Transcript

- Hello, ladies and gentlemen, and thank you for joining us. Today, we have Dr. Dennis Spencer, Harvey Cushing professor and chairman of neurosurgery at Yale University, Department of Neurosurgery. He's been a special person in my career. I have done a fellowship training under him and he's been an amazing mentor. I'm very appreciative that he's here today with us, talking about evaluation of the temporal lobe epilepsy. We're also gonna discuss controversial Issues related to topic. This will be part one. In the second part, we're gonna review technical nuances for anterior temporal lobe resection and selective amygdalohippocampectomy. Dr. Spencer, thank you and please go ahead.

- Thanks Aaron. I appreciate your asking you to do this and will be happy to go through our evolution in how we understand temporal lobe epilepsy and our evaluation during this first section. As you know, I'm a big fan of trying to morphologically classify the epilepsies, and that has evolved as we'll see a little bit later into a classification that involves the networks aside from the substrates. Using the substrate classification, what we mean by that is the seizure type plus the pathological and anatomical localization. It really helps us, I think, understand how we should approach the patient and how they're going to fall into categories that are gonna be more or less responsive to surgical treatment. So for temporal lobe epilepsy, obviously, mesial temporal sclerosis, neuronal loss in the hippocampus, and gliosis is one major category. We also see a number of patients that emerge, maybe less with chronic epilepsy now because of early MRI in patients who have their first seizure. We've seen patients with tumor and chronic epilepsy drop-off just because of the imaging. So neurooncological surgeons are seeing these patients rather than the epilepsy surgeons. And it means in fact, that we've done a good job in preventing the continuation of temporal lobe epilepsy with the identification and resection of the benign leiomyomas. Vascular lesions. Primarily, cavernomas are the next category in substrates and they also respond to, you're directed to surgery. Of course, with the caveat is that you must resect that hemosiderin astrocytically involved a region around the cavernoma. And then an increasingly, more important group are old patients with developmental abnormalities of the variety of cortical dysplasias and heterotopia means that we see our new genetic changes that we see in temporal lobe epilepsy. So let's move from that after looking at the substrates to the medial temporal lobe epilepsies. We noted that sclerosis is the most common pathological substrate. There are also the lesionals, which would be the tumor developmental or vascular. And they often lead to, or may lead to what we've coined paradoxical medial temporal lobe epilepsy. And by that we mean, if we wind up recording from invasive monitoring, recording from electrodes in the hippocampus, we may record the seizures actually beginning in the hippocampus, but in the setting of other pathologists or in the setting of a normal volume metric, they are hippocampus. And we may see this in tumors or in dual pathology, most commonly, in the developmental or cortical dysplasia patients. So we know that there's a long history of the description, the early description of neuronal loss and gliosis and emphasizing the gliosis. And of course, Jackson who actually took this pathology from Charcot is not his original description of medial pathology and associated that with the limbic seizures at that time. Lateral cortical onset was emphasized by Penfield with recordings by Jasper early on of the interictal spikes in the temporal lobe, and use those to define and describe their resections, which were primarily initially lateral temporal resections Murray Falconer in the UK, then concentrated on the historical evolution from Charcot and Jackson and began recording the lesions that we're seeing in medial temporal lobe epilepsy, and then described the five to six centimeter temporal lobectomy that involved also in mesial structures. And as we know, sort of simultaneously in the late '70s, Weiser in Switzerland was using basal electrodes to describe what you thought was immediate onset in temporal lobe epilepsy. And of course, Paul Crandall, who's literally the pioneer of intracranial recording. Paul beginning in 1971 was so strong in developing the techniques of intercranial recording, evolved those electrodes and described the medial onset of temporal lobe epilepsy. We practically use both Crandall's initial initially Crandall's approach, but different intracranial electrodes and a different technical approach to come to the conclusion that the medial temporal lobe, specifically the hippocampus, adrenal cortex, and amygdala were the most responsible for onset of temporal lobe epilepsy, then designed an operation to be based upon that medial onset. As we move on to the syndrome, I think that most people are familiar with this. It is frequently an injury or febrile convulsion under the age of four or five. That's important, that age or transition, usually of laying down language is a developmental transition in injury before that time often results in hippocampal disease. The Auras are psychic phenomenon and gustatory, or olfactory hallucinations. These, the limbic kinds of auras semiology, which we don't necessarily see all the time. But certainly, if you do see contralateral dystonic, if you see dystonic posturing is almost 99% of the time contralateral to the hippocampus kippocampal epileptogenic region. And scalp is variable. You certainly can see anterior temporal spikes, but they may be bilateral and that doesn't tell you that this is non-ipsilateral syndrome. And then of course, in the late 1980s, early 1990s after MRI had been around for a while, we still had not appreciated, but did appreciate then the ipsilateral keeping the epileptogenic region, the ipsilateral hippocampal atrophy with increased signal changing. We'll look at a little more carefully, and this is the most common pathological substrate.

