Nuances of Microvascular Decompression for Trigeminal Neuralgia

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- Colleagues and friends, thank you for joining us for another session of "The Virtual Operating Room." My name is Aaron Cohen. Today we have a special guest, Dr. Mojgan, or Moji, Hodaie from University of Toronto. She is a world-renowned neurosurgeon on management of trigeminal neuralgia. Mojgan, it's truly an honor to have you. In addition of being the professor of neurosurgery at University of Toronto, she's also Greg Wilkins-Barrick Chair there. Really, she is not only an incredible surgeon, an amazing academician, and always a pleasure to work with, really having all the great qualities of an academic neurosurgeon, and I can't be more excited, Mojgan, to have you with us, and specifically learning from you about microvascular decompression surgery for trigeminal neuralgia. So, with that, let's go 'head and get started. And thanks again, Mojgan.

- Aaron, thank you so much for inviting me. It really is a pleasure to be here. I have been watching the videos of "Virtual OR," and it's really an honor to be a participant this time.

- Thank you.

- So, I thought I would start by talking a little bit about the historical context. In my view, it flavors the work that we do, Aaron, and as I do a lot of cases for trigeminal neuralgia, to go back in the history and look at what has been done previously and where all of this interest in trigeminal neuralgia started is fascinating and I think contributes also to our learning. So, based on what I've read, it appears that the first treatment for trigeminal neuralgia was suggested by Galen, who was in fact interested in the facial nerve, and of course, anatomically, that did not quite correspond to the cause of the problem. And someone by the name of Mareschal, who was a surgeon to Louis XIV, started by approaching the facial nerve with a consequent paralysis and no effect for the pain. And as we know, obviously, the treatment of trigeminal neuralgia has consisted in medical treatment alone for a very, very long time. This is Mareschal, and we see that he carries his tools with him. Quite interesting and descriptive as to what surgeons used to be like in those times. And eventually, there was an interest and approaches that consist in extirpation of the nerve, resection and removal of the Gasserian ganglion, excision of the upper jaw, and also attempted removals of the ganglion via approaching the foramen ovale, which in times where hemostasis and adequate visualization and proper lighting and microscopic approach were not available, they seem to be extraordinary, and in fact, Sir Victor Horsley has an interesting description. 1890, when he would take these copious notes of the cases that he would do, and he said that he considered the possibility of dividing the fifth nerve behind the ganglion, and he did so by resecting the zygoma, and the operation went reasonably well. He thought to himself, "Well, maybe I shouldn't have resected to zygoma. Maybe that wasn't necessary." The patient never made it out of surgery and had an autopsy afterwards that did not show a hemorrhage, and importantly, he felt that the patient likely died from shock from being so debilitated from not having eaten and being nutritionally poor secondary to the pain. So, it's quite amazing what patients have endured for, really, centuries before our current approach and technique for treatment of these patients.

- I want to mention something, Mojgan. In fact, there is a story of Harvey Cushing visiting Horsley and following him around at the time when he was a young surgeon and there was a patient with trigeminal neuralgia, I believe, and Horsley takes a cab with Cushing, they go to the home of the patient, and Horsley asks the cab to wait while they perform the operation because it'll be pretty quick. So, they all run upstairs, Cushing holds down the patient in the kitchen room of the patient, and Horsley makes an incision under minimal anesthesia for subtemporal decompression. So, they make a linear incision, bone pieces coming out with a huge Horsley rongeur, and in a very aseptic manner. As you know, Cushing was obsessed with aseptic technique. And eventually they find something under a very minimal lighting, obviously, and do something, and there is massive bleeding coming from the cavernous sinus while patient is moving extremely violently, obviously, and then he just packs it with sponge and closes, and they just sort of walk downstairs while the cab was waiting. The whole process, I believe, taking 20 minutes, and that was the single procedure that, in fact, Cushing became very much disenchanted with Horsley, who was at the time the father of neurosurgery and may have been the initial insult that made Cushing become so obsessed with the aseptic technique and so obsessed, or over-obsessed, with just a meticulous operation, that time is not an issue. So, it's just a very interesting historical perspective, and lets you know how far we have gone. This is not in any way questioning the greatness of Horsley in the era where he was. Many of the techniques that we think he should have used were not even available at the time, but one should not forget the incredible contribution of Horsley as the pioneer and the father of neurosurgery in its infancy when Cushing is the father of modern neurosurgery. So, I just wanted to add that as an interesting sort of historical perspective. Go ahead, please.

