ablation location. And the team there calculated positive predictive values and negative predictive value maps of angle outcomes that were associated with, you know, at least one year follow-up with each voxel that was ablated against a normalized atlas. And they came up with what is the ideal ablated volume that's, ideal ablation, that's what's in green, and then the unfavorable ablation, what's in red. So the volumes aren't really that different, but the difference is in what was ablated. So there were better outcomes with anterior ablation that covered the amygdala, the hippocampus, the parahippocampus, the gyrus, and the rhinoceros. Next slide. Age doesn't matter, seemingly, either. Pediatric people, you know, patients who had this have similar outcomes to the adults. Next slide. So now let's talk a little bit about what do we know about, let's, beyond mesial temporal lobe epilepsy. Here we are venturing deeper and deeper into the, you know, smaller case series, what's published here and there, so the level of confidence, I would say, in these, in the findings would be less. We think that it may be effective in small, localized, lesional extra-temporal lobe epilepsy. And this is the, you know, the data to support that. So in the figure, you know, the A, the graph that's in A, the survival analysis, you see there's higher rates of seizure freedom between the lesional and the other group. But, you know, look at how, like, blocked off and the wide confidence intervals. I mean, these numbers are so small. This is not really like a survival curve that you really trust. But, you know, that's what's out there. And it's not surprising, because it's only 32 patients. The figure B, there is the distribution of the patients by angle classification. Basically, it's, you're saying the same thing, but with two different figures. The angled one is the darkest blue that's in the bottom, and you see it's the highest in the lesional group. And then by lobe of 3-section, it's now completely unraveled. But then D is interesting, because here they looked to correlate the seizure onset pattern, the activity that you would record with intracranial EEG, with SEEG, for the onset of the region that you chose to ablate in the extra temporal distribution. And the best outcomes, the higher proportion of the angle one scores, were seen when the seizure onset pattern was either low voltage fast or repetitive spikes. You see how high, you know, the blue, the dark blue is in those groups, versus how low it is when the seizure onset pattern was anything except for these two patterns. And again, the way I would interpret this is it's the pattern itself is not really the key. It is what that pattern means. A seizure onset pattern on SEEG that is in the form of localized low voltage fast or localized repetitive spikes is simply a signature of we localized the epilepsy well. We are confident with where it is coming from. So, of course, if you have that, then that's a successful SEEG evaluation. It helps you localize the epilepsy well. And then that is the key. Afterwards, how you choose to treat it with a resection, ablation, radiofrequency, you know, LIT or radiofrequency ablation, that's secondary, right? The step is that we localized it. That's what this means. And then all other means that basically what you got were stress patterns. And the epilepsy, you found a seizure onset pattern in the one electrode, but that's not really where the seizure truly is coming from. It's probably coming from somewhere else. And what you got there is bad. You don't know where the epilepsy is. It doesn't matter how you treat it. You're not going to make that patient seizure-free. Next slide. There is also literature out there on using LIT for treating low-grade epilepsy-associated tumors. This is a small study. You see the numbers. So seven people, patients who underwent nine open resections, six patients who had LIT alone, one person who had an open resection followed by LIT. So those numbers are really very small. We can't really draw robust conclusions from them. They found that at the one year, 50% seizure-free with resection, 57% with LIT. And talk about trends and all that. But here, I'm showing this not because the numbers are obviously very small, so we don't really know. But this brings up the question of, well, when we're talking about a brain tumor, one could think about, well, so the value of pathology, looking at histological definition of what we're removing, which you get with resection. You don't get with laser. So that is probably why those numbers are small and why they might continue to be small. Because in situations where histological review of what we see as the cause of the epilepsy is important, that is one area where no matter what, LIT isn't going to do that job. Next slide. So the patient selection, then, having said everything that we looked at, I think that the same principles apply here as the patient selection for any intervention. Basically, the first place to start from is to know what's out there, know what to expect. And then be transparent about those expectations with the patient. And help the patient weigh the risks versus the benefits of the option. And then keep the door open for other therapies, which is particularly important when it comes to LIT. So thinking through these criteria, specifically now for laser ablation, the first step means we have to be transparent with patients about what this procedure can do and what it cannot do. Meaning we have to say, you know, the expectation as far as becoming seizure-free with this procedure is this much. The expectation if you have a resection, it is this much. But the expectations as far as risks with cognitive problems, with memory issues, with how long to stay in the hospital, also, you know, this is what you expect with path A. This is what you expect with path B. And then work with them, you know, so they can choose which of the two might make the most sense for them. And then the patient might be comfortable with, you know, this is a less-guaranteed procedure, but I'm willing to try it at the first pass. And then if it works great. If it doesn't work, then I'm going to have a resection afterwards. This is a very different