Well, good evening, everyone. And welcome to our ASSH webinar on the management of neuropathic pain. We've got an outstanding faculty for you today, including Omri Ayalan, Kyle Eberlin, Brian Loeffler, and Holly Power. So your audio as a participant will be muted during the presentation, and this webinar will be recorded and sent out to you. And I encourage you to use the Q&A section to submit your questions to our panelists. And the Q&A session, we'll be monitoring that throughout the talk, and we'll hit some of the questions in between talks, and the rest of the questions, we will respond to you directly through the webinar. And if there's any technical difficulties, you see there the number you can contact for web support at ASSH. For your CMEs after this, if you go beginning next Tuesday and log into ASSH.org, go to your login and go to My Dashboard, as you see here, and click the My CMEs, and you can capture those CME credits. So with that, our first talk is going to be by Holly Power. Take it away, Holly. All right. Thanks very much. I am just figuring out my screen share here. Can you see my slides? Great. Well, thanks. It's an honor to be included on this webinar. I'm going to talk about the non-surgical management of patients with neuropathic pain. So this is actually a pretty basic talk to get things started. And there is a ton of literature out there in the pain world that, as surgeons, we're probably not always familiar with. So getting right back to the basics, sorry, I'm trying to get rid of this thing that's blocking my view here. So what is pain? We all learned about this in medical school. Pain signals are transmitted to the brain when specialized nociceptors are stimulated in the periphery. But what we're probably a little less familiar with is that once these signals reach the cortex, there are three centers, sorry, my screen is frozen, okay, there we go. There are three centers that modulate the sensory, affective, and cognitive elements of pain. And based on output from these regions, the descending pain signals are modulated and transmitted back to the periphery. And this becomes important when we're talking about treating central pain. So we all know that people perceive pain differently, and this is influenced by biological, psychological, and sociocultural factors. And it's important to recognize that treating all of these elements can be important for these patients. So when we think about types of pain, there are three types. Nociceptive pain occurs in response to damage and activation of nociceptors. Pain that occurs independent of nociceptor activation is neuropathic pain, and mixed encompasses both types of pain. Neuropathic pain is typically defined as peripheral and centrally mediated. And you can see common etiologies listed there. As surgeons, some of the more common etiologies of peripherally mediated pain that we treat would be compression, traction, and symptomatic neuroma. So we all know that when nerves are cut, they tend to grow neuromas, but only some of them are symptomatic. And this is a great paper that was actually co- or senior authored by one of my co-panelists, Dr. Eberlein, and I think is really important in diagnosing a symptomatic neuroma. So I use this all the time in my practice, and patients should have all three of neuromatous type pain, symptoms in a defined nerve distribution, history of nerve injury, plus one of either a positive Tonell sign, a neuroma identified on imaging, and a positive response to a diagnostic nerve block. So for centrally mediated pain, in addition to those peripheral mechanisms, the chronic afferent pain signals can lead to altered pain processing in the CNS, or so-called central sensitization. And many of the medications that we use to treat neuropathic pain act on these descending pathways. Complex regional pain syndrome is something that we commonly see and dread in our practices. Type one occurs after no identifiable nerve injury, type two is associated with a nerve injury or compression. It can be sympathetically mediated or not, and the diagnostic criteria that is most commonly used would be the Budapest criteria. In terms of your evaluation, a couple of the key points that you want to actually assess when you're dealing with a patient with neuropathic pain are risk factors that might predispose them in our line of work specifically to symptomatic neuroma. So risk factors would be a traumatic mechanism, a proximal amputation level, psychiatric or chronic pain history, and interestingly, older age, diabetes, and hypothyroidism do appear to be protective. Evaluation of pain in an objective and serial fashion is very useful to assess the severity and burden of injury, as well as to determine the prognosis and possible alternate contributing factors. So, for example, if you're about to go in a room and see a patient and they have this pain diagram, that's much different consultation than, for example, the one on the top. Your examination should seek to determine the location and distribution of a nerve injury if present, and you want to perform a detailed motor and sensory exam as well as assessment of vasomotor, pseudomotor changes. If you're dealing with an amputation patient, you want to assess the residual limb for alternate causes of pain, such as bursitis or bony prominences. You may want to include electrodiagnostic testing on your workup if you suspect compression or if there's a nerve injury with a viable distal target. MRI and ultrasound, both useful for detecting neuroma size and location. But the key here, I think, and I'm sure my co-panelists will agree, is the diagnostic nerve block, particularly for symptomatic neuroma. This can be done with ultrasound guidance or using surface anatomy and is generally local anesthetic injected adjacent to the area of concern. The key thing here is a pain diary is really critical, so you want to assess the patient's response while the local anesthetic is active. So non-surgical management, I think multidisciplinary care is very important for these patients. So as surgeons, we can remove the symptomatic neuroma, give it a new job to do, prescribe medications to improve their pain, but the functional, sleep, mood, social, spiritual consequences of pain must also be treated, and that's where our allied health colleagues come in. One thing in particular that I use a lot in my practice is graded motor imagery, and this is a helpful behavioral therapy that targets the cortical representation of the amputated or injured limb, and you can actually get smartphone apps now that patients can use at home to do this therapy when they're outside the clinic as well. So in terms of the medical management, again, there is a whole host of literature out there that surgeons were maybe not exposed to. I thought that this was a great reference here at the bottom of the slide. This paper actually amalgamates a whole bunch of different international guidelines into this easy-to-digest algorithm, and I'll go over some of these medications in turn, the more common ones. So gabapentin, we're all familiar with that, large safety margin, patients complain it makes them sleepy, makes them have a brain