- What do you think, Dr. Spencer is the most common misdiagnosis in temporal lobe epilepsy these days? You see people sort of seizing for a long time, they may not have a true convulsion and they're not diagnosed as seizures. What are your thoughts, if you don't mind?

- I think we're very much better in making this diagnosis, but if you look at the standard radiological picture across the country as I've been lecturing at different institutions and talking to radiologists, there still is quite a heterogeneous approach to making this diagnosis and certainly moderate hippocampal atrophy and similar change is missed in many, many instances. And it's often the neurologist, if they have the training and the interest that will pick up the hippocampal atrophy because they're concentrating on this rather than the radiologist. So that's probably the most common mistake and the second is the actual, the opposite. When you have somebody who has bad hippocampal changes and particularly signal changes on T2 and FLAIR, they may be called tumors. And obviously, it's just severe mesial temporal sclerosis.

- Thank you.

- And this is just an illustration of your origin and I think we'll just move on. It kind of describes the dystonia contralateral to the hippocampus, that of origin the seizures and the ipsilateral automatisms and then of course, secondary generalization, which can occur. This is a patient's scalp EEG that just illustrates the periodic spikes. Luckily, decremental on 70 in the periodic spikes, that one sees in a temporal lobe epilepsy. And this is commonly seen, more commonly seen when one is recording directly from the hippocampus those periodic spikes are a signature of the hippocampal onset.

- I thought we'd go ahead and review a video of a left temporal lobe seizure. This is an older video, and I think the physician involved does all their actually description of their presentation. It's really pretty classic and left temporal, I would say. So if you don't mind, let's both of us listen to watch. Thank you.

- Notice that his unresponsive when people are speaking to him and that he has purposeless movements of one hand, as well as some swallowing automatisms, and this all goes on for about a minute and a half. Notice the mouth movements. Clearly he seems to be awake.

- [Woman] Kevin, Kevin.

- [Dick] But seems somewhat confused.

- [Woman] Kevin.

- Another important finding-

- Kevin.

- and looking at this attack is that there's a clear asymmetry

- [Woman] Kevin.

- [Dick] with some tonic posturing of his right hand.

- Kevin, can you hear me?

- [Woman] Kevin?

- Hmm.

- Can you hear me, hmm?

- Hmm?

- [Dick] His fiance tries to speak to him,

- Oh.

- [Dick] but he's unable to respond.

- Can you hear me?