- Very interesting, and I think perhaps this is relevant, as well, in terms of keeping meticulous historical notes of events that we see, that maybe at the time they do not appear to be hugely significant, but I think in the spectrum of time, for instance, the story that you mentioned or the notes that Horsley described in this case are incredibly relevant, and at reflecting on these events that have occurred in the past and how we approach cases now, I find that it flavors our approach to this condition and what we are good at and where we need to improve. So, I think this concept of neurovascular compression is now very much noted by us in the modern neurosurgical era. The fact that there is a blood vessel that comes very close, either contacts, compresses, or, frankly, distorts the nerve, and this is really the key aspect of our surgical approach for patients with trigeminal neuralgia, and particularly microvascular decompression to remove this compression off the nerve and allow patients to have greater ability of a pain-free status. And we focus on this, of course, but we know to have to say that between patients that have, say, distortion or compression, we don't really have a clear mechanism of saying, well, if you have distortion, your pain is going to be worse from having compression. So, that will take me later on when I talk a little bit about the research that we do in this area and where I focus my interest, but the purpose of our conversation today is obviously neurovascular compression and our approach to patients with microvascular decompression. And I start, obviously, by looking at the MRI of these patients, and we see, for instance, in this MR image where the images have been reversed, you can clearly see that on this side, the structure of the nerve is poorly seen, because in fact, a blood vessel that is just looping has clearly distorted and almost bisected the nerve to split it into its different fascicles, whereas on the other side we actually see it traveling into the cisternal space unimpeded. And again, we can look at nerves in many different ways on the MRs, and importantly, visualizing them, looking at the actual microstructure of these nerves with diffusion tensor imaging and drawing values and metrics from what the microstructure of the nerve is and how this might be affected. And I'll talk a little bit as well later on about how the brain is contributing to the understanding and expression of this pain. So, microvascular decompression is not the only procedure that we have available. Of course, as you know, we have multiple procedures. Microvascular decompression deals with the compression at the root entry zone. Gamma knife radiosurgery addresses generally the cisternal segment where we deliver a sharp beam of radiation to that spot trying to minimize the dose to the brainstem so we'll stay outside of the brainstem. And of course, the rhizotomy procedure approaches the area of the Gasserian ganglion, and preganglionic edges. And we know as well that the closer we are to the nerve entry zone, so microvascular compression being the key example of that, there's the greater likelihood of long-term effectiveness of the procedure, so this is very important as we share this procedure with patients and as we also share the risk complications, and of course, the important benefit and long-term benefit that they draw. So, this procedure, of course, is focused on the anatomy of the posterior fossa. This is extremely important to know and be aware, and I think the nuances that I would like to discuss with you today and how I approach these cases as I tackle them really relate in many ways to the anatomy of the posterior fossa. It's a critical area and it's very important to be aware of certain aspects of this anatomy that will permit the safe performance of this procedure, minimize risk and complications, and really deliver how beautiful this procedure can be. I have to say when I was a resident I saw only a few cases of microvascular decompression, but I was always impressed with the elegance of this procedure and how approaching the CP angle to see the nerve which is, frankly, anatomically intact, but to be able to decompress and come out without leaving too much of a footprint, save for a piece of Teflon, seemed incredibly elegant and it remains so. And of course, that's the goal of every surgeon, to make sure that that surgery that we perform remains in its elegance and beauty. So, in the posterior fossa, of course, we see the area of the cerebellopontine angle, we see the root entry zone of the trigeminal nerve, and we see that neurovascular conflict on the mri, which, of course, it's incredibly important, and I start all of my cases by studying the MRIs, reviewing the MRI in detail. I use either FIESTA or CISS sequences, something that allows us, and of course, different sequences have their own specific names, but fine-cut sequences that allow for maximal visualization with trigeminal nerve root entry zone and the anatomy of the trigeminal nerve itself. I look at the sinuses, their position and caliber, as well as the bony anatomy of the posterior fossa, and in Toronto for my patients, in the morning of surgery, the patients have a neuronavigation study, which is generally a CT with contrast, and this allows us for intraoperative neuronavigation and mapping of the position of the sinuses, which I do diligently, and I find that to be extremely valuable for our surgical approach. So, there are two anatomical considerations that are very valuable. The first is the position of the transverse and sigmoid sinus anatomy, and this is important for minimizing intraoperative bleeding and avoiding thrombosis of the sinuses as well as deep venous drainage of the cerebellum