Good morning, everyone. Can you hear us okay? Yay. All right. Welcome to PreCourse 3. This is the current treatment of nerve injuries, gaps, and neuromas. And our original title was Nervous About Nerves? I don't know what happened to our original title. But anyways, thank you all for coming. Welcome. We are going to, my name is Shelly Noland. I am a plastic hand surgeon at Mayo Clinic in Arizona. And I'm Amber Lee. I'm a plastic and hand surgeon at the University of California at Irvine. And our goal today is to get you all of these wonderful talks and be on time as much as possible. We are going to aim to finish at 11 o'clock sharp. So we'll keep everyone moving along as best we can. If anyone has any questions, it's a pretty small group, so we'll keep it informal. And feel free to raise your hand throughout the course if any questions come up. Okay. Okay. So the first round of speakers, if you could please come to the stage, Dr. Dee and Dr. Atkins, if you are here. Okay. Oh, she's prerecorded, I believe. So just so you're aware, about eight or nine of the talks will be prerecorded. So we'll do some live, mixed in with some prerecorded video talks as well. Okay, and our first speaker will be Dr. Elzinga, who is going to discuss preoperative considerations. Good morning, everyone. Thanks very much for inviting me to speak. It's a real honor to be here with such an amazing group of peripheral nerve surgeons. I'm just going to go through some of the basics this morning, and then other speakers will focus more on the treatment and management. I would highly recommend Dr. McKinnon's book on nerve surgery. It's a wonderful resource for anyone interested in this field, and it would give more details about anything I'm going to speak about this morning, if you're interested. And of course, her website is also a wonderful resource. So starting off with some nerve anatomy, uninjured peripheral nerves are composed of unmyelinated or myelinated axons that are opposed by Schwann cells. Individual axons are surrounded by collagen fibers, which form the endoneurium, and these are grouped into fascicles contained by the perineurium. Between the fascicles, you have your internal epineurium, and outside of this, you have the external epineurium, which encompasses all the fascicles that group together to form a single nerve. Nerves are able to accommodate shortening and lengthening during flexion and extension, and during some stretch injuries by their epineurium and the bands of fontana, which are undulations in nerve fibers. From Dr. McKinnon's group, for example, on the left side, and then another group out of Spain on the right, we know now that even in proximal extremity, the motor and sensory fibers are grouped together topographically. There's quite a bit of plexus formation between fascicles proximally, and this decreases as you go more distal in the extremity. Anatomical knowledge and intraoperative nerve stimulation are extremely helpful to help you identify motor and sensory topography, and can allow for proper nerve repairs, grafting, and transfers. No nerve course would be complete without mentioning the Seddon and Sutherland classification systems from the 1940s and 50s, and then the sixth degree injury that Dr. McKinnon's group added, which is the not uncommon situation of a mixed nerve injury at the same level of injury, where neurolysis can be helpful, and you can treat different nerve fascicles based on their level of injury. Starting off with the first degree injuries, these are neuropraxic. They represent an ischemic injury with possible segmental demyelination, but there's no interruption in continuity of the axon, and no disruption in the connective tissue continuity. An example of this would be a tourniquet injury. There'll be a localized conduction block, but the axons themselves are not injured, so regeneration does not need to occur. Remyelination and recovery should be prompt within about 12 weeks. Second degree axonomatic injuries have intact connective tissues, but the axons are disrupted. The axon distal to the injury will undergo valerian degeneration, but approximately nerve fibers will regenerate at the rate of about a millimeter a day or an inch a month, and you can follow this with the Tenel sign. Recovery should be complete, as distal motor end plates will undergo babysitting protection by uninjured distal axon collateral sprouting. Third degree injuries have disruption in fibrosis of the endoneurium, and this can result in incomplete or mismatched end organ renervation, as we'll discuss later, and these cases may benefit from reverse end-to-side nerve transfers to allow for babysitting protection while the proximal axons regenerate. Fourth degree injuries involve a neuroma in continuity. Spontaneous recovery cannot occur because the axons are blocked with scar, so at this level of injury we would recommend neuroma excision and treatment with nerve grafting or other procedures, which again we'll discuss more this morning. Fifth degree neuromedic injuries have disruption of both axons and connective tissue, and therefore surgery is required for repair. And it's generally thought that if a nerve can regenerate on its own, so a Sutherland grade 2, some grade 3 injuries, then it's best to allow the nerve to have spontaneous recovery and generally an excellent outcome when we can only consider nerve repair to have modest outcomes in these scenarios. So this is why sometimes it's best to wait a few months and to continue to examine your patient before undertaking surgery for a nerve injury in continuity. Recovery following a nerve injury is influenced by the distance of the injury to the cell body and the changes both proximal and distal to the site of injury. Following injury, axons will retract to a node of Ranvier and the neurons will undergo a change into a regenerative phenotype. Schwann cells in the distal stump de-differentiate into a pro-regenerative phenotype, and the activated Schwann cells along with macrophages will prepare the distal stump for regenerating axons from the proximal stump in the process of valerian degeneration. Regenerating axons will sprout from the node of Ranvier and regenerate towards their end organ target. As the axons regenerate distally, Schwann cells will myelinate the portions of the axon closest to the site of injury. Schwann cells are pro-regenerative and allow remyelination and guide regenerating axons to their appropriate targets along residual endoneurial tubes known as the bands of Bunger. If the distal growing axon sprouts become entrapped in collagen during wound healing, a neuroma will result. There are many patient and injury factors to consider when prognosticating a patient with a nerve injury. Partial, sharp, recent nerve injuries in young, healthy patients will do better than complete injuries which may be delayed, that may have additional avulsion or stretch mechanism, which may have soft tissue damage and vascular compromise, and older patients with multiple metacomorbidities will have worse outcomes. After long periods of denervation, 12 to 18 months in a human or 4 to 7 months in a rat, Schwann cell reinnervation will be limited by two factors, one, irreversible muscle fibrosis and two, as the Schwann cells in the distal nerve stump become less supportive of regenerating axons. We do know that electrical stimulation can enhance the regenerative ability of Schwann cells following a nerve injury and this can be a helpful adjunct in nerve repair and again we'll hear more about this later. There's multiple methods of doing your sensory examination including two-point discrimination, sometimes Weinstein monofilaments, vibration thresholds, pressure thresholds. The TEN test is a relatively easy one to apply with good reliability. You have the patient rank the quality of sensation in the affected peripheral nerve distribution and compare that to their normal contralateral anatomical site. Use a scale from 0 to 10 with light moving touch. 0 is no sensation and 10 is normal. This is a helpful test because you can use it repeatedly and can monitor recovery with the nerve is recovering spontaneously or after surgery. Everyone in this audience is likely familiar with the MRC motor examination grading and provocative nerve tests and I think people are becoming more familiar with the scratch collapse test. The neurophysiologic basis for this test is not well defined. It may be related to a response to the touch stimulus and increased substance P in an area of nerve irritation. The examiner will lightly touch over the patient's skin at a site of possible nerve compression and the patient is then asked to resist isometric shoulder external rotation. If the arm collapses in with this rotation, then that's a positive test and it's indicative of nerve compression potentially at that site of provocation. This is particularly helpful when the electrodiagnostic studies may be normal, other provocative testing is negative, or in a patient where you're worried about multiple levels of nerve compression. Finally, some investigations. Our next speaker will talk more about electrodiagnostic testing and then we're quite lucky that the field of imaging keeps evolving. The top photo here shows the anatomy of a normal nerve with ultrasound and the bottom photo is quite in contrast to this and it shows abnormal appearance of multiple tumors in a patient with neurofibromatosis type 1 in an MR neurography study. These tests can be helpful both with diagnosis and following injuries if they're not recovering as you may expect. So that's just a quick introduction to some nerve anatomy examination investigations. Our speakers this morning will expand upon this and talk about these concepts more in relation to treatment. Thanks very much for your time. Thank you. Our next speaker will be Dr. Di discussing electrophysiologic studies. I don't know why I just uploaded it. Okay, good morning. My name is Christopher Dee. I'm from Washington University in St. Louis. Thank you to the course organizers. Congratulations on organizing an excellent program, and I'm excited to be here. So this is from an older textbook, Dr. Gelman's textbook earlier in the 90s. I think the sentiment here from Dr. Dellin still rings true. For Dr. Electrophysiology, NCSEMG, put in your consult only when you're careful history taking and detailed sensory motor testing indicate that testing is necessary to answer a particular question. Have confidence in your clinical skills that your judgment, not the printed report, will be the final authority. I think that's a really important principle to keep in mind as we talk about nerve studies. They are a tool. They are an extension of your exam. They are not the end all, be all. And these are pretty overwhelming. I remember as a trainee being overwhelmed by them. A lot of it was demystified by some of my mentors. My goal is to try to teach you how I use this information to help myself, and clearly I'm still learning as well. As I mentioned earlier, nerve studies are a tool to complement your exam. They are imperfect. They are only as good as the examiner, and their usefulness relies on you, who's interpreting them. The essential questions to answer when you're ordering your nerve studies typically are where is the nerve injury, any other lesions, and a lot of this you can get on your physical examination, as our last speaker mentioned. How severe is the nerve injury, which the nerve studies can help with, but cannot answer every question. Will spontaneous recovery occur? They can detect things earlier than we can on our physical examination, and then they can also help you discern your options if you are looking at reconstructive options. For all of these questions, you're using a combination of your history and your examination as well as the nerve studies, and perhaps some imaging as well. So in terms of starting, I usually use this analogy. If anybody's visited us here in St. Louis, we do have two separate sites where we work. One of them is downtown, not downtown, but over by the central west end and over by the zoo over here, and this is where our main hospital is. Then after conference, before COVID, you would have to rush over and try to make it to our ambulatory surgery center and outpatient clinic, which is not terribly far. It's only about 16 miles, but you can see there are different points of traffic that can choke you up. So if you use this analogy, like you're driving, how long it will take you to get there, that's the latency component of the nerve conduction study, and then how fast you're going to go is the conduction velocity. Both the latency and the conduction velocity are based on the same data. They're just different ways of presenting it, and then what's under the hood? Are you driving the Prius or are you driving the Tesla, and that's the amplitude, the number of functioning motor and sensory fibers that are actually working. So here is an illustration of what an actual electrodiagnostic study is. Now this is a sensory study. You can see the stimulation is applied. Now in this case, it was through the ring electrodes. A lot of people will use kind of adhesive ones now, and you want to see how long it takes for that stimulus to go from the index finger to your recording electrode, which is just proximal to the wrist. So this would be like a carpal tunnel study. And then for a motor study, it's reverse. So you apply the stimulus at the level of just proximal to the carpal tunnel, and you pick up the stimulus, and you see how long it takes for it to get from point A to point B. It's important to talk to your electrodiagnostic team, whether that's a physiatrist, a neurologist, whoever's doing your study, about their normal ranges. These are the normal ranges that were used in Dr. Gelbman and Dr. Weiland's classic randomized study for endoscopic versus open. But every place is different. They usually will give you a normal value either on the same table, or they'll give you a separate page with their normals. Let's understand that the sensory components are a little more subject to technical factors, and the motor components are a little more reliable. For cubital tunnel, this is Dr. McKinnon's article on elbow flexion compression testing. And you can see the standard they use there is typically was 50 meters per second, or a decrease of 50% across the elbow. Again, you're looking at point A to point B. You want to talk about the normal range in your lab. And then testing across the elbow, again, is vulnerable to a lot of technical factors, it's super important to have familiarity with who's doing your study and confidence in their ability to help you get the information you want. This is something that Dr. Dellin included in his chapter back in Dr. Gelbman's textbooks, and I like it. It talks about this reporter in the sky pitfall. So if you have a reporter that's, you know, saying, in St. Louis, I-64, and they're telling you traffic is flowing really well, but they're only seeing the fastest running lanes of traffic, they're missing this huge pileup on the side of the interstate. And if you're in those lanes, that matters to you. And the nerve conduction studies, which, again, are your latency and your conduction velocity, will only pick up the fastest running fibers, so those large myelinated fibers. So you may miss what's going on in the pileup traffic lane, which sometimes correlates more with earlier aspects of disease. So you want to trust your exam. If you have a tunnel sign, if you have a positive elbow flexion compression test, or a Durkin's or a Phelan's, whatever it is for your compressive neuropathy exam, or a scratch collapse, trust your exam and use the electrodiagnostics as an adjunct. As I mentioned just now, there are no electrodiagnostic correlates to pain and paresthesias. These typically are smaller and lesser or unmyelinated fibers, which are not going to be picked up on a nerve conduction study as well, because, again, the NCS is picking up those faster, larger myelinated fibers. Nerve studies typically reflect the pathophysiology of the disease. Early on, carpal tunnel is a focal demyelinated condition, but as it advances, there can be axonal loss and internal fibrosis of the nerve. Cubital tunnel tends to be a bit of a mixed condition in terms of demyelination and axonal loss as it progresses, because it is intrinsically a little bit different from carpal tunnel, because it's both traction and compression. Guillain's canal on a nerve study is a bit hard to detect early on, just because of the challenges of sensory conduction, but you will see axon loss. Neuropraxic injuries, so moving from compressive neuropathy into nerve injuries, will show you a demyelinated conduction block. You won't see any signs of axonal loss, just slowing. And then on an axonomatic injury, you'll see actual axonal loss. So another analogy, if, say, you have a relay team, the conduction velocity and the latency reflect the fastest runner on your team, not how the entire nerve is doing, just the best runner on that team, and what the amplitude is going to do is reflect how the entire team is doing, the entire nerve, tell you the function of that nerve, so it's important to think about both of those when you're reviewing your nerve studies. So to hit these concepts again, conduction velocity and latency are the fastest runners speed and time, and you'll see some of those changes with early carpal tunnel, early cubital tunnel. As these conditions advance, and you see internal fibrosis within the nerve, and then you actually see some of your clinical findings of motor weakness and then eventually muscle loss, the amplitude will start to decrease. Now the amplitude can decrease for other reasons, but it does tend to match directly to the clinical findings, and this is a paper that Holly Power published in JBJS a few years ago showing the correlation between the CMAP amplitude on their motor studies and things like grip strength and pinch strength for cubital tunnel patients. I think that was an important paper that was very helpful to me. So here's a figure that we used in a review article that we published recently. So this is a normal FDI CMAP amplitude, and you can see the amplitudes listed over here, but this patient does have some element of disease because it is slowed across the elbow. It's a little bit slow, and that again matched with their exam, but this is an earlier stage presentation. You can see that the motor amplitudes, again, the number of actual functioning fibers in that nerve are healthy. Here's a different patient, and here is an ADM study. So it's a little different. The normal values are different, but you can see just graphically on the right, you can see how small and short that excursion for the amplitude is, and that's reflected in the values that you can see here, and how different it is compared to the normal value. But still, the onset is still okay because you still have some fast-running fibers that are getting the job done, but clearly the entire nerve is not working terribly well. Then you can also see some element of slowing across guillain canal as well as a substantial amount of slowing across the elbow. Now a decrease in amplitude, like I said, could be due to a number of reasons. It could be an advanced presentation of ulnar neuropathy. It could be CAT1 radiculopathy, or in some cases, a double crush from even something like thoracic outlet. I know that's a controversial diagnosis. Also nerve injury, and we'll talk a little bit more about that. No talk about nerve studies wouldn't be complete without discussing the potential downsides. There is added cost. There are accuracy issues that come with it. You can have false positives. John Fowler, who is our program co-chair and in the room with us, showed 40% false positives among the nerve studies in those that have a CTS6 score of zero. The sensitivity is really, really wide across the board in terms of the electrodiagnostics for cubital tunnel syndrome. So I think it's important to evaluate what your goal is. Are you trying to make or confirm a diagnosis? Are you trying to determine prognosis and severity so that you can counsel your patient appropriately and help select the appropriate treatment? Or are you trying to identify concurrent or contributing pathology? And to close with nerve injury, we talked about some of these concepts, but demyelinating and axonomatic lower grade injuries are going to be reflected in the conduction velocity and the latency. And then as you get into that, the Sunderland II, Sunderland III, and Sunderland IV, you'll start to see those axonomatic injuries show up with the lower amplitudes. So for the EMG, this is the part that intimidates a lot of patients. You need to talk to who is doing your studies and know the limits of it, because when they put a needle in one spot, that's only one neuromuscular unit. Now they tend to move it around in order to get a better sample for you. But again, it's very technician dependent. And there are different phases of the nerve study. There's the initial part where they put the needle in. This is Dale Colorado putting a needle in me, and it was quite uncomfortable. But I've had it done before, and I think it's important to have your trainees experience it too. And when the needle goes in, that's the insertional activity. That is just a yes or no, there's something abnormal. Now when the needle's sitting in the muscle and the patient's not contracting the muscle, that is your spontaneous activity, and you're looking for any signs of denervation. Typically early on, that's fibrillations and sharp waves. Later on, it's fasciculations and polyphasic potentials. And then when you ask them to fire the muscle, you're looking for any voluntary activity. How much activity is present? Is it organized? And then this is a very qualitative component of how they describe it. It's either full or normal, it's reduced, it's discrete, it's single, or it's absent. Now this really depends on who's doing the study, and you want to make sure you talk to them to see what they are hearing, because it really is them looking at a waveform and then listening to it. We can skip through this. I think that, you know, I learned a lot from Dr. Shin's Mayo Clinic brachial plexus course when Brian Crum gave a really nice presentation. And these links will be in your handout that you can go back and listen to these, because I think it is important to understand how qualitative this assessment is. And then you're trying to understand these questions. Where is the nerve injury? How severe is it? Will spontaneous recovery occur? What are your options? Now the EMG will give you the distribution of the findings. The nerve conduction studies will give you a sense of those loss of motor amplitudes, and you're looking for any motor units that are present. If it's completely gone, you know that's a very advanced injury. Spontaneous recovery, you're looking whether you have a chance to still save that nerve and that muscle. The capacity to re-innervate is typically reflected by the fibrillations and sharp waves. And then EMG is typically useful to assess the health of your donor. Now your clinical exam is the mainstay for that, but there is a nice paper out of Scott Wolf's group demonstrating that if you have a compromised donor, while you still can get a good result, it's clearly not as good as if you have a healthy donor. Does not mean if you have an electrodiagnostically compromised potential donor for a nerve transfer, you shouldn't use it. It just should give you a sense of what to expect. So I'll skip the case in the interest of time, but I hope that talk helped to solidify some concepts and I appreciate your attention. Thank you. Our next talk is pre-recorded by Dr. Atkins, the Timing and Indications for Nerve Reconstruction. Hello, my name is Sarah Atkins and I'm a consultant plastic surgeon from Oxford. I'm going to talk to you today about the timing and indications for nerve reconstruction. First of all I want to start by asking you what you would do with this boy who unfortunately had quite a delayed presentation at six months and after a fall where he sustained a fracture dislocation to his elbow. He had a median nerve dysfunction that was both profound and getting worse. So would you operate straight away and if not, when? We'll come back to that later. First there are two key aims of the operation. The first is diagnostic. It enables assessment of the area of trauma and gives a greater understanding of what's happened and a chance of recovery. You're able to directly assess the nerve and any associated muscle damage that would affect the outcome. In addition you can decompress tight areas and wash out hematoma that I think probably aids recovery. The second aid is simple. It's to repair the nerve if it's been damaged. Our experience is that there's usually some change that accounts for the nerve dysfunction that you see. It's not necessarily complete division but what you may see is the nerve being squashed or skewed by bone, pulled into a very acute angle. This may or may not be accompanied by fascicular damage that needs repair. It's very difficult though to predict operative findings and that's why we find exploration so useful. Our indications for exploration then are broad. It's any loss of nerve function that suggests either complete or partial injury of the examined nerve or nerves in the context of trauma. There are some caveats to that. So first you may have to delay for the polytrauma patient with multiple life-threatening injuries to be stable and to have other procedures. Secondly for those patients with nerve loss associated with lower energy, closed injuries like a shoulder dislocation or a direct compression or viral illness where exploration is unlikely to identify any abnormality, especially with ongoing improvement, then we would instead review through our MDT and explore only if recovery deviated from expected. The timing of operation is ideally as soon as possible. Because one of the key aims is diagnostic, we would prefer to get on with it. What does that mean in reality is it can be pretty much immediate right through to up to a week ideally. The other key aim of early exploration we said is early repair and we think this is very important for a few reasons. Firstly, from the patient's perspective, having sustained a life-changing injury is a very low point for someone and it's great to be able to support them on a positive road to recovery. But that is really only possible if you have both the diagnosis and you've treated the problem. Otherwise, they're in limbo and I think this increases anxiety and depression in a group that we already know are prone to this. An early rehabilitation plan with achievable goals gives them a very useful focus. And logistically for them, the overall downtime is therefore minimal and the prognostic information helps them make changes to their future straight away. Considering the neuromuscular unit, I think most people would agree that with a cut nerve in front of you, it would be best to repair it as soon as possible. The relative slow time it takes for nerve growth and the danger of muscle motor end plate atrophy is a concern and minimal time for sensory re-establishment and avoidance of painful neuromas is beneficial. So this 24-year-old man with multiple injuries, we explored at five weeks as his suprascapular nerve and axillary nerve had no function. The findings were that suprascapular was scarred but intact, so we just did a neuralysis and the axillary nerve required a five centimetre nerve graft for complete transsection. So this is him at 18 months. And would we have got a good as repair if we hadn't have repaired it or if we'd have waited a further three or six months? Finally, from the