New techniques have not only made treating seizures safer but can help kids understand what’s happening in their own brains. Pediatric neurosurgeon Kurtis Auguste, MD, discusses using the latest tools to localize seizure foci, plan and perform procedures, and educate patients. Bonus: help figuring out when it’s time to consider surgery and an update on neurostimulator devices.
Thanks for joining uh like to talk a bit about how things have changed in my practice over the past 12 going on 13 years now where we've been changing how we manage epilepsy patients specifically how we image and how we treat them in the operating room. Uh We are in the midst of an evolution of sorts being much more sophisticated with how we we investigate these parents, these patients and and much less invasive with how we treat. I want to kind of share with you some of the more recent advancements. Mhm. So we have some objectives to cover for the evening. I provided them ahead of time and you've probably seen them already. But I wanted you to be able to differentiate among some of the different imaging modalities we use for seizure focus localization by the end of the talk. Um I want to show you some of the minimally invasive techniques that we're using right now diagnosed to treat the seizure faux side that we find. Um I'm looking forward to you guys seeing how some of our advanced imaging techniques are being used now to plan for surgery, to train our residents and medical students um and also to engage our patients in a much more meaningful and fun way. And I want to show you how we're using some of these tools to communicate all this information. A lot of it's really complex. We're talking about three dimensional anatomy. It's really hard to communicate those things with traditional, more traditional means. Um and some of our advanced techniques can really cross barriers of race and ethnicity and educational and socioeconomic status. So, um, um, this is really what we're gonna try and cover here. My disclosures I felt obligated to before launching into the advances. Just the few words about childhood epilepsy, because these are these are common questions I'm sure most of you get and I I still get even though I'm in a coronary care facility and by the time patients see me there are pretty much ready for surgery. But I think it's important. We kind of take a step back and rewind a little bit and answer just some very fundamental questions about childhood epilepsy before they even get to me, just to kind of help you along the, along with answering those questions as well and your practices. So, let's start first by just talking about the natural history of childhood epilepsy. Because the question comes along a lot. What's the likelihood? You know, johnny's had his first seizure? What's the likelihood that he's going to have a lifetime of seizures? and so this is a study from 2000 and That followed about 150 patients. And they showed that about 30% of patients enter a mission in that very first year of being treated for procedures. Um, almost 20% of these patients are resistant to any kind of medication from the very beginning. But overall two thirds of patients will eventually achieve terminal remission will eventually stop seizing their childhood epilepsy will end. And of that two thirds of the vast, 86% of them won't need any meds to stay seizure free. So the good news here is that just because you had some seizures as a kid and maybe you've had a couple and you actually required medications that you actually stand a good chance. Oh, effectively outgrow your epilepsy and won't need to have medications as you get older. So, that's the good news for a very worried that the parents who our managing seizures for the first time. Yeah, a common question that we get is, alright, so, I'm on seizure meds, um, and they're not working. So should we just keep trying? Maybe we go into the second or the third? And this is actually a paper out of the new journal from 2000 That is close to 500 patients. And it showed that after the first drug, more than half of them were still having seizures. And then if you look at the population that we don't have a second drug, 40% of those patients will still have seizures, um, third drug, 36%. So you're getting diminishing returns with each drug. And so what I often tell patients is that once you've started drifting into the 2nd and 3rd drug, the expectation isn't really that a 4th and 5th on trials is really going to make much of a difference. In fact, it's less likely as you try more and more. Another question is um okay well um we have had medications were still seizing. Do I really really need surgery and to answer that question? Um We really only think about surgery for patients who are medically refractory. Um Where despite the medication trials they're still seizing. What would we use this criteria for failure. So for us if a patient's tried to trials of one drug or one trial of multiple drugs then in our for our intents and purposes they are kind of inching their way into this medically refractory status. Um And the studies have shown that About 5% of patients only we'll have six months, three seizure free periods with each additional E. D. trial. So that's 90 patients won't even get to six months of seizure freedom with the with the additional medication. So um for our purposes, once you get past that second that second med or that probably that polly trial you're medically refractory and we should really stop. But I'm surfing. Mhm. So um you now have gotten to the point where you don't feel you've outgrown your childhood epilepsy or the side effect profile from the medications is very high or you've tried and all the drugs and you failed. Um We are thinking now more about surgery. Well how do we get to a point where we can consider someone a surgical candidate? Um So the very big question that we have to answer is where where the seizures are coming from? And so we have to employ a series of tests to answer that question. And the most common of course is gonna be the E. G. And um as you might imagine, where we're gonna sit with these patients for a little while to understand geographically, where do we think the seeds are coming from? Um It's not enough though to just listen to the the electro physiology of the brain. It's very important that the first tier that introductory pass of regulating these patients should involve a very good