and the potential risk of late infarct, and these are, again, vascular considerations for this procedure, and again, I consider these very important. We know that the petrosal vein is very much in proximity to the trigeminal nerve, and maybe I'll take a few minutes to talk about this anatomy, which is valuable to be aware of. So, the petrosal veins, Aaron, as the prominent surgical entity in this area, the posterior fossa empties into the petrosal sinus, and this sinus connects a cavernous sinus to the transverse sinus. The important point to note is that it has a variable position, course, and length, and in fact, this variability of the anatomy of the posterior fossa, and particularly the venous anatomy, is crucial in my view for awareness of a safe performance of microvascular decompression. There is indeed a variable drainage pattern of the petrosal vein, and for instance, we have the transverse pontine vein that passes rostral to the trigeminal nerve, the ponto-trigeminal vein, the vein of the middle cerebellar peduncle, the vein of the cerebellopontine fissure. These are all very nicely described by Rhoton. There's a variable number of branches of the petrosal vein, and as I mentioned this, the sinus, the petrosal sinus, connects the cavernous to the transverse sinus. So, the important thing to notice is that the superior petrosal veins can be terminal ends of bridging veins. Some are formed by the terminal end of a single vein and others are formed by the union of numerous veins, and therefore unless we do a full venous anatomy study for every patient, it's difficult to say whether the vein that you're about to take is one that is very much necessary for the patient or not. So, when I first started as staff, I used to fairly routinely take the petrosal vein, and I was actually giving a talk at a meeting and someone remarked that maybe that is not as necessary, and that made me think as to why did I follow that habit, perhaps probably because that's how I was trained to do. And then I started considering not taking the petrosal vein, and frankly I cannot recall when was the last time I had to do one. One can very easily work around it. It allows a much greater safety, and again, minimizing the risk of an infarct in the patient is, of course, paramount, and I have to say that following the specific maneuvers of keeping the vein safe and still approaching the trigeminal nerve is far superior than taking the nerve and then worrying about it. So, again, the anatomy of the trigeminal nerve root is such that the petrosal vein is always in close proximity. This vein is positioned either immediately above or cranial to the trigeminal nerve root, but not below. Definitely multiple branches may be present. Occasionally, there's a branch that is very lateral, i.e. as you approach the CP angle, it appears superficial, and this is really important to note because as the cerebellum is retracted, then this branch might be torn, causing significant bleeding. I take my time allowing for cerebellar relaxation, and this really helps in avoiding any transaction of the petrosal vein or interruption of the sinus. And I'll talk a little bit about positioning. I find that to be paramount in approach. Small craniotomy, focused dural opening, and again, dynamic relaxation. One of the key things that I pay attention to, and again, is this variability of the course and structure of the sinuses, particularly for small craniotomy approaches. In order to have a small craniotomy, the course, the position, and the junction of the transverse sigmoid sinuses are mapped out, and this is why I find neuronavigation so helpful in this area, and this allows me to have a much more direct assessment to the trigeminal nerve, direct approach to the trigeminal nerve with a smaller craniotomy and shorter operative time. So, from skin to skin, the operation takes in the order of about I would say 75 to 80 minutes, rarely longer than that if these steps are followed accurately, and sometimes I joke with the residents that the more time we spend positioning the patient and making sure that all these aspects are attended to, the shorter the operation's going to be, and the reverse is correct as well. The less we focus on positioning and we just quickly get started, then likely the actual operative time will be longer. These are some examples of sinus anatomical arrangements in patients. There can be rather different. We can see the positions of the sinuses from an ipsilateral and contralateral approach. You can see that it comes down, then goes up again. It's thicker in one spot, thinner in another spot in terms of caliber. And this can be a little bit disconcerting initially for those that are being trained in how to do this procedure, but again, it's very important particularly the day of surgery as we have this three-dimensional arrangement with neuronavigation to focus on these to make sure that the extent of craniotomy is actually kept safe and the craniotomy does not breach the sinus. And again, we know that the sinuses are not necessarily symmetrical. So, for instance, this side has a much different caliber than this other side, and this is important to be aware of. And although this is not an absolute rule, if the side that I approach has a smaller transverse and sigmoid junction, then, in fact, I am more careful about the deep venous structures, thinking that they might actually rely on deep cerebellar drainage through those veins much more than they would on the basis of drainage into the transverse and sigmoid junctions. One would conceptually think, "Well, you know what? Big sinus. Be careful going in." Yes, of course we have to always be careful, but the important bit is what's happening here, and whether we're