- So that was Dick Mattson, our senior neurologist describing a patient with a classical left temporal lobe seizure. Also, what we didn't follow up with was commonly some difficulty with language, which would carry on for a while. Most often after this, after a temporal lobe seizure like this when we see confusion. Patients may complain of a headache, but it is a more prolonged recovery than somebody with neocortical seizure onset, particularly above the Sylvian fissure in the frontal or the parietal lobes. What we are looking at now is just a confirmation of what we've been talking about, that you see this small hippocampus in this pathological illustration. We now move to an old but the MRI that shows that same, those same changes with the decrease in volume of the hippocampus, so with or without a signal change. And in this instance, we see, again, this decrease in size of the hippocampus. We also should note that the pair hippocampus may be smaller, it also may have some gray-white matter diffuse changes. And of course, if look with higher like three-Tesla anatomical studies, you see loss of architecture in the hippocampus. And then it's just illustrates the signal change that we see in this left hippocampus and with flux, either just increased water content around astrocytosis, whether it's associated and can be directly associated with increased numbers of glial cell counts. The pathology is fairly straightforward and classical, a medial temporal lobe epilepsy with neuronal loss and gliosis. There's a damage to CA1. We have associated this with the loss of cells and major increase in glial cells. Glutamine synthetase is also lost, which in the CA1 region, specifically. And this is one con. Usually, it's when we see loss of cells and CA1, you see in common at loss in both the dentate CA4. And people talk about how CA2 is less injured. That's true, but it also may have 50% cell loss. You may see 75% neuronal loss in CA1, CA4-dentate, CA3, but CA2 is still affected. It just looks relatively spared, but it's not really spared. And then with this cell loss, you see sprouting, obviously from the region of the dentate into the projected axons. Now this is the most common form of the temporal lobe epilepsy. And as we noted, it has this distinct, electric clinical pathological findings. This is just, will not dwell on this, but it just illustrates the density of sprouting that you see in the mossy fibers of the temporal lobe. It's still controversial, according to the sprouting and is an indication of excitability and epileptogenesis or is it reflect inhibition, increased inhibition in an area that has been injured. There's a lot of evidence that the maturation of the epileptogenic tissue has a lot, has more to do with gliosis and implicates the astrocyte as a singular pathological entity in the medial temporal lobe epilepsy. Now, how do we work these patients up? This is a standard devaluation paradigm in which we start with, of course, the history of the physical phase one, which is we divide our monitoring of the phases. Phase one is all your visual scalp or EEG monitoring. You know it's important if you saw from that video, if you look at the behavior, it is critical to look at the scalp and describe how bilateral those spikes are. And of course two, it is important to see if there's ipsilateral epidural onset on the scalp, although that's not necessary to come to the conclusion that one temporal lobe is responsible for the seizures. We know that imaging is taking an increasingly, important role. Since the 1990s, the MRI scan is showing that hippocampal atrophy or tumors or developmental lesions and then devise our treatment based upon those substrates. There's a number of other imaging that's used today. PAC MR Spectroscopy, ictal SPECT. Now all of those are just adjuncts of the critical anatomical, MR description. And then some controversy exists, whether the water test or the intra-arterial studies of memory and language are necessary today. I think that one must look at each individual patient. Our tendency is to still do the intra-arterial studies in those patients with temporal lobe epilepsy, the design being to look at memory capacity with the contralateral temporal lobe. But in many instances, now you can skip that if the patient has asymmetric memory with the bad memory on its lateral side and spared on other side. And they are certainly noted to be fairly dominant on both functional MR instincts. So given this workup and what's not mentioned here, but it was important, now clearly important is the neuro psychological findings, the neuro psych testing. The temporal lobe epilepsy is often disparate in terms of both temporal lobes being implicated. As we note, both hippocampi may show changes in size and segments, even though only one of them is responsible for the seizures. Likewise, the neuro psych testing may show memory changes, bilateral memory changes, even though only one temporal lobe is responsible for the seizures. But you can not afford to not do neuro psych testing in all of your patients with any form of medical intractable epilepsy. But in and of themselves, each of these tests is not sufficient, to lead you to one temporal resection. only if you get concordance of all of those non-invasive testing, can you then go to a substrate directed surgery, which may be in the case of mesial temporal sclerosis and medial tumor, it would be directed to the tumor. If it's a vascular lesion directly to the vascular lesion with in our hands. We do not use electrocorticography cognitively to make a decision about additional tissue to the resect, but we make sure that the lesion is resected to normal pathological margins in the case of tumor and carvenomas And I think that's a critical distinction, at least in our program. When there is no substrate or there's discordance in your evaluation and most of the time, it all developmental abnormalities. Then we move on to invasive intercranial recordings, which have provided the gold standard of how we define localization related epilepsy. So if we move to substrate director to surgery that I mentioned in the last slide or mesial temporal sclerosis with all the imaging and EEG concordance. One can go directly to a medial temporal resection for those patients that have developmental tumor I mean, aplasia and this is in medial temporal lobe. Then if it's in the medial temporal lobe, it may require resection of the hippocampus to our best control. If it's a lateral tumor and the hippocampus looks normal, then one should spare the hippocampus, unless there is something in the workup that implicates the hippocampal and position other than medial temporal lobe or tumor one can spare the hippocampus, if it's not otherwise involved. And that means good neuro psych testing, that means no signal change, and no accurate date. And then when they spare it and certainly if it's dominant temporal lobe and certainly should . And it's the same paradigm with the cavernous hemaningioma as one of the most common forms of vascular lesions to cause medial temporal lobe epilepsy. Other forms of vascular lesions such as higher flow AVMs may cause problems at a distance from the AVM and you have to look at it differently than when you're circumscribed cavernous hemaningioma. Aaron, any issues from your point of view?