quality MRI. And most centers now have access to three. Tesla MRI is 1.5 is the first preliminary passes is typically sufficient. Um And the MRI is gonna look for allegiance. Is there some kind of tumor? Could there be some kind of focal focal cortical dysplasia or distortion of the grey white junctions? Just something anatomically that would explain um why this patient is seizure. And our hope would be that if we see it actually co localizes to where the electro physiologic abnormality was on the E. G. Um If you have things that are starting to line up uh and you still have questions about the extent of the the location of the seizures source, then there's a second tier of testing and this is these are some of the typical tests that we use at UCSF. Um The pet scan and spect scan are basically physiological tests to look for changes in metabolism. Um And those changes in metabolism light up differently on the screen. And those will be indications of where the seizures are coming from. So the pet scan and spect scan are tests to look for where the seizures are coming from. So when when we're answering a question where we don't want to just know where is the seizure coming from? Where's the bad brain? It's also pretty important that we answer the question. And to do that we have to start testing the brain to see where the what we call eloquent cortex is or the functional cortex is. And for that purpose we employ functional mris for patients who can participate and we actually have them do tasks in an MRI scanner. And as they are using those those parts of their brains, those parts of our brains physiologically light up they their metabolism increases and so we can label those parts. And then another way to kind of physiologically answer where is the good brain is with an M. E. G. Scan or a magneto and settle a gram. And the M. G. Is nice because you can not only test for function in these uh scanner. You can also answer the question of where, where this is coming from as well. So I'm not going to show you the images of pet scans and spect scans again, those are just a physiologic bright and dark spots that we're looking for. And uh the honest truth Pet and Spect scans alone aren't enough to guide me, a surgeon to the very precise spot of where seizures are coming from. And I can't plan a surgery solely on a pet or Spect scan. So I won't go into any detail about those, but I just want to kind of uh spent a couple of words on an FmRI in a mexican. Um This is just a little bit more background on for the first year pre surgical video E. G. S. Um This is for the purposes of prepare to, you might see in clinic about, well, you know, if we go and we get a longer video, E. G, or 3 to 7 day inpatient admission, what's that going to look like? Um That's for the patients who don't seize very frequently, um and may need a little bit of help to coach their seizures out So to do so we want to have them admit it. We in their medications, perhaps we may actually also want to sleep deprived them. We basically want to, in effect provoke them to have a seizure, but we want to do it in a controlled setting like that. And so we would often admit them, and it's essential because when a patient sees is the way that that seizure manifest the scene ideology of that, that seizure can be a tip off as to which part of the brain is actually involved. Um And so we want to get many of their typical seizures as possible. Not something that's kind of a flavor of their seizures, but it's their absolute a stereotypical seizures because that's the one that's most accurately gonna tell us hopefully which side decisions are coming from but ideally which region are part of the brain is season. So um um to complete the the comprehensive evaluation of a pre surgical work up, um you see, we we also add the nurse to see where patients baseline deficit strengths and weaknesses are. Um It can also give us an idea of how well are they going to tolerate surgery. Some of the neuropsychological tests will tell which parts of the brain are most involved with their functions. And by doing surgery in those, those loads, we may actually create some processing problems or concentration problems or memory problems. Um It also helps us tell, helps tell us if we have to do mapping on these patients bring room or outside of the operating, how cooperative would they be or how successful would that testing be. And then obviously if we have a baseline understanding of what their strengths and weaknesses are before surgery. Hopefully after we are able to do a surgery, we can do the same time and monitor some kind of improvements. Um If for example, we have localized or partially localized someone seizure focus to their speech centers. We really now need to know how close to their their speech centers. Um to do that we do language assessment um with a classic test called the water test where it's an invasive testing effectively put half of the brain to sleep while we're asking patients to do language testing. Um one side at a time. Um And it's true it's using an interventional radiology technique. Um Less invasive means which we're using more and more again involved the FmRI and the M. E. G. Which I want to tell you about now. So here are just some pictures. Some examples of what these machines look like patients are lying either in their MRI scanner and they are given a button to uh signal when they are answering questions appropriately. On the right is a picture of an M. E. G. Machine where that little cut out on the on the top pieces where the patient's head fits. These are non invasive tests. They give you the ability to do the test multiple times to confirm your findings. So you can pass with multiple trials and get a really consistent data. Um We obviously want to try um uh two lateral eyes where patients problems are um But ideally if we can localize and get much more specific. Um we'd love to do that and it's nice to have FmRI is for localization and lateralization of language and mdgs for seizures and function the weaknesses that um these machines will show you which parts are involved but not really how how involved are there. it doesn't really differentiate, differentiate between what's necessary versus sufficient. Um And so that's a bit of a drawback. So we don't typically just rely on Fmri RMG data to to tell the whole story. These are tests that are kind of adjuncts to the other tests that I