going to potentially cause any injury to deep venous structures, which is, of course, something that we want to avoid. So, again, adequate approach to the cerebral pontine angle will permit manipulation of the veins without requirements of their section. If by the chance there is multiple branches and some of them are directly in the way, I might take one of those branches but leave the general drainage intact, and it needs to, it's worthwhile mentioning, as well, that the skull-based anatomy, the bony anatomy, and in particular the distance between the promontory of the acoustic meatus and the tentorium is very variable, as well, and the smaller this distance, sometimes it's quite broad and there's a lot of room, and one can easily work around it, but the tighter it is, and as you know, Aaron, sometimes the tentorium almost appears to be touching this promontory, then the more challenging it is to work around the vein, but still very much doable with patience and good exposure. So, in my view, the best way to get around this is to really work with the brain using time and a relaxed brain and really not fight it. This is the positioning that I use. I use the patient position in a park bench with the head turned and slightly flexed. I always check with anesthesia to make sure that we haven't put too much of a kink in the neck that might result in some kind of venous obstruction. I use, of course, neuronavigation. You can see the fiducials on the patient here. And this neuronavigation allows us to map the position of the sinuses, and I'll talk a little bit about the use of intraoperative doppler, as well, which I use with quite a lot of help during surgery. I'll talk a little bit about the points on the craniotomy and how a smaller craniotomy really has its own challenges that one needs to be mindful of and be aware of what type of impediments those might create. One of the things that I find very helpful is the surgical bed allowing movement. So, I use that very liberally to tilt the patient rather than the surgeon moving, and this comes into the field of surgical ergonomics that is becoming a big concept, but to put it in simple terms, a surgeon that's comfortable will operate better, and therefore the patient will be more comfortable, whereas a surgeon who's struggling because our body position is very awkward or our neck's starting to hurt or our back is not reaching properly, that translates directly into patient discomfort, as well. So, surgical ergonomics is very, very important. I'll talk a little bit also about opening of the dura. The leaflets are really lifted against the sinuses. So, I cut the dura in a Y-shaped manner. Really, the width that's necessary to approach the trigeminal nerve adequately is about roughly 1.5 centimeters, so we don't need a huge opening, and dynamic relaxation is key. I don't have permanent retractors, but I use dynamic retraction. So, this is roughly the incision that I make. You can see it in this patient, and I will go to the next slide and then come back to this one. So, we can see the position of the ear here. This is an animated slide, and this is roughly the position of the sinus. And the interesting thing is what I call the index finger rule, and that is roughly if you take into account the width of my finger, which is not very big, but still, there's roughly one finger-breadth's distance between the position of the sinus and the tip of the ear here, and if the mastoid is roughly placed here, the second index finger rule is that my incision will be placed, again, roughly one finger-breadth away from the tip of the mastoid, and I find that this is a rough rule, that in a sense it serves to double-check my neuronavigation mapping. At times they're really off, which will make us potentially a bit wary and I will map again to make sure that I have good certainty of where the sinus is before we start the craniotomy. And you see again here, there is a rough distance of one finger-breadth, and assuming the tip of the mastoid was there, there's another finger-breadth here, and that's where I make the incision. You can see that it is a straight or maybe a gentle curve that follows roughly the curve of the ear, and the opening comes to this distance. I have mapped the sinus here for our visualization, and we are good to go at that point. So, again, the incision would be roughly there. I place the first burr hole such that the superior aspect of it would be just under the transverse sinus and the lateral aspect of it would be still a little bit of distance from the sigmoid sinus. I don't whether it's your impression as well, Aaron, but I find the sigmoid to be more difficult to deal with if there's bleeding compared with the transverse, and oftentimes, there might be during the craniotomy a little bit of a tear in the outer layer of the dura. If we're off the sinus, not a big deal. We're good. If they're on the sinus, that is a big deal. So, I really, really want to minimize that, and the position at the final craniotomy is to be roughly so. So, I have a video here that is edited, and one of the key aspects is that as much as possible, I try to follow the cerebellar sulci. We get, again, with dynamic relaxation and with a flat retractor, start gently retracting the cerebellum. I use suctions that are graduated. They're not on permanent suction. I think that's extremely important. If on a structure that is not to be disturbed, I can quickly remove my thumb, and the suction will stop working, which is exactly what I want. I also have gentle suction. I don't want it to be sucking aggressively so that I have maximal care of these very fine structures that we're trying to protect. Again, gentle dynamic retraction will allow quite a lot of relaxation of the