fog, and there have been many, many studies conflicting results, particularly with residual limb pain and peripheral nerve injury, but a large Cochrane review found in over 5,000 patients that more than 50% of patients actually did not have worthwhile pain relief with this medication. Likewise, pregabalin, similar mechanism, more favorable pharmacokinetics in a meta-analysis involving more than 11,000 patients. Some had good pain relief, but many had no benefit. Again, I think it's important to highlight that a lot of this literature is neuropathic pain in general, so that includes diabetic neuropathy, post-traumatic neuralgia. The literature specific to post-traumatic neuropathic pain is actually quite limited. Amitriptyline, a tricyclic antidepressant that works via serotonin-norepinephrine reuptake inhibition probably has the most compelling evidence of effectiveness for neuropathic pain. Large meta-analysis, 588 patients found that the number needed to treat for at least 50% pain relief was only 3.1 patients. The downside is the side effect profile, because this also acts on histamine, epinephrine, acetylcholine, so patients sometimes won't tolerate it. Duloxetine, another SNRI with a more targeted action than the tricyclic group. Large meta-analysis, more than 4,000 patients with all types of chronic pain, not specifically neuropathic, they found that patients who took duloxetine were two times as likely to achieve substantial pain relief compared to placebo. So if we look back at this algorithm that I presented before, the recommendation is to trial for four to six weeks one of these first-line agents. If that's not effective, you can trial one of these second-line agents or combo therapy, and if an adequate response, they should be referred to a pain specialist. Now I know access to pain specialists is probably a lot better in the U.S. than where I practice in Canada, so maybe you do this earlier, but this guideline is kind of targeted towards PCPs, so you can go ahead and apply it if you don't have good access to a pain specialist. A couple words on neuromodulation, so spinal cord stimulators traditionally thought of as a last resort because it's quite an invasive procedure. Leads are implanted in the epidural space, and then the stimulation actually suppresses the neuronal hyperexcitability. There's no denying the literature that these stimulators tend to work quite well for refractory pain. More recently, peripheral nerve stimulation has become more popular. This is where a lead is implanted adjacent to the peripheral nerve proximal to the site of injury, and then there's an external pulse generator that transmits the impulse wirelessly to that electrode, and there's several commercially available devices. Early literature suggests that this works quite well in post-amputation pain and other types of nerve injury, but I think more research is still needed to clarify the stimulation parameters, etc. Last couple of slides here, just a few words on complex regional pain syndrome treatments. So of course we want to prevent it from happening, avoid tight dressings, don't injure the cutaneous nerves, respect them during your dissection, vitamin C, not harmful, little downside but maybe not effective after this study in JBJS refuted previous studies, and of course all of the previous mentioned treatments that I talked about can be applied in CRPS as well. Additional specific therapies, so steroids can be used in the acute phase as a short course to reduce inflammation, bisphosphonates, which act on bone mineralization, may work in patients that have profound periarticular demineralization, but again there's not very good high quality evidence to support this. In patients with sympathetically mediated pain, they may respond to a sympathetic block such as a stellate ganglion block, but again the evidence is definitely not high quality. Traditionally we're taught not to operate on patients with CRPS, but certainly there is a subset of patients with clinical evidence of compression that may benefit from a nerve decompression, so the most common scenario I guess would be a distal radius fracture with carpal tunnel syndrome, and there's definitely good literature suggesting that these patients do remarkably well in terms of pain relief after decompression. So as a segue into the next talks focused on the surgical treatments, who should you operate on? Symptomatic pain I think that limits function and quality of life. Patients that have the diagnosis of a symptomatic neuroma or peripheral nerve compression and have failed non-surgical management, I think you should operate on those patients as soon as you have those criteria met. Thanks very much. Perfect. Thanks, Holly. Brian, you'll be up next. Brian's going to talk on RP&Is. Brian, you're still on mute. Brian, you're still muted, just so you know. So, okay, I just got my screen share. It's great. Am I off mute now? You're off mute, just no slides, but not bad for your first time at Zoom. You're going to get it. Yeah, no, thank you. Thank you. So I'll just kind of do those first few slides again there. Thanks for the opportunity to talk to you about RP&I and some indications and technical pearls, and then expectations with these are my disclosures. So just a brief introduction, RP&I, as I'm sure everyone knows, was developed by Paul Cederna in his lab at the University of Michigan, essentially involves taking nerve endings and implanting them into free muscle grafts. And then those muscle grafts survive the same way the skin graft does through imbibition, observing the vascularity and nutrients in the surrounding area, and then revascularizing into the muscle to prevent necrosis of the muscle. And there have been many studies on this since it was first described, showing its efficacy. And just an example here, a radial sensory nerve, you can see there's a left forearm where the nerve's been transected distally, and then rerouted up into more of the proximal part of the forearm, and the muscle wrapped around the end of the nerve. So there's, I have some overlap with TMR, and I'm not stepping on Omri's toes at all, I hope, but I do think that they are hand in hand, and there's expanding indications for both. And we can kind of talk about why we may use one approach versus another, but certainly for non-amputees as well as amputees, they can both treat and prevent neuromas, perhaps treat neuropathic pain even, and prevent that as well. So this is in the context of nerve management strategies, including traction, anorectomy, end-to-end nerve repair, analograft, nerve-to-nowhere, TMR, and then RP&I, and we kind of have a lack of head-to-head studies to show really which ones are best, but we'll review the literature and you can see that RP&I, as well as TMR, are really quite effective in nerve management. So this is just my own personal algorithm and what we actually do at OrthoCarolina for the most part. So TMR really is preferred in the upper extremity when a myoelectric signal is needed from that donor nerve. So when we're trying to create intuitive control and create an additional signal for myoelectric control, it's important to perform TMR. And in