mentioned. So this is an example of what a functional MRI um scan looks like. Um The very vivid, colorful pictures where a patient is doing a task and those elements of the brain light up um corresponding to the parts of the brain that they're using. So on the left are all those areas, those pertinent areas lighting up on two dimensional slices. And as you might imagine we can then take all these two dimensional slices and line them up and construct on the right a three dimensional model. And then this these three dimensional models are much more pertinent to my world where I have 23 dimensionally plan and in my mind's eye rehearse surgery and and and this this kind of three dimensional. Ization is really key in and optimizing. Um when when we go to the operating room. So this is this is someone's speech cortex for an F. M. R. I. Um The next set of images of M. E. G. Um And what an M. E. G. Does is it it takes advantage of the fact that when neurons fire they they create a distortion of a magnetic field distortion. And these tiny little devices called squids can detect those distortions and so every time a function happens in the and the appropriate neuron fires these little squids detect those distortions. So that's a way that we can design tasks to map their motor cortex. We can map their sensory cortex. Um We also have modules for auditory and visual cortex. Little by little. We're understanding language mapping better with MGs. I wouldn't say that it's the gold standard by any means but those paradigms are evolving. Um It's a nice way by the way to not just map the brain functionally but we can also run an E E. G. Simultaneously and we can map those E. G. Spikes in addition to those pertinent areas of function on the same pictures. And all these pictures can be added to what's called frameless steri, ataxia or neuro navigation. And I'll show you what those are those. This is a very very useful. It's basically the standard of care in a contemporary neurosurgery, operating room. Euro navigation is key. So MG scans and FmRI scans. Both of those scans can be loaded to my operating room imaging and Australia picture of those. So um this is an example of what happens when we do M. E. G. Motor mapping. This is uh tasks of the right hand where we're asking the patient to move their index finger on the left or their pinky finger on the right and those will correspond to firing of the first dorsal interest on interest this muscle um and the abductor digital Minami respectively. And when those neurons fire the squids will detect that firing and label on the brain in in in stereotype Actiq manner where those spikes are. So this is a way for us to map and then the label where the person parts are. So that green 1.2 you're seeing is actually this patient's hand motor knob on the left side by moving his right head. Um And as I mentioned, the nice flat Mbg is that we're not just mapping their cortex for function. We can also run the E. G. Simultaneously. And those spikes can be put on the same images. So this is an example of a patient who has seizure spikes on visible on the right hemisphere. And then the somatosensory evoked field on the left hemisphere. Yes. So this is a picture of what neuro navigation looks like. This is actually a picture from our our neurosurgery O. R. And Oakland Children's Hospital. That's one of the few hours with a with a window which is one of the nice things to watch the sunset as we're drifting into the evening with our surgeries. But in my hand is a wand there are four gray um spheres that a camera can see and that camera projects to that screen that I'm looking at that screen is this patient's MRI. So as I'm moving that that wand with my right hand in real time the images on the TV screen are moving and it's basically like GPS for brain surgery. So I I use this to find out where the problem is. Um and based on that information, I can design the perfect craniotomy based on the craniotomy, I can design the perfect decision. So everything is custom made now can tailor made. It's it's not it's not a one size fits all um surgery by any means. It's exactly what that individual patient needs. And it's also very helpful as you're actually performing the surgery. So for example, if we're taking on the tumor and we want to monitor our progress, we can place this wand into the tumor bed and see how far along we are and how much time are may be left. So when I was discussing the FmRI and MG just know that the screen that I'm looking at, we have the ability to label all that information and take it with us to the operating. And so it's it's taking a lot of the guess work out of the surgery. And it's keeping us very, very safe. So the next part of the talk is about localization. So we've now again, we're taking patients in the operating room and the answer still is where? And we attempted to answer that question with imaging and advanced imaging alone, FmRI is MdGS Pet Spect. But sometimes that's still not enough. And we need even more precise mapping of the brain to answer the question where and so what we would typically employ if we wanted to be thorough about it is we would design a surgery where we would make an exposure of the area of the brain in question. And we would lay down a sheet of electrodes, like the one you see on the right here. And as you can see each of these electrodes has a number associated with them. It's a see through grid. Um So what would happen is we would place this grid and then we would actually close the craniotomy, leave the grid in place, having taken pictures as a guide to. And this would this would happen on monday for example. And typically we would then listen on it for Tuesday or Wednesday or thursday um and listen and wait for seizures and the seizures happen from a particular gyrus of the brain. It would light up the corresponding electrode over it and now we have a numbered map of where the bad brain is. The seizures are coming from. We also have the ability to one by one, stimulate each of these electrodes. Um while patients are doing tasks. So for example, if they're counting and we stimulate electro 24 and while they're counting their counting stops And then when we stop stimulating. Um number 20 for their counting restarts. We know that number 24 is overlying an area of brain that that patient is using for speaking and for counting. And we would label that as good brain. So over the course of two or