- Well, I think there's a couple of points I just wanted to stress. I think this is a very nice review. The first issue you described was I'd use a water test. I assume that if somebody is right-handed with a right medial temporal lobe epilepsy, you do not perform water on those folks. Is that correct?

- No, it's not corrective. It depends upon the neuro-psych testing of the contralateral temporal lobes.

- So if somebody has-

- Okay.

- They right-handed and they have right temporal lobe epilepsy, but their verbal memory is terrible on this psych testing, then we would do a water test on that patient to make sure that they do have capacity for memory support if we resect the right hippocampus.

- Okay. And the second question comes down to the issue of resecting hippocampus for temporal lobe epilepsy associated with lesions. So I assume you're much more lenient in removing right medial or right hippocampus, if it is in close the vicinity of a lesion that's epileptogenic versus the left one. And it depends how far they are and what the neuro psych testing again, leads you made you in terms of contralateral verbal memory function. Is that correct?

- Yes, absolutely. For resection of the right hippocampus, we have a much lower threshold. If the tumor is adjacent to it, we'll certainly remove it even if it looks as though it has normal volume. And if the neuro-psych testing doesn't demonstrate any visual memory loss but it's adjacent to it, we would resect that hippocampus. It's completely in opposite paradigm on the left side, if we should say dominant versus non-dominant rather than left and right. But on the dominant side, it all depends on their verbal memory. We happen to use the selective reminding test as a way of quantifying this. And if that selective reminding shows more than two standard deviations of verbal memory loss, we know from hundreds of patients that we studied, that we can safely resect that hippocampus and not having an additional decrement of the patient's full memory. However, if they have no verbal memory loss or if it's only a standard, one standard deviation, then that hippocampus is functioning and oftentimes you must kind of think about this, that if the hippocampus is functioning normally then it certainly may not be a part of the initial substrate of the patient's seizure onset, and you'd feel more comfortable both leaving it and resecting an adjacent tumor or cavernoma. And I think it's mandatory to do that if you have an adjacent tumor that's wall circumscribed or a cavernoma and a normal functioning hippocampus, then you should, this is means dominant hippocampus. One should leave the hippocampus alone. We did studies in the 1980s where we removed portions of the anterior hippocampus, along with a tumor or cavernoma . And it's from that data that we demonstrated the patients to have a significant functional deficit in their verbal memories. So they were at most risk because they had normal verbal memory and had only a tumor, but did not have hippocampal onset of their seizures.

- So it makes a great sense because what you're telling for me to summarize is that for patients who have a good verbal memory and are better than two standard deviations below the average, you have a very high threshold for removing the dominant hippocampus. You really, really have to have a very strong reason because those individuals will get a big hit. So, no matter what, if you're doing well verbal memory-wise, you shouldn't have your dominant hippocampus out. Am I correct?

- Yes, that's been our philosophy. And I think there's strategies that are different and there's obviously a spectrum of how people interpret verbal memory and that what their threshold is for removing the hippocampus. But as a way of looking at this, certainly from an early experience, if you're beginning of practice in epilepsy surgery, one should always spare in a very functional dominant hippocampus, unless there's just absolutely no way to do that such as a medial temporal lobe, a tumor that is being converted into a more aggressive tumor and you are trying to decompress the tumor and remove the tumor for oncological purposes, not for epilepsy.

- Thank you.