general, we'll use this more preferentially in large mixed motor sensory nerves. Now RP&I can be preferred when you don't require a myoelectric signal for prosthesis control, for example, in the lower extremity or even in the ulnar nerve in the upper extremity. If you have a good grasp signal or hand-close signal from the median nerve, the ulnar nerve becomes kind of an accessory signal. For sensory-only nerves, it makes sense to do RP&I. I believe we can preserve more of the natively innervated residual limb musculature, which can help retain muscle bulk in the residual limb. When you denervate an entire muscle and do TMR on it, it does get reinnervated, but not to the same bulk and tone as the residual limb. And so that can be helpful for fitting of a prosthesis. I think when you're working through a wound and you have muscle graft that's locally available or if it's being excised, it makes sense to just go ahead and put that to use. And similarly, when you're working through the incision to perform the amputation or the other procedure that you're performing, to avoid a second incision or raising up large skin flaps, you may choose to perform RP&I over TMR. So if I think about some technical pearls, I think a properly sized graft, measuring around 3 by 1 by 1 centimeters in size, I think it's important that when you have large or nerves that you divide the nerves so that you reduce the axon input to each of the grafts so that the axons aren't overwhelming the muscle graft, the number of motor end plates available. So for example, for the radial sensory or lateral lenobrachial cutaneous nerves or oesophagus, we will probably just do one nerve ending into a free muscle graft of that size. If you're looking at the ulnar or tibial or peroneal nerve, for example, probably divide those in half. and then I've even done this in the sciatic nerve, and we really divide that in the tibial and peroneal nerves and then split those in half as well, so I really end up with four free muscle grafts for a sciatic nerve. The way we perform it, depending on the size of the nerve, will be anything from 6-0 to 8-0 nylon for the nerve to muscle repair, two or three sutures to secure that and create that RPNI, and then we will perform a muscle wrap, so essentially creating a collar around the epineurium with the muscle graft to prevent any axonal escape. We then like to create a pocket to bury that RPNI unit so that it's not on a weight-bearing end of the limb or an area that's likely to get mechanical stimulation, and we also want to make sure that there's no tension on the nerve when we bury it in that location. So nerve management with RPNI is effective treatment for established neuromas, and then during amputation definitely an opportunity to prevent and treat chronic pain. So if we look at a recent systematic review looking at the results, a nice summary of the literature available on TMR and RPNI, you can see that in 75 to 100 percent of patients in different series that the neuroma pain is improved when we're treating a neuroma, and then half to all of the patients in these series have reported no neuroma pain postoperatively, and then you can see somewhere around two-thirds of patients or so will get a significant reduction in their phantom limb pain, resulting in anywhere from a two to six point reduction on a scale of ten in pain on a numerical rating scale, so pretty significant improvements for the treatment of neuroma-type pain and phantom limb pain. If we look at prophylactic treatment for RPNI, you can see significant reductions in phantom limb pain in the RPNI groups compared to controls, so one study showed 50 percent in the RPNI group versus 91 percent of controls had phantom limb pain, and then again, you know, about two-thirds of patients, no phantom limb pains when undergoing RPNI prophylactically. Similarly, a significant reduction in neuroma formation, anywhere from 50 to 100 percent of patients around 75 percent with no neuroma pain, and this also has been shown to increase prosthesis wear without increase in complications, just a couple of references there, so I'll just show a few different case examples where we would use RPNI and our current algorithm for the management of a distal forearm just to illustrate some of the points. So, we would use TMR actually for the median nerve to get a hand closed type signal. We use pedicle pronator quadratus when it's available, and that helps us with neuroma pain as well as with prosthesis control, and then we may choose to do RPNI for the ulnar nerve as well as radial sensory nerve, and so you see there we have split the ulnar nerve actually in this case. We really don't need that for a myoelectric signal. We have plenty of muscle available for those free grafts through that incision without raising large flaps, and we can perform that for both of those and tuck those away without any proximal dissection. It also eliminates the, again, mechanical stimulation that you can get when you have a tightly fitting or well-fitting prosthesis, so as opposed to, you know, what we may do in a proximal forearm where you have the nerve transfers, either TMR or the RPNI that's in the region where the prosthesis is fitting, you can bypass that by doing it all through the distal incision. Just an example of a radial sensory nerve being reflected approximately in the setting of a transradial type amputation. You can see we try to keep, you know, little tension on that RPNI unit there. For partial hand amputations, we may do this, for example, in conjunction with starfish procedure, so when we're doing, as you can see in the upper right there, that's the RPNI unit. We may be excising a vulnar interosseous to prevent myoelectric crosstalk, and so it's readily available right there, a very effective means for treating those common digital nerves at that level and setting the patient up for successful prosthesis wear in preventing or treating neuromas. We also may do this in the setting of a ray resection or post-operatively if a patient has symptomatic neuroma following a ray resection, and again, as you can see in the lower right corner there, once we create that RPNI unit, we will then bury it and tuck it away so it's not going to be stimulated. We'll close, we'll use the vulnar plate, we'll use extensor tendons to create kind of a sling to protect that so the nerve is not stimulated. As I mentioned with osteointegration, this is transfemoral level, we're doing, oftentimes we're actually doing it just through a distal incision, so not even extending this along the lateral aspect of the thigh. This one was, the sciatic nerve was retracted more proximally, but very large and painful symptomatic neuroma. This obviates the need for a second incision going more proximally or posterior, and we can kind of do it through the same incision in the same operative setting as the osteointegration procedure, and I mentioned we divide the tibial and perineal nerves and then split those further such that we have those free muscle grafts in place and then no tension on those as we tuck them away to an area that's not going to be weight-bearing. We also use a combination of RPNI and TMR for trans-tibial