approach from this works the same as resection. You could do this or that and present them as being equal in their potential. Because if the laser doesn't work, then these patients will not go for the resection. Then we would have wasted a chance instead of gaining a chance. If there is a patient who is now left with the opposite path, if there is a patient who has bad epilepsy, who's very worried and scared of the risks of an open resection, and for them the option is do open resection versus nothing, then that's not right either. And for that kind of a patient, going for laser ablation is a chance at becoming seizure-free. So the procedure in and of itself could either be a chance at becoming seizure-free or it could be a risk of losing a cure from epilepsy. It all depends on how it's presented. It all depends on the expectation setting and the relationship that a surgeon and an epileptologist have with the patient. Next slide. So how? What's the path forward? I think we owe it to our patients to give them those answers and to get those answers. So the way to improve our patient's action in the future should be through more robust evidence that we collect, and the scale of evidence, length of evidence that we have for lead, you see where we are for mesial temporal lobe epilepsy, but I would hope that we also explore it for other types of epilepsy. Our patients with MT&E are, in a way, the easiest ones to treat. The challenging ones are everybody else in our practice, and those are the ones where we need to get more information. Next slide. So the main takeaways. In well-selected patients, LIT offers a safe and effective therapeutic option. It has the same efficacy as radiofrequency ablation, lower efficacy than open resection, but it offers lower risks for naming decline. And the last takeaway is that we need more research to produce rigorous and long-term insights on its success. So I will stop here, and I think this is the part where we open it up for discussion. Yes. Thank you, Dr. Jahar. So the questions are coming in, and I'll give a few minutes for our audience to type more questions. So let's circle back to that case which I presented and pose some questions. So the classical case of mesial temporal lobe epilepsy had a febrile seizure, semiology, having an MTS, PET, neuropsych. And as you highlighted, these cases are becoming a bit unusual, but we still see them. And that was a dominant temporal lobe epilepsy. So three questions, Dr. Jahar. One is, is this case enough to directly proceed with a LIT, or would you, even in the cases which are lesional and concordant, would you still investigate? Especially for the dominant side, will you investigate with FEG or proceed directly with a LIT? I think that patient already had memory impairment, right? Right. Yes. So the neuropsychological testing already demonstrated that there is a memory hit that this patient already had. And from what you showed, it seemed that there is a hippocampal sclerosis on the MRI, and the EEG is consistent with mesial temporal lobe epilepsy also, right? Definitely. Yeah, correct. And the history is consistent with the history of the febrile seizure. So in a way, what this patient is, there is a textbook presentation of epilepsy arising from hippocampal sclerosis. It is in the dominant hemisphere, but they already have their memory impairment from the hippocampal sclerosis. So in a patient like this, I don't think that stereo EEG is indicated because there is no, you know, we would be making up a question that doesn't really exist. The localization is pretty, you know, we're confident about it. And as far as the discussion about LIT versus resection, this is a patient where, you know, the memory impairment is already present. So in a way, for them, the risk of memory decline with the open resection is less than, you know, someone who has a, you know, a normal-looking hippocampus. So for this particular patient, as, you know, I guess the one, two, three that I highlighted, I would explain, you know, I would tell them with your type of epilepsy, we have a couple of options. We have one option where you could get a laser procedure. It is less likely to work than the resection, but you will be, you know, you will be in and out of the hospital within a day. And if it doesn't work, we always have the second option of doing the open resection. And I have patients, you know, and I've had this conversation with many people, and there are the patients who just don't want to be in the hospital for too long. They don't want to have a big surgery unless they really need it. They understand that, you know, the laser may not work, but they're okay with trying it. And if it works fine, if not, then they get the resection. There are other patients who just want to get the therapy that has the highest chance of success, right off the bat. They don't want this back and forth, and we try, and we try this, we try that. They're much more, give me the treatment that is the most likely to get rid of my seizures. And then for that group of people, they may feel like to just go with the resection. So it's not, I don't think that as physicians it is our job to tell people what to do. It is our job to make sure that they understand the consequences of what they do. Sounds good. So Dr. Juhai, that was a lesional case. So let's assume if I remove NTS from the finding and let's leave rest exactly the same, would that influence your decision converting from lesional to the non-lesional, but still be highly suggestive of mesentemporal lobe epilepsy? So this would be a fictional case, because usually if everything is as clear as you have, you know, you will see something on the MRI. But say it is non-lesional and it is then the dominant temporal lobe. Then the first question was, do we do a CEG then or not? I think we should do a CEG then, because the hypothesis then for where the epilepsy is coming from then opens up quite a bit. If it is non, and then the risks also go up quite a bit. So if it's non-lesional, their memory is not going to be as impaired as this one. So the risk of a memory decline will be higher. So you cannot just do anything, laser or resection, you know, to the hippocampus that looks normal on