surgeon's perspective, exploring these traumatic injuries is certainly easier in the first few days. The zone of injury is more obvious. The tissue planes are still congruent. After a couple of months, the scar, the tissues become scarred and friable and it's very unpleasant. And by six months, it's essentially a scar dissection and nerve resection, which is both challenging and takes experience. Interoperative decision-making is easier earlier because the injury is more apparent and the choice is mainly between direct repair or grafting for the mainstay. A key point here that I think is that by delaying the operation and repair, you're converting what may have been a relatively straightforward nerve injury and repair that could have been done by several people into something more complex that can only be performed by a few. And that doesn't make sense in terms of service provision. From a logistical point of view, early exploration means we are then clearer about what the patient is likely to require in the future, and you're able to see them at three, at six months, knowing that if you don't like what you see, you still have time to do other reconstructive procedures. So if we look at this now, 22-year-old male with motorcyclist versus car, eight and fractured humerus, other injuries as well, no function in any of the terminal branches of the plexus. What I was able to see here was that the area of trauma was at this level, not higher, that all the nerves, although they had signs of trauma to different degrees, were all intact with the exception of segmental loss of the medial head of triceps and its branch from the radial nerve. But you can see here that the planes are nice, got rid of all the hematoma, and I've now got a much clearer idea in terms of chances of recovery and what to be specifically concerned about. The key to achieving early exploration is to see patients immediately or very soon after injury. And I think to do this, you need to have a unit ethos of early exploration, and then everyone around you knows where they stand and that they should act on that. The UK trauma networks have changed, and we now have designated major trauma sensors that you can see here, and that means that they take all major trauma directly. As a result, there's been a much more significant collaboration between us and the trauma, and that's meant that on the ground, it's much more easier for these injuries to get flagged because we work so closely. In addition, I formalized local pathways in combination with a nerve MDT, and that's resulted in improved patient care process. The other aspect, which I've already alluded to, is our wider team skillset. We have a group of specialist trauma consultants who are the first point of contact and will very nicely repair straightforward nerve injuries. Something more complicated will be filtered to the nerve team, and stratifying the work in this way means that we don't de-skill the team and that the patients aren't waiting to see a smaller, ultra-specialist group of people. Just a special note on children, because I think that the nerve damage is often underappreciated in this group, either because they've not been examined very well or because the injury seems fairly innocuous. I think they need examination, ideally by a surgeon who is experienced with children and with nerves, and the signs of injury should be taken seriously. So this is a case in point. This is a 12-year-old boy who had a closed fracture, conservatively managed, with median nerve signs thought to be neuropraxia, but at three weeks with no resolution, I saw him and operated the next day, and you can see here that the nerve was trapped within the fracture. I've actually removed it from and had to pick away the callus, but once out I could see the fascicles were all intact. He got an immediate improvement and then a slower improvement, and by 18 months he's got a full recovery. So going back to our first patient, we explored this child immediately, and you can see at the top here the median nerve is acutely angled into a very small part of the fracture. Half the nerve was trapped and needed to be resected, the other half was exterior to it, so we had to resect and directly repair those fascicles that you can see here. But if we had have gotten earlier, I may have been able to just simply unhook the nerve and not have to do any repair at all, and you'd certainly be a lot faster on the way to recovery. Thank you very much, and I hope you enjoyed the presentation, and thank you for listening. All right, we're going to move into the next section of the talk, which is nerve gaps. I'd like to invite Dr. Isaacs and Dr. Safa up to the stage. I thank you, Amber, and thank you, Shelley, for including me this morning. That was an interesting talk. We just heard a little bit. I'm going to, I guess, disagree with a couple of the points that were made, but that's what I'm supposed to do because my title is Principles of Nerve Repair, and to try to provide some tips and pearls, which I will do. Please pay attention to my disclosure. Several of them are relevant to these topics. Everybody sitting in the room who does nerve repair is used to being disappointed. Maybe a little bit of the problem with the last presentation I'm showing these great results of early repairs is that you have to balance it with the not-so-great results that we're all experiencing. Every nerve surgeon experiences that. The literature tries to sugarcoat it by calling an M3 a good result, but nobody in the room, if you were the patient, wants an M3 as a result of your nerve repair. Obviously, fixing is better than doing nothing, but clearly there's some room for improvement. The first question that we have to ask ourselves is, why do repairs do so poorly? It turns out that it's a multifaceted problem that starts with the fact that many of the neurons don't even survive the trauma of the nerve being cut. If they don't survive, they can't regenerate. Axon regeneration we know is a problem. Axons are misdirected. They're lost. They peter out and just stop regenerating. Atrophy of muscle and of nerve and corticoplasticity, which is referring to the fact that the circuitry between the brain and the periphery after regeneration, after repair, is going to be different than it was beforehand. The more different it is, the harder it's going to be for the brain to adapt to use these new signals. I think most people would agree on these principles. Time is your enemy. We just heard a talk really emphasizing that, and I couldn't agree with it more. We know that suturing a scarred or injured nerve to scarred or injured nerve gives you scar tissue. It does not give you pathways for regenerating axons. Excessive tension is bad, and we know that during the repair, you have to direct the axons into the distal endoneural tubes. Once an axon is cut while their regeneration begins and the clock starts ticking, and our goal as surgeons is to get those axons into the distal endoneural tubes so that regeneration can occur before denervation atrophy of the muscle occurs. Denervation atrophy is this loss of muscle mass, fiber size, changes in contractile proteins, even scar tissue forms around the end plates, preventing the axons from making contact. All those reasons, all those things make it so that the muscle can't recover even if the axons reach it. And then we also know that there's an effect to the distal nerve stump. With time, those endoneural tubes collapse down, filled with proteoglycans. The Schwann cells become inactive. There's a loss of guidance cues and growth factors. So as we just heard, and again, in principle I completely agree, the earlier that you can do a repair is better. We already heard a bunch of biologic advantages to that, and Dr. Atkins pointed out that there's many practical advantages, less retraction, less fibrosis. You can see the markers on the outside of the nerve better. But you have to counter this with the fact that sometimes nerves are so traumatized that they need time to demarcate, that when you get in there, if you explore early, you can't tell what part of the nerve needs to be resected. And in fact, in open fractures, this has been reported by Dr. Ring, very, very high percentage of failed repairs with early exploration and early repair of radial nerves in that particular case. So I would argue with closed injuries that it's not early exploration, that you actually have to wait and give it some time to see if you're going to get spontaneous recovery, or to at least give yourself enough time that when you explore, you can assess the nerve and determine whether or not that nerve has a chance of continuing to regenerate. The best results we're going to see is when nerves spontaneously regenerate, and in my opinion, it's hard to replicate that with surgical reconstruction. When the decision is made that you need to fix the nerve, the first step is you have to cut away the damaged nerve. You have to cut back the healthy nerve. There's a variety of ways that you could do that, ranging from some very sharp on-the-market scissors to many people like to use a scalpel and a tongue depressor. I like this system. It's a they're nerve-holding forceps. You can get a disposable razor blade that you can use to make these very clean, fine cuts. And I like it because I could do several, a few millimeters, one or two millimeters at a time if I want to, so I could minimize the resection, but keep going until I see these nice fascicular patterns. From the proximal stump, you should see fascicles pooching out. When you touch the nerve, it should be soft. So hopefully, you haven't had to resect much, but you resect what you have to resect. And once you've done that, then you have to assess how much tension there's going to be on your repair. And we know, and everybody agrees, excessive tension is bad. It affects the Schwann cells. It affects axon regeneration. It affects the perfusion of the nerve, but you have to counter that with the clear fact that direct repairs do a lot better. Look at these results. 16 out of 18 primary radial nerve repairs, M4 or M5. 90% out of 75 owner nerve repairs, these are direct repairs with good recovery. 51 out of 65 median owner nerve repairs that were direct repairs with good or excellent recovery compared with autograft reconstruction of median owner nerves. This is three different series, 39, 33, 31% good results, a marked, marked difference. So I would argue, try to alleviate the tension. Mobilize the nerve proximally and distally, the median nerve particularly in the forearm. You can get another four to six centimeters. The owner nerve, you could transpose it at the elbow. You could transpose it from Guillain's Canal into the carpal tunnel, and you could get a little bit more length. But I also have shifted in my thinking over the years that temporary tension relief may be a good idea as well. And some of the reasons why I switched my thinking was the results of Oberlin's work on sciatic nerve injuries. Gunshot wounds to sciatic nerve, six centimeter defects treated with knee flexion to get the nerve ends together, primary repair, knee flex for six weeks, and then gradually stretching it out. M4 in five out of six patients with a six centimeter sciatic nerve injury from a gunshot wound. You cannot do that with autograft. Dave Roosh and some others have looked at this as well using an animal model where they placed an external fixator on a rabbit limb, got nerve ends together that otherwise would have had a gap, fixed it, and then gradually stretched it out, showed that it worked. They've also shown in patients that it works as well. Here's a patient of mine, median nerve laceration presented late for a variety of reasons. You can see the top screen there. I cannot get the nerve ends together directly just by pulling on them. And I think that looks to me like it's even pre-resection of the damaged area. But with mobilization, you could see that, sorry, that white arrow there is pointing towards what I call a tension relieving, such as a 6-0 proline kind of spin in the whole thing. Elbows flexed 90 degrees, gradually stretch it out after six weeks, and one of the best median nerve results that I've seen. Alignment is important. Alignment's important for two reasons. Number one, the body does not do a good job of telling axons where to go. We call this end organ specificity, telling motor axons to get to motor targets, sensory axons to sensory targets. So it's important to get the general alignment correct, which usually we use stuff like the fascicular pattern, or you can sometimes use blood vessels on the surfaces markers. But we try to get the alignment as well as we can from that perspective. But there's even something more fundamental, that you have to get the fascicles facing other fascicles. If you don't do that, it doesn't matter what your rotational alignment is. This is, yes, a cartoon, but you could see in the upper right corner there, all those fascicles pooching to the side. I believe that happens. Many surgeons tend to overtighten their repair. This is a cadaver study that we did specifically looking at this question. And you see in the lower right corner, that's a median nerve. Those are fascicles pooching out of the side of the median nerve. About 40% of the suture cadaver nerve repairs looked something like that. I don't think anybody in the room, if that was your median nerve, wants their repair to look like that when the surgeon is done. Getting the nerves together to do the actual coaptation sutures are still probably the gold standard, and they can be placed in the outer epineurium. This is the least traumatic, least control over the alignment, but it's done well. And just barely getting the nerve ends kissing, like you see up on the screen there, certainly is a reasonable approach. If you want to have complete control of your alignment, you could dissect the outer and inner epineurium, suture each fascicle together individually. It's called a fascicular repair. If you're off one click on your rotation, everything's going to the wrong place. And even if you're perfect, the amount of trauma you've done to the nerve probably outweighs the benefit. And though there are advocates of this technique, it's never really been shown to give better results. So what most of us do is what we call a group fascicular repair. We are trying to minimize trauma to the nerve, but maximize alignment. So we identify a group of fascicles, like you see here, and they own a nerve, suture those together, and then complete the repair. So maximizing alignment while trying to minimize trauma to the nerve. And part of minimizing trauma to the nerve is probably using as few sutures as possible. Yes, they're time consuming and technically demanding, but they do also generate some scar tissue. So because of that, there's a variety of alternative strategies. Fiber and glue has certainly been described. I personally like the idea of intubating the nerve. You could see you could use a small connector to go around your repair. In the bottom right corner is actually what I more commonly do. I split the connector and wrap it around. I believe that in the past, I've had patients that had bad results after I put a conduit around because the nerve swelled and caused too much compression. So I like to slip the connector so that it allows the nerve to swell if it needs to. And a little bit of theoretical benefit. You get a protected microenvironment, maybe block scar tissue, block axons. But to me, the real benefit is that you splint and direct the fascicles so they're aiming towards each other. And to me, this gives you a much better chance of getting a well-aligned repair. And from the same cadaver study I already referenced, you can see that we did show that a high percentage of surgeons were able to get well-aligned repairs. Postoperatively, I protect the patients for three to four weeks if at all possible. Sometimes, as you heard, a little bit more than that, but at least three to four weeks. So getting good results, yeah, I think it's an uphill battle. But if we emphasize principles, and I think importantly, avoid algorithm thinking is the path to the best results. Our next talk will be pre-recorded from Dr. Morehart. Hi, my name is Mike Moorhart from the University of Alberta, and I'd like to talk about emerging therapies to enhance nerve regeneration. No disclosures, post-operative electrical stimulation, or PES, is well described and was first described by Tessa Gordon in 2000, where they made a rodent model of a femoral nerve injury, where the femoral nerve was lacerated in the primary co-op patient, followed by post-operative electrical stimulation for various intervals of time. They showed with this study that PES reduces the degree of staggered regeneration and improves preferential motor re-innervation. The effects of short-term e-stim at one hour were similar to that of long-term e-stim at two weeks. Pre-re-innervation and regeneration, however, is optimized by delivering not greater than one hour of PES immediately following nerve repair. Longer duration of stimulation conferred no significant improvement in regeneration and actually can be deleterious. In a study out of Edmonton by Josh Wong in Ming Chan's lab, who's the clinical scientist, we had a group in a study of digital nerve lacerations. 18 were repaired primarily, and 18 were repaired primarily and had one hour of post-operative e-stim at 20 hertz. These patients were followed for six months and assessed for functional and sensory re-innervation. We have shown a static two-point discrimination as well as SEMS-Weinstein monofilament testing to be significantly better with PES. We also showed improvement in cold and warm detection threshold. The first randomized clinical trial, however, was with the Purple Tunnel and PES, again out of Dr. Chan's lab, published in 2010. Here we show that the stimulated PES group had considerably better terminal motor latencies over time, up to 12 months, compared to pre-operative. In association, the sensory conduction velocity also improved compared to pre-op. The stimulated group actually had 33% more functional motor units than controls. In a nice study by Dr. Holly Power, a resident at that time, published a paper in 2019 on cubital tunnel with and without PES. 31 patients with severe cubital tunnel were randomized again and double-blinded. The control group had 11 patients that had surgery only, and 20 patients had surgery plus one hour of PES. Patients were followed for three years, and after which assessed. The PES patients had recovered double the number of motor units compared to controls, as well as almost double the grip strength. The PES patients also had 65% better key-pinching controls. Therefore, post-surgical electrical stimulation enhanced muscle renervation and functional recovery better than surgery alone. How does this work? Well, Tom Brushard and Tessa Gordon, in 2002, published a paper showing that PES does not influence the speed of axon regeneration. However, what it does is improve staggered regeneration and preferential motor re-innervation. A conditioning lesion is considered the gold standard for enhancing nerve regeneration, and in 1987, Val Verge was the first to show that a crushed nerve seven days prior to a cut nerve in coaptation resulted in upregulation of genes for regeneration, a decreased latency period, and an acceleration of axon growth up to five times. Obviously, this is not clinically applicable, as we don't want to injure normal nerves. Therefore, we wanted to find an atraumatic way of conditioning, and again, electrical stimulation. We looked at this as a conditioning lesion, comparing this to a crush lesion. And you can see from the graph on the left, the length of regeneration for both CES and crush were very similar in axonal regeneration. This was also associated with an upregulation of regeneration-associated genes, specifically GAP43 and BDNF, seen on the right. What was interesting is that CES was shown to increase sensory recovery compared to crush, and this is shown in the picture below, epidermal-epidermal junction as the number of fibers were counted. Again, this is Jenna Lansinger's work, a PhD in the University of Alberta, and she is a resident. CES also enhanced motor recovery, as the number of neuromuscular junctions was significantly superior to crush alone, and you can see the staining for green, for ACH, ACH receptors. So then we wanted to compare conditioning electrical stimulation to PES, and you can see in the upper left that the greater sensory recovery was noted with CES compared to PES, as well as the muscle. The CMAPs were significantly better with CES treated, and this is depicted in the pictures on the right. With CES, after cut and coaptation, the length of axonal regeneration is significantly more than PES alone. When we compared CES and PES together, this had a deleterious effect, the result of we're still not entirely clear about the mechanism. What is the clinical relevance of CES then? So we picked three paradigms. One is an autograph, where a tibial nerve model was used. The tibial nerve was cut after conditioning one week prior, and then a 5-millimeter autograph. You can see on the bottom that the length of regeneration is considerably greater with CES compared to PES. This is associated with a greater sensory recovery with the diagrams and pictures on the top, as well as on the bottom with a greater motor recovery of CES compared to PES. We also wanted to look at nerve transfers. So the common tibial nerve was crushed at day zero, then at day seven, CES was applied to the tibial nerve. Seven days following that, the tibial nerve branch to gastroc was then transferred to the common tibial nerve. You can see in the graphs on the top left, dorsiflexion at 10 weeks was significantly greater with CES. This is associated with a greater force generation as the animals walked on footplates, and duty factor was greater with CES compared to no CES. Again, this was published by Dr. Sanger. In chronic nerve injuries, in which we have a tibial nerve cut and the animals convalesce for 12 weeks, then get a one-hour CES at 20 millihertz, and then a 10-millimeter autograph applied and co-active. Through this, again, this was published in 2021, a longer length of regeneration through the 10-millimeter autograph using CES with enhanced sensory and motor reinnervation. In summary, CES causes an upregulation of regenerated associated genes, acceleration and axonal outgrowth, improvements in both motor and sensory reinnervation. The effects of CES are greater than that of PES, and these are consistent in all models, including nerve grafting, distal nerve transfers, and chronic nerve injury. What's interesting is post-operative exercise therapy. In English's lab in 2008, exercise was shown and known very well in spinal cord injuries. However, in 2008, they published a paper showing that exercise therapy following nerve repair accelerated nerve regeneration, improved both motor and sensory recovery. And this can be depicted in the picture on the right. As you can see, axonal regeneration with the exercise-treated animals compared to the unexercised control. We thought, can we make this better? And our current study, which Jenna will be publishing shortly, we investigated the effects of combining preoperative CES with post-operative daily exercise therapy in a nerve transfer model, as I described already. So the groups are CES, exercise, CES, and exercise. And all the animals were taken, and the preliminary results suggesting a synergistic effect with preoperative CES and post-operative exercise. You can see on the right, or on the left, the length of regeneration is considerably longer with CES and exercise compared to CES or exercise alone. And this was also shown with increased dorsiflexion. FK506 is very current as far as nerve regeneration. This was shown by Lyon in 1994, basically showing the application of FK506 accelerated motor recovery, increased the number of myelinated fibers by almost threefold, and increased the regeneration rate of sensory axons by 16%. Obviously, the systemic effects of immunosuppression are worrisome. However, there has been an interest in local delivery with the use of bioengineered delivery devices right at the site of nerve repair. This proves to be very exciting. The last topic I want to just touch on is polyethylene glycol fusion. This is a hydrophilic polymer. It works with fusion of axolemma, the cut ends of the axons, restoring nerve continuity. This would, in essence, given at the right time, a time-limited window, prevent malaria and degeneration. There is only one clinical study by Bama, which on four digital nerves showed extremely fast return to two-point discrimination. Obviously, the clinical utility of this is time-dependent and has to be done within about 24 hours or less before malaria and degeneration has been initiated. I would like to very much thank Dr. Genelyn Sanger, as well as Dr. Holly Power and the rest of the group, Dr. Jared Olson and Ming Chan, for their immense contributions. Thank you. All right. We are running about 10 minutes behind at this point, so I'm going to try and expedite my talk here a little bit so we can get ourselves to up on line. Momentarily, okay. All right. So, I will be talking about autologous nerve grafting, the disclosures that I teach at the oxygen nerve repair courses, but this talk is going to focus on data for autologous grafting. And I think, as we have seen through some of the talks today, that we're trying to think about how best to manage these nerve gaps. As Dr. Isaacs pointed out, if we can primarily repair the nerve, obviously, that's going to be the best situation for the patient. But if you can't do that without tension, Malisi has shown since the 70s that a grafted repair will do better than a primary repair under tension. And as we have understood this more, it has really changed our paradigm as we approach nerve gaps. It's really important, I feel, to range the joints through the full range after the repair and ensure that your tension is sufficient to tolerate that. So, what do we use to fill gaps for these? Let's review the options in the literature for bridging nerve gaps. And it's important to just remember as we go through this that we're talking more than just serral nerve when we talk about autograft. There are so many options for autologous nerve donor sites. We can tailor these to the needs of an individual patient, looking at their particular traumatic wounds or what potential needs they may have to try and consolidate sites for them. There are advantages and disadvantages to each of them, but this is more than just serral nerve. Technically, when we talk about bridging gaps, we have conduits available to us and allograft and autograft as well. And I want to touch briefly on the data for conduits because I think the literature really doesn't support them as the best choice for gap repairs. This is a 2019 systemic review of published data looking at the use of autograft, allograft, conduit, and primary repair of digital nerves. And obviously, you know, randomized clinical trials would be the best data for these things, but what this review presents is data showing that the highest percentage of patients with normal to near normal sensory recovery was seen in allograft and autograft repairs. The darker the color, the better the results here. And the results are better even than primary repair, which I think, again, is a testament to the detrimental effects of tension on nerve repairs. And when we talk about digital repairs and allowing patients to range afterwards, I think that's a situation where we end up with tension on the repair. The same paper found that nerve conduit repairs reported