- This is a paradigm that we can follow. This is what I call a logic tree of trying to sort out what you do and how you evaluate, and how you treat a patient with an MRI mass lesion and temporal lobe epilepsy. So many times, particularly these days now we know that a lesion is going to turn out to be a tumor, or a tumor was definite. Everything goes along with the tumor as the causal epileptogenic lesion and things are concordant. Then we resect that tumor to normal margins and as I said, and we don't necessarily pay attention to electrocorticography. If however, this is a non concordant and does not, and everything does not line up, again, one needs to obviously study the patient, both for onset of the seizures to make sure that your diagnosis of the oncological diagnosis is correct. And of course, to malfunction. Let me emphasize that we will, we are commonly doing most of our dominant studies with the grids and the electrodes and doing language mapping in the epilepsy unit and not necessarily as an awake case. Certainly those situations come up when patients have a known tumor. It's sitting in your lateral cortex of the dominant temporal lobe and everything's concordant and you're gonna do a resection, then you'll do that away. But otherwise, if you have to study the patient, you can just study language at the same time. Now if just the tumor it is not clear, but it's a tumor or a developmental abnormality, oftentimes the clues to that on are more distributed, more psychological abnormalities, and the difference in EEG onset. But if you're epilepsy surgery program evaluation is concordant, then one may follow one or two loads here. You can biopsy. We know that if this is a tumor, then circumscribed resection of the tumor cranial margins would give you the best control in the long run of the tumor and control of the patient's epilepsy. If however this turns out to be a developmental abnormality and then, because this is the tip of the iceberg frequently, once you do an intracranial study to define the ictal onset, and it is the ictal onset which is critical to resect along with the structural lesion itself. So if you see an intracranial study that the seizures begin on the edge of an area of cortical dysplasia, one can not remove just that region, but you have to remove all of the pathological substrate, along with anterior ictal recordings. And cortical dysplasia, just let me add here is the one place where that rule of electrocorticography not being helpful, fails. In fact electrocorticography may be very helpful in cortical dysplasia because of the sort of seizure-like signature on that one scenes in electrocorticography. And we talked about if we know that this is tumor and it's in functional cortex, then one should do neurosurgery. If it's in the temporal lobe, obviously with language mapping and if it says in other functional cortex, primary cortex, such as motor sensory, then one can do this with stimulation during surgery and you don't necessarily have to do it awake.

- And this is very helpful, I think, as a decision tree and just wanna emphasize again, that the north threshold for intercranial monitoring for cortical dysplasia, although one sees that T2 signal change or hyperintensity on FLAIR, the epileptogenic volume is usually much larger and seizure freedom improves significantly the chance of it, if you can do intracranial monitoring to define the ictal volume and really the true epileptogenic. So thank you.

- And then here, if we best move on to the intracranial monitoring substrates. So if we have a developmental or gliotic substrate, or we don't see anything on MRI and it's very... These days, it's in fact, very common for our studies to be in patients with neocortical epilepsy, without an MR abnormality. And that's a whole different talk in discussing your cortical epilepsies, obviously. But we're concentrating on the temporal lobe at the present time and when we can define that the temporal lobe is the source, but we don't know whether this is lateral or medial or how much of the temporal lobe is involved, and one is doing an invasive study with localization to the medial temporal lobe structures. And your study should be designed to look, as we're gonna talk about later to look at the network of the temporal lobe. It's not sufficient in an intracranial study these days to put two or three electrodes in the hippocampus and look at the neocortex. one really must put your strips in a fashion that will look at the two most common networks of our temporal lobe. That's temporal occipital network and the temporal frontal network. So you need to cover a frontal lobe and you need to cover occipital lobe, when you're concentrating on an invasive study for temporal lobe epilepsy. Once you've discovered that this is medial temporal lobe in onset, and it's non-dominant one can move to enter medial temporal resection. And particularly, if it's in the dominant hemisphere, this requires verbal memory be down by at least two standard deviations in R sharp anyway. And there's good verbal memory with onset in that dominant medial temporal lobe are all our paradigm at the present time is to put them out those patients on our list for a responsive stimulation when that device, the responsive stimulation devices are approved by the FDA. And these are the group of patients that did best in the clinical trials for stimulation. Our first line of treatment would be stimulation rather than to move, to remove normal dominant hippocampus.

- Thank you.