three days we can map both the good and the bad and we would take that map back to the operating room, remove this sheet of electrodes and then remove that one place of the brain that might be seizing. And um I often explain this to the families that you know, it might seem um a bit a bit much to have to take out brain tissue. But you have to remember that this tissue, the only purpose that this this tissue has now is to be a seizure generator. And it's it's very rare that the good and the bad co localize um For those situations, we'll talk a little bit later and talk about what we do for those patients. But this is just to give you an example if we still don't know where all the seizures are coming from and we still needed to do a more deep dive into where this is one means of doing it. But as you can see, this is this is a pretty big deal. This is a pretty big surgery. It's a it's a decently sized exposure. It's two surgeries. It's a surgery and a child. It's an inpatient stay with wires attached to the child. They can't leave the ICU. So if there is a means of answering that question where to a less invasive technique and we're all for it. And so I want to begin to tell you a little bit of how we made inroads in that regard. So this is what we would call grid and strip electrode mapping. Um This is an example of one of the maps that we would get from the grids where the red part is, where the bad brain is the season brain. Um And that's what we would plan on respecting. And then the colored parts respond to where the patient had a facia when we stimulated in purple, where their frontal I. Fields stimulated some eye movements in green and then where we map the patient's motor cortex, their thumb moves, there are moved their risk movement. We stimulated those yellow electrodes. So this is an example of the map that shows the good and the bad. But again, I'll bring your attention to the fact that this is quite an extensive exposure and it's a big surgery and if there's a way to get to get the information through other means. So, um to answer the question of where um specifically which side one of the older techniques was to do very small verticals. Um and I'm not sure if you can see my my arrow, my cursor moving. But um on this X ray shows a little grace circles, those are actually holes in the stall that we float strips kind of like if you've ever seen people doing ice fishing where they they carve a hole in the ice? And they put their fishing lines in and hope to get some fish. We basically have carved a hole in the idea and we slide these strips in multiple locations. Um And um each of these is like fishing lines and we're hoping to catch some fish. The problem with this, even though it's relatively minimally invasive small incisions, little hole is that we have really no particular control over where these trips end up. We don't know which particular gira they correspond to. These strips are flat strips and they're just sitting on the surface. So it's only giving us two dimensional information of a very limited territory. It gives us no three dimensional information. Um So to fan out and and answer the question of where using strips is long outdated but it was an attempt at least to be a bit more minimally invasive if at all possible. So let's fast forward to now and uh talk about how we are um advancing the field. And with a much more minimally invasive technique. But with with much more precise data extracted, this is a figure from a paper we are that's review right now. Um That's looking at stereo E. G. Stereo E. G. Is a technique where we use these long electrodes that are very thin. They usually take an incision that's about a millimeter or two in the skin. Um And we float these wires down into the actual tissue itself. You might think that, you know, is there some danger involved? There was sure there is. But we spend a lot of time studying the the mris ahead of time to see where the patient's vasculature is. And we use neuro navigation and steri attacks is to thread the needle between all those important structures so that we can do three dimensional recording now of multiple lobes. And if we wanted to both hemispheres simultaneously. So this this address is a lot of the shortcomings of that last picture I showed you where it's all that was only two dimensions and there's no precision as to where you're listening to. This is quite the opposite. This is very precisely placed um deliberately placed electrodes into multiple locations safely. So this this concept of stereo E. G. This is this is currently the wave of the of the present I would call it. Um Where most centers are moving wholesale over to stereo E. G. As an investigation for where where where are the seizures coming from in these patients? Instead of doing big craniotomy is like I showed you with large incisions um And the associated discomfort and pain that might be associated and the associated risk of infection. We make these very fine twist drill holes in the skull through again, 122 millimeter Nixon the scalp because there's no big incision, it's much painful and the recovery from the little nicks in the scalp is much quicker? The planning is very precise because we are studying this patient's mris in detail for days ahead of time. And we are using the computer software to navigate our way through the sea of blood vessels to precisely place each and every one of these electrodes. It thereby gives us access to the very deep three dimensional structures that we couldn't see with either grades or strips. Um And it allows us to study multiple lobes bilaterally if we want to. Um I showed you our technique which is frameless. There are some centers that place these with frames lexical frames C. R. W. Frames. Um And the good news here is that there's actually quite a low risk of infection. Um and hemorrhage. Our rate is about less than 1%. Um And the reason why we keep that rate so low is because we do spend a lot of time having these patients undergo the appropriate and geographic tests ahead of time. Like an M. R. Angiogram, R. C. T. Angiogram. And we use our software to get a step safely. This is an example of one of our plans for one of our patients where you can see that this patient had a prior neonatal infarct the needle stroke. Um And the E. G. The surface E. G. Implicated a lot of this right hemisphere. So the question was what really which which parts of this right hemisphere