imaging without confirming that it's really involved in the epilepsy. So I would do then a stereo EEG to localize, start by localizing where the epilepsy is. And then based on that, we can decide what to do. You know, if you find with a stereo EEG that the network that's involved is larger, you know, than what could be addressed directly with laser, then, you know, LIT is not appropriate. If you find that it is very well localized, then you go back to the discussion with the first guy of, you know, we localized it, we could do this or that, you know, that's the trade-off. Right. So the follow-up question on that, Dr. Jha says, I believe a couple of questions are showing up in Q&A also regarding that, is how much percentage of people who fail LIT, you either do a redo LIT, or if they do go within a standard ATL resection, do you see any complications after laser surgery going towards an ATL? Well, the complication that I see is it just messes up, it makes it harder to investigate and localize the epilepsy properly. You know, because you've already disrupted that network somehow, the anatomy is not clean anymore. And I would say if the, you know, if the first one didn't work, for me, that's the patient where you really need to explore more carefully, and I wouldn't just do another LIT without learning more. It comes back to this issue of right off the bat, how we're presenting the two options, you know, the LIT and the open resection. There is a, it's a very slippery slope where, when we start equating them, they're not equal, they're definitely not equal. So the way they get presented should not present them as being equal options for, I just saw a patient last week who had three lasers done, none of them worked, and then we're looking to see about the resection, and it took him years between, and his frustration was, you know, when people talked to me about it first, they told me I could either do this or that, it's the same. Like, he, at least that's how he understood it, that the LIT or the resection were, you know, equal options, and he just, if the LIT didn't work, that's it, it just didn't work, and there's nothing else that he could do. And that's just not right, you know? So, that's why I wouldn't keep going down the LIT route if it's not successful. And in your talk, Dr. Jaha, you did cover some of the challenges, it's a new technique, and I understand that we all are going to learn this technique, and I'm expecting this number will also get better in the coming few years. And some of the challenges you beautifully highlighted, anatomy, the structures being targeted, the more amygdala, hippocampus, and entorhinal cortex, which was one of the challenge, and Chen Hu is also on, he's highly advocate of adopting two-trajectory approach to target and update these structures. What's your thought on piriform cortex? Does that also need to be updated to give a better seizure freedom with LIT? Maybe, we don't have the data. So, I, you know, it's probably good. I mean, the data with it, with 3-section, we have some good quality data that it's involved, but it's not been uniformly confirmed in every single study that looked at 3-section of the piriform cortex and its impact on outcomes. I would expect that the same would apply to LIT. See, even the paper with the anterior involving the favorable versus unfavorable distribution of the ablation, at its core, what this is speaking to is the removal of the parts of the brain that are involved in this epileptic network, right? So, however that's done is fine. So, we can, so that's why I think one could extrapolate some, like that's why I said it probably would with the piriform cortex with LASER because of the data that we have with 3-section, but I'm not aware of a specifically, you know, of a paper that specifically looked at that in the context of LASER, you know, controlling for any other things that could be confounding. But the, you know, the point you made about the innovations that are happening, and not just like innovate, but just learning, it's a procedure. So, the more you do, the more you learn, the more you improve with it, and, you know, of course then your outcomes, or we hope, you know, that your outcomes will get better over time. And that's another challenge with the literature that we have with LASER is that it's, you know, of course people, you know, we needed to publish because we, but we needed to see what we are learning, but that meant that we lumped people who had LASER very early on with people who are having it now. And when you start to split to look at the effect of, you know, this learning curve and the experience, it gets hard because then your numbers become smaller and smaller. So, that's why, right? So, that's why there is more evidence with resection just because we've been, you know, doing it longer. There's more people who have it. They've had longer follow-ups. You know, we've had more opportunities to adapt and evolve. So, with LASER, I think it's a very exciting time for us to learn, you know, as we learn more, how it fits together with radiofrequency ablation in, you know, minimally treating those patients. But what I really like to emphasize again and again is that we have to do all of this and stay humble and stay true to what the limits of what we are excited about really are. Like, in a way, we don't have to present LAS as being or equal to a resection for it to be valuable, right? Like, there might be value in, there's always value in a minimally invasive procedure for anything just because it is less invasive. And patients take these risks on all the time. Think of other disciplines, like in the orthopedic world, for example. People do, you know, arthroscopic stuff all the time, knowing that it may not work as well as a replacement for any joint, but they do it as a first thing. And, but the thing is that when they're presented with it, or when they buy into it, they know that this is not as good as that. But I'm still choosing it for the reasons that I have. And that doesn't take away from how important, you know, the arthroscopy thing is relative to what the replacement. That's how I think of the LIT relative to the resection. Sounds good. And I'm going to pop a couple of