- This slide just describes the subtypes that I've alluded to, the paradoxical temporal lobe epilepsy, medial temporal lobe epilepsy is one of what you have a normal working hippocampus on MRI normal volume metrics if you measure those. And when you study them pathologically, only 25% of cell loss, however, electrically, the seizures have been done in the hippocampus. One must be more careful that this may be just part of a network of seizure onset and that with resection of this, your results, which are usually around 70% and control may drop down to between 50 and 60%. And then there's neocortical temporal lobe epilepsy, which is lesional versus non-lesional and that's pretty straightforward, as we've talked about the lesional substrates in the past. And then dual pathology is very interesting. Most of dual pathology is in fact, cortical dysplasia in the neocortex and hippocampal sclerosis medially. And the literature is in favor of certainly removing both the neocortical pathology and the hippocampus, but you have to have, of course, the caveat that if that dual pathology involves a normally functioning hippocampus, then you have to be aware of the consequences of removing the dominant functional hippocacampus. But otherwise, when you see dual pathology, it means you need to address both the neocortical and the hippocampal changes. And this is just a slide I was talking about with the paradoxical medial temporal lobe epilepsy. And so we can move on and just note that that is certainly a category in and of itself, and it's certainly worthwhile onto resect is hippocampi. You just have to be aware that their seizure control it's not as good. And this is a case presentation of somebody with paradoxical medial temporal lobe epilepsy, a 51-year-old female with complex partial seizures since 37. So she doesn't have the classical history of a febrile or injurious seizure under four, and then onset in adolescents of, or complex partial seizures. She starts later on in life, and so that's certainly a red flag that this is not gonna be typical. Here is just a portion of a study. As I said, when we studied these patients with intracranial electrodes, our 3D map would look like an entirely new critical coverage with a grid of the temporal lobe along with strips that cover the temporal lobe and look at the network of the occipital and the frontal lateral cortex. And this just illustrates that we have two electrodes in the hippocampus. Now, just as an aside for the last 20 some years, we've also measured micro dialysis in all of these patients and now have a robust findings in about 100 patients that we put together demonstrating that glutamate, the excitatory neurotransmitter is always elevated in the epileptogenic region. In normal EEG, our physiological regions it is normal, which is two to four micrograms. And interestingly enough, it is also elevated in the first node of a projection. So for instance, it could be 15 or 20 micrograms in the hippocampus here, and might be also elevated even a little bit more in an occipital region that was the first projection. So that is some interests. This study would be coupled along with grids on the outside. And if we locate the seizure coming from absolutely the hippocampus, then our decision to resect it would be dependent upon neuro psych testing. This is just an illustration. I think it was down here and this is an illustration of at least two different kinds of strips that you can use to study the basal region of the temporal lobe. This is the more common strip that I use with the anterior medial strip that follows the sphenoid and almost always reproduces this same pathway and provides for you a just robust EEG of intrarenal cortex, and then reflects both amygdala and hippocampal onset and gives you the ability to look along the length of the pair hippocampus, as it overlaps to a fusiform. This strip covers the fusiform area, certainly better and can be used for basal language mapping on the left side, now which is really not that well-understood the significance of basal language, but certainly, can be a problem in recording because of the dural pain that comes with stimulating the basal electrodes.

- I would like to mention something about the electrode that you just discussed, and maybe leave a little bit detailed for the viewers. This really works beautifully, and sometimes may even replace using depth electrodes if you have a difficult time putting one in is that, as you're working on the craniotomy site to pass this one by 10th strip parallel to the superior temporal gyrus, it follows the anterior temporal tip. And as you sit invariably, ends up right where you want it to be because of the tentorium and the dura along the middle fossa. So, not many people know about this trick and it's really a beautiful trick I learned from you, in terms of passing the strip just parallel. And you really don't know where it's going because obviously, the craniotomy that's open is right here. But I've never seen it end up anywhere else, but just exactly where you want it to be. So I really encourage our viewers to try it. I think it's very safe. You have done it for many years, we brought it up as a technical note together, and I think it's under utilized, but it's a great technique. Thank you, and please go ahead.