are really involved? Where is the seizure generator? Where does the seizure start? And where does it travel? Because those those those parts of the puzzle matter. And so we deployed, we had this plan of deploying this array of depth electrodes. Um this is a two dimensional representation of the model on the left. This is a three dimensional model of the, of the patient on the right, you can see we put in orange here, the patient's motor tracks and his yellow visual tracks. And we use this software in this technique to thread the needle between those structures so that we would avoid the patient's motor cortex and their visual cortex um and deliver these electrodes safely. So this is what it looks like in the operating room. So again, instead of a big large question mark incision with a shave and a lot of pain associated with it. We make these little postage stamp shades and the hair just so that I can get a really clean sterile spot. Um the purple kind of overestimates how much of a nick in the skin you need. But I've gone ahead and marked where each of our planned electrodes will be ultimately on this patient and then after I placed them, this is what they look like they are for lack of a better analogy, like little tiny Frankenstein bolts that that sit without moving um fixated to the skull and when it's time to remove them. These caps come off, they are true and some places just put a little bit of skin blue. I like to put a little bit of stitch. I like to do it in the operating room and it takes about three or four minutes per per removal. And patients go home the very next day. Very very different than the grid and even the strip patients. Um And so we have employed stereo E. G. More and more. And this is one of the primary minimally invasive ways of answering the question, stereo Eg. Okay so we talked a little bit about how we are in a minimally invasive mean by by a minimally invasive means answering the questions. Were studying the patient monitoring the patient. What about delivering kit? What about it actually treating epilepsy through a minimally invasive means. So I want to talk a little bit about how we are approaching that. Um so this is some um some art cover work from one of our papers from 2018 where we discussed very deep seated lesions that cause epilepsy specifically a type of epilepsy called elastic seizures. The hypothalamic martoma. You can see on this corona MRI in the very center of the head here, there very light gray mass that's attached to the underside primarily at the underside of the left hypothalamus here. And this is very classic appearance for a hypothalamic martoma and you might not be a neurosurgeon. If I were to ask you, how would you treat this and how would you get there? I mean just looking at this picture you I'm sure are disturbed by the fact that in the very center of the head, so all the structures are surrounding it. There's no way to get to this, no way to get to abnormal tissue without going through normal tissue. So there's a lot of risk. Um One thing you should know about doing open brain surgery is that the deeper you go, the narrow your gets, you are effectively working in a cone. And that already would be challenging. It's dealing with bleeding or problems that may surprise you in a very narrow space. That real injuries can happen. So um even though we have open surgical options for this is this is how we used to treat it uh meditating 10 years ago we would elevate the temporal lobe and slide in this space and try to get this out from underneath. Um We've completely abandoned that because we have access to a very of sophisticated, minimally invasive approach of deploying a laser. So laser ablation is something that we continue to test the bounds of of of how useful it can be. So most centers will place these with a head frames. So we need stereotype Actiq coordinates to place these very carefully and most places use frames. We at UCSF we use a scalp mounted head frame so it's not a frame that goes entirely over the whole head, it's just right over the location of where we're going to be implanting this uh This laser we use the M. R. I. Scan to target to create a target to create a trajectory. To get our laser in place the laser is inserted through a very small twist troll. Not not very different than the twist drill holes that we use for stereo E. G. Um Usually patients have to have a head frame place in the operating room and then they are transported to the MRI scanner um to see where their laser ended up. But we have the advantage of having an inter operative MRI suite um at mission bay. And so when we when we do these cases we actually do everything from start to finish in the actual sweet and the patient doesn't have to move everything is right there ready. Um And the advantage of that is that instead of transporting a patient with a laser already in their head that may have been placed incorrectly and then has to go back to the operating room to have a new laser place we don't find that problem because we actually watch our lasers be placed on the fly. And so if any adjustments need to be made were already in the entree operative MRI suite. And so it lets it lets us take care of any adjustments right then and there. Um And then once the laser is deployed and um the seizure focus is burned, everything is removed and they go to the I. C. U. For recovery and those patients usually stay in the hospital for about two days. So this is an example of some of the anchors that we used to secure the laser in place. Um So in this case there wasn't even a minimal head shape, there's no need for it because the neck and the skin is so small. This is a picture from our inter operative MRI. Well I've already gone ahead and gotten the laser all the way down. This is a a wire applicator basically a hollow bore needle long needle that delivers this laser to the hematoma. Um And so we can watch it go on its way down. And if it deviates a little bit we can adjust on the fly and get it to its destination. We then tell the the module um uh where we want the heat the laser to burn. Um And we also can assign these thermal safeguards. These are basically do not burn areas. These X marks are constantly measuring temperature and should the temperature elevate beyond a dangerous um level that could potentially hurt important structures. The machine automatically turns off. So real time mar thermography is being