higher rates of complications, and these included infection, extrusion, and subsequent removal. I think most of us in practice in this room would agree that conduits for gaps larger than a few millimeters are really not standard of care. I personally teach my residents that they should only be used as a tension offloader, or as Dr. Isaacs mentioned, kind of guidance for the axon regeneration, but never the primary method of management of a gap repair. Every few years, another literature review comes out that attempts to parse out the different techniques for digital nerve reconstructions. This one is the most recent one. It was an attempt at a meta-analysis, but obviously there are so many limitations in the data sets available in the literature that you can kind of think of this as halfway between meta-analysis and halfway between literature review. But what they showed is that for their static two-point discrimination outcomes, where they graded scores less than six millimeters excellent and scores from six to 15 good, scores greater than 15 were considered poor, what we see is that the autograft repair resulted in the greatest chance of an excellent sensory recovery and the lowest chance of a poor sensory recovery. Technically, there's no statistical difference here between autograft and allograft repairs. It's important to point out. And as an aside, we again see that primary repair yields a significant number of poor results. Again, just thinking about the tension on these repairs. For their SEMS-Weinstein outcomes, each repair technique was, most of them ended up producing results in the diminished light touch category, and this was 85 percent of the autograft repairs and 51 percent of the allograft repairs. But when they pooled normal sensation, diminished light touch, and diminished protective sensation and then compared that to the rates of loss of protective sensation or anesthetic outcomes, so the more meaningful kind of recovery distributions, there was no statistical difference between autograft and allograft repairs, whereas both autograft and allograft were statistically superior to conduit repairs. There were only four studies that they could find that looked at surgical complications. For allograft, these complications were reported as minor things, including prolonged pain, effusion, or wound exudates. And for autograft complications, all these were reported as donor site complications. So I think we can take away from the available literature, at least for digital nerves, that conduits for gaps are inferior to autografts. This is a very unscientifically rigorous format, but a recent Instagram poll from the ASPN account looking at a one-centimeter digital nerve gap. And although the results were about 50-50 split for whether people would use allograft or autograft to bridge that, two-thirds of the respondents specifically said they would not use a conduit for this repair. And so I think this is starting to fall out of favor. But what about our higher-stake injuries? Forearm trauma is one of the most common types of trauma we as hand surgeons encounter clinically. We often see injury to the median and or ulnar nerve. And due to the intensely important functions of these two nerves, these are very disabling injuries for our patients. So what does the literature show for reconstruction here? In reviewing the literature for conduits, it's really difficult to make an evidence-based conclusion regarding their use for mixed and motor nerve secondary to the incredibly large number of variables. But this was a nice 2016 paper. Thank you, Dr. Shin. Looking at the published data for treating mixed and motor nerve injuries, and they found 15 studies that were applicable. The best evidence for nerve conduits came from the two prospective randomized controlled trials that they evaluated. And for those with nerve gaps less than 6 millimeters and with diameters between 3 and 7 millimeters, excellent reports were, excellent outcomes were reported. But given the diversity in the pool of data, the author's conclusion was that autografts should remain the gold standard for mixed and motor nerves with especially large gaps and wide diameter nerves. So what does that gold standard data look like? And obviously, we are looking at, I think, a sea change in nerve reconstruction as so many emerging therapies and technologies are on the verge of becoming clinically available. But really, we haven't gotten far past currently clinically for our patients what we've been seeing published in the literature for the past couple of decades, which has been a tremendous number of retrospective views that people are looking at what their outcomes have been. This is a retrospective series of 32 patients looking at the group vesicular repair with sterile nerve. And what they were able to show in this, again, diverse population is that reasonably good results were obtained with sterile nerve grafting. The gaps were divided as less than 5 centimeters, between 5 and 10 centimeters, and more than 10 centimeters. And unsurprisingly, the patients with the smaller gaps did better. And we see that, again, kind of just shown out in their data here with the smaller gap and the less delay to time to repair. And this is things that we all understand intuitively, but it just kind of gives us a sense of how that breaks down. We know that the sensory recovery tends to be better than the motor recovery for mixed nerves, and this is a meta-analysis that demonstrated that well. They had compared this with conduit repairs, but looking at the data for autograft, we're looking at better sensory recovery than motor recovery for both the median and older nerves. And what about our hard cases? What about the patients that show up in a delayed fashion? This is a nice series of delayed presentations that were treated with either sterile or medial antebrachial cutaneous nerve grafting for the median nerve. And again, findings are not groundbreaking. Long gaps, long delay, proximal injury in older patients do less well. But it does give us some nice parameters for what they were able to see clinically, who did well and who did not. So for the very delayed repairs, even if the gap was short, they did find that they were able to get some recovery for about 60% of patients. And I just use these kind of things as a framework for consenting patients and setting expectations as we go through the process. We know that autologous nerve is limited by graft length. We've seen that in the upper extremity literature, and we see that in the lower extremity literature as well. The curve on this is very clear that good results are seen for autografts less than 6 centimeters in length, and there's a dramatic drop off as these go from 6 to 12 centimeters for the repair. So let's see how we're doing on time here. Almost back on track. So we take this data and we try and apply this clinically. So this is an 8-year-old boy who presented to me with a congenitally short femur and hip dysplasia who was almost 6 months out from a pelvic osteotomy, who presented with an insensate foot and no motor function below the knee. He did have an EMG, which showed us some evidence of potential for renervation with articulations, but no active renervation with the motor unit potentials. And so I took him for surgical exploration. So to orient you, this is the way we're looking at things with the head to the left and the feet to the right, and we can see clinically what his sciatic nerve looked like at the time of exploration. And just as Dr. Isaacs mentioned, you can't put that scar together. You've got to resect back to healthy nerve. So following resection, this is about a 7-centimeter gap in the tibial division and a 6-centimeter gap in the perineal division. And so that's something that I treated with sterile nerve graft. It took both sterile nerves to get sufficient for this. But a year later, the patient is starting to show signs of clinical renervation of his gastrocs. And obviously, his leg is short, and I didn't do that to him. That's where he started. But that becomes then clinically relevant to him because it is sufficient, at least, for him to wear a prosthetic and play sports. And that was the last time I saw him because apparently he's doing well enough that he doesn't want to come back to my clinic anymore. So I'm going to end here so that we can get ourselves close on time. And then I think, Dr. Safa, you are up next. All righty. Great. Thank you so much for the invitation to be part of this fantastic pre-course. And I'm going to be discussing nerve allograft, important disclosure slide. I do work with Oxygen as a consultant, and also we do research for them as well. So my practice is primarily a trauma-based practice. And so we do a lot of replants, a lot of revascs, mangled extremities. And so this is kind of how we started using the allograft. These are processed nerve allografts from basically humans. And the reason I do this is because I can pretty much reconstruct everything at once, no matter what time of day or night. And I haven't been in the habit of harvesting allograft at 3 a.m. for a mangled hand, for example. And with regards to conduit, as Dr. Leis so nicely showed, I can definitely bridge longer defects than I could with a conduit. And so far in our experience, it does work. And I'll show some data to support that. So I'm going to show this case as an example. This was maybe about four years ago or so. Table saw dominant hand, and four digits are devascularized, but they're also hanging by skin bridges. And so at the time, let's say about 10, 12 years ago, we may not have had other options at the time other than conduits. But for this, we explore, obviously, widely and find all the structures. And then the decision here is, what do I use to bridge these gaps? At that time, maybe a decade ago, pretty much all we had were nerve conduits for that time, unless you went and harvested an autograft at the same time. But usually for the autografts, we would probably close up and come back later, unless you have something in your field. And however, with the conduits, our experience, as Dr. Leis mentioned, did not really mirror the Weber study, which was the main study that kind of put conduits on the map. And gaps over a centimeter just didn't do as well. So when we went back and looked at the existing data for nerve conduits, what we actually saw that even in their own data, their mean gap length was only 7 millimeters, so fairly short gaps. And even within their own data set, you could see as the gaps got longer, even between 5 to 7, now you have almost 40% poor regeneration. And this is in the Weber study. So clearly, their own data, I think, in my opinion, didn't really support the use of conduits for gaps more than maybe 5, 7 millimeters. And this makes sense. Many authors have shown that the longer the gap is in a conduit, you just don't have the ability to be able to bridge that gap. And you get this kind of hourglass-shaped regenerate that isn't able to support the number of axons that you need. So back to our case here now, my standard practice now for these, especially for sensory nerves, especially for these traumas, is I trim back aggressively and just bridge all the gaps with allografts. And again, I can kind of do everything in one setting and go from this to this basically after a few hours. And I think the results, obviously, in these cases, I'll show at the end of this talk. But in this case, after a number of revisions and tenolysis and z-plasties in the web space and so on, we were able to get S3 plus in all but one nerve in the radial digital nerve of the ring finger. We got an S3. So still a fairly good result for fairly long gaps, especially with one main reconstruction. I'm going to show a few other cases of fairly evolved parts. This is a thumb avulsion. You can see the nerves of all distally based. We replanted this with four centimeter long neuralografts for each of the two nerves, as well as a long vein graft. This is him about a little over a year out. And you can see a fairly identical appearance, functions excellent in that replanted thumb. The two-point discrimination in this case is not normal, but this is still decent two-point discrimination for a crush avulsion mechanism and pretty good light touch. And this has kind of become a standard practice for us when we have these kind of evulsive mechanisms. This is a rope avulsion to a small finger, devascularized. You can see a fairly wide zone of injury. And with trimming these nerves back, you can see how stretched and attenuated this is. And again, this is the importance of trimming this back beyond the injured segment. And we were fairly aggressive now that we have these allografts available. And we bridged these with fairly long, this is between four or five centimeter nerve allografts. One operation, no tenolysis in this case. Not perfect flexion, DIP's a bit stiff, but overall fairly good. Two point discrimination is not normal. I'm not gonna claim this is gonna give you four millimeter in every case, but I think for one stage reconstruction, getting S3 plus is actually quite good. This is a two and a half year old. Similar mechanism as the other thumb replant, except a much smaller part, and somewhat more distal. You can see again, evulsed nerves, again distally based, so we are gonna have a target in this case. Under the scope, this is our artery, this is our process neuralograft. We did a little endoside neurography of the radial lesion nerves. I couldn't find a good proximal target. Didn't want to fillet her whole hand open for a distal thumb tip. And so here she is now with the thumb replanted. We did bleed her for a few days. It's about five months out now. A bit of a cosmetic deformity of the nail, but overall function's excellent. Hard to do a really detailed sensory examination on a child her age, but she definitely had light touch. You could localize with that thumb. This has changed kind of the paradigm of what we do with other cases that traditionally we're not supposed to put back on, such as a ring avulsion. This is a ring avulsion in a, I believe a 52 year old gentleman at the time, or a batting type three. But now we have options available with regards to soft tissue coverage in the form of a venous flap, as well as nerve reconstruction at the same time. And so this is now a venous flap used to revascularize a couple of nerve allografts. Used, again, one operation is all this guy got. And here he is. You can see the venous flap's healed quite well. Did not get any two point on the ulnar side. So that was the downside of this, but got decent light touch. So S3 plus only on one side here. But function's fairly good. And again, I think, especially for these types of cases, I think these nerve allografts really come in handy. For really bad mutilated injuries, such as this case here, again, the concepts are the same. Just try your best to salvage what you can. In this case, we only could salvage three digits, branched vein graft. We allografted the thumb and index. The defect in the middle is too long, and so we still do a fair number of autografting cases. We did some vein grafts for drainage of the three digits here. Then we came back a few months later, took a nice serral nerve, and bridged the long gaps in the middle finger with the nerve autograft, the serral nerve. And here's a patient about a year out with decent function. Dominant hand, he's 26, so clearly he's gonna have this for the rest of his life. From a sensory standpoint, he actually did fairly well. But he wasn't much of a scar former, so I think we kind of got lucky in this case. So again, this is kind of another example of how these come in handy in our practice. The big kind of question or debate is mixed nerves. And admittedly, our data are somewhat limited in these. There aren't as many of these cases in the database, but I'm gonna show a few cases and then go over some of the data. This is the first case that I actually used an allograft in for mixed nerves. It's a young girl, had a delayed presentation on the nerve injury. You can see where the laceration is. She already has got some flattening of the hypothenia area. You can see some wasting of the first dorsal interosseous. We explored her. This is now about maybe four or five months out, and she would not consent to an autograft, and that's why this was our first case of using an allograft. Roughly two seminal defect, two allograft cables. At the time, we didn't have nerve connectors, so we just used some fiber and glue to augment the repair. Here she is about 14 months out. Really good finger abduction. Already able to cross her fingers, which she couldn't do before. You can see the hypothenial muscles are firing. Lumbrical is working quite well. Granted, she was 18, so that always helps, but this is our first experience. And what we do now in many of our cases for high nerve injuries, such as this case, here's a guy in his, I think, about 20 or 21 or so, is we basically explore the proximal nerve and bridge that with nerve allografts, and then go distally and do a nerve transfer. I think this makes sense because you're gonna be closer to your target, so this is our couple of nerve allograft cables. End-to-end AI into ulnar motor transfer in this case. I just didn't think from the mid-brachium I could get anything at a hand in time, so I just did an end-to-end. We know that that works fairly well. But the allograft is expected, in this case, to only innervate the FCU and the ulnar innervated FTPs. So what I want to show here is the FCU firing against resistance, and here's a video of me resisting his reflection. That FCU is at least M4+, and this is, again, all due to the allograft. There's nothing else that could explain this. A few cases of colleagues around the country, radial nerve injury for courtesy of Fraser Leversedge when he was at Duke. This was a five-centimeter defect once he trimmed this back from a fairly bad humerus fracture. Here's a patient about 20 months, almost two years out. You can see good wrist extension. Finger extension's excellent, and he's got a pretty decent sensory return in the radial sensory branch. I'm gonna actually skip, in the interest of time, to one other case here, courtesy of Prosper Benheim. This is a deep ulnar motor nerve injury. This was an ice pick that, interestingly enough, was a pinpoint injury that specifically got the deep ulnar motor branch in this case. So Prosper explored this. I apologize for some of the photos in this case. So he's compensating with his AI, and as you can see here, the ulnar entrances are not working. Not able to abduct or adduct or cross his fingers. So Prosper did a fairly wide exposure and bridged the nerve gap with a one-centimeter long, so fairly short, nerve allograft. Here he is about 12 months out. Fairly good abduction, adduction, and able to cross his fingers, which he could not do before. So fairly good results here. And then just kind of one last one that I wanna show. This was a spaghetti wrist combined with a thumb revasc. Both median ulnar nerves are out, so nothing to compensate, nothing to crossover, to kind of cheat in the results, for example. So in this case, again, wide exposure, get everything out. Here's a median nerve, and this underscores the importance of good wrist section. You can see a good two, three centimeters of that are really contused and bruised. So you're gonna trim this back to a really nice, healthy level, as Dr. Isaac showed. See those fascicles pooching with the tourniquet down. Make sure it's bleeding well. And we have, it doesn't quite show here, but both the ulnar and median nerves bridged with nerve allografts in a group fascicular fashion to try to best, as best you can, match the motor and sensory groups. So again, with one operation, we've gone from this to a revascularized thumb and we parallel the spaghetti wrist structures. What I wanna show at six months, and this is fairly impressive for a guy his age in his mid-60s, this is just extrinsic function, so nothing crazy here. But in this video, you can actually see after just having to make a fist, when asked him to oppose his thumb. And so here, you can see he actually has a fairly good thumb opposition of firing of his thenar muscles. And again, both ulnar and median nerves were out in this case. And this is just a different case, spaghetti wrist in a young nurse in her late 20s. Her left, our right, was the repaired side. You can see some flattening of the thenar muscles. But from a functional standpoint, with a three centimeter long nerve allograft, she actually has excellent thumb at a short abduction and opposition. So these are all in the individual cases. So how did the actual data look? We do have the Ranger database, which is basically a registry of all the nerve allografts that have been done in almost 30 centers now. Admittedly, these are not prospective trials. There's a lot of heterogeneity in the data set. And so there are certainly shortcomings of the study. This is a motor and mixed cohort that we published a couple years ago in PRS. And we defined functional assessments to be used for each nerve that was injured. And I just wanna jump to the results here on the bottom. You can see the meaningful recovery percentage. Now, as Dr. Isaacs mentioned, M3 is, in my mind, not really meaningful. But the reason we use that threshold is because most papers have used that threshold to publish their data in the past. And since we don't have a control arm, we have to compare our data to others. And so you can see in the short gaps, 80% meaningful recovery of M3 and above. Once you use M4 and above, this drops down to somewhere in the high 50s to low 60s range, which is also in line with nerve allografts. Breaking this down, you can see there are definitely a couple of patients that didn't do well, got M0, one M1 and three M2, but the rest are M3 and above. Between the nerves, we saw that all the nerves didn't do as well. And this mirrors our experience with autografts as well. You can see that all the nerve only regenerated 43%, meaningful recovery, versus median nerves that did a lot better. And these are the long gap cohort within that, up to seven centimeters. You can see one patient had no recovery, but three of them had M4 or M3 regeneration. The only thing that we found that was significant in the cohort was smoking status. So significantly worse outcomes in patients who were smokers. And this is how we pair up with autograft papers out there. As Dr. Isaacs mentioned, most of these papers basically show a 50-50 shot of M4 or better, and slightly better than that of M3 or better. And our results, again, not prospective randomized, and no control arm, but historical controls seem to match fairly well. And from a sensory standpoint, much larger data sets in much larger numbers, and these also seem to match very favorably with historical controls out there. So this is basically our results with a neurobiograph, and I'm looking forward to the case debate coming up. Thank you so much. All right, our final talk of this session before we go through the case debate will be another prerecorded talk from Dr. Liu Chang-Jung. Good morning, good afternoon, everyone. My name is Johnny Liu. I'm a plastic surgeon from Taiwan, from the hospital, Chang-Jung Memorial Hospital. Today, my topic is the use of vascularized nerve graft in long nerve gaps. I'm incredibly honored to be presenting in this pre-course, hosted by Dr. Holly Powers and Dr. Shelly Nolan. Thank you for giving me this opportunity to present experiences from our hospital, from our team. I have no conflicts of interest to disclose. When we're talking about long nerve gaps, technically we're referring to gaps that span more than 10 centimeters. And in peripheral nerve injuries, it can be seen in radial nerve, in ulnar and medial nerve injuries, or in lower extremity. Also, it can be seen in brachial plexus injury, which can be really common, especially when there's an abortion or injury involving the CAP1 roots. And so today, with my experience more in the brachial plexus injury component, and how I would use the vascularized nerve graft in that instance, that is where I will focus. And given the fact that nerve transfer is more prominent used in peripheral nerve injuries, and the extremity nerve injuries, I will not go into detail there. It is generally accepted, and for me personally, that nerve autografts is the golden standard to bridging nerve gaps. There, however, is unpredictable outcomes when the nerve gap is long, or when there's a prolonged innervation of target muscles. But all peripheral nerves, you should always regard it as any tissue in the body, any tissue needs vascularization. And I believe that, you know, for a nerve graft to really work, there has to be a good vascularization. And it can come from three different sources, either an accompanying nutrient vessel, all nerves in the body have an accompanying pedicle vessel that directly nourishes nerve, and it can be extrinsic, leading to intrinsic vessels going into the nerve. The nerve graft can also have vascularity from, profusion from longitudinal inosculation from the nerve stumps. And in one of the studies from Dr. Shin and Dr. Safari, they showed that it came more from the proximal side. You can also have a centripetal revascularization from the surrounding tissue, mainly the wound bed, which can really bring neointrogenesis inside and bring intrinsic blood supply into the nerve. In non-vascularized nerve grafts, there is no direct nourishment from the pedicle, and so it comes mainly from the longitudinal and all those centripetal revascularization. And usually to have a adequate fast-forward vascularization that occurs by the third day. And that is why it is better to do multiple cable grafting because you are able to prevent central necrosis and to bridge the gap and to introduce more axons this way. But when you do have a vascularized nerve graft, and here the abbreviation, I use BMG, when you do have the common pedicle nourishing directly at the nerve graft, the vascularization occurs the first day or the first 10 minutes when the arterial and venous blood supply are established. And this enables trunk grafting. And so commonly, aside from the superficial radial nerve, the vascularized nerve graft that was introduced by Dr. Taylor in 1976, one of the more commonly used is the seronerve graft. And here, figures depicted by Dr. Doi in which you can separate the nerve into multiple cables, but at the same time preserving the fascia in between to preserve the blood supply. The vascularized neural graft is another nerve graft that has been commonly used in literature, especially for brachial plexus injuries involving, has to involve the revulsion of C8T1. And it's more commonly used as a pedicle nerve graft with the blood supply mainly coming from the superior onocollateral vessels. And in the study that was published by Dr. Pertelli, where he bridged the ipsilateral C-fiber to the musculocutaneous nerve on the same side using the pedicle, the UMG, he cited, he showed very poor results, none more than M2, and he cited a vascular insufficiency, excessive axon sprouting within the trunk nerve graft and the chronic denervation of the nerve graft before the surgery as possible factors for the poor outcomes. Well, for us, when we look at the entirety of the ulnar nerve, from the wrist all the way close to the axon, given this long nerve, you can see that the blood supply mainly coming from the ulnar artery and the superior onocollateral, you can see that the ulnar artery is more at the center of the entire nerve. And, you know, given this information, given this presentation, it does seem with a larger caliber of the ulnar artery and the ulnar vein, it will provide