Good afternoon, and thanks for your attention. This is Rich Barn. I'll be talking to you about brain tumors and epilepsy, particularly in regards to mesial temporal lobe tumors. These are my disclosures. So I'm going to cover the problem and the opportunity of mesial temporal tumors and epilepsy efficacy in treating this, talk about why we have lesionectomy failures, talk about approaches, and then I'll talk about surgical safety. As a general rule when we're talking about epilepsy surgery, positive factors for deciding on epilepsy surgery are high frequency of seizures, good localization, lesional, younger patients, and already having neuropsychological deficits from the lesion that you're operating on. And the negative factors would be the opposite. It's important to know a couple of important studies. This one by Kwon and Brody proved that we could identify early on who would be refractory in epilepsy. So we really only needed two or three medical trials to determine that. And then this trial published 20 years ago was our first randomized controlled trial of epilepsy surgery for temporal lobe epilepsy, proving that surgical therapy was better than medical therapy and medically intractable epilepsy with a lesion, that lesion in this study being mesial temporal sclerosis. What we're talking about today is tumors, which we are going to extrapolate from this data. So as far as our outcomes go from a seizure standpoint, comparing mesial temporal sclerosis versus mesial temporal tumors, we took a look at the literature, we took a look at our outcomes, and they're about the same. We're talking about for low-grade gliomas as they are for mesial temporal epilepsy, just so long as you get a gross total resection of the tumor. So how is surgery in the limbic system different? Well, there's different pathology, embryology, cortical structure. There's stereotypical tumor growth patterns that we see. And then there's complex regional neurovascular anatomy, which is less familiar to general neurosurgeons. And we have to remember that the limbic system, the mesial temporal lobe is connected into the limbic system, which continues around as the cingulate gyrus and also the olfactory system and the hippocampus on the left and right connect via the hippocampal commissure, as we see sometimes happens with spread from one hippocampus to the other of tumor and epilepsy. So when we're deciding which patients to operate on, these patients who have mesial temporal tumors and also have epilepsy, I think this is a reasonable paper that just sort of laid it out here. It really depends on how aggressive the tumor is versus how bad the epilepsy is. The more aggressive the tumor, the more likely you're going to offer surgery. The more aggressive the epilepsy, also the same. And then there's the glio-neuronal tumors, where we really proceed if we think that we're less likely to hurt the patient with surgery than with persistent seizures. And then we go for gross total resection if we can. This paper, I think, is an important addition to the literature, just talking about the extent of resection, which predicted in their series seizure freedom in low-grade temporal lobe tumors. Looking at the data, you can see that the more tissue you took out beyond a lesionectomy, if you took out the hippocampus, hippocampus plus cortex, you're more likely to be seizure-free. But you certainly had to at least get a lesionectomy. It's also interesting to note that using electrocorticography did not seem to matter. This is consistent with our experience with chronic epilepsy associated with low-grade tumors in the temporal lobe. And taking a look at our outcomes at the mean outcome past seven years, the vast majority of these patients do very well with a resection plus the epileptogenic tissue around. And this is true in our larger series of over 200 patients. Complete removal of the tumor or hippocampal sclerosis predicted in English class one very clearly. We had no major neurovascular complications in this series. But low-grade tumors tend to do very well with resection from an epilepsy standpoint. One caveat to that is they may retain their aura. Remember that an aura, unless it's an aura of panic, is usually not a disabling problem. Whereas patients with retained aura do very well from a quality-of-life standpoint. Let's talk about approaches. So the most direct approach to the mesial temporal lobe is just an axial straight-in approach transmittal temporal gyrus. This is one of my favorite approaches if there's no easier way to get to a lesion. This is the transcortical axial approach right there. You can see a small incision, small transmittal temporal gyrus approach usually gets the job done. We can also, on the dominant side, go sub-temporal. You can put a lumbar drain in and come in sub-temporal through the fusiform gyrus. Or we can go trans-sylvian or trans-lumen insula, as in this description of the anatomy. You can get very large tumors out with this approach safely. So I think this is a good paper talking about resection strategies and tumoral epilepsy and just going over the