Next, we're going to have Dr. Andrews speaking us on temporal lobectomy for seizure control outcomes and predictors of seizure recurrence. Hi, everyone. My name is Johnny Andrews. I'm a fourth-year medical student at Yale and incoming intern at UCSF. And I'm going to be talking a little bit about temporal lobectomy for seizure control and also with an emphasis on seizure spread and mechanisms of surgical failure. So, we studied patients having a standard anterior medial temporal resection without extratemporal resections by the senior author between January 2000 and December 2015 at Yale. So, AMTR is a standardized resection of the temporal pole, a complete amygdalaectomy with the hippocampus divided where it turns behind the brain stem. And so, for intracranial EEG, neocortex was studied with a combination of strips and grids and mesial structures sampled with depth electrodes. MRI reconstructions and IEG power mapping, which you'll see later, of seizure spread were carried out with MATLAB and in-house software. So, just a little bit about the patient cohort we're dealing with. So, we had greater than one-year follow-up in 118 patients and greater than 10 years follow-up in 42 included in this study. We did intracranial studies on 30 of these patients and the most common pathology was mesial temporal sclerosis. So, this is just looking at continuous angle one seizure freedom since surgery. And in this cohort, by far most of the recurrences that happen are in post-operative years one through three. And after 10 years, our rate of continuous angle one seizure freedom was 65.6%. And so, this is looking at similar data but cross-sectionally, right? And so, just showing that high rates of angle one seizure freedom through 10 years post-operatively. And then, on the right, the breakdown of what's encompassed in that angle class one outcome, showing about half these patients who are seizure-free long-term, have been seizure-free since surgery. And the other half is split up between those who have isolated auras, those who have had some rare seizures after surgery, which were subsequently controlled for greater than two years. And also, patients who only had seizures with AED withdrawal. So, looking at predictors of outcome, we found three significant predictors in our cohort, one being discordance between preoperative PET and scalp EEG, two being non-lesional pathology, and then selection for intracranial EEG. And when we put this into a multivariable predictive model, only selection for intracranial EEG came out as a statistically significant and reliable predictor of poor outcome. And so, we really wanted to say, you know, look at this high-risk cohort where most of our failures are occurring and look a little bit deeper at this intracranial data and maybe there's a way for us to see a difference between patients for whom surgery is not working, who keep having seizures, versus those who we're able to make seizure-free. And so, we're poised to look at seizure spread because of our broad neocortical coverage, sites distinct from the mesial structures. So, we worked with our neurologist who's trained in interpreting intracranial EEG and defined first spread as seizure activity greater than 2 centimeters away from the seizure onset zone. And when we looked at the spread of times to first spread, it ranged from 1 to 55 seconds. But what we saw was the patients who had recurrent seizures, almost all of them were in the group that was spreading below 10 seconds. And so, sure enough, when we defined 10 seconds as our cutoff for rapid seizure spread, that 90% of our failures were in this cohort and all happened within the first three years. So, again, so now we have this idea of seizure spread and what does that really mean? And so, we wanted to look at, well, where are they spreading to? Because that could be of consequence and especially with respect to the surgical margins. So, when we looked at the interpretation of the EEG and the electrographic spread, what we found was there was a pattern of mesial to lateral. So, you know, we'd have the onset zone in either mesial structures or temporal pole, which are clearly within resected margins. But then where they would spread in these first 10 seconds is often laterally. And so, to visualize this, we made some MRI reconstructions of these patients' brains. These are just two examples of patients showing this rapid spread phenotype. And then mapped on fast beta gamma power activity, which correlated with where the seizures were spreading to. And you can see that, you know, we have, you know, onset in the anterior temporal pole. I'll go into this further in a little bit. And then projecting from the posterior hippocampus and then spreading to more lateral temporal neocortex and often outside resective margins. And so, when we compared the actual power of the lateral temporal cortex outside resective margins, the patients who had recurrent seizures had significantly more power than patients who were rendered angle one seizure free. And so, to finish off, I just want to really look at what this phenotype might look like of this rapid spread. And so, I'm going to show a couple examples. Both of which, on top, we have a patient with rapid spread. And compared to a bottom, a different patient who was a slow spreader. And so, you can see at time point zero in the rapid spread patient, we've got our first hotspot projecting from the posterior hippocampus. And then sort of going up into the mesial structures. But by seconds, you know, two and four, it's kind of curving around the temporal pole and just marching up the STG. And so, you can see that by second ten, it's even beyond the temporal lobe. And in contrast, a patient with slow spread who had much lower power in this seizure, you just see it starting to heat up in the uncus. But by second ten, all the hotspots are really within those mesial structures still, which are going to be taken out with our intermedial resection. And so, here's another just different view. Because not all of them looked alike. But on top again is the rapid spread patient with the initial hotspot at second zero in the temporal pole. And then this kind of discontinuous blossoming of seizure activity or of high beta gamma power activity in the posterior temporal cortex, which is spreading again to more orbital frontal and outside resected margins by second ten. And then another patient below, a slow spreader, where you see the initial hotspot in ITG around the temporal pole. That even by ten seconds, it's just kind of cupping the anterior temporal pole and just barely within resective margins. And so, in conclusion, networks of seizure nodes outside mesial temporal structures may underlie a significant portion of surgically refractory mesial temporal lobe epilepsy. And high failure rate in patients with seizure spread outside standard resective margins suggest that early sites of seizure spread may have epileptic potential. And the clinical implications would be that these areas of seizure spread might be investigated as targets of resection or responsive neurostimulation. So, I'm just going to acknowledge some funding by the HGMI Cure, my co-authors, and two of my wonderful mentors, Dr. Hal Blumenfeld and Dennis Spencer. Thank you. I'm going to ask Dr. Tong to come up to the stage to prepare while we field questions up here. Was duration of epilepsy correlated at all with these outcomes in your data set, as it has been in the literature? I don't have that in front of me right now. I didn't actually look at the duration of epilepsy. But yeah, no, that would be a very good idea to look at. Yeah. Previous studies would suggest that patients with more rapid or broad spread probably have had epilepsy longer, which makes sense for spreading out of the original onset zone, if it was indeed medial temporal. Also, to what extent do you think the fact that these are mostly grid and strip-based studies that don't sample areas of failure, such as posterior cingulate or insula or deep orbital frontal, do you think missing some of that sampling might perhaps relate to some of these changes in outcome? And to what extent are the patients that fail, does Dr. Spencer go back and restudy them? And where has he found the actual failure to be? Where is the onset now in a patient that's already undergone this gold standard, I would say temporal lobectomy? Yeah. No. So those are great points. And I think we actually often do have coverage in some of the cingulate. And so we're not, you know, since this is going on a limited basis, not every patient has equal coverage, but we did see some hotspots in the cingulate. It was just more, it was very clear that there was a lot of this activity in the lateral temporal cortex, which seemed most significant. And there have been very few patients that have been restudied, but obviously that would be the way to say, okay, you know, where are these seizures that are recurring actually coming from? But because there's just so few, we can't say for sure from this data set right now, but would love to look into. Thank you.

seizure recurrence

temporal lobectomy

seizure control

seizure freedom

surgically refractory epilepsy