cerebellum. I don't use lumbar drain, I don't use mannitol. I ask anesthesia to drop the end-tidal to roughly 30, and this is, again, sufficient. As you can see, I start taking the arachnoid. You can see there Cranial Nerves VII and VIII roughly here, and the first, maybe we can pause the video for one second. The first thing that I look at, which was not obvious in this video, is to determine the position of the tentorium. So, I angle the microscope, I take a look at the tent and make sure that we have that, and once the tentorium is visible, we see here the promontory here, its bony prominence, and VII and VIII will be right under it. So, visualizing these two structures, the tentorium as well as Cranial Nerve VII and VIII will define the working window that we have. The width of this paddy is half an inch, 1.25 centimeters, so that gives us a view of what the working area is that we're working with. And it's out of focus right now, but the dural leaflets are these two triangles, one there and one there, and these have been retracted and held back. So, that's, again, very helpful for us. And you can restart the video. So, again, with gentle relaxation, we're now opening the arachnoid. There's always, of course, at least one leaflet of arachnoid over Cranial Nerves VII and VIII. I try not to disturb it. At the very least, it serves as a buffer so that I don't have any incorrect moves. And needless to say, I have brainstem auditory evoked potentials during all of these cases. Sometimes the arachnoid just falls apart. You touch it with a dissector and it opens itself for you, and sometimes it needs to be cut. Sometimes it's actually rather thickened. Maybe you can pause a video again, please. We can see, again, the structure of the petrosal vein here. It has multiple branches. In this particular case, there's another deeper branch here that is not quite obvious just yet, but it will become obvious. And there's always an arachnoid cuff around a petrosal vein that one needs to be aware of. I find arachnoid to be a rather interesting structure onto its own, and sometimes I joke that I have arachnophobia because of it. It is incredibly tense, although it appears to be rather soft, but sometimes, for instance when the actual microvascular decompression is being performed and I try to put the Teflon and there's resistance, and that's because there's probably an invisible band of arachnoid somewhere that is actually preventing me from properly placing the Teflon. And similarly with this arachnoid band around the petrosal vein, sometimes one might have a tendency of retracting the vein without adequately looking after the arachnoid over it, and that can cause injury. So, it's very, very important to be aware of the structure of arachnoid and to what degree they actually contributes to all of these anatomical structures that we're trying to work with. Yeah, so we see in this video, you can see how, maybe you can pause it for a second. Again, VII and VIII are here, and this is the trigeminal nerve, and you can see when the video stops, it's paused, it's actually just completely kinked like this, and the compression from our perspective is from underneath. You can restart the video. And you can see the substance of the pons, the vascular structure underneath that I'm now going at it with a microdissector and pulling it off, and that is one satisfying move to decompress the nerve like that. It's a double loop. I'm mindful always, 100%, of Cranial Nerve VII and VIII just millimeters away from where I am or working, and that needs to be permanently embedded in the mind or in the view of any surgeon doing this procedure. And there is the microvascular decompression and the placement of the Teflon. I don't use Evicel. I don't use any system except for the decompression using Teflon. In my view, I find thrombotic agents such as Evicel or Tisseel and so on to be thrombotic, and potentially they might result in some level of interruption of the venous system, and I don't want to really take that risk. So, this completes the procedure for me. Maybe one other thing that I would add is that the microdissectors that I use are long and flat. I find that any curve in the microdissectors at the depth that where we work, which is roughly six or seven centimeters, gets very much exaggerated, and I find that in my hands, obviously microinstruments that are narrow and fairly flat are the ones that work best. I have a set of Rhoton micro dissectors, and Number Five appears to be the better one, and I generally use something like a Six or Seven in terms of size of the suction, that as I said is a graduated suction. So, risk and complications of this procedure. Again, sinus injury. We've discussed that. Cerebellar injury can occur. Dynamic relaxation minimizes that. Brain relaxation minimizes that. Dynamic retraction, sorry. I don't use lumbar drain or mannitol. I think in all the cases that I've done, there's been just one time that in retrospect, I wonder whether the patient had some level of intracranial hypertension that required the use of mannitol. But we generally are very, very good with just positioning patients and time. Anesthesia can titrate end-tidal CO2, which is extremely helpful. And I also find that good microsurgical instruments and a graduated suction tip minimizes the risk of deep vascular injury. I might use tiny, tiny, tiny pieces of gel foam if I see any kind of bleeding. I just put it there. I wait a little bit. That looks after the problem. Brainstem auditory evoked potentials are crucial for minimizing the risk of cranial nerve injury. At times, if there is unintended retraction of the cerebellum, which is more than it should be, then we see changes in the waves of Cranial Nerve VIII. I relax things