- This is just an illustration of a lateral strip. We would probably in looking, as I said at the network these days, we would have a grid, eight by grid that would cover frontal and temporal lobe. And specifically, of course, you would have that a grid on the dominant side so that one could follow up your ictal onset with language mapping. And then we would also use strips that would go from a poll, of the, we now use an orbital strip that is a little bit like the anterior medial temporal strip in that, the orbital strip almost invariably crosses the falx and allows you to study the contralateral frontal lobe, maybe a little less consistent than the anterior medial strip. But over the last couple of years, I have not seen it not go through the falx or under the falx and allow you to study the contralateral frontal lobe. So that's just another strip trick. And then some strips around the occipital lobe, a strip that goes just at the division of occipital and temporal lobe and directed slightly posteriorly, almost invariably also will occur under allow you to cover the posterior fusiform face area or language string sign area on the dominant side, and will then curve up and provide for study of the medial electrode right here at the tent. And usually, either just a posterior to the vein of Labbe and invariably will allow coverage of medial occipital lobe along with a fusiform region. And this is just a poster and this is an older post-op illustration, or how one can locate your electrodes on a 3D surface. We now, or given 10 years ago, we spent about five to six years developing a BioImage Suite, which allows us to do 3D formulation and placement of electrodes and all of your dynamic studies on a 3D brain and take that back to the operating room so that you can identify anatomically where each of these electrodes are. But there is a good illustration of the intra-medial strip, a grid of usually larger proportions in this. And then we'll often use three or four frontal in three or four occipital, plus this posterior temporal occipital electrode that I talked about before. It's just another illustration that Aaron spoke about the anterior medial strip. I've just recently, after hundreds of patients, we had a patient about three months ago where I could not get the anterior medial strip to follow this pathway. And in fact, this was a patient that we were trying and we were looking up for peculiar temporal versus frontal lobe epilepsy. And we discovered in our recordings that the strips that we can not get around the temporal lobe, our electrical onset was, followed clinical onset. So we were obviously not in the right place. I took the patient back and put a two depth electrodes in the temporal pole and the seizures were coming from this anterior medial temporal pole. And there were adhesions, basal adhesions that had restricted this electrode from going in its usual category. So if it doesn't go, you might think that there there's some pathological lesion. So neocortical temporal lobe epilepsy is certainly or must be aware that not all temporal lobe epilepsy is the temporal lobe epilepsy in about that. Like other areas of the neocortex that may follow in proportion to the volume of that lobe maybe lesional or non-lesional and often has the same sort of limbic onset as medial temporal lobe epilepsy. Although in some instances, you may see more early motor involvement, you may see head turning, or you may see whole body spinnings perhaps. And I think one of the key is to being able to predict for patients, their outcome or a resection of the temporal lobe epilepsy is this finding of secondary generalization. So somebody who has frequent secondary generalizations besides having a complex partial seizures runs an additional risk of not responding to resection and it drops their outcome percentage from about 70, to again, about 50 or 60. They follow the same sort of outcome as paradoxical temporal lobe epilepsy. This just illustrates an observation we made several years ago. And if you do volume metrics of the temporal lobe and you see a decreased volume of the whole ipsilateral temporal lobe, that's a clue that you're going to find neocortical temporal lobe epilepsy and not just medial temporal lobe epilepsy. So those with the most significant atrophy of the temporal neocortex that the whole temporal lobe will feel better than those patients who have normal volumes. We've talked about lesional temporal lobe epilepsy. They do represent a significant portion of those patients presenting with seizures, but probably represent, as I said before, less volume of cases or the epilepsy surgeons that they're seeing earlier. Certainly, the developmental tumors are very epileptogenic. Gangliogliomas, DNETs, and all of the cortical developmental abnormalities, and vascular malformations that you see a highly epileptogenic. Now on the occasion that we have, had the opportunity to put a micro dialysis catheter in cortical dysplasia, which is more common than in a tumor, which is studied less frequently. We see the highest levels of glutamate that we see in any pathological substrate. So you may see 100 to 150 micromolar glutamate in a patient with a tumor or with cortical dysplasia. There so, it is uniform that this rudimentary is elevated in epileptogenic substrates. I've not seen one epileptogenic substrate that's not had an elevated glutamate, which is probably reflects the pathology of the glial that are supposed to handle glutamate uptake. So when we were talking about paradoxical temporal lobe epilepsy, but also the tumors and other developmental lesions certainly may look just like medial temporal lobe epilepsy. And our goal in resection, as I've said before, is to remove the lesion because the seizures, as we've demonstrated in studies in the 1980s, seemed to come from the edge of many of these lesions. So you need to have normal brain as the margin of your resection. And if you have that, you're going to have the best control of lesion and best control of the epilepsy. And this just reaffirms our feeling about preserving the normal dominant