better blood supply than the SUCA. But the SUCA is often used, given that you can use it as a pedicle nerve graft to, you know, link this entire nerve and hook it up to the proximal nerve, the proximal stump. Well, what if you harvest this nerve graft as a free flap, so free vascularized ulnar nerve graft, and, you know, base it on the larger caliber vessels? It will definitely provide much better perfusion to the entire nerve graft at both the proximal and the distal stumps. But in order for this to work, you have to have a good proximal nerve stump, and this is a very critical and very complex ingredient. And it is a very important imperative to determine if that proximal stump that you're using for this vascularized nerve graft, is it a ruptured nerve root, or is it a evulsed one? Even a partially evulsed nerve root does not justify the use of the vascularized ulnar nerve graft. And so we have an innovative way of determining the healthiness of the proximal stump. This was done by our team, the radiologists headed by Professor Yao, in which she used MRI, namely the PSW, to look at the rootlets within that nerve stump and to really determine if that is a healthy nerve. And he accurately depicts, you know, the active fascicles within that nerve stump and to use it in that study, it does show a high correlation between his evaluation and the surgical exploration. And so with that, you know, with the reverse C-shaped incision that we use to explore all nerves, you can see here with this extensive dissection, all the way to the transverse process near the vertebral foramen, you can have, you know, with the information given by the MRI preoperative examination, this is the type of nerve stump that you want, mushrooming of the fascicles and bleeding from that stump. So next up, you want to look for good donor vessels. And this again correlates to a good, decent dissection from the neck. Going in the neck, you're not just looking for the nerves, the donor nerves, you're also looking for good donor vessels. And you try your best to preserve, such as here, the EJV, to preserve these recipient vessels, to preserve these donor vessels for your nerve graft. And so aside from dissecting the spinal accessory nerve and also the phrenic nerve, you also want to preserve the transverse cervical vessels in order for you to anastomose to your vascularized nerve graft. If there's, if it's too extensively injured, you know, in a severe avulsion case, you can also look for your thoracolacromial vessels in percolicular vein. Here, the thoracolacromial vessel in the cephalic vein to be possibly used to reinnervate or to revascularize your nerve graft. Next is the graft harvest. Once you have those two criteria, you can go ahead to put harvest here. And the vascularized nerve graft, or it should be a nerve flap, is definitely one of the more easier flaps to harvest. And what you do mainly is you do not separate any of the connective tissue in between the ornar vessels and your nerve graft. And you try to harvest the dorsal cutaneous branch in case you want to hook it up to two targets. You can also harvest very long, you know, for contralateral side, for the contralateral C7. And you can also divide it into two nerve flaps, you know, in different instances, different situations. We also use the sore nerve graft here in this picture from my colleague, Dr. Tommy Chang, in which you harvest the skin paddle, you know, and you can definitely break up this nerve graft into multiple cables, but at the same time, harvest the artery, pedipal, and lesser sevenous vein to drain the flap. And then next up, you look for the recipient nerves. This is very important. You know, we look for our recipient nerves more mainly in the region closer to their target muscles. And so we look at it at the, you know, splitting up the PM to look for the muscular cutaneous nerves, the muscle, the medium nerves. And it is important to pick your target nerves. And it is important to have these target nerves within the field that is less scarred. You can definitely choose all these targets, but in our preference, we do tend to use the muscular cutaneous nerve and the medium nerve. And, you know, once you decide your targets, you can definitely access your route. And in one of the studies from Dr. Bertelli, again, many thanks to his contributions here, he mentions that, you know, having a long nerve graft, the aim is to reach your muscles and to co-act at a location that is closer to your target muscles. And one of the studies that he's shown here with non-vascularized nerve graft, you know, even with distances, I'm sorry, even with distances more than 15 centimeters, they are able to show that you have good results when your target, when your distal recipient nerve is closer, distal co-activation is closer to your target muscle. Another study by Dr. Sklodowsky, again, showing that if you have, even with a longer nerve graft, when you co-act closer to the target muscle, you have a better post-op strength index. And so given this information, you know, that is what we want to do. We want to co-act a very good proximal nerve stump to the very distal nerve recipient nerve closer to the targets with a very well-vascularized nerve graft, you know, like a highway, you know, to speed up the re-nervation. Again, you place your nerve graft underneath the clavicle. You have to be very careful to look for any sites of compression or any scarring. Remove that scar if possible. And there's a diagram here depicting how we do the actual co-activations and the re-nervations to the re-vascularizations to the transverse cervical artery and the HAV. Again, you can also use this nerve graft to bridge the contralateral side to your ipsilateral median nerve. And here, you have to be careful of the tunnel. Again, be careful of any compression. Treat the pedicle, treat the nerve graft like a pedicle of a pre-plant. And here is another diagram how we show how we re-vascularize this. And we use the contralateral transverse cervical arteries with the ipsilateral vessels. And when you use the sternal nerve, definitely, you know, given the size discrepancy between your donor and recipients and the nerve graft, you can definitely fold it into multiple cables. And with the skin paddle, you can definitely monitor the perfusion. So my concept here is always treat the vascularized nerve graft as a pre-plant. And given the prevalence of super microsurgery in pre-plants nowadays, it is no longer a hard thing or a challenging thing to do. You know, and so vascularized nerve graft, you have to always accept that these, it is liable to compression and traction. There can be size discrepancy between your artery and veins. And also there's a possibility of esophageal thrombosis. Another thing is you have to also look at the graft length. Graft size is something less of a problem given that when you use a trunk-sized graft, it is more, there's less of a size discrepancy between your proximal nerves and your nerve graft. And then you can, at the same time, harvest a skin paddle to help monitor the perfusion. It is a very good sign, usually to detect venous insufficiencies. And here, we would always recommend doing the arterial anastomosis first and the venous anastomosis first before you do the coaptation. And here you can see very good bleeding from the perineural blood vessels of the nerve graft. And this is the proximal stump. Again, here, you can see the perfectly sized match between the proximal ruptured nerve root and your trunk-sized nerve graft. Here, the vascularized on the nerve graft just before the coaptation, seeing good bleeding. So here's some case demonstrations of total paralysis patient with a pre-op identification of a C5 ruptured root. Here's the pre-op presentation, completely paralyzed. And you can see that post-op, very, very strong elbow flexion. Definitely more than M3. And you can see active finger flexion, showing resistance. And then a very interesting here, a good pronation and supination movement. It definitely is helped by gravity, but again, you can see a very good grip, not letting the ball go and allowing him to place the ball at a location, to grab a ball and place the ball. Here again, it's another case of total paralysis, where we do have a ruptured C5 root. And when you hook up to a vascularized on a nerve graft that's more than 25 centimeters long, we hooked up to two targets. And again, you can see here, active finger flexion, even thumb. You can even see FPL movement here. And with that movement, as well as the shoulder, you can see that and you can actively hold that door knob and push the door, anteriorly pull it back with the elbow flexion and to show active control, good control of his limb. This is a case with a contralateral C7 with a gap. It's definitely longer than 25 centimeters. But again, still able to show finger flexion on the index side. Here again, this is before orthodesis. You can see that he has very active pronation of his forearm and then also finger flexion seen from his fingers. Although the grip is definitely a bit weaker. But in instances where it is a weaker grip, you can use a harvested functioning free muscle and to innervate this muscle, you can definitely use the downstream branches of the innervated medium nerve from the vascularized on a nerve graft to help with the grip. And here, as you can see, this is the functioning free muscle. This is the vessel anastomosis. Here you can use multiple branches, not just the AILN, but you can use pronator terrestrial branches, and definitely a hookup to this functioning free muscle that have power. I think you can see here a case with a contralateral C7 to have strong finger flexion after the functioning free muscle innervated by the distal end of the median nerve that was previously innervated by the vascularized on a nerve graft. So in conclusion, vascularized nerve graft is not difficult. You have the ability to re-innervate very distal multiple target muscles, even in very extensive nerve grafts. It is not a dream, it is not impossible. The vascularized on a nerve graft, I think the donor side morbidity is justified in total paralysis. We do prefer a free vascularized on a nerve graft to definitely help with the inset and to use the ulnar artery rather than the superior ulnar collateral to ensure adequate perfusion on both ends of the stump, ensure that highway access of the axons going from the proximal side going straight into the distal muscles. So again, I want to thank you for your attention. Thanks for giving me this opportunity to present here my contact information. Please feel free to ask any questions. Thank you so much. All right, we've eroded a little into our break here. And so what I'm gonna do is put up our case for discussion and ask each of our panelists to just give us their thoughts briefly, and then we will move right into the next section. If anyone needs to stand up or stretch their legs, please do so. We don't wanna trap you all in your chairs here. So I'm going to skip ahead to the second case in this presentation. This is a 60-year-old gentleman who's a maintenance worker who was involved in an industrial accident with this degloving injury after, pardon, in a motorcycle accident with a degloving injury. He's some other associated and relevant traumas including an open femur fracture and tib-fib fracture and multiple rib fractures. He's gone through many, many washouts and it's important to know that there's actually a sufficient soft tissue to cover that wound just so we don't have to worry about that. But going through his ulnar nerve preparation because he had a large ulnar nerve gap here. This is following resection of the ulnar nerve with tourniquet off to healthy bleeding fascicles and this is the deficit that remains. So you can see we have about a 6-centimeter gap just distal to the elbow. 60-year-old gentleman, poly trauma. Dr. Safa, what would your strategy look like for this case? Yeah, this is a tough case because an ulnar nerve gap of 6 centimeters is fairly significant and I think the data shows that even with autografting this typically don't do very well. 6 centimeters is definitely pushing the limits of allograft. We don't really have too many cases to justify or to show that it works that well up to 7 centimeters. So I think for this, I think what I would do is if the gap is 6, I'd probably use a mixture of maybe MABC, which is probably fairly close in your field, just go a little more proximal. It's hard to get enough cables of that, so I would probably do a mix of that and allograft together. If this is a shorter gap, especially more distal, I probably would just do allograft because I've done plenty of those and the results have been pretty equivalent in my hands with the autografting. But for this, that's probably what I would do. I think if it was more proximal, then I would also consider doing kind of a nerve transfer as well if it was more proximal, but I think this is fairly kind of mid-forearm. Dr. Isaacs, your thoughts? I basically agree with Babak other than I don't like to take sensory nerve from an arm that already has a sensory nerve deficit. One thing Jamie Bertelli also showed us was that there's a lot more overlap in sensory territories than we would get just from relying completely on netters, and so I think that having preservation of medial interbrachial cutaneous nerve does give some sensation to the distal form that would be useful to this person, and so I would take several nerves, but I would also fix it with autograft with that size gap. And the question that everybody wants to know, do you supercharge or not supercharge, and that's tough because your supercharging is almost still within your zone of injury practically or not much farther down from your zone of injury, but I wouldn't have a problem with supercharging here, but I think that primarily at that level with a good autologous graft repair, you have a reasonable chance of recovery. The only other thing I'd mention is I've only done a couple, so I can't advocate for it, but I do find that new nerve transfer that, again, Bertelli sure is getting a lot of credit for that thing, isn't he, that Bertelli described doing the distal, doing the pulsus oponens motor branch to the distal branch of the ulnar nerve, it's not an easy transfer, anybody in the room who's tried it, very tiny nerves, difficult dissection, but it's very intriguing for restoring a pinch, so I would potentially do that in this patient, too. My only comment about the MABC would be that it's traveling right through the territory of that wound, so I think the MABC branches distally are probably mostly transected anyway. That's fair. That's the only comment there, but I think in general, I would agree with you, though. Well, then I agree with your point also. I mean, for me personally, when I look at these cases for a 60-year-old patient, you have an enormous gap in an elderly patient, I mean, elderly by the literature standards, there's no judgment on anyone's age in the audience here, but I really don't think that patient has a good chance of motor recovery from this type of injury, no matter what I put in there, so this is a patient I did do an AIN transfer that shortens the distance enough that I at least think there's a chance he's going to get his intrinsics back, and so then I look at this gap and I'm like, what is my management of this gap for? My management is primarily for a hope of sensory reconstruction and to prevent painful problems later, and so this is a patient I used a purely allograft reconstruction for and then did the distal transfer, but these are the kind of debate points. If I had the same gap injury in a patient who was 20, I would put sterile nerve in that, but at 60-years-old polytrauma patient, I think my best bet is with the transfer and then just grafting him for sensory. I'm sorry, did you do end-to-end or? I did end-to-end for the transfer. Yeah, that makes sense. All right. We're going to shorten this debate so that we can continue on with the session just a few minutes behind now. Thank you all for your patience and for being here. Thank you. The next discussion will be Principles of Nerve Transfer, Tips and Perils to Optimize Outcomes by Dr. Quick, and this will be prerecorded. Well, good morning everybody. My name is Tom Quick. I'm a UK surgeon working in nerve injury and brachial plexus injury. I work at the Royal National Orthopaedic Hospital in London, England. I'm also an Honorary Associate Prof at University College London. I have no financial disclosures and I'm here to talk about nerve transfers, the what, why, when and how, rather more flippantly, which, why, where and why. The key question when assessing nerve injury is how to re-innovate function. Mainly this is motor function but occasionally, and it's not something that I will touch on here, we also use it for essential sensory function in areas where the sensory function is going to make a difference to overall function. So, for example, the palmar aspects of the thumb, index, middle, finger, perhaps plantar surface of the foot. Why would one want to re-innovate function? The majority of my work is through injury to the nerves but also re-innovation via nerve transfer can be used in spinal cord injury. This is either traumatic or inflammatory. The use of free-functioning muscle transfer or FFMT is a technique bringing in new muscle and attaching inflow and outflow of vascular supply to bring muscular tissue that is novelly de-innovated to re-innovate. As there is a concept within nerve injury that de-innovated muscle, once it's been left de-innovated for a period of time, and this commonly is considered to be somewhere under 12 months, is then recalcitrant to re-innovation and even if axons are brought to that muscle after this point it will not re-innovate. A similar concept to nerve transfer is targeted muscle re-innovation and it's not something which I touch on particularly here but it is a similar concept taking one motor function and utilizing another. Generally in TMR this is not to create novel biologic function but to grow a transected nerve so it would not create a neuroma but also to create the possibility to trigger and control myelectric prosthesis. So as I mentioned there is this period of nerve injury leading to de-innovation of muscle where the muscle remains capable to be re-innovated and this biologic process is little understood. The process of de-innovated muscle means over time the muscle loses bulk, it loses density of vascularity, it creates increased fibrosis and all of these processes continue and progress over time but something occurs to the muscle cells themselves where they will not establish a new neuromuscular junction at this terminal period and become recalcitrant to re-innovation and that is when the nerves completely transected that both the afferent and the efferent functions have been divided. In some conditions spinal cord and particularly the acute myelitides and particularly AFM or acute flaccid myelitis akin to polio we have loss of the efferent function the control from the alpha motor neurons but there is sensory return from the muscle and it is thought although still not yet proven that this prolongs the period at which the muscle is available for re-innovation and anecdotally colleagues have reported re-innovation at three or four years post flaccid onset and I myself have had a case at two years but I think it is difficult to know exactly whether this is a complete lack of efferent function or whether the afferent function itself has had some ability to maintain the muscle as receptive. So the questions on how nerve injury processes often come in common patterns and so we develop set plays and nerve transfers and their interaction in treatment with tendon transfers really are still yet in many conditions to be exactly laid out. Tendon transfers are a lot more reliable produce function very quickly and as we'll see nerve transfers have less reliability and take a while to become useful. Acute flaccid myelitis is an effective condition of hyper-inflammatory myelitis associated with a an enterovirus d68 most probably although perhaps a number of other viruses as well. This is well known as an international pandemic before the one that took all the news and we here in the UK were expecting an AFM peak last year but obviously that didn't happen due to our COVID lockdowns. But this takes out the the dorsal, sorry this takes out the ventral horn and produces a flaccid muscle and there's been great benefits across the world reported with utilizing nerve transfers to re-innovate this and it's becoming a growing part of my practice. The key thoughts at the beginning here which I'd like you to consider and we only have six minutes more on this talk but is that nerve transfer is a technique and not a treatment in the same way split skin grafting or tendon transfer or osteosynthesis is a technique and so it needs to be deployed along with other techniques towards a treatment aim. We've seen many cases where there's been a lack of functional recovery even though there's been re-innovation and this has been seen in my practice for example when trying to use nerve transfer for foot drop taking non synergistic nerves for example lateral head and gastroc as a donor and attaching this to the common perineal trunk to hopefully re-innovate dorsiflexion and eversion is a non synergistic transfer and even though the nerve can re-innovate the muscle function is often not restored and I think this is what we're learning more and more as we hone this technique and so cortical plasticity and re-learning function is key and therefore planning prehabilitation and rehabilitation are key. Surgery is often relatively straightforward but we have to work out what we do when it fails or goes wrong. So to come to exactly what a nerve transfer is either but we did that until now but essentially it's using a working nerve which is connected to the brain and robbing Peter to pay Paul so taking a function off a muscle or taking innovation away from a muscle which is working and controllable and redirecting those axons to grow to control another muscle. It often doesn't degrade the donor function significantly but the key to restoring function is this concept of having the ability to change function of the cortical area which used to control the donor function and has to relearn the recipient function and this has a number of challenges. There are many patients who have nerve injury following trauma who have significant head injury. There are many patients who are of a prolonged age and we identified both of these as risks for not having the ability to easily relearn that nerve transfer function. My pediatric patients appear to adapt incredibly quickly and develop these novel functions with great ease. The adult head injured the elderly struggle and find this a lot more difficult and it's very simple to see a de-innovated muscle and just think let's throw a donor to that and many many techniques have been described but to simply go through the process and again I'm well aware we have a very mixed audience and I'm going to go right back to basics I make no apologies for that. Axonal regeneration occurs when an axon is cut so just like a worm if you cut it in two the distal half dies, degenerates and the proximal half tries to regrow. We can direct that regrowth by utilizing nerve channels so if an axon like a worm is cut in the middle and its tail is directed to grow down an endoneureal tube particularly with Schwann cells we can make that axon grow in the direction that we wish towards the target that we wish. And in simple terms this is taking a broken TV and recognizing that you have a working lamp next door and taking the wire or one of many wires from the lamp and using that to restore the TV so it's redirecting working nerves the time taken as that worm regrows down that tube with the Schwann cells tempting it along takes time but then that function has to be relearned. The approach here in London really is is one that we don't ever go primarily for nerve transfer treatment. If we have for example a road traffic accident a young man commonly on a motorcycle and we have correlation between clinical history examination and imaging and neurophysiology showing that there are avulsion injuries that diagnosis is clear but so often that is not the case and there is some lack of correlation between maybe there is a tunnel in the neck for five or six even though we think there may be a pseudo meningocele and so therefore I see exploration of the zone of injury as being mandated. Obviously in the spinal cord injuries that is not practically possible but in the brachial plexus injuries absolutely so. It is very tempting to go away from the area of trauma where you know there's disruption of tissue planes, bleeding and risk and goes more distally and identify lost function and transfer nerves but this as I mentioned can fail if the patient fails to relearn that function and it can be occasionally in the neck that significant conduction block is identified and that there is no need to undertake distal surgery and indeed combination of local grafting and nerve transfers often gives the best outcome and so exploration of the zone of injury is mandated. Of course it involves intraoperative choices but to optimise those it is essential to plan preoperatively, full examination on at least one occasion and certainly absolutely on the morning before surgery to assess if there's been any interval change since first meeting the patient and deciding on surgery but also to understand exactly what the patient requires in terms of function or their prehabilitation aims have been and what the rehabilitation plan is and this involves teamwork and quite simply put the surgery is relatively straightforward but the work for the patient and the rest of the team to gain best function from this and to be honest to make the outcome anything near useful is done by a wide team and it's not something which is done by an individual surgeon. We're well aware of the utility of nerve transfers they provide a great deal of force and power my research unit has been working on using nerve transfer as a model for assessing re-innovated nerve function and I just want to highlight how we would assess functional recovery. We have traditionally in orthopaedics and plastics utilized the Medical Research Council MRC grade of muscle function most of us agree in a Delphi exercise that I undertook that re-innovated muscle could never be assigned a normal or five out of five power however most patients will attain a four out of five peak force perhaps a third of the pre-injury force but what is it about us and about our system that puts emphasis on peak volitional force? Patients tell us they don't care what the strongest contraction that they can create is because they do that once and then they're not able to do that again for a number of hours or it's uncontrolled or it doesn't have gradeability or control or it doesn't feel like it's their muscle and it doesn't integrate with other functions or they have to continue to drive it with co-contraction of the donor muscle they may get cramp they may get afferent pain from the muscle all of these features of muscular re-innovation are deemed to be more important to the patient than peak volitional force so a subject which we've all presumed was objectively measurable is actually something where the subjective experience of the patient is key and whilst I encourage you to plan to engage your colleagues and to utilize this technique of nerve transfer wisely my biggest message is listen to your patients about the outcomes and let's assess the advantages and disadvantages of using donor functions rather than the reconstructing the