indications, and again, similarly, combination of the two, the sensory-only nerves like serral and saphenous are more likely to do RPNI, whereas we may use TMR for the larger mixed motor sensory like tibial and perineal, and here's just a quadrilateral amputee who's had a combination of TMR and RPNI for both upper and lower extremities just working on it there on the exercise machine there. So I think we're still really, you know, refining the TMR and RPNI indications, but just to summarize, again, they, you know, both strategies can reduce phantom limb pain as well as residual limb pain in amputees, and it can be used as a prophylactic measure or to treat neuromas for both amputees and non-amputees, and it's really been performed now essentially for all peripheral nerves with many case series now demonstrating benefits for pain and neuroma management. It may play a selected role in neuropathic pain management, but further study is certainly required for that. And I would just say TMR, as we know, is a very effective strategy for improving intuitive prosthetic control, and RPNI really does have the same potential as well. Unfortunately, at this point in time, it's not widely available, but with implantable electrodes into those spring muscle grafts, it's been demonstrated that electrical signals can be generated with RPNI as well that can control myoelectrics in an intuitive way. And finally, I think, you know, in order to determine superiority and the exact indications for TMR and RPNI, well-designed studies would need to be done, but I would say that in general, the literature really guides us that both of these seem to work quite well. So, thank you. Thanks, Brian. As we switch over to Omri, there's a couple questions that kind of overlapped in terms of just how are you coding RPNI? So, the code that we use for RPNI is 15770, so I think it's something along the lines of a free muscle graft. I will say that we've been told, at least where we are, that there's an MUE or maximum units that can be charged of two, so if you do more than two, then there's a separate code for just burying a nerve into a muscle that can be used as well if you're doing more than two RPNIs in one setting. Yeah, and you're joining that with a neuroma excision code, of course, if it's not acute. Right. Perfect. Omri? Thanks a lot, and that was a great talk, Brian. Thank you. Okay, so I've been tasked with talking about TMR. Can you guys see my screen okay? Yep. Perfect. Yeah, so I'm excited to talk about this, I guess, relatively young technique that's really taken off and when done appropriately can have some exciting applications, many of which have been developed and examined by members of this panel, so that's also exciting for me. So, in the world of amputation surgery, neurogenic pain is very common, and we see it all the time. It can be debilitating and prevent someone from using a prosthesis, which is the goal, like this gentleman here, and TMR can play a role in treating his pain and also allowing him to start rehabbing his life and using his dominant hand in a meaningful way. This is what we'll talk about here. So, just briefly, what is TMR? It's a technique that involves transferring injured or amputated, they're usually often mixed motor nerves to motor branches of functionally expendable units, and it's important to mention that even this definition doesn't necessarily have a clear consensus among surgeons that are performing these procedures, so that's something to keep in mind. So, the idea here is that we're taking an amputated or a neuromatous nerve that isn't connected to the CNS, and then by performing TMR, we're closing the circuit, and it's been said, I'm sure you've heard, that we're giving the nerve somewhere to go and something to do instead of just churning out neuromas and soft tissue. So, a little bit of history. The first description was in 04 from Todd Kiken and Greg Dumanian at Northwestern, and they discussed a case of a bilateral high-level disarticulation at the shoulder level, and they were simply trying to increase the number of myocytes to control a myoelectric prosthesis. And, of course, to our delight, they observed some wonderful benefits, such as a decrease in neuroma and phantom limb sensation, along with increasing their myocytes. And so, after that, the wheels started turning, and how are we going to translate this experience to managing transected and injured nerves throughout the body? And so, now we're seeing this sort of explosion of applications, not only to neuromas and in amputation surgery, but in treating potentially chronic and neuropathic pain, and even vascular paths to some extent, which we may touch on a little bit. So, I think the workup and the indications are, as if not more important than the actual surgical technique here, because it can really make or break the patient's outcome in TMR. So, just like we said before, we're getting a good history of a nerve injury and a focused exam, being able to reproduce the pain with a TINL, and the patient being able to describe a dermatomal distribution of the pain is super important in ensuring that the problem is peripheral as opposed to central, which, you know, as a peripheral nerve surgeon, I'm not able to manage central pain. So, we routinely use selective lidocaine injections in the office, and sometimes we get the radiologist to help us out, which can definitely confirm and then predict your outcome after these. So, when you're planning a case, such as various amputation levels, there sometimes are recommended or prescribed transfers, but those are really just guides because there's lots of different ways you can get to the same place, but it's important to understand which motor targets are available at each level, and you want to make sure that you don't burn any bridges by doing TMR, especially you don't want to negatively impact the patient by denervating a muscle. Like was mentioned, you may lose some bulk, which may change the soft tissue envelope, and obviously you don't want to create a motor deficit. So, it's important to understand the patient's goals, which may be simply pain relief or actual muscle control, and of course sometimes you need to be flexible, and this creativity is one of the things I enjoy about this kind of surgery. So, the first step when you're doing these cases is find your targets. If you're using a nerve stimulator, which you should be, it kind of makes the finding the targets kind of foolproof, and it can be very helpful when you're digging through prior scar. Just a little note is you only have about 30 to 45 minutes of good stimulation time when using a tourniquet, so you want to kind of jump on this quickly, and then once you have a good target, you should denervate the remaining innervation points to that muscle, and you want to make sure that your transfer is the only input that that muscle is receiving. So, next you'll excise the neuroma or the damaged or amputated nerve, whatever you're dealing with, and you want to make sure that you have enough length to create a tension-free coaptation without much redundancy, and that coaptation should be at a point that's close to the innervation