hippocampus. And in fact, this particular subject is somebody with a lesion that we thought might have a dual pathology because the seizures were so limbic in nature. And the EEG pattern was more like medial temporal lobe epilepsy in neocortical epilepsy and this peculiar lesion prompted us to say, "Well, we have to understand that the medial structures are involved because this is the dominant temporal lobe." And so we did a study this patient with depth electrodes and interestingly enough, the depth electrode in the lesion showed a glutamate of over 100 and in the hippocampus, the glutamate was normal and the EEG onset was certainly sparing of the hippocampus. And so the lesion was removed and the hippocampus was spared with excellent seizure control. And this is the resection with now, probably 10 years of seizure control. This is just an illustration of tumors for whatever reasons. When look at the volume of the temporal lobe and the frequency of our tumors that are associated with the intractable epilepsy, it seems that the amygdala is a favorite origin for these seizures. And we have a number of patients with the pure amygdala, developmental lesions and developmental tumors that respond to resection locally. When you to talk about, when we do our technical piece of the temporal lobectomy, it is really critical, obviously in these patients with amygdala tumors and anterior hippocampal tumors to be able to remove all of the amygdala, right up to the basal ganglia region and to the diagonal band of Broca, because your control of seizures depends your resection of all the tumor. And we know now from long literature that our best control of these low grade tumors is also dependent upon a good resection. Just another illustration of right medial temporal lobe tumor. This is a slide about dual pathology. We have talked about this a bit before illustrating that if you have dual pathology and the function of the hippocampus on the dominant side is down or if it's a non-dominant side that shows hippocampal atrophy, one needs to remove both the hippocampus and neocortical pathology. The bilateral hippocampal atrophy patients are very, very interesting. This is found, maybe 20% of patients. Although, I think if you look carefully with volume metrics, you see contralateral hippocampus changes in more than 20%, perhaps 50% of patients will have awesome changes in the opposite hippocampus. And we may see bilateral seizure onset even than monitored intracranially. One can make a decision about whether the patient is a candidate for resection of one of those temporal lobes, actually not based upon which hippocampus is having the most seizures. That is not the best criteria, but if one uses the criteria that the most sick hippocampus, the one which is most functionally affected, if one removes that, you get very close to the paradoxical temporal lobe epilepsy seizure control, around 50% of control. And I think that that was a bit enigmatic when we first described this in the '80s and early '90s. However, as we now understand better the network of epilepsy, we understand that we may in fact be successful if we resect some of the nodes in an epileptogenic network and that that network probably follows functional networks. And in the case of the medial temporal lobes, the hippocampi are tightly connected. When you see seizure spread from one hippocampus, it predominantly will go first to the opposite of hippocampus, almost simultaneously to the neocortex of the ipsilateral temporal lobe. But this is a very important phenomenon that one should pay attention to, that if you do intracranial study and you have one hippocampus that is just devastated will not potentially lead to a neurological problem with resection. Then despite the fact that seizures may be coming from both the temporal lobes, removing the functionally dysfunctional hippocampus may lead to control. And this brings up of course, the issue of contralateral functionality. And if you removing a very dysfunctional hippocampus, but the contralateral temporal lobe can support memory and is functionally better, then you don't run into the worst of all possible outcomes, which is, you don't get control of the seizures and you cause a cognitive deficit, and that is to be avoided. Certainly, that leads to very unhappy patients. Just an illustration, as you can see bilateral hippocampal. After they looked at both in this case you don't even need to do volume metrics, you can see with naked eye. And so I think that the evolution in understanding temporal of epilepsy has certainly changed over the years. It's the one form when everything lines up that is unchanged in terms of its outcome for many, many years now. In some respects, we've not improved our ability to change outcome, regardless of how one approaches the medial temporal lobe for resection. And we have a long way to go to understand the network of the medial temporal lobe and understanding the relationship of neocortical temporal lobe to mesial temporal sclerosis. So we continue to have a lot of need for you searching in this area. We're at the present time looking through the American Epilepsy Society, the changing patterns of epilepsy surgery. I think that most institutions have seen a significant drop off in the surgery of medial temporal lobe epilepsy. And so at the present time, we're trying to look into what does this mean? Does it mean that there are more smaller centers that are doing mesial temporal resections? Actually, I have control of cortical seizures change the epidemiology of medial temporal lobe epilepsy is the entity, is the syndrome actually disappearing and leading to fewer surgeries. Or have the newer, we have 13 new medications in the past 12 years. Have some of those medications actually made a difference in control of these patients?

- Dr. Spencer, thank you for a spectacular talk. We ask our viewers to also please review the second session, will be discussion of ticker neurosis or antrum medial temporal lobectomy and selective amigo hippocampectomy. Thank you.

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