issue of, is lesionectomy enough? In this discussion, what they found was complete resection of tumor and epileptogenic zone tended to lead to no epilepsy failure. Residual margin of irritated epileptic zone or residual lesion or recurrent lesion tended to lead to recurrence. So why do we have failures of epilepsy when we do lesionectomies in the mesial temporal lobe? Why would some of these patients continue to have seizures? Well, they may continue to have tumor that may go up through the basal ganglia, through the amygdala into the basal ganglia. Remember that the claustrum is deeply connected through most of the brain, or they may have persistent seizures from the tail of the hippocampus, should that be left. Remember this is a very complicated area, so just taking out the amygdala and the hippocampus doesn't necessarily disconnect all of the connections of the mesial temporal lobe, as we can see here. And then it is very, very deeply connected brain. So the limbic system, as we found out when we did stimulation from Neuropace, is very connected, not just regionally through the lobe and the mesial temporal lobe, but also through the claustrum extreme capsule to the other side through the hippocampus. So how about the pathological hippocampus? What about pathological hippocampus in memory? If you have a case like this, in this right mesial temporal sclerosis case, and if all of the data is concordant to the right side, if the patient truly has hippocampal sclerosis, their neuropsychological data will likely prove that that right hippocampus really doesn't work very well, if at all, and that taking it out won't make a big difference. This is not quite the case on the left side, where it's a little more complicated, but if the hippocampus is already deteriorated, it's less likely that the patient's going to notice any difference from neuropsych testing. We came to understand the importance of the mesial temporal lobe through the case of H.M. This is actual imaging of H.M. later on in his life. You can see that Scoville only took out the anterior portion of the hippocampus bilaterally. Obviously, you can't do this bilaterally. We learned this through H.M., but the posterior portion of the hippocampus was still there, but H.M. was amnestic for the rest of his life. This proves that just taking out the anterior portion of the hippocampus will possibly make a neuropsychological deficit. You can see this is the approach that Scoville took in H.M.'s case. How about factors about resection of the hippocampus? Positive factors about taking out the hippocampus would be if there's tumor involvement, if there's hippocampal sclerosis, chronic epilepsy, poor memory scores, and if the contralateral hippocampus is normal. The negative factors would be the opposite. Sometimes you'll run into cases like this, where there's what appears to be a DNET on the left and a hippocampal sclerosis on the right. These are more complicated cases. In our experience, when we do a right temporal lobectomy for somebody who has hippocampal sclerosis, as you can see here in the dotted line, if you compare the neuropsych scores at zero here with improvements being above and worsening being below, it does appear that immediate memory in some of these patients may get a little better because they're having fewer seizures, and then delayed memory maybe not so much. But the patients who have hippocampal sclerosis overall tend to be less affected than those who don't have hippocampal sclerosis, as you can see. And this is a more profound effect on the left side, where patients who don't have hippocampal sclerosis may notice significant changes in their immediate memory. It's also true that the more you do of this, the more safely you can do it. This is data looking at the relationship between hospital surgical volume for epilepsy surgery and perioperative adverse events. You can see that there's a decline now in high-volume centers and a rise in middle-volume centers. In general, the best outcomes from a safety standpoint seem to be coming from the high-volume centers, as you can see in the stroke and neurologic complication category here. So as far as keeping it safe, what are the pointers for keeping mesial temporal lobe surgery safe for a tumor or otherwise? I would just follow these points. Open the ventricle inferiorly to spare the optic tract. Identify anatomical fiducials within the uncus and the ventricle. Identify the mesial resection, sparing the mesial temporal pia. And then identify the endorhinal axial line. The endorhinal axial line is the chordal fissure to chordal point, vellum terminale, intralimbic gyrus, endorhinal sulcus, lumen insula, and M1. And then the hippocampal resection should spare the mesial pia and disconnect from the hippocampal sulcus, the hippocampal perforator, posterior cerebral artery. Where people go astray here is typically around the amygdala. As you can see, there's no stop sign for the amygdala. It just merges into basal ganglia. And then you can see the optic tract, just mesial there, and the anterior choridal artery. This is where a lot