performed on the lesion, we're safeguarding the structures around them and then a little by little. The software is estimating how much tissue we've actually a plated how much of the seizure focus has actually been heated so high for so long that that tissue has now been effectively erased. So this is a a very sped up video of both the M. R. Thermography in blue and green and you might see a little flash of different colors to show that the heat lighting up in the center and then on the right you're seeing pixel by pixel a little a little island of orange. Um That's the ablation um A bladed tissue, the a bladed hammer toma from within. And it's all done through this 122 millimeter twist drill holes. So very very different than when we when I first started treating these in 2000 and eight. Um By traditional means which would would would would require a much more extensive incision and much longer hospital stay. So we are kind of walking our way down the continuum of of less invasive not just less invasive listening and monitoring but less invasive therapy. I've shown you the current state of affairs for minimally invasive laser ablation. But there may be cases where we don't even want to oblate the tissue. We don't want to accept it with an open surgery. We don't even want to a blade it with a fine laser. Perhaps you want to leave the tissue in place and do what we can to modulate the neuronal activity to uh to modulate the circuits that are firing in an inappropriate way. And you may have already gotten a taste of that, that kind of approach with the device called the vagus nerve stimulator. Um And this is some of our work from 2000 and 12. Um The VNS is an implantable device um that sits in a pocket in the in the in front of the pectoral muscle, so it's just underneath the skin, it's above the muscle. I'm showing you two examples of the VNS. This big rounder one is uh is the older model which we no longer implant. This smaller one is the shape of the current model. The model 1000% Eva. Um and uh it's a little bit smaller than an egg effectively. And it's it's thinner than your cell phone. Um and it sits in a pocket in the in the chest wall. Um It's it's a device that we implant for patients who are not candidates for any cranial surgery but are still medically refractory. Um The exact pathway, the exact mechanism of how this device works is not entirely known. We do know that the stimulation travels in a retrograde fashion from the vagus nerve through the brain stem up into the cornices. Um It's effectively for lack of a better analogy, like a pacemaker for the brain and it's providing a drumbeat a march. It's a march, a little marching band for the, for a chaotic environment of an epileptic brain. So little by little. These chaotic circuits would rather march to the beat of the VNS drum and be organized by the rhythm of the VNS then to chaotically um discharge in in their epileptic fashion. That's the best way I found to kind of describe this function in generic terms to our families, who I'm trying to understand how this works is it's just, it's providing a rhythm, is providing a cadence to the brain, but it's doing so in between seizures. The primary function of the VNS is into Richtel discharges. Its intricately in between seizures providing a pattern. It's not, it's not typically doing anything during seizures. That is the, that is the prior way and the only way that the VNS used to work. Um, and we talked to the device through the skin, batteries tend to last somewhere between 6-8 years if we were just talking about the intellectual device. But the newer devices sent Eva that I mentioned is not just intellectual. Um, so it uses heart rate elevations as a surrogate marker for a seizure that's coming. And the reason why this is important is because leaving over the company that distributes these devices Released a report that on the order on the order of about 85 Three, of patients before they have a very large seizure will have a statistically significant elevation in their heart rate. And so this device is not specifically listening for a seizure per se. Um, but it is using the heart rate elevation that most epileptics have as a surrogate marker for a seizure to come. And then when it detects that heart rate elevation, it will provide an extra stimulus, much like a magnet. These patients who get DNS are sent home with magnets and they are taught to swipe across the face of the VMS with the magnet in the event that they're having a big seizure and they try to use it like a rescue met. But the heart rate stimulation, the heart detection function of the of the device is like an automatic magnet. It basically stimulates when it detects that heart rate elevation um and it does so um interactively as well so that that function is also listening for actual seizures. So it has anecdotal element to it as well. You can pre programme the scent Eva so out of convenience for families who are traveling from afar and it's especially during this covid era where we're trying to minimize how many trips these families have to make. You can pre programme this device um to uh graduate to the next uh settings automatically. We still have to coordinate with the families and check in with them that these the most recent adjustment was okay and this side effects but we can cut down on the number of its um that we have to schedule and uh and a lot of these um graduated steps can be done remotely or automatically. I should say. There is a another function that is not quite yet gone live. Leonova hasn't yet activated but there is a function of the device because it is positional e sensitive, much like our cell phones are if a patient is having a seizure in this device, text it and the patient is prone and this device to text the patients prone, it has the ability to alert caregivers again. That hasn't gone live. But it's one of those functions that I was told is is in the device and they can activate it when they get clearance and it just hasn't hasn't had. Um So the VNS is our kind of our first foray into this, this this um treatment approach of neuromodulation. We're not taking any tissue out, We're trying to corral and and take care of the circuits without respecting them or uploading them. Um When we looked at uh the literature on VNS is, and we did our own meta analysis of VNS literature in 2011. Um we found that on average 45 uh there's a 45% reduction in seizures