point to decrease the re-innervation time and hopefully decrease the time to symptom recovery, and like any good nerve surgery, obviously you want to cut back to healthy pouting fascicles, and in most cases we do, at least where we are, tend to excise the blind distal neuromas, even though they may not be a neurogenic source of pain, they may just kind of create a mass effect that can be bothersome for patients, especially with prosthetic use. So, as I said before, there's no real consensus on the exact coaptation technique. Obviously, everyone thinks that their technique is the best, but you do want to make sure that you have a tension-free coaptation, and if you're worried about the size mismatch, which we'll touch on in a second, you can bury your coaptation in the muscle to help prevent exon spread, and we generally use 8-0 nylon and some fibrin glue. So, some basic principles here. You want your coaptation close to the target, like I said, to limit the time to re-innervation, and sometimes there's this mismatch in size which may make you a little nauseous looking at it, but the truth is we aren't exactly sure how much the size mismatch contributes, and it may be less bothersome than we initially thought. Some ways that you can potentially avoid this mismatch is, like I said, invaginating the coaptation in the muscle, or you can perform fascicular dissection and do separate transfers for fascicles, which we routinely do on the larger mixed motor nerves, like the sciatic nerve or even the radial nerve, more proximal. So, there's some evidence, some kind of weak evidence, that potentially axonal pruning is what is preventing this recurrent neuroma based on this size mismatch. So, another principle of TMR is, I think is really important, is denervating the muscle to make sure that there's only one signal getting through, but you also need to remember, as Brian said, that this muscle will lose some power and bulk, and so you need to make sure that that won't affect the patient negatively depending on their goals. So, some unsolicited opinions of mine in terms of what to expect before we get to some literature is that I do think the vast majority of patients improve. This, for example, is a video of a gentleman who's only a month after transhumeral amputation. He's already able to intuitively control a virtual myoelectric hand. Another point is you need to tell them that potentially their symptoms are going to get worse before they get better. I mean, we are, after all, creating nerve trauma, and there's something kind of magical about the three-month mark that we've seen is that patients sometimes at the three-month mark start to improve in terms of their symptoms and their control of a prosthesis. So, a little bit of literature here. So, this was a prospective study looking at severely traumatized limbs that showed pretty remarkable improvement in neuroma pain, and it was allowing these people to actually use a prosthesis, which is kind of like the holy grail for us. And then in thinking about TMR as a prevention, this was bore out in the study just highlighting that the technique can be therapeutic as well as preventative, especially if you know that you're going to develop a neuroma like in amputation surgery or in, let's say, nerve graft harvesting. So, what are some drawbacks? You know, with any new technique, we want to make sure that our enthusiasm doesn't outpace our data or experience, which represents definitely room for a lot of new investigation. I think that recurrent neuroma is a real problem, and it may potentially be due to size mismatch or incomplete denervation. Unmasking happens, and it can feel a little bit like whack-a-mole. You take care of one problem, another one pops up. And so, that's something that the patient needs to be aware of as well. And, you know, not every case is a home run, at least not in my hands, and it could be due to issues at the coaptation site or potentially our lack of understanding of clear indications for the role of TMR, for example, in vasculopaths. I think that question is still unanswered. Like, for example, in those patients, I may more lean towards doing RPNI. And then, in terms of CRPS, I think that TMR is great, obviously, when you have an identifiable nerve lesion like in type 2, but I think the jury is probably still out on type 1. So, some common examples here that may come up, or applications, I should say. So, for neuromas in the common digital nerves, they can easily be transferred to the interossei. And this is a nice schematic showing the innervation points of the volar and the dorsal interossei. They can be a very helpful roadmap for you. This was actually an amputee, a transmetacarpal amputee who had some symptomatic neuromas that was handled with a transfer to the volar interossei. And then you can also do TMR for sensory nerves. And then, obviously, the debate is going to be RPNI versus TMR. But there's lots of targets you can use, for example, for the wrist extensors, just transferring the nerve more proximal in the forearm. Another one that's gotten me out of some trouble is the terminal AIN branch where it innervates the pronator quadratus. And actually, that nerve reaches nicely to the palmar cutaneous branch, the dorsal sensory, or even the superficial radial nerve there. And one final common application that may come up for a lot of surgeons, even those not taking care of amputees, is we harvest the serral nerve oftentimes. And sometimes we think about it as benign, but it can create painful neuromas. And a dependable transfer can be to the lateral head of the gastroc or the soleus. And so just finishing up here, some final tips. I think it's important to have realistic expectations. Remember the three-month rule that your course can kind of change around that time. Spend some time planning your case ahead of time. And the importance of diagnostic blocks ahead of time cannot be overstated. A nerve simulator should just be part of your booking for these cases. And try to find those motor targets as soon as you start. The size mismatch, try to limit it just like any good nerve surgery. And do your coaptations close to where they innervate the muscle. And don't forget to denervate each muscle fully. Of course, be flexible. And I think that this TMR has excellent potential. And when you can prevent, it may actually decrease the times you see these painful neuromas. And like I said before, I think that our enthusiasm is really high about this technique. And I think that the opportunities are really, really great. But we should probably, as a specialty, do a little work towards standardizing a technique. And like was mentioned before, think about some prospective head-to-head studies with these techniques that we're talking about. Thank you. Thanks, Amr. That was great. And I know in the chat, Jeff had a great question. We're going to come back to that one. I want to use that after Kyle's, because I think that's a good question. You touched on it a little bit too, which is do you take out the distal neuromas? We're going to save that one. But while Kyle's loading up, something that kind of crosses over what you said and what Holly