of the morbidity comes from this operation. So it's very important to understand this area and how to operate there based on surgical landmarks. It's also important to understand the embryology. The embryology sets the stage for the anatomy. It's true that in a 12-week embryo, the human embryo will have the hippocampus dorsal. It's actually dorsal and above the thalamus. And then by the 22nd week, most of that tissue migrates into mesial temporal lobe, causing the upward and medial migration of the uncus and leaving these connections. So the hippocampus then connects to the fasciolar gyrus, which then connects up to endosymbresium above from where the embryological remnant is. Most lower mammals still have their hippocampus dorsally, which is why we can put depth electrodes into mice from above. This is what it looks like here on MRI imaging. So it's all of these C-shaped arcs. And it's just very important to understand these arcs, the importance of the choroidal fissure, which outlines the C-shaped arc. It's important to understand that limbic just means bordering on the diencephalon. So a couple of pointers here. The endorhinal sulcus can be seen just above the uncus and the amygdala. It's an important surgical landmark. And then identifying the inferior limiting sulcus of the insula is also an important surgical landmark. And then more posteriorly, you can see the relationship of the hippocampus to the choroidal fissure. And finding the choroid plexus allows you to find that. And then just above that will be the lateral genicular body. Here's what it looks like during surgery. If you look in an axial plane, you can find M1, draw a line posteriorly from there, open up the ventricle, and then identify the choroidal fissure. You can see the choroid plexus there. Empty the intralimbic gyrus, which is the posterior most gyrus of the uncus, and then the amygdala will be between M1 and the line that we've drawn here in the choroidal fissure. So here's a couple of limbic tumor case examples. You can see a little bit of residual tumor here in this patient that was medically intractable. She'd had surgery approximately 20 years earlier at another institution. It looks like they had a perforator event there, and she had a hemiparesis from it. But there's a residual hippocampus residual tumor, so we decided to go in and take that out. And this is what that looks like from a cadaver standpoint. You can see that relationship here between the head, the body, and the tail of the hippocampus, the choroidal fissure here, and then the thalamus just above. Very important to preserve those perforators at the roof of the choroidal fissure. And then during surgery, it's important to identify the intralimbic gyrus between the head of the hippocampus and the amygdala. This is a key spot because when you take it out, it's very thin, and you'll be able to identify the ambient cistern just below. So this is what it looks like during surgery. You can see the amygdala just in front of our retractor, having opened the ventricle. We identify M1, and then we take the amygdala out in that axial plane. These landmarks will keep you out of the anterior choroidal artery and the optic tract. Here we are taking it out with CUSA. And then more posteriorly, it's just a matter of mobilizing the hippocampus off of the hippocampal sulcus in a way from the perforators coming out of the posterior cerebral artery. Here we've identified the body of the hippocampus. We've elevated the roof of the ventricle. And then we spare the mesial pia there and leave the posterior cerebral artery alone, other than detaching the perforators and the hippocampus. Here's a case example. This is actually a limbic tumor. It looks like it might be a basal ganglia tumor, but it's a limbic tumor. It's all maintained below the coital fissure. You can see here on the coronal, you can identify the temporal horn there coming up over the tumor. So the tumor is actually below the ventricle, unless it's a limbic tumor, it can be resected safely. Here it is afterwards. We've gone through a small window in the anterior temporal lobe to take this out safely. And this is what it looks like at the end. We can take out very, very large tumors this way. Here's a 12-centimeter tumor, and this is important to see because this was a high-grade glioma. We were able to take out all visible tumor, and this person is still with us and working about 15 years after surgery. So in conclusion, the connection between mesial temporal lobe tumors and temporal lobe epilepsy is fairly obvious. For higher-grade tumors, we obviously have to be very aggressive about the tumor and think more about the tumor than the epilepsy. For the lower-grade tumors, if we can get a good, complete lesionectomy, we can monitor from the hippocampus and decide whether or not the hippocampus needs to come out as well. And then we need to do it safely. So all of these pointers about mesial temporal lobe anatomy and safe surgery I hope will be helpful for you. Thank you.

brain tumors

epilepsy

mesial temporal lobe tumors

surgical approaches

safety precautions