for patients to get these devices. And there's actually a significant benefit for patients who have both generalized epilepsy and who are Children, which is good news for our practice. Also good news for our practices that patients who have a history of tuberous sclerosis also do a bit better with these devices and and so many of our kids, especially our Oakland campus Children who wear the Oakland campuses a tuberculosis center. Um they do particularly well with the NSS and the last group to do very well. Our post traumatic epilepsy patients, it's very rare and I make I make it a point to be very clear with the families that it's very rare to be completely seizure free With these devices. And I tend to quote on the order of about 5% of patients will be completely seizure free and that's a moving target. It's it's really hard to predict who will be seizure free. About a quarter of patients we found um didn't have any particular benefit just as an aside, um sometimes patients won't have these devices implanted. Um uh because if it if they fall into that 25% category uh they are being told that once this device is in it's in it's never coming out. And if there's any remnant of a. V. N. S. N. Even if someone attempts to take it out, they can never get an MRI again, which is true. Um But uh I always had a problem with that and um a while back I had a patient who absolutely needed to have their VNS out to be enrolled in a an epilepsy study. And um so I I I decided to do my best to take off the entire device and um that was the first one that I did in 2000 and eight and now 27 patients later of complete VNS removal? I no longer tell families that once it's in um it's actually inaccurate to say that. And we are publishing one of our papers are checked. Nicole knows to show how do you safely take these out? Um I don't I don't want for that to be a potential deterrent for patients to not receive the VNS. Is that well if it's in I can't ever have an MRI again that's not that's not true. And it's important that families know that. So the next wave of neuromodulation. The smarter of the two implantable um CNS devices is the neuro pace the neuro stimulator. This is actually the device sitting in my hand. It's about the same thicknesses of VNS and just a little bit longer than the device. You can't tell from the picture per se. But it has a curvature to it. And the reason why it has a curvature is because this is not implanted in the subcutaneous tissue of the of the chest wall. It's actually implanted along the surface of the skull. Um And those four wings that you're seeing at 10 to 4 and seven o'clock. Those are the little wings screw into the bone um surrounding it. You have to carve out a little shape for this in the in the skull and that sits in that depression on the skull. And um coming out of this this this little gray port here are plug ins for up to two electrodes. So so what does the neuro patient and what does it do? So um neuro paces, the responsive neuro stimulator. This is not a device. Um that is meant for patients who are responding to medications. Um It's for patients who failed at least two meds and have had at least three seizures per month. Um ideally you want to have one seizure focus or at most two senior posts I and the reason why is because as I showed you, there's only an ability to put into electric. You can put into strips or to depths or one of each. But if you put it any more than that, you're just gonna have to cap it and leave it in place. And um what we've been doing actually for even more complicated patients is sometimes we do in fact do that. If we are limited to, we'll put in as many as we can and only use the two most likely wires. But at least we can save a patient additional surgery if there's a potential for the use of a third or fourth and we leave those caps. So you plug two electrodes and at the time these are for medically refractory patients. And if you remember and think back to the scenario that I discussed with our grid and are stripped electrode mapping patients most of the time. The good brain and the bad brain are completely separate areas of the brain. We will accept if they're right next door to each other. But what we don't want and thankfully we don't see very often is if they co localize if eloquent cortex and see your focus is one and the same. Sometimes we can get away with removing even that tissue if that's your tongue motor cortex where your face motor cortex, we actually have a pretty potential a pretty significant potential to recoup that function from the contra lateral side. But you cannot do that with hand motor cortex. You cannot do that with leg or and you certainly can't do that with speech. So what do you do for those cold localizing areas of the brain? So you can place these strip electrodes or these depth electrodes into our on those areas of the brain, plug them into the RNS. And this E. G. Recording will show you um here at the beginning of the recording is spontaneous seizure which this device detects once it to text it, it immediately provides an electrical stimulation to the electro that's embedded in or are sitting on top of this user focus. And then as you can see it interrupts that that seizure wave all you need to do is basically train these these hyperactive circuits to to not propagate and it will not manifest into a full on seizure. And what they found with the european group found in with longer term data is that Although they had 38% reduction in seizures when the euro pace was first place when they when you first put in the narrow pace, that's how much you get reduction. After a year it bumps up to 44 After two years it bumps up to 53%. So you're seeing this phenomenon as you give this epileptic brain more time to listen and work with this device, you achieve more and more seizure control. And and we've put in quite a few for our kids now, unfortunately is not fully FDA approved for Children and it's a case by case um physician to physician clearance process. But we're working on, we're going to be part of a trial, Hopefully soon to bump that age limitation down from 18 to at least 14 so that more and more of our kids can get these FDA cover. So the last element of this talk that I wanted to chat with you about. The fun part of the job is um is really advancing our our ability to image these patients and to not just imaging, but explore the imaging and share the imaging in