a bit, I wait, and generally they return to normal. Irrigation results in firing of Cranial Nerve VII. We're comfortable with that as well, but it's a good warning. A system similar to a seatbelt when we're driving in the car. Most of the time we put on the seatbelt, we drive, nothing happens. It's just a one time that you might be in a difficult situation and the seatbelt will come to save you. And similarly with this case. I should maybe talk for a second about how I use intracranial dopplers. When I first perform the craniotomy, the burr hole, I should say, I check with dopplers as to where the position of the sinuses are, and again, this is helpful. Sometimes we are above, we are on top of the sinus, which is fine. Sometimes the sinus is just slightly above the position of the burr hole. That's fine also. We never, never want to be in a situation in which the sinus is sort of on the inferior edge and we're sort of in the area of the occipital lobe. That is to be avoided. So, the position of the transverse and sigmoid sinus can be checked with an intraoperative doppler, and that is very, very helpful. Particularly if I've identified any type of venous structural anomalies in the CT, I want to make sure that we follow the anatomical curve of the sinuses and we don't breach them. So, that really takes me to the sort of technical aspects of the procedure, but, Aaron, as you well know, trigeminal neuralgia is just one of the syndromes of trigeminal pain. We have multiple. We have patients with trigeminal neuropathic pain, deafferentation pain, postherpetic neuralgia, et cetera. So, a big question in my mind is, yes, of course we do microvascular decompression. Patients are for the most part better, although there's about upfront 10% of patients that are not better from surgery. And why is that? Why do we have this variability in the anatomy? We have patients that have evidence of neurovascular compression. They've been imaged for something else. They don't have any pain. As you know, that comes to roughly 17% of people in the normal population have evidence of neurovascular compression of the trigeminal nerve but don't have any pain. Interestingly, and these studies point to older studies, some of them done by the group in the 2000, I think, 2009, where they did a broad study looking at the incidence of neurovascular compression patients, trigeminal neuralgia, as well as healthy controls. Roughly 40% of patients with trigeminal neuralgia have, in fact, evidence of bilateral neurovascular compression. The pain, however, is uniformly unilateral. The incidence of bilateral compressions is indeed higher in trigeminal neuralgia patients than in normal population. There's also a substantial percent of patients of trigeminal neuralgia without obvious neurovascular compression. We can blame some of that on imaging. Maybe we just have not picked up the right level of the nerve to detect the compression. Maybe the compression is not directly compression by a vascular structure, but perhaps a cuff of arachnoid. I have seen that. I've seen very tight arachnoid on top of the nerve that needs to be cut with scissors or an arachnoid knife, and it has, in fact, left a mark on the trigeminal nerve. So, all of those might be missed by MRI. I take that into account. But there's no doubt that the current understanding of neurovascular compression based on imaging is insufficient in giving us the adequate information that we need to adequately define this entity in these patients. And my research goal has been for the past 10 years to move beyond clinical criteria as a sole identifier of these syndromes, and in such really start introducing images, imaging of the trigeminal nerve and the trigeminal fibers to understand better what this structure is like, and not so much focus on the blood vessels, which I think has been our go-to because we really have not been able to image the nerves well, but focus on imaging of the trigeminal system itself, draw metrics from the different parts of these structures, and try to understand better what is happening to the trigeminal nerve, and, therefore, what is resulting in this condition. And try to understand, for instance, whether we can distinguish brains of patients that have trigeminal neuralgia from those that don't, and for that we've actually moved on to the use of AI techniques to classify brains in this manner, and also walk essentially step by step, voxel by voxel, along the nerve within the fibers of the brainstem, within the cistern, at the nerve entry zone and beyond to see what the structure of the nerves are and how they might be affected in patients that don't have any pain, they don't have trigeminal neuralgia versus those that have classical trigeminal neuralgia, and potentially those that have MS-related trigeminal neuralgia, which as you well know can have an almost identical expression of pain, but we know that, of course, in those patients, the primary problem are these plaques within the brainstem, and not so much neurovascular compression. After having many, many of these patients, we've actually identified a new syndrome, and that is a syndrome called a single pontine lesion trigeminal neuralgia. These patients, of which I've collected roughly 30, and we've described that recently, are, again, those that present with classical trigeminal neuralgia symptoms, but when we study their imaging, and particularly interestingly in T1 images, we see this one single plaque whose entity is not clear and not understood. You can see it here with the red arrow, but also highlighted here for you. And there's nothing else in the brain. These patients do not meet the criteria for multiple sclerosis, and the important thing to know in these patients is that when