mentioned as well that we've seen is this challenge of patients that have had chronic pain prior to their amputation, and they're on high doses of medicine. So they've almost got that cortically imprinted pain cycle. And we got burned on several of those patients early on, not recognizing the need to wean pain medicines in advance. So I wonder, you guys' personal strategies quickly on, do you wean them down at first, or do you rely on surgery to do all the work for you? You want that, and then Holly, just real quick before Kyle goes? Yeah, I think it's like anything we've seen, that the more work you go into the workup pre-op, I think the better their outcome is. So if you can get your pain colleagues involved and have them understand where you're headed, as well as the OTs to try to decrease their requirements pre-op, I think that they definitely do better. Yeah, I agree with that. The other thing that we routinely use is a peripheral nerve blockade. So usually we put in a peripheral nerve catheter so that it's bolus before they wake up from surgery. And I guess the thought is that that can kind of reset the pain cycle. And then we have our acute pain service, our anesthesiology specialists in pain follow the patient in hospital and help us manage all the medications. All right, Kyle, I'll bring us home and then we'll finish up with questions. Great, well, thanks a lot for having me. I appreciate the opportunity to be on this panel. My charge is to talk about alternative approaches for the surgical treatment of symptomatic neuromas. And I've really enjoyed all three of the talks that have been given so far. Here are my disclosures, which are relevant here. My other disclosure is I take care of a lot of patients with tons of pain. And this is a patient that I did an above knee amputation on about two weeks ago who had a tattoo that was circumferentially done on his thigh that says cut here. And he should have crowdsourced the level a little bit because we amputated a bit more distal, but this is a challenging patient population, which we all know. So in the next nine minutes or so, I'll briefly talk through an algorithm and how I think about neuromas. We'll talk about management of neuroma incontinuity as well as some alternative techniques for end neuromas that you could consider using in your practice. So we all know that any incision in the body can cause neuropathic pain. And everyone listening to this talk can look at this picture and know exactly what the nerve problem is in this case, because it's very common and any incision can cause neuropathic pain or symptomatic neuroma. And germane to the talks this evening, it's not only about TMR and RPNI. We don't know which techniques are the best. And in fact, as a peripheral neurosurgeon, our job is to have many tools in our toolbox and to have a large armamentarium that we can use for the right patient. And we really need to figure this out. And I think the next 10 years will likely yield that. This paper by Amy Moore and colleagues in the journal Pain in 2018, I think is quite a good one. I'd highly recommend it. And this is clearly a busy slide, but the whole summary of this paper was that they found that for all neuroma treatments, about 77% of patients got better, but there was no difference in this particular study between techniques. So if we know that most of them work most of the time, our job as surgeons is to really drill down and figure out what techniques are best for what patients. And I do think that we've shifted a bit in our algorithm, and this has been mentioned earlier. I feel quite strongly about this, that we are moving toward a more active or reconstructive approach to the nerve endings, which should guide us as surgeons in the care of these patients. So let's talk for just a moment about neuromas in continuity or a neuroma in which you have the terminal end of the nerve close by for you. There are many different things that you can do for these patients. I think reconstructing the nerve makes sense. And so there are ways to do that either with a nerve repair directly or a nerve allograft or autograft. So let's go through a very quick case, which highlights this. So this is a 45 year old guy, two months after a radial-sided wrist laceration at work. His skin was closed in the emergency room and he presented with pain and numbness. And he's got this soft tissue laceration, right? This is not a diagnostic dilemma. He has pain with ulnar deviation. He has numbness in his radial sensory nerve distribution. And when you explore him, he has these neuromas. Now this is not a neuroma in continuity or neuromas in continuity, plural, but you do have the terminal ends of the nerve right there. So I would argue in this case, our job is to remove the neuromas and why not reconstruct the nerve? Whether you want to use autograft or allograft, it doesn't matter so much. But again, I think that reconstructing the nerve when you're able to make sense. And this is a paper that we published looking long-term outcomes at digital neuromas. And if you reconstruct the nerve after removing the neuroma, they did better than if you proximally ablated the nerve. So all of this, I think to a large degree is intuitive. But if you have another case or a more challenging case where you have a neuroma in continuity with some function, this is where these cases get very difficult. So this is a young patient of mine who had a partial median nerve injury cared for twice by another surgeon. And she had a ton of pain in her wrist and she had no sensation in her second and third web space, but had preserved sensation in the radial side of her hand, the important side of her hand. And she had preserved thinner palmar abduction of her thumb, but this was all about the pain. And these are really challenging cases. And if you have a neuroma in continuity like this and you explore, we all know that when you find this, it's not going to be a 20 minute case. This is a much longer operation where you've got to bring out the scope. You've got to dissect out the intact facibles, which you can see here on the radial side versus the neuroma in continuity. But you have the opportunity, once you've resected this neuroma, you have a gap and you're able to rebuild it. In this case, this was purely sensory. I used a nerve allograft. I used a off-the-shelf nerve protector, but I also used autologous tissue. And I really like using autologous tissue to cover nerves. In this case, you can see the dotted lines and the radial aspect of the distal forearm. And I'm going to lift up the fascia based on the perforators off of the radial artery near the radial styloid and use that fascia carefully to cover over top of my nerve graft. So I think that anytime, and you can see this tucked here underneath the palmaris longus, but anytime you have the opportunity to use autologous tissue that's vascularized to cover a sensitive nerve, go for it. It's probably going to help. So when we think about N-neuromas and our techniques that are available, one of the questions about this came up in the chat. So I will spend just the last few moments going through N-neuromas. And we have this whole world of treatments