original function there are pros and cons of each and we should be well aware of what the patient's experience of doing the operations that we undertake are. I thank you very much for your time there's a set of two questions available as well online and I wish you a very good conference whether virtual or in person best wishes from London. Next we will have Dr. McKinnon pre-recorded discussing to supercharge or not to supercharge. Thank you so much for this opportunity about talking about supercharge which I think is a really exciting new addition to looking after patients with nerve injuries. Where did this idea of supercharge come from? Well in 1911 there were textbooks written that showed supercharge in it and all sorts of different nerve transfers but I got interested in this when Dr. Viterbo came from South America in 1991 to this meeting and he sat in the back room of the audience and he had these binders and in it he had his PhD work on nerve transfers so that was 1991 and that work that he had done was probably started you know four or five years at least earlier. At that time I thought that is sort of a ridiculous idea where you would take here's here's his idea you take the denervated nerve in pink here and you would sew it to the side of a donor nerve and then the donor nerve supposed to grow into that that seemed like heresy but having a laboratory I went to the laboratory and we studied that for a decade or more and you can see our publications were coming in his publication came out of that 1991 meeting in 94 and then you can see that we're publishing all through the the the period between 97 and 2008 and more so on the left side you can see his traditional end aside where he's saying a donor nerve will give me nerves and then the concept of the supercharge where you take the donor nerve and you put it into a denervated nerve so it's the reverse of one of the others exact opposite up and for a while I was calling it a reverse end aside but that implied I'd have to tell you about the end aside and so now we just chop call you what it is it is and it's a supercharge we're taking from a nearby normal nerve sewing to the side well where did I get that idea from about that first idea from Viterbo and the second idea was two papers published by dr. Isaacs in published in 2005 in 2008 and when I looked at it I thought that seems just as crazy as what Viterbo had but having the laboratory with these green transgenics we could study that so we could take a normal perineal nerve and my hypothesis is that this would not work take a normal perineal nerve and sew it to the side of a completely denervated tibial and again decades of research on just even controlling and studying and decide in the traditional way and I was shocked to see that by 35 days those normal perineal nerve and that would be sensory and motor busted inside that denervated nerve and move distally and re-innovated and we've got just as many nerve fibers if we did it end to end so we did that I didn't believe it I said we'll do it over again we did it over again and it worked and then that was it then off we go and the first patient I did was 2009 so 2009 this this is the transfer you guys are familiar with we have worked hard because as the innovator of this supercharged to the intrinsic ulnar motor I am anxious to disseminate this work safely but also in an active fashion so we have published many papers on this because I am so invested in it and these are just a couple of them so 2020 this is the study of 42 of our patients before that we presented the earliest group with 55 patients in 2015 looking at our results we published in 2019 in JBJS looking at the electrical issue electrical study issues and introducing this importance of the CMAP action potential as a surrogate for number of nerve fibers to determine severity of cubital tunnel as we were looking at this operation for patients with that and then another article just recently in PRS and refining the indication so people if they're going to try it at least we've done the best we can to teach people how we do it and of course Andrew Yi and I have got videos out on how to do this and Yahoo in 2016 a publication our first adopter from Mayo Clinic Heather Balser Dr. Rue and Steve Moran first adopters and now there have been a half a dozen early adopters but certainly not tipped and in the United States other countries maybe yes but not quite here so what's the basis for wanting to do a supercharge it stems from I call this Tessa Gordon's cliff so this was published way back in 1993 and you can see that the force or the function is maintained normal as you lose nerve fibers so as you denervate nerve fibers from 100% innervated to 100% denervated the the function stays on that plateau and then bang it falls off just precipitously falls off so here's our cartoon for this so you have normal function here and then a hundred percent of the nerve fibers and no nerve fibers and the experimental work suggests that you'll lose nerve fibers and as you lose nerve fibers the motor neuron pool just expand it'll expand five times normal so these these these these motor neurons can work five times as hard but once you've asked them once you've lost 80% and you say okay to the 20% left over you got to work five times as hard it's a short jump to falling right off that cliff so when you have nothing you would do an end-to-end nerve repair or nerve graft if you've got a neuropraxy of course you have all the nerve fibers just need to remyelinate axonotematic to Sunderland to you have enough nerve fibers to maintain on the plateau but this supercharging is to get you up on that plateau if you're in that precarious position there so it's really for the axonotematic three injuries and we'll come back to that concept at the end of this very short talk so we published a study answering these questions like when would you do a supercharge and there's a lot of this is a clinical dice of cubital tunnel and then this is the supercharge way down here at the bottom there's a lot of no no no no no supercharge there's only one indication for doing a supercharge in my opinion for the AIN to the ulnar motor and that is well first of all I guess dot you have an intrinsic weakness yes okay do you have a decreased CMAP the CMAP amplitude is surrogate for the number of nerve fibers so if you look at your CMAP amplitude and it's relatively normal then you you don't don't do a supercharge because you've got all the axons that you need you could have a demyelinating process and you've got all sorts of normal axons but they have no function but if you got a normal CMAP so you have to have a need you have to have the intrinsic muscles needed the CMAP is down yes okay then they have to be receptive you can have a terrible CMAP but if you don't have fibrillations positive sharp waves then that means you have no motor end plates to receive your nerve transfer and then so if you have the CMAP down and they're receptive the muscle that's left is receptive the end plates are receptive then you need a normal donor and if you have an ulnar nerve and someone has some C81 radiculopathy your PQ may not be normal that's the route to when to do a supercharge an actual fact what we do now is we do that supercharge and then in the early 2020s before we started COVID we started taking doing a turbocharge where we take the ADM nerve and move it to the side of the motor component of the ulnar nerve putting it on the side where the topography is FDI so the topography of the internal of the ulnar motor is the ADM is is medial the FDI short flexor is radial and then the lumbricals and interosseous are in between so we we're we're doing this sort of Stets procedure we call it supercharged turbocharged and decide here's an example of that so after Guillaume's canal is decompressed and we've released the deep motor branch we'll then pull the entire ulnar vascular bundle radially and we'll look for this branch that's going towards the hypothenar musculature and then we'll confirm with the nerve stimulator that that's in fact the abductor digitum minimi and you can see when we stimulate that that it's the function that we're getting oftentimes you'll see that the vascular will appear rather large distally but as it's neuralized approximately from the motor branch it does get quite narrow now in some patients you will have a little bit of function in the ADM so you want to do that stimulation right away and others of course you just have to know the anatomy and learning that anatomy is key because it's not an easy thing to find if you're not used to finding it so also we do supercharges now for everything we pretty much do an end-to-end for if they have a third degree injury if they have a third degree injury so I think you're familiar with the supinator to pin the spin and but basically the double fascicular transfer so someone with diculopathy and no elbow flexion and something but not great then you if they're if the lower you don't see 81 radiculopathy then you can take the the typical donors for a double fascicular transfer so we're doing end-to-side supercharges for everything now and this is the algorithm we use for that and then this is my last slide so you do the EDX someone's got a nerve injury say their axillary nerve injuries not working or axillary nerves not working and then you'll do an EDX and if you see in increased insertional activity fibrillation some positive sharp waves you know that there are some motor in place that are disconnected but if you don't see that then you should expect recovery it would be a neuropraxia and if they don't recover then it could be for example in quadrangular space it could be that they've got compression at the quadrangular space with the conduction block there but if you do see those fibrillations and positive sharp waves at three months the power of a single month at three months predicts an axonotomatic injury predicts you're going to be on that plateau if you can deliver those collateral sprouting axons will deliver a muck for you at three months then it you should anticipate an axonotomatic injury with great recovery no surgery and if you don't see that over a period of time then there could be a conduction block and again you could do a decompression now and and the algorithm for that would be you do the decompression so it's an axonal you think it's an axonotomatic injury you don't think they need any end-to-end nerve transfers and interoperatively use when you decompress you see great distal stimulation then then then you're you'd be done no more surgery it's not no surgery you're done surgery but if you stimulate and you see a weak response after you do the decompression then you could say well this is a severe axonotomatic injury bordering from a two to a three and then you can do the sets there so we have an indication for a sets right there and that is even if they have mops at three months if they're not recovering an appropriate time time way either electrically or clinically then you suspect it might be conduction block decompress you don't like the stimulation distal view of sets now what if there are no motor units at three months repeated at four months and then if you get some mops at four months then in my experience of 40 years doing nerve surgery if you get if it takes four months to get to get a motor unit then that is going to predict you're going to be severe second or axonotomatic three and then I would supercharge there so there's another indication for supercharge by contrast if there's no motor units at four months then I would proceed with whatever your favor is with respect to treating neurotraumatic injuries nerve transfers or nerve grafting thank you very much for that opportunity to talk about when to do a sets okay next we'll have dr. Bertelli discussing nerve transfers to restore shoulder function Ladies and gentlemen, I am Dr. Daniel Bertelli from Brazil and I will talk about nerve transfers to restore shoulder function. There are four important nerves that move the scapulothoracic joint and the glenometral joint. For the scapulothoracic joint, the accessory of the long thoracic nerve and to the glenometral joint, we have the suprascapular and the axillary nerve. All of these nerves will be addressed in my presentation. Regarding the accessory nerve, if the proximal stump is available, it should be grafted because the results of accessory nerve grafting are very rewarding. However, if no proximal stump is available, the only possibility to treat such reason is by means of nerve transfers. When I talk about nerve transfers, I am telling you that it is not a single nerve transfer. I use several nerve transfers to address all the branches of the trapezius muscle. We have the first branch here in which I repair using the cervical plexus. We have a second motor branch to the trapezius here. Mostly, we are interested in the upper trapezius. I did a transfer of the suprascapular nerve to the motor branch of the trapezius. The distal stump of the accessory nerve was divided here. I connected it with the posterior division of the upper trunk, mostly targeting branches to the axillary nerve. This is a clinical example. This girl underwent a robotic surgery with paralysis of the trapezius and the sternocleidomastoid. We did the surgery we just mentioned and this is the result three years post-op. The long thoracic nerve is the next important branch that should be repaired. The vision of the long thoracic nerve stemming from C5 and C6 that join the contribution of the C7 at the level of the axilla. In the thorax, the distal portion of the long thoracic nerve is mostly important because it stabilizes the tip of the scapula. I have no experience with grafting the long thoracic nerve because most of my cases are originated from prosthodontics. So the proximal stump is not available. We have to consider as donors the subscapular nerve, the thoracodorsal and the axillary nerve. Considering the thoracodorsal nerve transfer, the results are not impressive because there is no spontaneous stabilization of the scapula. It is linked with respiration or shoulder adduction. But if we add another transfer together with the thoracodorsal nerve, things begin to ameliorate. So in this case, I did the thoracodorsal and I also did the transfer of the subscapular nerve to the upper division of the long thoracic nerve. Another branch that is possible to be connected with the long thoracic nerve is the branch to the middle deltoid. I think this is an important alternative because the motion of shoulder adduction and external rotation is synergistic with scapular stabilization. An example, this is a patient with an open injury of the neck with a division of the long thoracic and axillary nerve. So I did a nerve graft into the axillary nerve. I connected one branch of the axillary nerve with the subscapular and the long thoracic nerve I connected in the posterior division of the upper trunk. In the axilla, I connected the thoracodorsal with the distal stump of the long thoracic nerve. And this is the patient preoperatively. Difficult and limited motion on the shoulder, scapular pain, shoulder pain. And this is him three years after surgery, after the nerve transfer and nerve grafting. I just comment on it. He has no complaint about this shoulder. Then we arrive to the axillary nerve. Just a little reminder about the anatomy. The axillary nerve has two divisions. One that goes to the posterior deltoid until it's minor and gives off the cutaneous branch. And another one that curved around the shaft of the humerus. Travel along the shaft of the humerus to innovate the middle and anterior deltoid. In brachial plexus paralysis, we should try to improve abduction and external rotation. And we target the anterior division of the axillary nerve. But also, we are interested in reconstructing external rotation by the innovation of the tennis minor. And in those cases, I use the axillary approach to reconstruct the axillary nerve. In pure axillary nerve paralysis, there is no lack of motion. But mostly, there is a wasting on the shoulder and the lack of endurance. For pure axillary nerve lesion, I prefer the trans-deltoid approach. And my nerve transfer is lower medial head and non-cuneus model branch. This is a close-up view of the trans-deltoid approach for the axillary nerve. The vessels are cranial regarding the axillary nerve. Isolated lesions of the suprascapular nerve are very rare. And the cases I found, they were related to the parsonage duct. Combined with lesion of the suprascapular and brachial plexus are not totally rare. And they should be probably more common than we suspect. This extended lesion of the suprascapular nerve should be considered when we have bone problems. And here we see the classical approach to transfer the axillary nerve to the suprascapular nerve. And here the extended approach in which I do an osteotomy of the clavicle. The bone fragment attaches to the trapezius. And then we reach the suprascapular fossa and then we suture it back. Just an interesting image, this is the transverse superior scapular ligament. So we see here the ligament and just against the bone, this is the margin of the scapula. And in this superficial position, we notice the suprascapular nerve. We divide the transverse superior scapular ligament. When we free the nerves from all the connection, I move it from the scapular node. We check for the integrity of the all branches of the suprascapular nerve. This first one is the first branch of the supraspinatus muscle. We check for continuity of the nerve. Here we have the spinal accessory nerve. And then, because we have dissected very distantly, we could connect it to the distal stump of the suprascapular nerve, very close to the muscle end point. Our next speaker will be Dr. Shin discussing nerve transfers to restore elbow function. Sorry about that. We'll do it freelance. I don't think I can plug in anywhere, but I just need my computer here. It's closed. Well, it's always exciting when you have no slides and you have to give a talk. So despite loading them up, it didn't happen. So we're going to do this a little freelance. And what we really want to talk about are nerve transfers for elbow flexion. In brachial plexus surgery, nerve transfers have been around for a long time. In fact, in 1903, it was the first description of a nerve transfer for elbow flexion. And between 1903 to 1994, where Christoph Oberlin basically described the Oberlin transfer or the Ulnar fascicle branch to the biceps motor branch, since 1994, very little has happened to advance nerve transfers for elbow flexion. If we think about elbow flexion, there are three really, really important motors that drive elbow bending. That's the biceps, the brachialis, and the brachioradialis. The brachioradialis is actually a really, really dumb muscle, and it's really hard to use. So we really want to try to get the biceps and the brachialis to work. And when we think about how to do that, in the classic findings of an upper trunk brachial plexus injury, you lost elbow flexion, you have loss of shoulder function, and loss of flexor carpi radialis and pronator. In the C567 group, you basically now lose triceps, latissimus, and radial nerve. And in the pan plexus, you have absolutely nothing. The indications for nerve transfers for elbow flexion first involve having a good donor nerve. The second is a presentation of time within an appropriate period from injury. Third is orthopedic stability and mobility. And fourth is carefully looking at age. When we look at donor nerves, they have to be a redundant function, and we heard earlier they have to be synergistic. We heard from Dr. Quick on his talk that if they're not synergistic, you really have a hard time activating them. And then the final thing is, can you use a previously injured nerve that has recovered? And there's this wanting to do a donor nerve fascicle transfer so, so, so bad, that even though the donor nerve has only recovered to a grade 2, a lot of people will say, I'll just do it because it's so easy. And so our studies have basically shown that if you have less than a grade 4 donor nerve, you really shouldn't be doing a donor nerve fascicle transfer. But unfortunately, there's not a big prospective study where you have grade 2s, 3s, and 4s and say, I'm going to just try it and let's see what happens. So be very, very careful using redundant nerves. In terms of time from injury, three to six months is ideal. Six to nine months is feasible. And over a year, you really have to have a discussion with your patient on whether or not you're really going to use that. How old is too old? I always say that if the patient comes in, they're Dr. Bishop's age, who's my partner, they're really old. If they're two years older or within five years of me, they're young. And then if they're like the resident's or fellow's age, they're babies. And so how old is too old? You really have to look at the patient's physiology. Because I've had some really old people chronologically that are physiologically young, they're a very, very, very different type of patient. Does BMI have effect? Martin Mariano-Sokoloski basically says yes. All our data says yes. But it's really not just the weight. It's the type of injury they had. So if they were traveling on a motorcycle at 500 miles an hour, a really, really, really big guy on that motorcycle would have much, much more injury than a little guy on that motorcycle. So you have to look at the whole injury pattern. So we have some good stuff hopefully coming out. In terms of decision making, you have to figure out what type of nerve injury it is, where it's located, and there are a couple basic principles. You have to understand the soft tissue. I have a patient that came in to me, and he was riding his Harley Davidson and knocking down mailboxes with a baseball bat which is a fun thing to do in Minnesota when there's nothing else going on. The mailbox took out his biceps and his soft tissues here, and the surgeon did a latissimus flap to recreate it, and another surgeon went in there to do an Oberlin transfer. There was no biceps. There was no brachialis. Yet he went in to do that. So if you're going to reinnervate the muscle, you have to make sure it's there. It's stupid, but come on. You have to understand that. So it's hard to reinnervate a biceps that's missing. The second thing is patients will come in, and they're missing elbow bending, and you go and move their elbow, and their elbow is completely locked. And you're like, what the heck? And you get the x-ray. It's dislocated with a whole bunch of heterotopic ossification. You can't do a nerve transfer in that situation and expect to get elbow bending because the joint doesn't work. So you have to optimize joint function and determine yourself whether a nerve transfer in that situation would be of benefit. There are a lot of different nerve transfers. Intercostals, if you have a panplexus, do quite, quite well. It's a real nonintuitive way of bending the elbow. I always tell my young patients, pretend you're like farting and don't fart, or take a deep breath and play. Dr. Bishop always says, why don't you pretend like you're playing an oboe? He's an oboe player. And I go, that's the stupidest thing I've ever heard. And so they understand how to fart and stuff like that. So what will happen is it's really nonintuitive, but they start learning that after a little while. In terms of intercostals, it does a great job in these panplexus patients. And before Christoph Oberlin came out with the Oberlin transfer, that's what we used to do a lot. But we could get up to 72% M3 activation and bending, and it's important not to use an interposition graft. You can use a spinal accessory nerve, and this is a real great nerve to use with a graft underneath the clavicle. It's a long graft, 15 to 20 centimeters. But it can give us 72% M3 or better outcomes, and it's a great nerve to use when you're really, really damaged and have to bypass a lot of vascular issues. The ulnar nerve fascicle transfer, everyone knows about 94% good outcomes in the Oberlin series. There's a huge debate on who came out with it first. We were doing a brachial plexus meeting, and I had Susan as one of my team members, and I had Christoph Oberlin as one of my team members, and they came in and they both converged on each other, and they had a major marital about who did the first double. And so from that, we basically don't even talk about it, so we call it the double fascicle transfer or the single fascicle transfer, and we try not to use eponyms. But a lot of controversy exists because you can't always do a double, especially in patients that have median nerve injured for like 5, 6, 7, and so you have to be very, very careful. All our data, the data from the South American group, shows that 2 is equal to 1, and so we typically just use 1. There is controversial data out there that says maybe 2 is better than 1, but it's really you have to read it and be very, very careful in your patients on how you choose it. In terms of other transfers, you can do contralateral C7. We don't do that. You could use phrenic. We don't also do that because of the BMI and breathing issues. You could use pectoral nerves and latissimus nerves, and those are very, very popular, so you have to look very, very carefully. I think Tom Quick said it really nicely. It is a team sport, and you have to be careful not being a distal nerve transfer person only. If you have viable routes, always use those viable routes for something. I think we always explore the brachial plexus, and unless it's a very, very late case where you're not going to use anything, you don't have to do that. I think the last thing I really want to talk about is measuring outcomes. There are many modifications of BMRC. Grade 4 consists of 96% of the entire scale, and we are so biased. I want my patients to know they do so good. I'll see something, and I'll bring it in and go, that's a grade 4 plus, and then I have my friend Rob Spinner come in. He goes, uh-uh, that's like a grade 2 plus or a 3 minus, and then we start arguing. I'm like, come on. The patient's sitting there like this, looking at you, and go, oh, you failed. We are so biased on that. In fact, Rob Spinner, Alan Bishop, and I took about 100 of our patients that had elbow surgery for elbow flexion, and we went retrospectively and got all the grades. We had grades between 0 and 5, and we then took them to the lab and had them do torque measurements. And every single one of the patients that I graded as a grade 5, or Rob or Alan graded as a grade 5, were at 40% compared to their opposite side. So in my books, even though in some of my own papers that I've published in my early career where I said I have grade 5, to me grade 5 is impossible to occur or have in any type of nerve surgery, I don't care who you are, but it's impossible to have compared to the opposite side of grade 5. And so you will not see too many of my papers now ever seeing a grade 5 because I don't think it can happen after nerve reconstruction. So lastly, I want you to say that there's a lot of controversies out there. You have to pick what's good for you. You could always do tendon transfers later, triceps transfer, latissimus transfer, a bipolar pec, or a free-functioning muscle if you have the ability. It's really critical to do good decision-making, good preoperative planning, careful comparison across units and within your own field, and know the options for failure. So I apologize for not having slides, and hopefully it was a little entertaining. Thank you. All right, our next speaker will be Dr. Leversedge discussing nerve transfers to restore extrinsic finger function. Alex, how did you get up on the stage here? It's a big step. Well, good