we map, when we use advanced imaging technique, we map their brainstem fibers to the fibers of the trigeminal nerve, and the vast majority of these patients, to a rate of 95% of them, do not have long-term benefit from conventional surgical procedures. They might have benefit for, say, a few months or so, then their pain recurs and recurs and recurs. So, some of these patients were mine, some of them were referred to me after not having had good benefit elsewhere, but we've mapped into these conditions. So, in fact, this syndrome is more of a central syndrome, obviously. It's in the pons. We are not able to really address it with conventional procedures, and in these patients, I have now moved to the use of peripheral field simulation, or essentially neuromodulation techniques, which I find are much more effective, rather than these patients having procedures again and again. We would like to really come to a point where we are able to image the trigeminal system of patients individually in such manner that we actually have a proper conversation about the odds of them, of that one patient, being better from surgery and not merely relying on general statistics for patients, and tell them, "Well, the likelihood is 90%, but we don't know how that refers to you in particular." And again, this goes back now to 2019 where we first published our paper that looks at the machine learning classification of the human brain predicting classical trigeminal neuralgia versus normal controls and how the networks that are important in these patients are different in normal controls versus patients with trigeminal neuralgia, and importantly, how the brainstem, in fact, serves to contribute as well to the prediction of pain, so patients, this is a collection of patients that have gamma knife radiosurgery, patients that are going to be responders. This is a priori. This is prior to us performing a procedure in these patients. They have microstructural changes in the nerve that refer primarily to the cisternal component, whereas the ones that are non-responders, these changes are now in the pons, suggesting they, in fact, we're dealing with two different types of patient populations, and maybe if we are able to investigate this a priori, again, we would have a different conversation with patients as to what is the likelihood of them benefiting and what are the procedures that are options for them. And the last bit is our work focusing on the brain and using the brain as a predictor of likelihood of surgical outcome, and it turns out that the brain is, in fact, a much better predictor than the brainstem, suggesting that, in fact, the input that we have, the input that we have in control of pain is quite important, and that is an important area of investigation for us. Again, it's valuable to know that it refers to networks, and these are networks that we've identified that, again, allow us to a priori determine what is the likelihood that a patient would be in the responder population versus in the non-responder population. So, both the brain, the brainstem, and the nerve, each of them contribute to our understanding of how likely it is that a patient would be a responder or non-responder. And I think as time has gone by, and I'm going to go all the way back to our very initial slides of our historical development. We see that we have now moved away from this general conceptual understanding of trigeminal neuralgia and are now focusing on much more direct, objective measures, and if there is one legacy that I would love to have is one that allows us to have a greater level of objectivity for the understanding of pain and how all of these physiological anatomical metrics contribute to the expression of pain and how we can actually intervene to provide the best outcome for our patients. So, I just want to end with this slide before we have our conversation. This is a philosopher by the name of Walter Benjamin, who in 1935, so we're going back, really, to before World War II, was talking about the concept of art and how art had changed tremendously, and his words are as follows, that in the arts, again, this is 1935. "In the arts there is a physical component which can no longer be considered or treated as it used to be, which cannot remain unaffected by our modern knowledge and power." And "For the last 20 years, neither matter nor space nor time has been what it has been from time immemorial." So, it refers to how rapidly the world is changing and art is changing with it. That "We must expect great innovations to transform the entire technique of the arts, thereby affecting artistic invention itself, and perhaps even bringing about an amazing change in our very notion of art." I would be bold enough to say, Aaron, that as surgeons, we are also artists, and to be able to affect the life of our patients in a positive manner, whether it's treatment of trigeminal neuralgia, where there's resection of a complex tumor, where there's clipping of a difficult aneurysm, where there's removal of a chronic subdural hematoma, all of this, in my view, also amounts to art, and I think that is an important concept for us to consider because it's that layer that adds to the way we do things, the approach that we take, the way we think about the procedure, and the way we really put the patient at the center of that procedure that really delivers all of these aspects. And again, I want to maybe note the group of students that I have that help me do the research, but importantly, focus also on the amazing surgical team, my colleagues at the University of Toronto and the team in the OR that really allows me to do these procedures. And with that, Aaron, I want to thank you again for asking me to participate in "The Virtual OR."