available to us. And we've heard a lot about TMR and RPNI, which are frankly my favorite techniques and the ones I use most commonly, but they're not the only ones. And you should have an open mind for the other techniques that exist. And I'm going to talk through just a few of them. So what are our alternative techniques? The first one is combining TMR and RPNI. Why wouldn't you? If they both seem to work, why would you not want to combine them and use the get the best of both worlds? You can have your cake and eat it too. So there are many different ways to do this. This is a way that my partner Ian Valerio and I kind of independently started doing, and then we kind of wrote it up. But the whole idea with the way we do it almost all the time is, we will do a standard TMR nerve transfer where you have some degree of a size mismatch, but we will also take nearby muscle that is vascularized, but denervated, and we wrap the coaptation with it. So if there's any axonal escape, similar to an RPNI, it gets captured by that denervated muscle, which is really the key, I think. And other techniques have been described that are similar to that. This is Sammy Tufaha, who described vascularized denervated muscle targets, which is somewhat similar. I recommend reading this paper if you haven't and learning about it. It's really interesting. And there's another technique called TMRPNI. But all of these are variations on the same theme. Let's combine the two techniques, because you can, and you can do it most of the time. Number two, this one's a little off the beaten path, but it's one I've done quite frequently. Maybe not quite frequently, but I've done with some frequency, I should say. Something called the reset erectomy. And this is only for non-critical sensory nerves. So do not do this for a median or an ulnar nerve, please. But here's the idea. I was taking care of lots of patients with crush injuries to the nerve. And I thought, gosh, what if I were just to go proximal to that nerve? I'm going to cut it anyway. But if I send the axons right back down where they came from, and I basically just did a Control-Alt-Delete for the nerve. And this seems to work pretty well. You got to go more proximal than the nerve injury itself. Here's a little diagram of it being done in the lower extremity here. In a case scenario where you have a lower extremity, sorrel nerve, neuropathic pain patient, where she wants to preserve some sensation or sorrel nerve distribution if she can. So if you go proximal to the ankle where it hurts and you cut either a segment of the nerve or just cut the nerve itself, you sew it back together. In this case, we used a small graft, but you can send the axons back down. In the last two minutes, I'll share just a couple other techniques. Brian mentioned this earlier, the technique of relocation nerve grafting, which I do like in the hand, actually. And my indication for this technique or nerve allograft to nowhere very often stems from a neuroma case where you have a short length of the nerve, where it's hard to get it to where you want it to go. And you're also trying to redirect the axons away from a painful surface. So here is a patient who had a thumb, index, and middle finger amputation. There was pain in the first web space. To no one's surprise, there are large neuromas of the digital nerves here. And I resected the neuromas and I wanted to get the painful segment of the nerve away from the working bolar surface of the hand. And so I used allografts to send the nerves dorsally. It can help peter out the nerve signal a little bit. And I do find this helpful in my practice. The final thing I will say before we hopefully move on to some discussion is like mentioned by Holly earlier, I've been using a lot of peripheral nerve stimulators for the most challenging nerve pain patients. Guess what? We as peripheral nerve surgeons are operating around the nerve. So we can place the nerve stimulator directly next to the nerve. The pain management folks have to use ultrasound and do it percutaneously. And I think that we are best suited to be using these. So I would recommend considering this. This is, we've written this up for amputees. We have a series that we're gonna be publishing soon, but I have no disclosure with the company, but the one that I use is a stim router. You can see that you place the lead deep to the skin as Holly mentioned, and then patients are able to program their own device and there's lots of different settings. So I think that this is another thing that should be in your toolbox as a peripheral nerve surgeon in 2023. And this is what it looks like. So I wanna finish by saying that your approach to neuromas must make sense. You can use any of the techniques shown this evening. I think that it's important to do the thing that you feel is best for the patient in their particular problem. And we also need to study this. And my whole research efforts right now are really centered around the biology of neuropathic pain and neuromas. And we've built this pain center and hopefully in the next few years we'll come up with some interesting things. So thanks a lot for your time. I look forward to the discussion. Wow, that was awesome. Yeah, let's start right in with, I think Jeff's question, all of us, we're kind of nodding our heads and feeling the same way, which is the question of a patient has a neuroma distally, you're gonna go more proximal to do some procedure, RPNI, TMR, whatnot. Do you need to go take out the neuroma at the end? Because when I started my practice, the answer to me was, well, only as Amri alluded to, if it's causing some sort of mass effect or something, but then we had a series of patients come back and kept hurting right over that neuroma. And at first it seemed non-intuitive, but maybe there is something to peripheral nerves around that growing in and being a source of pain into that area. So we can kind of run around. You wanna lead us off, Kyle? And do you go take those out routinely now? Yeah, I mean, I'll be brief, but I do think that resecting the neuroma is a good idea. Let me give you a very clear example, which is common in hand surgery. If you have a distal radial sensory nerve neuroma near the wrist, as a result of CMC arthroplasty, de Quervain's, whatever, if you just go proximally and cut the radial sensory nerve and do whatever you're gonna do with it, you can still have trophic input into that neuroma from the lateral endobrachial continuous nerve or any of the other nearby branches. And if you do not completely remove the afferent signals from the neuroma to the brain, I've been burned three or four times. I'm a slower learner than Glenn and Brian, but I do think it's important to remove it. So I've gotten in the practice of almost always removing the terminal neuromas. Yeah, that mirrors ours. Omri, Holly, anything to add? Are you guys taking them out routinely? I think when we first started, we weren't. And especially for the lower extremity, when patients are bearing weight on a prosthesis or manipulating one with the upper extremity, I think that the mass effect actually was what led us to start removing it. And I think that our results