a fun way that doesn't require big words and fancy terms. Um and we've been using more and more immersive virtual reality to study these patients and to operate these patients and to share with these patients their problems. So this is a picture of one of our trainees who has an immersive VR headset on. He's holding a hand controller and he's actually navigating through a case that we recently did where we were going to implant some electrodes into a patient's singular gyrus. This is that kind of sherbert color uh sausage shaped structure here where we had a couple of wires implanted and he's actually going to be flying down virtually into this patient's brain on traveling along the planned trajectory. So this is a way to rehearse your potential surgical corridors. This is a way to weigh one option versus another. Well before the patients under anesthesia. The last thing you want to do is find out on your way to a to a path that the path is obstructed. It's much better if you can rehearse all these things ahead of time and save save the patient any undue risk. Um, so we use this routinely to practice and rehearsal surgeries. We share the cases with our trainees, but the really fun part is to share it with our kids. And a question I have is, well, how young can you go? Obviously the teens and tweens, they most likely already have one of these headsets and these controllers on there, kitchen table or coffee table already. They're already even more well versed in the use of these devices than we are. Um but this is a picture of one of our four year old, he's currently one of our youngest before a four year old navigating. And of course you can. This is different things that a four year old will get out of the experience than a 14 year old. But each of the family members. The patient is mom, you're not seeing it, but dad and I all have headsets and I'll have controllers. Um And it's a very vivid uh participatory experience to fly through anatomy. So this is an example of the kind of fly through that you would see. This is that stereo E. G. Patient that I showed you before. We have a little Frankenstein bolton and skull This this fly through gave me an opportunity to check on all my electrodes. And what I found with this fly through is that number two the red one here is tagging one of these vessels right there. So number two, that red electrode was one that I had to adjust before I took this patient to the operating room. But all the other electrodes threaded the needle really nicely among the blood vessels, The motor tracks the optic tracts. Um And so it's a really reassuring way to know that we were staying out of danger before we implanted all of these um these uh electrodes. Um But whatever I'm sharing all of this with the patient, and this is meaningful to me as a pediatric specialist because we often ignore the patients, the Children during our patient engagement sessions. But it's time we change that this is this is an example of us of us changing that. This is a, this is a video capture of me walking through a patient's brain showing her her red tumor, um that was causing her seizures. I'm we're flying through the brain. There are little avatars that each of us can see of each other. This is dad, this is my patient. This is me and mom is floating out there and there should be some narration here. I'm hoping you can hear it. Mom and dad say, me, we're going all the way inside jane's right. Tell me when you get there and I'm gonna turn up. Okay? All right. So you can actually fly past a dad. If you can actually fly past eight, um, and get yourselves on either side of me says, I'm not blocking you. There's something I want to show you even more even more. I'm going to go away with it. Okay. And then dad, could you look over your right shoulder all the way behind you? You could keep going and going and going, can you see this arrow that I'm pointing up all you guys? Because I'm pointing the tumor. But on top of the tumor there is this blue thing like shaped like an S that's yet another button mouse that's hiding on the other side of your tumor painting, like it's actually hidden meaning if I went through your tumor jade and I kept going, going going to eventually gonna hit this guy. That's my stop sign. So imagine imagine you had a brain tumor and someone's pointing to a flat gray and white picture on a screen and M. R. I. Screen. And then you were given an opportunity to actually fly into your brain as a as a as a child. And I've seen this firsthand. Um It is such more of an inviting experience and it's an empowering experience for them. Um They feel they have ownership of this thing, they understand where it is and what the surgeon is gonna do. We actually create little fly throughs little mock travels through their brains and we mail them card. We can mail them cardboard boxes that turn into VR headsets with their phones and then they can fly through their own brain anytime they want and they can share it with you know, uncle bob and aunt jo whenever they want who didn't get to come to the clinic appointment. So it's it's really a nice way to to share that this otherwise really scary experience with them and teach them about their own and that. So I try to make sure that we stay within our time frame and stay within our, I want to say thanks to the many many players, team players, both in Oakland and san Francisco. This is a comprehensive list of all the names that you may come across if you if you call either of my um offices. Um It's very difficult to do brain surgery. And the only way we can get it done is with a really fantastic team in both sides of the day. Um like this this this to these two lists here. Um anytime you want to send a patient our way um welcome any referrals or second opinions. Um 877 you see Child is the is the fastest way to our pediatric access center. And um you know, in this era of covid, we were very, very sensitive to keeping our kids safe, our parents safe, our staff safe. We have a, You know, a job to do and we can't we can't risk anyone safety to do so. And you know, as of right now, about 90% of our outpatient practices. Um it's all telehealth and all remote. And so that's certainly an option that we would make available to all of our families until I figure out how to do brain surgery remotely. Um The surgery will still have to happen in person. But we we found pretty creative ways to do everything else remotely