morning, everyone. I would just add to the comment from Alex, when we test our own patients and we look at our outcomes, when you do get to that 4 plus 5 patient that you really want to say is a 5, then just check how quickly they fatigue compared to the other side. We don't often take into consideration the fatigability of the muscle that's being reinnervated, and I think that has something to do with our outcomes as well. So thank you to Shelly and Amber for putting on this course and for the invitation to participate. This morning my challenge and my charge is to discuss nerve transfers to restore extrinsic hand function. And I think, as we all recognize, there's many challenges that go into our decision-making and our patient evaluation, and many of these have already been discussed, so I won't belabor them, but time is obviously one of those, both in terms of the time when we see our patients, our serial examination, and our decision-making process really is determined by the time from the injury to when we do a procedure and the time that it takes for that nerve to regenerate as a nerve transfer, again, meeting up with its distal motor end plates. The distance for which it has to travel, obviously an AIN reconstruction using a nerve to the brachialis in the upper arm has a little bit further distance to travel than if you use a branch to the extensor mechanism in the forearm. There are often few expendable donors, and this is really critical when we're thinking about extrinsic hand function because many times if you've got a mixed plexus injury, generally speaking, your ulnar and median nerves may be involved, your radial nerve may be involved, and there may be some smattering of recovery, and it's hard sometimes to determine what may be a good expendable donor. And then there's anatomic variations, and for those of us who do nerve transfers, we're probably being seduced by these in part because of our love of anatomy, and if you love anatomy and you're creative, you also have to recognize that sometimes when you explore the pronator teres as a donor, there may be only one donor branch as opposed to two, and you have to realize that this may be an influence on your decision making, sometimes not until you're actually doing your surgical procedure because it's hard to know about these in advance. So there's not always the easiest route, and I think we have to be able to have it's having plan A, B, C, and D when you go into the operating room sometimes, but it's also being open and aware for many of these cases with your patients, and it's not, as I think many people have already identified, it's not always doing the same thing for the same problem every time because you will run into problems if you're just a distal nerve transfer surgeon and you bypass the time when you need to do a tendon transfer, and some of these examples will highlight this. So there are many considerations for extrinsic recovery in the hand, and I've included, even though it says hand, I've included the wrist and to a certain degree the forearm in this, but any of these injuries, spinal cord, brachial plexus, median radial ulnar nerve, injuries in isolation can all require some consideration for what we do, and I'm going to walk through this in reverse order from the standpoint of time, and probably the easiest one is the ulnar nerve because for extrinsic functional recovery or reanimation, we really don't have many procedures related to nerve transfers, do we? So most of the time when we're looking for an extrinsic defect or deficit, we usually may have FCR, so then we've got a redundancy, and obviously in terms of finger flexion for small and ring finger FTP, which remember as you think about restoring and reanimating the hand, as was pointed out for distal nerve transfers in the hand, we're trying to get functional pinch and grasp on the radial side of the hand, but our power grasp and heavy lifting really comes from the ulnar side of the forearm and wrist, so from a finger flexion standpoint, this is important to consider. So if you have a high ulnar nerve injury, as in a patient like this, it's isolated perhaps to the ulnar nerve, you have to say, well, what are we going to do here to restore not only intrinsic but extrinsic function, and I would just caution everyone, this is a nice paper by Dr. Pertelli that identifies that actually many times if we carefully evaluate our patients, we don't always have a deficit in terms of extrinsic function for finger flexion when you have a high ulnar nerve palsy or high ulnar nerve deficit. So that's something to consider, but obviously a tendon reconstruction side-to-side tenodesis is often what we may do if we need to restore extrinsic function. So really the workhorse of this talk is towards the radial and median nerves in terms of extrinsic function. The radial nerve, obviously we see injury either with a plexus injury, we see a high radial nerve injury, perhaps with a humerus fracture, et cetera, and so these are not uncommon, and time is often many times our decision maker. How many times do our trauma colleagues send us a radial nerve injury at the time of the injury? Many times they're sending the patients to us for distal transfers, tendon transfers, not even nerve transfers, because they're so conditioned that tendon transfers do well. And so the extrinsic deficit here, obviously wrist extension, MCP joint or extrinsic extension, and then also consider the thumb perhaps separately from the fingers. The challenge with tendon transfers, as we're all aware, is in order to extend the fingers, many times our patient has to drop their wrist in deflection just to get their fingers up and away. And as many of us also recognize, it's sort of like doing this to your fingers because your tendon transfer effectively is a tenodesis procedure, so you don't get back individual finger function. They're all essentially linked together to whatever tendon you've used as a donor motor. So Dr. Bertelli published this series of patients. Again, these are all going to be based on variations in the injury, so you do have to take into consideration timing to presentation, timing to surgery. But in general, his observations, I think, for many of us that do nerve transfers for radial nerve injuries at the appropriate time, the two differences here, as he points out, one is patients with nerve transfers rarely have to flex the wrist. They usually can do relatively well with the wrist in neutral or even extended position to get their fingers extended. And then you don't have to obviously go back and do a re-tensioning of a tendon transfer. And those are probably the two advantages, along with the theoretical advantage of having individual finger extension and control for reanimation. This may not be the case to do this, so if you consider the PIN as a distal nerve transfer, if you have a biceps tenodesis button that was erroneously put through into the forearm and your biceps tuberosity is not far from your PIN, as I think we all recognize by turning over the arm, and you may not have a good recipient, so these are things to consider when you're considering a nerve transfer. You say, ah, surgery happened with one of my colleagues four weeks ago. They have no PIN function. I'm going to go and do a nerve transfer. Well, the state of your recipient motor branches may not be there because of the trauma that the nerve took at the time of injury. So these are things to consider when you're doing your nerve transfers. Again, beautiful anatomic studies, and again, variations in anatomy, but the classic here for nerve transfers, AIN, using the AIN distally at the PQ innervation to transfer to the ECRB was described here by Dr. Bottelli. And again, finding the distal branches of your AIN, obviously preserving your FPL and your profundus branches, but taking your PQ allows you a very long leash, if you would, to serve as a nice donor for reaching your muscles of the extensor forearm. Again, it goes back to synergy and synergistic recovery, both in terms of aiding the patient in their recovery and their therapy, using, relatively speaking, these donors in a synergistic fashion. All you have to really do is think about what you might use for finger extension. You flex your wrist, easy tenodesis. For relative wrist extension, you're going to be flexing your fingers. So if you do have the ability to donate, and remember, for FCR, you oftentimes just have one motor branch from your median nerve, and so you do have to recognize that that would be, then, your redundant donor. Thumb extension. Again, here we're looking at the distal AIN to the deep branch of your PIN, favoring thumb abduction and extension. A small series here again, but showing that there was significant recovery of the trapeziometacarpal joint motion with these distal transfers along with FCR to PIN and PT to ECRB, obviously for full radial nerve function. And then, as John Lee pointed out, radial nerve recovery also depends on the extent or the zone of your injury. This is not, obviously, these are not patients from an isolated radial nerve injury. These are patients from a brachial plexus injury or above. And so in this circumstance, you can use, when you're injury, when your nerve to the supinator, again, relative origin of your nerve to the supinator is from your PIN, but it comes off higher up in the brachial plexus. And in terms of your spinal cord injury patients, so nerve to the supinator can be a donor to your more distal PIN musculature. And then PT to AIN transfers will, again, favor the more lower plexus injuries or higher plexus injuries using the intact lower portion of your brachial plexus. The median nerve here, remember, you can have a wide variation of injury, particularly with a plexus injury. Your extrinsic deficits here are going to be your forearm pronation. We live in a pronated world now. We used to live in a supinated world, but now we're doing everything in pronation. So that actually does, is a little bit more considerate in what your patient's expectations and what they're looking for. And obviously, wrist flexion and digital flexion are an important part of these injuries. From a pronation standpoint, use of the FDS motor branch, as Susan McKinnon identified, in both case study, case series, and anatomic dissections, remember the variations in the anatomy. And that's really critical because if you steal one branch from your PT but you don't confirm that there are more than one branch, you may be then losing PT. So in pronation, using FDS to restore pronation, using variations in your motor donors here. This is a nice and recent article in terms of anatomic dissections showing the variability of the median nerve branching within the cubital fossa. Next time you explore the cubital fossa, it's a good one to look at. And again, for pronation, obviously depending on what nerves are intact, using the transfer ECRB. If you have your radial nerve intact, considering the relative local anatomy, your nerve to the ECRB to PT, and in this case supinator to AIN may be a way of restoring pronation. I'm going to consider AIN and spinal cord injuries together just from an anatomic standpoint, but obviously they're different in terms of kettle of fish. But in the time that we have and not wanting to run over, I think it's important just to think about this from an anatomic standpoint, but your indications may be slightly different. This is a C6 spinal cord injury patient. This was actually six years prior to surgery. You can see here what's intact. Deltoid biceps, wrist extensors, limited wrist flexion. But here you can see the deficit. So just being able to pinch and grasp and use for finger function for, say, a motor scooter is very challenging. This is a nice schematic from Ida Fox, and it identifies it within a spinal cord injury, different than a peripheral nerve injury. You have functional muscle that is proximal to the zone of injury within your spinal cord. Within the zone of injury from your spinal cord, these are times when you may, the reinnervation is time sensitive. But then caudal to the zone of injury within your spinal cord, you do have the ability, because remember this is a central injury now and your anterior motor horn is still intact, that you have intact muscle to which you can still do a graft. So that lower portion, the inferior portion of the intact cord, is to where you can consider a nerve transfer. There are various strategies that I won't go into. This is not a talk about spinal cord injury patients, but they're just things that you have to remember strategically before you commit to a procedure because there are things that can affect your outcomes. Electrodiagnostically, remember just, if you haven't done this before, your donor should be normal, and then your recipient, which is not functioning, but still has to have no denervation, so no fibrillations, and no relational control. So you're below that level of injury in the spinal cord. So just as an example, if you think about this patient, they have, this patient has, she has intact elbow flexion with supinator, or sorry, with biceps and brachialis intact. That means you've got a redundant donor in terms of nerve distribution. So in this case, because you've got an intact biceps, you then have a redundant supinator. So if your supinator is intact and it is functioning, you can take your nerve to the supinator and transfer to your PIN, just like a radial nerve injury, distal PIN. And this requires a little bit of dissection. This is an example of the same patient. You can see in stimulating the PIN intraoperatively, she hasn't been able to extend her fingers for six years, and we're able to stimulate the nerve and actually gain motor function. And then here is stimulating nerve to the supinator. And so we're confirming that this donor is intact and the recipient is a hospitable recipient. In similar fashion, looking to try to restore AIN function, again, for a high motor or nerve injury or for a brachial plexus injury, or in this case, a spinal cord injury, because your brachialis and your biceps are intact, your brachialis becomes a donor and your AIN is a hopeful recipient. And so in this case, you're identifying the fascicle to the AIN within your median nerve, and it's not far. Just like when we're doing a double nerve transfer for elbow flexion, this is just the reverse. And here you can see, again, the same patient, FPL and FTP to the index finger hasn't worked for this patient for six years, and we're stimulating it intraoperatively. And then we're confirming here nerve to the brachialis and nerve to the biceps, branches from the musculocutaneous nerve, which is intact. That's your brachialis, and then here's supination and resisted flexion here from your biceps. So those are some considerations in the patient with the AIN nerve injury. Remember doing a nerve transfer up in the upper arm in the brachium does take a little bit of time to recover, so you have to consider that in terms of what your patient's expectations are. This recent, well, not too recent, from 2017 article from Jaime Bertelli showed with these patients that underwent either brachialis or ECRB transfer to the AIN, that in general their observation was that the nerve to the ECRB did somewhat better than those from nerve to the brachialis. This may just be a distance and a time issue, and in part that can be affecting your outcomes. Even for 18 months, two years from the time of nerve transfer, you'll still see patients making progress. And then finally, just from a wrist extension standpoint, if you have a brachial plexus injury, or sorry, your spinal cord injury, nerve to brachialis to ECRL is also an option because, again, your biceps is intact depending on what your patient demands are. And in general, remember these are also patients where other strategies may be considered, whether it's arthrodesis for stabilizing the wrist and so forth, but you do lose tenodesis. So in summary, a quick review of extrinsic nerve transfers. Remember, consider all of the challenges that were brought out at the beginning, from the time, the zone of injury, that includes soft tissue injury, just like trying to reconstruct the non-present biceps. I think that was a classic example. Be creative. We all love anatomy, and so your creativity is what's going to help your patients because you recognize what's available and what's not available. But also be cautious because you have to recognize the anatomic variations. We're all invested in making sure our patients do well, but we have to remember that sometimes we're not in control of their particular anatomy and their zone of injury. And then it's obviously important for our patients to know what their outcomes might be in terms of expectations along the way. So thank you very much for your attention, and I appreciate the invitation to participate. Our next speaker will be pre-recorded, Dr. Giuffre discussing nerve transfers to restore intrinsic function. Good morning. Thank you for giving me the opportunity to discuss nerve transfers to restore intrinsic function. I have no conflicts and nothing to disclose. The most distal intrinsic muscles in the upper extremity are mainly innervated by the ulnar nerve. As we know from the literature, motor end plates within the muscle undergo irreversible changes in atrophy approximately 12 months following denervation. This means that middle to distal form ulnar nerve injuries tend to recover sensory and motor function. However, more proximal ulnar nerve injuries, although they may recover sensation, are unlikely to recover intrinsic motor function. The anterior interosseous nerve to ulnar motor nerve transfer was introduced to provide a source of axons closer to the motor end plates in order to innervate the intrinsic muscles prior to their irreversible atrophy. There are really three scenarios in which an AIN to ulnar motor nerve transfer is performed. The first scenario is in a babysitting situation. In this case, an end-to-side nerve transfer is performed in patients with a recovering proximal ulnar nerve to preserve the distal motor end plates until the native axons fully regenerate. The second scenario is when an incomplete nerve regeneration is anticipated. In this case, an end-to-side nerve transfer augments the regenerating nerve with additional axons to more completely reinnervate the target muscle. The third scenario is when nerve regeneration is not anticipated. In this case, an end-to-end nerve transfer is performed to restore any intrinsic muscle function. Our technique is performed through an incision made ulnar to the thenar crease and continued approximately in a zigzag fashion over the wrist crease into the form overlying the FCU. The ounce canal is decompressed and the fascia of the hypothenar's muscles is incised to decompress the ulnar motor nerve branch. An interfacicular nerve dissection is then performed, dissecting the motor branch away from the sensory branches. Once a crossover between the motor and sensory branches gets complicated, I then enter into pronis space to identify the anterior traceus nerve at the proximal extent of pronator quadratus. Pronator quadratus is then divided as the AIN is followed distally to its trifurcation, and I cut the three branches of the AIN into pronator quadratus to give a bit more extra length of the AIN. The AIN is then transposed adjacent to the ulnar motor nerve branch, and any additional dissection of the ulnar motor nerve branch proximity is performed. If the transfer is end-to-end, the ulnar motor nerve branch is cut, and a neurophase is performed without any tension. If an end-to-side transfer is performed, an epineurial and perineurial window is created. I actually cut into the fascicle, so I'm looking at edematous neural tissue. Often the ulnar motor nerve branch has several fascicles, therefore the AIN trifurcation is then laid across the ulnar motor nerve branch fascicles, and a neurophase is performed using nyno-nylon and covered with Tassil. We retrospectively reviewed all of our patients who underwent an AIN to ulnar motor nerve transfer between January 2011 and October of 2018. We included any adult patients with MEOWIN3 severe ulnar nerve compression of the elbow confirmed by electrodiagnostic studies, any patients with proximal ulnar nerve lacerations, and any patients with ulnar neuropathy secondary to a brachial plexoscopy. We performed an end-to-end transfer of patients presented with complete intrinsic muscle atrophy and the constellation of clawing of the fingers following of the first web space positive Hortenberg sign, positive Froman sign, and an inability to cross and uncross their fingers. We performed a supercharge and decide or a SETS transfer of patients presented with some intrinsic function. Patients were excluded if they had followed less than six months or incomplete medical records. There were 65 patients who presented with an AIN to ulnar motor nerve transfer, 25 patients did not meet the inclusion criteria and therefore were excluded, leaving us with 40 patients. Out of these 40 patients who underwent the transfer, the average intrinsic muscle recovery was 2.7 out of 5 and the average time to surgery was 14.4 months. When looking at this further, we did find that those patients who underwent surgery less than a year and even less than seven months did significantly better than those patients who underwent surgery greater than a year. What was interesting in those patients who had surgery less than seven months, three patients had no recovery of function. Two of these patients had transected ulnar nerves and one patient developed CRPS post-operation. We further looked at end-to-side versus end-to-end transfers and its effect on outcome, and to our surprise, the end-to-side transfers did statistically significantly better than the end-to-end transfer. Those patients who underwent surgery less than 12 months and underwent an end-to-end transfer, five patients had no recovery at all. Two patients had transected nerves, one patient had a blast injury, one patient had a gunshot wound, and one patient had surgery 10 months following a severe beating. All of our patients who had surgery greater than a year had severe chronic ulnar neuropathy. We identified 32 patients that were classified as severe ulnar neuropathy by EMG nerve conduction studies. Therefore, we decided to look at this subset of patients separately. There were 32 patients who underwent a simultaneous cubital tunnel release as well as an AN to ulnar motor nerve transfer. Their average intrinsic muscle recovery was 2.9 out of 5, and their average time to surgery was 14.1 months. We define this as the average onset of motor symptoms to surgery. When looking at the length of time of symptoms, those patients who had motor symptoms less than a year did statistically significantly better than those patients who had motor symptoms greater than a year. There were 15 patients that had the constellation of clawing of their fingers, hollowing of the first web space, inability to abduct and adduct their fingers with a positive Bortenberg sign, positive Froman sign, and inability to cross and uncross their fingers. These patients underwent an end-to-end transfer. There were 17 patients who had marked intrinsic muscle atrophy, however, still had some intrinsic muscle function. Therefore, these patients underwent an end-to-side transfer. When looking at the end-to-side versus end-to-end outcomes, again, to our surprise, those patients who underwent an end-to-side transfer did significantly better than those who underwent an end-to-end transfer. Our electrodiagnostic studies at our institution reported mainly on severity of all neuropathy and conduction velocity across the cubital tunnel and wrist, and did not report on C-maps or fibrillations. We did have 17 patients with sufficient electrodiagnostic studies to demonstrate a trend in that both low C-maps and positive fibrillation tended to have better intrinsic muscle recovery compared to those patients without fibrillations. What was really curious in our patient population was that patients reported subjective improvement in hand function and dexterity despite their BMRC grade. So we randomly surveyed 25 patients and asked them, would you recommend surgery, and 76% said yes. We also asked, given your current function, rate your satisfaction with the operation from 1 unsatisfied to 10 extremely satisfied, and the average was almost 6 out of 10. When trying to compare our results with that in the literature, what we found was that there's a considerable amount of variability in the assessment on their intrinsic recovery. This author assesses recovery different. Some reported improved grip strength, other on key pinch, lateral pinch, opposition to the fifth finger. And as we know, these measurements are all multifactorial and cannot be solely due to intrinsic muscle recovery. We graded our intrinsic recovery based on patients' ability to abduct their fingers, trying to isolate intrinsic muscles. However, even this assessment is subjective and likely has discrepancy. What we did note was that there was no patients with a perfect result. All patients had some wasting of their intrinsic muscles. All patients had a positive filament sign despite their BMRC grade, and some might regain the ability to abduct and adduct their fingers, but not cross and uncross their fingers. So we do believe that a more objective measure, such as measuring the distance traveled by the index finger from an adduction to maximum abduction position on a flat surface, might improve objectivity. When looking at our end-to-end-to-end-to-side outcomes, we do believe that despite severe ulnar neuropathy with visible muscle wasting, regardless of the etiology, the incontinuity nerve is still contributing some neurotrophic signals to the motor end plate, allowing for some intrinsic muscle recovery beyond the traditionally accepted 12-month window. By performing end-to-end transfers, the motor nerve is cut, thereby severing any axonal regeneration from the proximal ulnar nerve and any potential proximal nerve signal to the motor end plate, thus leading to a worse intrinsic muscle recovery. Another contributing factor to our dismal outcomes with end-to-end transfers may be that these patients were chosen to undergo an end-to-end transfer because they had more profound neuropathy. What was really surprising in our findings was that there did not seem to be a correlation between patient satisfaction and perceived hand function and their BMRC score. Despite low BMRC grades, most patients were satisfied with their results and noted improved hand function. We do have to remember that the intrinsic muscles of the hand are finesse muscles rather than strength muscles, in that they contribute to finger dexterity and hand coordination. So although BMRC captures intrinsic muscle strength, it may be that any improvements in intrinsic recovery, even if it's by one grade score, improves patient dexterity and therefore perceived function of the hand. So given the low morbidity of the AI end-to-ulnar motor nerve transfer and the potential for any improvement in intrinsic hand function and improved patient perceived dexterity, we offer this nerve transfer in all patients with proximal ulnar neuropathy with intrinsic muscle wasting, regardless of the etiology. We do know that patients who undergo surgery earlier and undergo an end-to-side transfer show improved recovery with higher BMRC grades. Thank you. Thank you. Our next speaker will be Cecilia Skotak, who is a certified hand therapist, to discuss therapy after nerve repair. Thank you, Dr. Noland. Therapy for nerve-injured patients falls into three categories, damage control or the prevention of complications, assessment of initial status and