are getting better. And so I think there probably is something to that trophic input. But we, I guess the answer is we routinely do resect them. Yeah, I believe it's sounding. I'm sorry, go ahead, Holly. Oh, I was just gonna say, yeah, same experience. We weren't taking it out at first. So the example I would use is a secondary BKA TMR case. So you're making that incision at the popliteal fossa. You're identifying the nerve. You've got the popliteal vessels there. There's all sorts of crossing veins. It is a nuisance to get that neuroma out. Like you gotta dissect real distal often. There's lots of vessels that have to be clipped. So we were maybe skimping a little bit at first and not doing it, but we definitely have patients come back with pain. So I think that trophic input is a real thing. Yeah, I was just gonna say, just a simple way to think about it. I think the surrounding tissues around the neuroma get secondarily, get sensitized. And I think that's kind of the mechanism for how the pain persists. Obviously they're not getting an afferent signal from the neuroma itself any longer, but the surrounding tissues. And I think that, what was I gonna say? Another thing I wanted to bring up, if you don't mind, was the role of the diagnostic blocks. Omri really harped on that. And we kind of were always doing that previously. But as time has gone on, we've gained more experience with it. I'm not sure what to make of those as much. I'm not quite as confident because we've proceeded with doing the diagnostic block in patients and didn't have a good response, still did the nerve intervention and they ended up with a good result. Had a decent result with the diagnostic block and still didn't get a great result with the nerve surgery. I think more commonly, it's no response to the diagnostic block, but still gets a positive response from the nerve surgery. So kind of wanted to bring that up for discussion with you guys as well, what your current role is for diagnostic blocks. Well, I think it's- Kyle, not only what's your role, but what if it's negative? Then what? So I think that for an extremity nerve problem in isolation, so not an amputee, but single nerve problem, I think a diagnostic block is incredibly effective and important to know if you can help that patient. That's for a single nerve. Amputees are a little bit of a different story. So like you guys and gals, we have not been doing diagnostic blocks in everyone. And in fact, in very few patients. So I use them if I really don't think that surgery is going to help. And they're getting the diagnostic block and I'm hoping it's not going to make a difference because I don't think the surgery is going to make a difference, but I want a reason to sort of prove that we shouldn't offer the patient surgery because otherwise they come in, as we all know, in a desperate situation that we want you to do anything. So I use them really to not do surgery, if that makes sense. Yeah, those are great points. I think that, especially with amputees, there can be so many causes of pain in the limb that may not just be the nerve. It could be from poorly performed amputation before, sharp bone edges, lack of soft tissue bulk. And so the injection can almost be like a diagnostic aid to say how much of this person's symptom is being contributed by the nerve. Almost like when you're evaluating wrist pain and doing selective injections to knock out certain entities in the wrist. So something we've done also is actually do this in the OR with the patient lightly sedated and do them right before surgery. Because especially in the severe, like crush injuries especially, a lot of that pain may be centralized. And so it's just another layer of confidence that your surgery is going to help. Yeah, I guess the only point I would make is that it really depends who does the block as well. So if another provider is doing the block, you're not sure if they got it in the right spot. Sometimes the patient's not sure, like they think the block is supposed to give them long-term pain relief. And they're like, oh, doc, it didn't work at all. And you're like, well, what about the first four hours? And they're like, oh, it was perfect. I walked to my prosthetic all around the mall, it was great. And you're like, okay, great. Let me run this question around to each of y'all. One of the most common things we do, obviously, is finger amps and digital neuroneuromas. Kyle showed us it's probably around 7%. Each one of you, real quick, your management of the nerve in a primary digital amp, primary ray amp, and symptomatic digital nerve neuroma. Brian, what's your run? Primary digital amp is just traction dyrectomy just because of the low incidence of having symptomatic neuroma. In a ray amputation, I usually will do RP and I. Primarily, you got muscle right there. You're dissecting back. You know the incidence is probably a little higher the larger the nerve is and the more proximal it is. In a revision setting, it's either TMR or RP and I. I think they both work well and done both. And I can't tell you which one I think is really better. Holly? So primary amputation, I'll do crush a few centimeters, maybe a centimeter proximal to the distal end on the McKinnonite, so creating that Sunderland second degree injury and then just transposing the nerve. Ray amp or secondary case, TMR, usually into a lumbrical motor branch. Omri? I think traction directomy if it's distal to the MP level. And then if it's more proximal, I think you can pretty easily do RP and I. If it's more of a ray amp or revision, I think the TMR to the volar interossei works well. Kyle, how about you? Yeah, the only thing I would add is that for primary amputations, I like to transpose the nerves for the dorsal side of the digit, just so they're not on the working surface and not painful. If I'm doing a ray amputation, TMR is my go-to, but I don't like to go to the volar side of the hand. I want to do a dorsal. I actually pull it through to the dorsal neuroses muscles because that's away from where the person is grasping. And then for secondary treatment of neuromas, I struggle with this, but my current thought is that if the nerve is proximal, or sorry, if the nerve is distal to the PIP joint, I'm not going to denervate the entire digit. I'm going to remove the neuroma and maybe do a central-central neurophy or something else distally. But if it's proximal to the PIP joint, then I have no problem going in the palm. But I don't want to go in the palm if it's really distal in the digit, because then you have a totally insensate finger or digit, and that's not helpful. Yeah. Well, it's nine o'clock. I think that's what time we're supposed to wind down, unless Alyssa tells me otherwise now. But thanks everyone, y'all, for joining tonight. And don't forget, you can collect your CME on the website starting Tuesday, and we really appreciate your time. Thank you. Thanks, Glenn. And thanks to the other panelists. Thanks, guys. Learned a lot from you guys. Thank you.

neuropathic pain

symptomatic neuromas

management

panel discussion

surgical treatments

patient evaluation

chronic pain

nerve reconstruction

diagnostic blocks

research