- Great work, Mojgan, really enjoyed it. I think the statement about being an artist is so critical and all the statements, you said the technical perils are so important and really, the issue that we all struggle with is where is the pathological entity residing in trigeminal neuralgia? Is it a central one? Is it a peripheral one? Is it a combination of both? Is it something that, in fact, some people are predisposed to and the vessel is in fact just a secondary insult? These are excellent points that I know your team have been working with and many others, but still, a number of question remains. What are your thoughts? Where do you think the initial pathological entity for trigeminal neuralgia resides?

- Aaron, that's the ultimate question. I personally feel an important culprit that needs to be taken into account is the junction of the central and peripheral myelin. I think that's a weak spot. I think there might be many reasons why that weak spot becomes, in fact, even weaker, And as you know, in the 2000s, there were some pathological studies, some neuropathological studies where they were, in fact, able to look at the root entry zone in patients with trigeminal neuralgia, and they reported, and these are studies by Love and Coakham, that reported areas of focal demyelination. I think those areas of focal demyelination trigeminal neuralgia are in fact accentuated at the junction of central and peripheral myelin, and perhaps the concordance of the anatomical junction of central and peripheral myelin, and the position of the vessel is really what results in neurovascular compression being such an entity for us. The key to consider, as you well know, is that the anatomy of the root entry zone is not a flat junction between central and peripheral. It's cone-shaped. And that cone-shape, in fact, allows for a range, perhaps several millimeters, over which sometimes one sees a very proximal neurovascular compression, and that can affect the patient, and sometimes one sees one that's a little bit more distal, and it's difficult to conceptualize, well, why would a distal compression be equal to a proximal compression from one patient to another? That might have to do with the detailed anatomy of the central and peripheral myelin. We have not been able to image that properly yet. Another thing to note as well is that of course the caliber of the number of fibers and the caliber of the myelinated and unmyelinated fibers within the trigeminal bundle. So, these are areas where we still have significant limitations in our imaging capability, but they're of great interest to me, and hopefully we will reach a point in which, again, on an individualized manner we'll be able to distinguish this key area, this key anatomical junction that I think is an important contributor to pain.

- Right. Yeah, and there are many individuals who have trigeminal neuralgia have no vessel compressing, and so these are especially younger patients, which I do believe people who are younger than 50 may have a completely different syndrome where the vessel is not present usually, and a rhizotomy procedure and negative exploratory operation with squeezing the nerve or doing any sort of other sort of ablative procedure may help for a while, but then the pain comes right back. So, it's been my conviction that trigeminal neuralgia is an extremely heterogeneous condition based on the age, based on many other factors, and we are still not able to understand this disease, which is so unfortunately problematic. It's extremely painful, most likely the worst pain humans have been afflicted with. So, it's a lot that we need to still learn about trigeminal neuralgia, unfortunately.

- Yeah, Aaron, I completely agree with you. It's very interesting because generally we qualify trigeminal neuralgia as a rather homogeneous condition in the fact that patients have certain aspects of their presentation that is rather uniform: lancinating pain, generally no pain between attacks, good response to medications such as carbamazepine, et cetera. But in fact, when we focus on these patients, and as neurosurgeons start looking into this condition more and more and the number of patients increases, we actually start to see this level of heterogeneity that you described and the aspect of the expression of pain, the general presentation of clusters of pain, for instance, several months and then they're good for like a year and then maybe several months, and slowly that wellness interval decreases and decreases. And these are, again, I think windows of clues that if we were detectives, we would pick on and think of how the trigeminal nerve can express itself from the very initial pattern of pain and compression to then a position where it's established and they come to us to seek medical attention or surgical attention.

- Well, I want to sincerely thank you, Mojgan. A tremendous lecture. Sincerely appreciate your contributions to neurosurgery, and we hope to have you again with us in the near future. So, thank you.

- Thank you very much again, Aaron. Thanks for inviting me.

- You're welcome. Thank you.

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