ongoing progress, and treatment to maximize not only the patient's final functional outcome, but also their function while awaiting recovery. Before I focus on therapy for nerve transfers, I want to review treatment for nerve injuries in general. Slings and orthoses are used post-operatively to protect the nerve coaptation and manage edema. Positioning is also important while awaiting reiteration to prevent contracture and joint instability, as well as overstretching. A muscle that is overstretched or shortened will have difficulty generating force once reinnervated. We typically teach patients with a brachial plexus injury stretching exercises of the shoulder. Some patients with distal injuries may prefer not to use an orthoses. If so, it is important that the patient is doing self-passive range of motion and that the therapist is monitoring tissue length and joint suppleness. Skin with sensory compromise is vulnerable to injury during functional use. Adaptations such as pads to enlarge and soften handles and silicone sleeves to provide protection can prevent injury. Patients are also taught to visually compensate for their lack of sensation and to moisturize frequently. Due to strength imbalances and compensatory function, many patients will experience myofascial and musculoskeletal pain in addition to neuropathic pain. Depending on the pain etiology, it can be addressed in a variety of ways. Minimizing cortical reorganization in response to limited and altered sensory motor input will facilitate functional use after reinnervation. Orthoses, slings, and myoelectric orthoses can permit use in a more typical motor pattern and prevent compensatory function. This helps to maintain cortical representation and thus quicker integration of motor and sensory input after reinnervation. Therapists assess sympathetic sensibility and motor function, but we also look at the whole person and consistently monitor how their injury impacts their psychosocial context. We help define patient goals and refine goals as they may change over time. Because nerve recovery is so slow, the therapist provides ongoing support and encouragement. Although sympathetic changes are inherent with the nerve injury, changes in this category may be indicative of CRPS, so they have to be monitored. Advancing to NELs along the course of the nerve, particularly if it does so at the expected rate, provides evidence of ongoing reinnervation. Steroagnosis and localization are typically assessed later to guide sensory reeducation. Sharing information in this type of format, where progress over time can be appreciated, is very encouraging to the patients. Motor function is reflected by muscle atrophy, the amount of active motion that can be generated, manual muscle testing, grip and pinch strength, presence or absence of signs such as bromance, and coordination. In our peripheral nerve clinic, the therapist will often see the patient first and repeat the manual muscle test, and then the patient, therapist, and surgeon will all meet to discuss progress. Both standardized and nonstandardized assessments are used to determine baseline function and progress towards goals. These may also help to determine if the patient's expectations are realistic. If not, education is needed. Timing of functional tasks or observing the patient engaged in a task allows for observation of prehension patterns, strength, and coordination. I will illustrate how the therapist can maximize function following a nerve transfer through a case. Preoperatively, this patient was seen by a peripheral nerve clinic team consisting of surgeons, occupational and physical therapists. The patient's sensibility screen was 10-10 in all areas tested. He had a negative to NELS over the radial nerve, full active range of motion, and full strength of his radially innervated muscles. We defined that his goals were to be able to do his job and to care for his infant daughter. Surgery was done jointly by an oncological orthopedic surgeon and plastic surgeon, Dr. with subspecialization in nerve surgery. Unfortunately, the radial nerve had to be resected. As anticipated, postoperatively, the patient had no function of his wrist, finger, and thumb extensors. We initiated postoperative therapy in the three treatment categories. Under the assess and track status category, we completed an assessment of motor function which showed limitation in his shoulder and elbow motion, as well as triceps weakness of three plus out of five. In the damage control category, a custom orthoses was fabricated for nightwear to prevent overstretching of his extensors and shortening of his flexors. He was educated in a range of motion program to address the shoulder and elbow deficits, as well as self-passive range of motion to retain the first web span and length of FDS, FTP, and FPL. With respect to maximizing his function, we initiated strengthening of the triceps. The patient found this orthoses on his own. It would not have been our choice because with the fingers covered, he didn't have sensibility. However, he was able to work to some extent in it and to carry his daughter with it on. Knowing he had upcoming surgery, he didn't want to explore other orthoses. Our goals at that time were to recover proximal motor, proximal motion and strength, and to prepare him for tendon and nerve transfer surgery. We did this by educating him using the analogy of rewiring a lamp to help him understand the nerve transfer. He was taught to identify and activate the donors, pronator teres for the tendon transfer and FCR for the nerve transfer. We also set expectations for time frames and ultimate function. The patient underwent tendon transfer surgery to restore wrist extension and nerve transfer surgery to address finger and thumb function. This hybrid approach allows for quicker restoration of wrist extension and ultimately individual finger function, which was important to this patient given his occupation. The immediate post-operative priority was managing the tendon transfer. Typically after the nerve transfer, we would give a rest period of two weeks. He was casted for four weeks to protect the tendon transfer. During this time, the therapist did damage control by addressing finger range, motion and edema. At four weeks post-op, he was transitioned to a removable orthoses for continued protection of the tendon transfer and to allow initiation of tendon and nerve transfer training. Therapy following a nerve transfer occurs in three phases. The first phase starts two weeks post-operative and lasts until trace function is present in the recipient. During this phase, the patient is taught to contract the donor muscle while passively completing the recipient motion. The patient is encouraged to flood the donor by completing the movement very frequently. As soon as it was safe with respect to the tendon transfer, the patient was taught to contract his FCR while passively extending his fingers and thumb using his other hand. At eight weeks after surgery, the patient had spontaneous activation of the tendon transfer, but of course not yet PIN function. He had recovered proximal motion. He demonstrated mild tightness of his extrinsic flexors despite doing self-passive range of motion. So in the damage control category, we had him resume nighttime splinting to maintain length of the extrinsic flexors and the first web span. We transitioned him to an orthoses that allowed for sensory function and use of his wrist extension. The orthoses made it more convenient for him to do his nerve transfer training exercise negating the need to assist finger and thumb extension with his other hand. The middle phase lasts from when the most proximal recipient muscle first demonstrates a twitch to when strength is three out of five. Initially the patient is taught to co-contract the donor and recipient on a gravity eliminated plane, then progress to resistance of the donor as the recipient is activated. The thought is that stronger donor effort correlates to greater recipient output. Motor control may be facilitated by biofeedback, mirror visual therapy, and electrical stimulation. At 13 weeks following surgery, the patient had EDC function of two minus out of five. Exercises done during the middle phase included flexion of the wrist as he actively extended his fingers on a gravity eliminated plane, bilateral MCP extension and wrist flexion as he viewed the reflection of his uninvolved hand, and then resisted wrist flexion with active finger extension. At six months after surgery, he had finger extension against gravity with 40 degree deficit in MCP extension and emerging EPL function, so the program was expanded to include thumb extension and radial deviation on a gravity eliminated plane. The late phase begins when there is full active motion against gravity. The end range goal is strength of at least four out of five. Separation of donor and recipient function is addressed, and last but not least so is functional integration. Unfortunately, the patient was not seen for his nine-month appointment due to the pandemic and was then lost to follow up, but as well as he was doing, I think it's safe to assume that he achieved an outcome similar to this other patient who also had transfer of FCR to PA, and this patient was able to keyboard the one that I showed. Thank you. Okay. Thank you. In the interest of time, we're going to forego the case discussion and move on to the next section. I'd like to invite Dr. Curtin up. She's on her way. We'll get her talk loaded here. Okay, so I was tasked with non-surgical treatment of neuropathic pain. And so what I want to do is spare you guys having to look through all the pain medicine literature because I just did it for you and I will get you guys up to date. Okay, I do have some disclosures but not really pertinent to this. So I'm going to go through the medications, the therapy options that have some evidence, and then also I'm going to spend a little bit about PNS because we've been using that a lot, peripheral nerve stimulator, and it's actually pretty terrific for some of your more tricky upper limb problems. Okay, so sort of this is sort of the things that I thought of when I thought I have someone with neuropathic pain. What medications might I give them? And so I went and looked. Looks like NSAIDs. Really not that good. I thought perhaps they would be better because of neuroinflammation, but turns out the evidence just shows for neuropathic pain, NSAIDs are not particularly helpful. Okay, what about steroids? There is some evidence that steroids in the acute phase, so you have a patient who comes back, you've done an operation on their arm, it is hot, it is red, you are worried, it's not infection, that steroids can be helpful in this acute hot phase. It was a 60 milligram taper was what I saw in one of the articles. So after that, not helpful, but there is some evidence in that acute hot phase that it could be helpful, sort of plus minus. Actually this is the medication with the best evidence for helping with neuropathic pain. They don't really know what the mechanism is. They started using it in CRPS because of bone resorption, but bisphosphonates are the medications with the best evidence for helping with neuropathic pain, in particular CRPS. Several randomized trials with good studies showing that bisphosphonates, the L-andronate, oh gosh, and I'm blanking on the dose, I think it was 40 milligrams for 8 weeks. I can get that for you if you need it. Basically L-andronate, either IV or oral at high dose, actually has good evidence for treatment of CRPS as well as potentially for neuropathic pain in general. All right, gabapentin, my favorite actually. I love gabapentin. Evidence is kind of middle. The thing is, it is a super safe medication. I think we all are a little bit afraid of it because we have to taper it, you have to do these things with it. There is no lethal dose of gabapentin. It has a bunch of side effects. It makes you sleepy, stupid, dizzy, but it requires active transport to be absorbed in the system. So if you took the whole bottle of gabapentin, you would just poop it out. So hey, we've had farts and poops in this session, it's good. But anyway, so gabapentin, really nice safety profile in general. It can make you dizzy. So if you're worried about falling, that's something you do need to be thoughtful of. And it does help, again, the evidence is meh, but it can help some patients with their neuropathic pain. Myself, I start with sort of the 300 for a small person, 600 for a larger person, TID. And I tell them, hey, take it just before bedtime and see how you feel. And if you feel really sleepy, stupid, or dizzy, then you don't have to take as much. But for most people, those sort of doses will work. And patients can actually titrate to themselves. So I have some people who say, I just take it at night. That's fine. Or I don't take it every day. I have a big work meeting. I don't take it. And it hurts more, and I'm brighter, and I don't have it. So this idea that you have to have this strict regimen, probably not appropriate, or not necessary for gabapentin. Last medication with some evidence are the antidepressants. There are two. There's the tricyclic antidepressants, which we probably all know, like amitriptyline helps you sleep. So that is actually quite nice for patients who also are suffering from neuropathic pain. The other one that is duloxetine, which is Cymbalta, that seems to have some nice neuropathic and is actually a very good antidepressant. Amitriptyline, not so good an antidepressant. So for people who are suffering with pain, they also get some mood impacts that you can sort of get two things for that. And there is pretty good evidence for Cymbalta as well having some benefit. So that's the medications. All right, therapy. There is very good evidence that graded motor imagery and this whole sort of series of type of therapies is beneficial for neuropathic pain as well as CRPS. And basically this is a training of the brain. This is working at the brain level to try and help with the pain that is perceived. It's very interesting if you have people with severe pain and you touch their hand, they'll have like their lip will hurt because of the way the homunculus is in the brain. The brain is very, very important and the connections to the brain in recovering for neuropathic pain. And so the one that I think most hand surgeons know about is mirror therapy where the people are looking at the uninjured hand and doing their exercises and that helps the brain sort of settle down and maybe think that the hand is not as injured and go through the recovery period. There are also graded motor imagery, which I didn't really understand, but it's actually quite interesting. It's the laterality of the hands that patients with pain have difficulty understanding the laterality of the hand. Again, the brain is getting sort of confused because of all this stimulation from the injured part. And so when you do these apps, because I checked it out before I actually showed you, I did not spend the $9.99. I tried the free one. There are two apps which actually do graded motor imagery that I found. And basically they show you a right hand and a left hand and a right foot and a left foot and you have to time it. And when you have neuropathic pain, you're actually slower and this actually helps you practice and actually there is good evidence that these things will actually help with your recovery from neuropathic pain. So those are the two apps that I found, one for free and one for $9.99 if you wanted to be able to give it to your patients. All right, and then this is the one I'll spend a little bit of time because I don't know anybody here using PNS for their painful patients. I see two hands. So this is actually a really cool thing. You have to partner with a pain doctor, but can be very helpful. And so this is nerve stimulation. I think we're all pretty familiar with spinal cord stimulation. And the idea is that when a nerve has a stimulation from the electrical stimulation, the brain has this gate and it can only allow so many things in at one time. So if you have the electrical stimulation, you have a tingling. It prevents the pain signaling from coming in. So the patient feels a tingle, but not a painful tingle and so they are able to feel better from it. And so we always were sort of having problems on the limbs because we used to have these big battery packs and these leads and they would like, you'd cross a joint and they would fracture or they would move or something like that. And this is the Bioness stim router. And so you can see that lead that's in the hand is the implanted device. It's really soft and thin. There is no implanted battery pack. It doesn't need to cross a joint. The battery pack is that Band-Aid that the guy is wearing on his shoulder and they charge it and I don't know, it works magically, putting the power through the skin to the lead. These are a couple of the ones that are out there now, the stim router, the stim cue, the sprint, which is temporary. These are all FDA approved. The pain doctors are normally going to be the ones putting this in for you. So for this, you really need to have an isolated peripheral nerve. So this is not for the person with all over pain, but this is great. I've had several people great where you've had like a median nerve laceration, you fixed it, but they still have that pain afterwards. This is actually quite a nice adjunct, you put it on the median nerve. Can they reach this area of stimulation to be able to put the adhesive on? MRI. They are plus minus MRI. You can go in the tube, but you can't have the arm in. So if they're going to need multiple MRIs, if they have tumors or something like that that need follow up, probably not the best patient for it. And then you can see things that they consider, if you think it's going to get better, then maybe you shouldn't do it. So this is my patient who had a median nerve laceration. He had the device implanted, and when he had CRPS type pictures, all the things, he couldn't even make a fist. And after implanting this, he was able to now make a fist and participate in therapy, and it really helped him get through the acute pain after healing from his median nerve repair. So this is, we've done it for all kinds of nerves. This is actually the hand society, but it's quite nice if you also take care of other parts of the body. I've done median nerve and radial nerves and SBRNs with good success. And just a quick look at our sort of evidence of what people had after a patient of PNS. Most of them got better, not perfect, but it's really low risk. They do it under ultrasound. Worst case scenario, you just take the thing out, and it can really get people off of medications. And I had just one patient who I saw five years out after her PNS. She's no longer using it, the device is still in, but she said being able to have something that she could turn on when she had a flare actually gave her such relief mentally that she stopped sort of worrying about it so much, and that actually helped facilitate her recovery. And over, now she's five years out, she doesn't use it at all. So there you go, the update on sort of all things non-surgical. Thank you very much for having me. That was a great talk and is going to kind of segue well into talking about conventional techniques for neuroma management, because neuropathic pain is the main reason that we treat neuromas at all. And so no disclosures. So today we're going to talk about briefly how and why neuromas form and discuss the challenges of neuroma management, how do we prevent neuromas from forming in the first place, and then understand the options for surgical treatment. These neuromas occur in the setting of nerve injury and are defined as this uncontrolled axonal growth that's coupled with fibroblasts, myofibroblasts, Schwann cells, and endothelial cells and can form in 60% or more of patients with nerve injuries. We all know from treating these patients that they're associated with chronic pain and are very psychologically and physiologically disabling for patients. Obviously this slide is nothing compared to the talk that was just given that was really spectacular, but I will say that a lot of these patients show up to our offices when they've exhausted the other methods for treating neuropathic pain. And I've had patients that have had phenol injections to their neuromas and the unexplainable pain that they experienced preoperatively, intraoperatively, and postoperatively after that experience has left them not only disfigured mentally, but also very distraught over their pain. And so nerve surgery and neuropathic pain is really a team sport. And so having a neurologist, a physical medicine doctor, a psychologist to help treat these patients is really key. The reason is is because not all pain is peripheral. There's centralized brain pain that occurs in longstanding neuropathic pain and makes it hard to predict outcomes when patients have had neuromas for a long time. There's the mechanical pain associated with the nerve ending itself from irritation, from excursion of overlying tissue, reinnervation into the skin. And then these patients, especially ones that have had these neuromas longer, have these depression and psychosocial issues that need to be dealt with as well. Operative treatment of neuromas, I kind of split into two categories, neuromas and continuity and the residual limb or end neuromas. And we'll talk about those separately. Neuromas and continuity, I think, for the hand surgeon are some of the most difficult nerve injuries to treat because they are not straightforward and you have the possibility of downgrading any existing function that the patient has. So a preoperative exam, knowing what is in and what is out is key. And then also having a discussion with the patient so that they understand what your options are going to be once you are in surgery and have identified what you can and can't do as far as resecting the neuroma and reconstructing the gap. Principles of management when you're in surgery involve identifying that zone of injury and then getting to healthy fascicles approximately. At that point, under microscopic dissection, your intrafascicular tracing of the healthy nerve endings to the neuroma and hopefully through the neuroma to excise that tissue and preserve your uninjured fascicles, which isn't always possible, especially in longstanding neuromas. And then treating the resulting gap with either autograft or allograft. The patient here is a median nerve, partial injury from a self-inflicted forearm laceration in a young patient I saw three months after injury. He had completely preserved first web space function, thumb sensation and motor function but had no sensation to his second and third web spaces. And so in cases like these, knowing your topography is really key. And in his case, the ulnar portion of the nerve was the second and third web space. Knowing that going in, we were able to separate that unhealthy neuroma tissue, excise it, and then in his case, we allografted. Now this is not always possible, especially in longstanding neuromas. And so your options at those points are either to partially excise the neuroma and jump graft around that or to completely excise the neuroma, downgrade their function and attempt to reconstruct it. And knowing what the patient's problem is preoperatively will help you in that decision. If their problem is pain, partially excising the neuroma may not be enough to treat their pain. And so that's where those preoperative discussions are really important. This is an algorithm from Dr. Eberlin and Dr. Ducic's great review in PRS Go in 2018. And I use this a lot to teach our residents how to think about neuromas and neuromas specifically. And they split it into two categories, is the distal end available or is the distal end unavailable? And if the distal end is available, your options are either allograft or autograft. Or if there's a very small gap, a hollow tube reconstruction. Although in my experience, most of the time after resecting these neuromas, there's a big enough gap to use either autograft or allograft. And in my practice, it's very rare that patients will opt to use autograft given that they have a neuroma, they have nerve pain already. A second site, a nerve donor site, is not something that they're usually interested in. However, it does happen. I had this patient who was a dog bite to her radial wrist. She had a chronic non-healing wound because she had a neuroma of her superficial radial nerve and a big gap at the base of it. So she did not tolerate dressing changes and was kind of languishing in these gel dressing things that the wound nurses were putting on. And so we went in, resected her neuroma, had a large gap. She was very much opposed to allograft reconstruction for personal reasons. And so we used an MABC autograft and eventually, and then at the same time, a skip flap to reconstruct her. But the more common scenario, at least in my practice, is patients will often opt for allograft if the distal end of the nerve is available, like this patient with another superficial radial nerve neuroma that got reconstructed with allograft. Now for end neuromas, these are our options. I'm not going to be talking about TMR, RPNI. Those are the talks following mine. And so we're going to talk about excision and proximal nerve implantation, nerve capping, centrocentral neuromorphy, and then acellular nerve allograft. Before all these therapies were kind of introduced or before we were thinking about treating neuromas at all, this is a patient that had three previous arm amputations, revisions from through the elbow to two transhumerals, trying to treat his horrible nerve pain. And each time, traction nerectomies were performed. And by the time he got to me, this was done in the 80s, he had neuromas of his entire infraclavicular plexus that we eventually treated with TMR. So thinking about treating those nerve endings at the time of amputation is important as well. So this work by Dr. Dellon and Dr. McKinnon is great. It was done in 1986, and they were treating patients with neuroma resection and muscle implantation. They treated 78 neuromas in 60 patients with 82% excellent results, which at the time, was a very high number. And their failures, they kind of attributed to putting the nerve in the wrong muscle, either too superficial or too much excursion, and they didn't have a great success with digital nerves, implanting them into the intrinsic muscles. Dr. McKinnon updated her experience in 2017 with 70 patients, and she included this proximal crush, which we'll talk about, as well as neuroma, excision, and transposition, and saw significant decreases in pain scores and depression, quality of life, and DASH scores all improved. So when we talk about treating the proximal nerve, this is key to preventing neuromas, especially in things like fingertip amputations at the time of amputation, as well as treating neuromas with the proximal transposition, and that is excising the neuroma, cauterizing the nerve end to cap regeneration, and then using this proximal crush, which is basically inducing a Sunderland II axonomatic injury that moves the area of regeneration proximal out of the zone of injury, and hopefully prevents that neuroma from reforming. And so that's how we treat fingertip amputations where TMR or RPNI is not possible. Treating the proximal nerve like that is really important. I'm not gonna spend a lot of time on these two therapies, as they're not very commonly used. Nerve capping was kind of a historical way of using various materials like silicone or nanofiber tubes, even veins to cap the nerve, but it's a passive technique, and it doesn't address axonal regeneration, and