questions here, Dr. Jhai. So one question, targeting is actually post-LIT, okay? When do you deem that, okay, this is a LIT failure at this time interval, and we should either revisit with SEG or proceed with ATL? Is there any fixed time interval? And do you do any post-LIT work of either a repeat neuropsych, repeat MRI brain? And any comments on that? So the question is, when do we, when do we judge that the LIT did not work? Well, let's see. So I would say, I would think about it the same as when do I judge that the resection did not work? I mean, basically, if it's going to work, it's going to work. So, you know, when people start having seizures again, so with a resection context, think about this one. So with a resection, we learned that acute post-operative seizures, so seizures within the first, say, month or so, are not necessarily predictive of long-term outcome. And we don't necessarily count those as failures, particularly when they're just convulsions and they're not the semiology that the patient had the surgery for. So we have looked at that, and we have documented it with the resection. I don't know that we've looked at that, that anybody has looked at that, with laser to see what is the implication of acute post-operative seizures. I know I'm giving ideas to people to write that paper, but that'll be an interesting one to do. With acute post-operative seizures with laser and their implication for long-term outcomes. But, you know, beyond that first month, typically, if a patient is seizing, they're going to continue seizing, you know, for the most part. So at that point, it is worth starting to at least prepare them or think about what would be the next step. I usually wait, give it six months, like unless we knew going in that we did an incomplete resection, say, of a malformation, and we wanted to see if that partial thing is going to work, and if it didn't, then the backup was let's just remove the whole thing. If it's a situation that's this clear, then you know it didn't work, you just have to do the bigger surgery. If it's not that clear, then it's worth giving it a few months just to see if this is going to run down, right, and settle down. And if it doesn't, you know, then at that six month mark, you would go, I would, you know, then you should go through an evaluation if the patient is still interested, right, in doing more of being re-evaluated, same as any surgical recurrence would, and that would be doing a whole other, you know, surgical evaluation, and typically what we do in those patients, they usually end up with an invasive evaluation, a stereo EEG, because you're talking, unless they had it the first time around, you know, because then you're talking about, well, we were not really sure where it is, and we need to localize it, it's the secondary section, we cannot keep bashing at this without knowing what we're doing. Perfect. We are drawing very close to ending this session, so let me clock some of the questions taking extra time for lobe epilepsy, and one of them is definitely the lesion does dictate whether LIT versus restriction would be an ideal, but I'm a bit more curious about EEG markers, when these patients undergo SEG evaluation, what are the, and which you did cover in your paper, looking out for the markers that tells you more that you are close to an anaphylactic zone, but are there any other markers that actually truly guide your decision that this could benefit from LIT versus, or the networks a little bit more broad where LIT may not be able to give a good justice, and could benefit more towards the section? Yeah, I think, Jay, the way you asked the question is absolutely right, it's not really an EEG biomarker for LIT versus this section, it's an EEG biomarker for restriction, it's an EEG biomarker for the localization of the epilepsy, the extent of the epileptogenic zone, and there, I mean, there's a whole slew of biomarkers that have been published ad nauseum, things like even the epileptogenicity index, and the connectivity measures, coherence measures, look at the extent of the epileptic network, and the distribution, you know, the extent of the anatomical regions that you see inter-ictal findings, and having multiple ictal patterns, for example, distinct ictal patterns, distinct semiological manifestations of seizures, it's basically, then, all of the EEG signatures that we have out there that reflect a poorly localized epilepsy. Multiple seizure types, clinical and extended epileptic network, in those situations, I mean, you really can't say that we pinpointed the epilepsy to a specific location, but then, the problem that you have is, if it is too big, I'm not going to do a resection that is too big, that's too risky, and, you know, that's too problematic. So, here, you are in a pickle. The challenge becomes, you know, because it's too big, right, like, it has to be the right size, if it's too big, then the outcome isn't great with a resection, either. So, do you really wanna do a big resection where the risk of deficit is sort of guaranteed, but then, the odds of seizure freedom are not that high? And then, is there room for something like CLIT to help at least disrupt those, you know, in that big network and see what happens? I have to say, I've tried this with a couple of patients and it didn't really work, but there is, you know, that's another area that we should study and look into more. So, it's a different way of thinking. Great, we are three o'clock, so, I believe I've covered most of the questions, but if there are some questions missed out, please don't hesitate to email us, I'll be happy to reconnect, Dr. Jha will be happy to reconnect on those questions. Once again, thank you everyone for joining today's Ask the Expert webinar. Please do remember to fill out the survey, which you'll be getting via email, taking this webinar. And thank you so much, Dr. Jha, for your time and giving this fabulous talk. Thank you, thank you so much. Thank you. My pleasure. Thank you, guys.

Laser Interstitial Thermal Therapy

LITT

drug-resistant epilepsy

patient selection

seizure freedom

stereo EEG

epileptic zone localization

minimally invasive surgery

epilepsy surgery outcomes

evidence-based guidelines