neuromas are still able to form. Centrocentral neuroraphy is a concept of splitting the nerve and co-opting it to itself, either with a connector or primarily, and is also used infrequently. And in the interest of time, we'll go to the last one, which is acellular nerve grafting. We already have seen how this can be used when the distal end is available. It can be also used for something called relocation nerve grafting, which is a technique that uses allograft to get the nerve out of the zone of injury to a healthier muscle, and then also to cap the nerve. In these two studies, you see at the bottom using long allografts to dwindle the regeneration through allografts that are five and six centimeters long to prevent the neuroma from forming. That concept is based on this study that shows the dwindling of axons over six centimeters of long acellular allografts. So this is a picture of the relocation nerve grafting into muscles. This is a picture from Dr. Eberlin's paper. I use this technique in ray amputation sometimes, but I often combine it with TMR to the interosseous muscles if I can't get the digital nerves to reach primarily. So in summary, the treatment of neuromas is complex. I always like to think about what Dr. Dumanian says, which is give the nerve somewhere to go and something to do. And we have to, along with that, address the brain pain or that centralized pain, like Dr. Curtin just talked about, the peripheral pain and the painful nerve without downgrading function, ideally. So moving forward, I think evaluating our results of these newer treatment modalities is gonna be key to figuring out which ones are the most appropriate. Thank you. Dr. Koh is on his way up. All right, good morning, everyone. So I'm going to talk about the painful nerve, targeted muscle re-nervation, and then Kyle Eberlin is going to talk about regenerative peripheral nerve interfaces. Here are my disclosures. This is probably the checkpoint nerve stimulator, which you may see. And so the story behind TMR, as everyone knows, was originally developed to improve prosthetic control for amputees. But then anecdotally, patients were saying, hey, I used to have a lot of nerve pain and phantom limb pain, and it's actually better. And so Jason Souza led the charge to look back retrospectively at San Antonio Military Medical Center and Northwestern series, demonstrating, at least in this retrospective review, significant improvement in terms of neuroma pain after TMR. And preoperatively, there was 15 neuromas, and then postoperatively, there was one, which was an MABC branch that was not transferred, but we counted it as a failure. But probably most importantly is 23 out of 26 patients were able to actually use their prosthetic, which they weren't able to before. And that's the real-life, day-to-day data that we needed. And so we took it to the bench. Peter Kim, one of my co-residents, developed this rabbit amputation model that the ACUC was very generous in letting us do. And he did a pedicle rectus abdominis flap doing transfers. But what he did, you could see in A at the bottom left, that's a normal nerve. B is a neuroma, and then C is after TMR, essentially demonstrating that TMR, by giving the nerve somewhere to go, something to do, gets you more to a normal nerve histologically. And so the thinking is that, again, denervated muscles hungry for axons to grow into it. You give the nerve somewhere to go, you give it a function, it's going to be happier. And so we took this back to the bedside. And then this is one of my first early patients when I was in Seattle. Shoulder-level disarticulation, essentially came to me with horrible neuroma pain, phantom limb pain, also has deficient soft tissue that prevents prosthetic wear. So I wanted to give him new, durable soft tissue, but also treat his neuromas. So designed a pedicle latissimus flap to resurface that skin, and dissected out shoulder-level TMR, transferred these, and used the thoracodorsal nerve as a target, which he then had good soft tissue, had not been able to wear a prosthetic for over five years, and finally, you know, this is him one year later, and you can see him developing that ulnar nerve actually grew into the latissimus, and he was being fitted for a prosthetic when I moved back to Chicago. And then this is one of our early cases when I was back at Northwestern, Dr. Doumanian's patient. He asked me to assist with the microsurgery, just because it was going to be a complex situation. A 20-year-old guy, traumatic short transradial amputation years ago, had multiple previous failed free flaps due to hit, excruciating neuroma pain. All of this is skin graft. You can see bones sticking through the end of the skin graft. That's his ulnar neuroma. He'd just blow on his arm, and he would jump off the table. And so, did TMR of the radial nerve to the triceps, and then ulnar nerve to medial biceps, and then median nerve to the motor branch of the vastus lateralis as a target for a free ALT flap. You can see here, finding that motor branch to the vastus, using the ALT with a segment of vastus as a target to resurface the whole area. And here he was, a year and a half later, no neuroma pain, no phantom limb pain, off narcotics, and was able to wear a prosthetic and had a job for the first time in years. We're seeing more of these in the literature. Partial hand amputations. Here's a patient. The digital nerves from the amputated finger were horribly painful. Also dorsal sensory branch of the ulnar nerve, also painful. So for this patient, doesn't really need his hypothenar muscles, so use that as a target. So digital nerves to the hypothenar muscles for TMR. And then kind of like the AIN to ulnar motor transfer, did a reverse one, dorsal sensory branch of the ulnar nerve into the AIN to the pronator, just to give it a target. And then as we were doing this, we were also starting to do these in the lower extremity transfemoral amputees. I'll quickly go through these. And also bologna amputees. And then we had a multi-center collaborative group, including Ian Valerio here when he was at Ohio State University, to do a prospective clinical trial. We were fortunate to get funding from the DOD to do this. We originally had aimed to get 200 patients, and you'll see how we had a hard time recruiting patients. We were able to get these patients at various time points, and Ian can attest, patients were coming from all over the country wanting TMR. And we said, hey, we have this trial, you can be randomized. And they said, no, no, no, I want TMR. And so we had trouble at all the centers, including the military sites, recruiting patients to be randomized. They all wanted TMR. So in the end, we had 15 standard treatment patients, 13 TMR patients. And then after one year, we had four people that actually failed the standard treatment, wanted TMR. And I'll show you those. We used numerical rating scales. And here's the avatar also for the phantom limb. And then we published this in Annals of Surgery in 2019. But you can see here, the standard treatment, which is just burying it in a nearby muscle, did not seem to have much of a difference in terms of nerve pain and phantom limb pain. And then looking at the NRS TMR, you could see after the TMR, significant improvements in phantom limb pain and residual limb pain. And then looking at the NRS data, same thing, red is bad, blue is good. And you could see after TMR, patients had substantial improvement in terms of residual limb pain and phantom limb pain compared to the standard treatment group. And then probably most telling are those four patients that failed the control group. After they got TMR, their residual limb pain just disappeared. Phantom limb pain also disappeared within six months. And then we included the patients who had come in and just wanted TMR. We did a separate study looking at that in core. And you can see here, significant improvements in terms of residual limb pain and phantom limb pain, much like the prospective randomized patients. And function also improves with TMR. And so if this works in patients with chronic pain, why don't we just do this at the time of the original amputation? So Ian Valerio led the charge. We started doing this at Ohio State and Northwestern and the military, looking at acute TMR at the time just to prevent neuroma formation at all. And then here's one of Greg Dumanian's cases where this patient was in the OR when Greg and I were both at ASPS and our phones were blowing up and they wanted, you know, wondering if we were around to help with this arm replantation. Unfortunately, just due to the avulsion, decided not to salvage this. And then Greg came back to Chicago a few days later and did a TMR acutely. And this patient did very well. No pain, no phantom limb sensation at three months, using a prosthetic thereafter. And so we started just doing these anytime we're doing an amputation at Northwestern, you know, and we have orthopedic oncology, orthopedic trauma, foot and ankle, they're all on board. So anytime someone's getting an amputation, they send the patient to Dr. Dumanian or me, and then we book the case together and we do the amputation and the TMR at the same time. So these patients come in, unfortunately need an amputation. This is my technique that I do just for transradial. There are various techniques that have been described. Single incision, volar form, and then transferring median to AIN, ulnar to FCU, dorsal sensory branch to the radial nerve to FDS for distal transfer or distal amputations. If it's a more proximal one like this one, chronic osteomyelitis, IV drug user came in wanting an amputation, you can do it through the wound. So again, depending on where you are, all your motor points are there approximately, can do it through the wound. And also for oncologic cases, advanced SCC, needing a partial hand amputation and soft tissue, so did a pedicle reverse ulnar flap, but also did TMR for the ulnar sensory nerves, preserving the ulnar motor branches. So again, using that AIN to pronator quadratus as a target. Here he is two years later, no pain. And then an 18 year old about to start college, unfortunately had to delay, had epithelial sarcoma. We just did a resection and then I did a soft tissue reconstruction. And then unfortunately he developed a recurrence and needed a partial hand amputation. Acutely, I did the amputation and the TMR at the same time and he's been doing well since then. So digital nerves to the motor branches of the lumbricals, transferring those. And here he is three months post-op. And then very briefly, we do these in the lower extremity too for transfemoral and trans-tibial amputations. Again, very collaborative relationship. And so here is our paper that was published in JAX with Ian Valerio as the first author just showing when you do TMR at the time of the amputation, you could see here on the far right, that's concurrent TMR, again, blue is good, red is bad. These patients do better than the patients that had chronic pain and then get TMR later. So this evidence just shows that, you know, when you have the opportunity, if you do the amputation at the time, or TMR at the time of the amputation, patients will do much better. So you're rerouting the deep perineal with the biceps premoris? Exactly. You'd know if you made this process part of the initial amputation, you could cut out the second surgery altogether. Huh. Yeah, add what, two, three minutes to the initial surgery? That could make a world of difference. That's a great idea, actually. Thanks. So pretty cool when Grey's Anatomy is talking about acute TMR. And this episode, I think, aired before our paper was published, so I suspect there was a mole amongst our group that may be sitting over there. So, so neuromas and non-amputees, I'll briefly go through this. Reconstruct the nerve whenever possible. Do TMR when you can't. This is something that Kyle Eberlin and Ivan Ducic talk about, and then Ryan Schmucker talked about also. But again, you want to give the nerve somewhere to go and something to do. And so we are doing TMR, non-amputees. Actually, a pretty big part of my practice is lower extremity neuromas after foot and ankle procedures. And we've published various papers on techniques that you can do in the lower extremity. And now we're doing TMR all over the body. Heads, inguinal hernias, plantar foot, with good results. So I want to give credit to Jason Souza, who gave me these slides. But essentially, this paper by Grant Kleiber is really good in terms of just showing the power of TMR at a high volume amputee center or amputation center. But you can see here, residual limb pain, phantom limb pain, significantly improved with TMR surgery. And that's in a very like sick patient population too. But this is a really good paper to look at if you want to learn more about TMR and how it is beneficial for pain. Lee Dellen basically saying, look, comparing TMR or RP&I versus just bearing and muscle, I think there's a lot that we still don't know. And that's the point. We are doing a lot of TMR. I think a lot of people in this room are doing a lot of TMR. Some are doing RP&I. There's still a lot we just don't understand about it. One thing I'll say about RP&I, I've done a lot of it. I think it works some of the time. This is the one clinical paper looking at RP&I. The one thing to point out is in their control group, what they were comparing RP&I to were 30% of them having suture ligation of the nerves. And so I think we have an issue with comparing apples to apples. I think it's important for us to do that. We probably need to do better multi-center prospective trials looking at TMR, looking at RP&I. And I think one thing to consider is maybe the pendulum's swinging too fast. TMR has really exploded as has RP&I, but there's still so much we don't understand about it. And this is Sousa's slide here where he looked through all the literature since 2014. And there are a few good papers showing actual good data regarding TMR and RP&I, including a prospective clinical trial. But since then there are 27 technique articles, 19 review papers, 10 invited commentaries. I do think there's still a lot we don't understand about TMR, but we're doing it. And I think it works, but we still need to kind of learn more. And so I'll end with this. Kyle, ironically, is probably one of the busiest TMR surgeons in the country, along with Ian, but he's going to talk about RP&I. But from his paper, I think of all the options that Ryan summarized, you probably want to do one of these two in the bottom right. Again, maybe I'm biased. And the key is you probably want to do it early. And so I think there's also a lot that we don't understand in terms of central pain and what manipulation of the peripheral nerve does to the central pain pathways. But thank you very much. So my talk is uploaded, I promise. I think the website's just not updated yet, but hopefully this will be the case now. Okay, great. So I know we're a bit out of time, so I'll try to be pretty expeditious here. I appreciate the invitation to speak. Thank you, Amber and Shelly. I'm going to be talking about RPNIs for neuroma management. I'll start by saying I don't have any Grey's Anatomy videos. I do agree with Jason that the orthoplastic approach and doing this as a team is really important. And Ian Valeri, my partner, and I do a lot of this together and do a ton of it every single week with the orthopedic surgeons. And I'm pretty much mostly a TMR guy, although I do think there's a role for RPNIs. I'll start out by saying that in my practice and the way Ian and I do it, the role for RPNIs are typically in patients where they don't have good motor targets. So if they just have really bad protoplasm, their muscle's all denervated. If you don't want to undermine or extend the incision proximally to try to find motor targets because you're worried about the perfusion, or if you don't have enough motor targets. So maybe you do a couple of TMRs and the nerves that are left over get RPNIs. So that's sort of where it fits into my practice. These are my disclosures. They are relevant here. And I'm going to, you know, I'll keep this to about five minutes. But I'll first try to define the problem just a little bit. I'll go through some of the principles that have already been articulated for neuroma management and then specifically talk about the data we have for RPNIs. So we all know about neuromas. We all know that it happens when the nerves are not connected. And that the principles of TMR and RPNI are to give the nerve something to do. So let's see if this video plays. All right, so these are neuromas of the median and the ulnar nerve. You can see here, this is the terminal aspect of the median neuroma. When we look proximally, you can see fascicular architecture here. But as we cut into it further, there's some evidence of fascicles here. More distally, there's just disorganized tissue, connective tissue, but no axons or no fascicles that we can see. So we've all seen that. We're starting to study these scientifically and looking at the biology quite a bit now. And neuromas happen for a lot of different reasons. They can happen after poorly performed neuropathy. They happen after amputations. And pain is generated both through the peripheral mechanisms and central mechanisms. Very briefly, I think when we talk about neuromas, we need to be on the same page with regard to diagnosis. And in 30 seconds or less, this is what I think you need to have in order to be diagnosed with a symptomatic neuroma. This is a paper we wrote in 2019. You need to have neuropathic pain, symptoms in a defined neural anatomic distribution, and a history of nerve injury or suspected nerve injury. You need to have at least one in the bottom blue rectangle, which is a positive TINEL sign, a positive response to local anesthetic injection, or radiographic confirmation of neuroma. I think this gets us on the same page when we're talking about how do we diagnose someone with a neuroma. So what are our principles when we're managing neuromas? Well, I think we've come a long way. I agree with everything that Jason just said and also Ryan in his talk. And I do think that we're in the midst of a paradigm shift for the management of neuromas. And what we're all trying to do here is to give the nerves something to do in whatever way that we can. If the nerve is in, if there's a neuroma in continuity or the distal end's available, deconstruct the nerve in whatever way you choose. The nerve wants to go to its distal target. But if you don't have a distal target, that's when the techniques such as TMR and RPNI come along. And I'm going to talk for a few moments about RPNIs. So I mentioned how they sort of fit into my practice. The credit for this really goes to the team at Michigan, including Paul Soderna and all of his folks that he's trained, including Ted Kung, who shared some of these slides kindly. But the whole principle of RPNIs, as we know, is to take the nerve ending and to take a denervated and dysvascular segment of muscle and wrap that muscle around the nerve. That's what an RPNI is. It is a lot easier to do than TMR. It's probably faster as well. And the whole idea is that we're leveraging the biology here. We're trying to use the concept that the muscle is going to revascularize, like a skin graft does. The nerve's going to regenerate. No matter what you do, the nerve's going to regenerate. And theoretically, you're going to reinnervate the muscle. And there's good experimental evidence of this. So from a technical standpoint, how is this done? Well, quite simply, you need a free segment of muscle. If you're doing acute amputation, by the way, you got a lot of muscle on the amputated part, assuming it's not infected or the tumor. So that's a good source. Otherwise, there's always local muscle you can find in the field. And typically, you want to start with epineural sutures. You can see in the center part of the screen here that you typically want to anchor the distal end of the nerve to the muscle. And also, often, you want to take epineural bites at sort of the interface of the muscle, and then you wrap the muscle around it. I typically use 4-ovicral sutures if and when I do this, and that's pretty much how it works. Here's a clinical photograph from Ted Kung about this. You can see the completed RPNI and then the in-progress RPNI. Now, I don't think we know everything about this yet, but you do want the muscle to not be too bulky because otherwise it won't neovascularize and you'll get central necrosis, which is probably not good. So that's about the right size for an RPNI, what you're looking at here. I think another important point, whether it's with TMR or RPNI, is when you're dissecting proximally in the limb and you have a large nerve, take the sciatic nerve as an example, it's a good idea to split the sciatic nerve into different components, thereby dissipating the axonal impetus for regeneration. So here you see with an intraneural neurolysis, you can often separate out the different segments when you're doing RPNI, and we do the same thing with TMR also. I have come to increasingly believe that this makes a difference. I think that the more you can separate the nerve, the better, within reason. And if we're doing TMR, we want to find as many recipient targets as we can for the amount we're going to split the nerve. And if you're doing RPNI, you need that many muscle grafts. And when you place them into the wound, you often want to spread them out in a different place. I mean, I've wondered very often whether if you just did an intraneural neurolysis, split the nerve into a bunch of different places, and put them into different areas, whether you would have less pain than just cutting the sciatic nerve, for instance, during an AKA, probably would be the case. But I think there's some benefit of giving the nerve or splitting into a number of different components. So I think here's the point when we're talking about TMR and RPNI. What we want to do is give the nerve denervated muscle into which to grow. TMR, conceptually, I think makes a bit more sense because nerves want to grow into other nerves. But it is also true that RPNI does that. So let's go just briefly to some of the data that exists for RPNIs. Just like the journey for TMR, this was a pilot study that was done to study the effect of patients with established pain that underwent RPNIs. Okay, so not prophylactic, this was a treatment group. And you can see here there were 16 amputees who had 46 RPNIs implanted. And the bottom line of this study was that, and I'll show some of the data in the next slide, but they seemed to work. It didn't increase the operative time to any meaningful degree, and there was no increase in complications. So this can be done relatively expeditiously at the time of amputation. And here are some of the data. So you can see neuroma pain score decreased pre and to post-op. The top right says phantom pain score. Pain medication was decreased in these patients, and the pain interference score, promised pain interference, went down. So here's the data for this pilot study of RPNIs. Then, just like with TMR, the next step was, hey, if this works in delayed fashion, why don't we do it prophylactically? So this is a study from PRS in 2019 looking at that. And here is the data from this paper. Essentially there were 90 patients. This was a retrospective cohort study. And to my knowledge, there are no prospective randomized trials with RPNI like there are with TMR. I would say the evidence is stronger for TMR, but this is the data we have for RPNIs. And the number of symptomatic neuromas in controls, you can see 13%, and then 91% had phantom limb pain. And for the RPNI group, there were no reported symptomatic neuromas, and 51% still had some degree of phantom limb pain. You can see the p-values here. So this is probably, in my opinion, the best data we have for the use of RPNIs is here. Now, really all has come from the Michigan group. I know other centers are doing this, and we do need more surgeons and more studies to validate this. But here's just another example from their paper of how this was done. They did this to many different types of nerves in both the upper and the lower extremity, which you can see here. The question always becomes, in the operating room, if you're doing a TMR for, let's say, a bologna amputee, which nerves should you do TMR, which nerves should you do RPNI? I think it's hard to decide that. The way that Ian and I typically do it is, for the nerves we think are going to be most painful or have the potential to be most painful, we will do TMR for those. And that includes typically the superficial perineal nerve, which is a bad actor for these patients, the tibial nerve, and interestingly enough, the surl and saphenous tend to be very neuromogenic. The deep perineal nerve, I think, is on the opposite end of the spectrum. It's very rarely, in our experience, a problem. And this has been published. This is a Clinics in Plastic Surgery article. And I'm going to finish by, because we're here at the ASSH, saying that this has been described for the use in digital neuromas. I think this may be a sweet spot for RPNIs because you can't really do TMR in the digit. There's no motor targets there. You can do it in the hand, and that's just like Jason showed, this is typically what we do. But in the digits, if you have, and this is an unsolved problem, by the way, symptomatic digital neuromas this far out, really hard problem to fix when they are far down this pathway. But here's one option is to do RPNIs. So we've all seen these. There's a digital neuroma. And what has been done is to take a free, small piece of muscle, typically from the brachioradialis, approximately in the forearm, small incision, get a little segment of muscle, wrap it around the nerve, or wrap the nerve in it, I should say, and then close. Now, my ideologic challenges to this technique are, number one, is that there's not a lot of space there. So you've got to be able to close it, which you'll see in a second. They were able to close it, and it apparently stayed healed. The second is that you need gliding of your flexor tendons, of course, which are right underneath there. And if I were to do this, I would be inclined to transpose the nerve dorsally if I was going to do RPNI, because I think you want that painful aspect away from sort of the working surface of the hand. So here's their data, 14 patients, 30 RPNIs, follow-up up to 37 weeks, 85% pain-free or improved. And my last slide is, I think you should combine these techniques. It doesn't have to be a battle between TMR and RPNI. And I think a lot of places are doing this. And Ian and I have written this paper where we essentially do TMR. If there's a size mismatch, we take vascularized but denervated muscle and wrap it around the coaptation. So we're trying to get the best of both worlds. We want our cake, and we want to eat it too. So conclusions. So there's many different ways to treat symptomatic neuromas. We want to give an active management strategy to the nerve endings. RPNIs, based on the data, predominantly out of Michigan, do appear to prevent and treat post-amputation pain and neuroma pain. They minimally increase OR time, as I mentioned, and they do not increase complications based on the study out of Michigan. And we do need better prospective studies to figure out when we employ which technique. So thank you very much for your time, and I appreciate the invitation. Thank you.

neuromas

painful nerve conditions

treatment techniques

targeted muscle reinnervation

TMR

regenerative peripheral nerve interfaces

RPNI

nerve connections

pain relief

evidence base

diagnosis

neuroma-related symptoms

nerve injury

advancements in treatment

further research