Hello, I'm Dr. Cindy Ivanhoe, Clinical Professor of Physical Medicine and Rehabilitation at the University of Texas, McGovern Medical School, and Director of the Spasm Program at TR Memorial Hermann. Here are my disclosures. Basically I'm on advisory boards or speakers bureaus for assorted companies that deal with toxins and intrathecal pumps or drug delivery systems. So I put together this course and asked my two colleagues to speak on behalf of the issues related to managing intrathecal programs with spasticity versus pain. A long time ago when we were first working with intrathecal baclofen therapy for spasticity, a pain rep said to me, I just don't understand why there's such a difference, you just put the pump in and you go from there, which isn't quite the case. There are many PM&R residents and fellows who are finishing now and are going into pain practices. There are now two intrathecal baclofen pumps available in this country, one from Medtronic and one from Fluonix, and these therapies for spastic patients have remained underutilized for quite some time. There are considerations regarding spasticity practices and pain practices in terms of how you practice, how you manage your practices. And the management of the patients is also different. There are different issues related to withdrawal from intrathecal baclofen or Leoracil versus different medications that are mixed in the pump for pain into any pump. And then finally, and this is coming from my neurorehab bent, there can be very variable philosophies of care in terms of when it is worth treating a patient's spasticity, not worth treating a patient's spasticity, what is or isn't spasticity. Pain can cause spasticity and spasticity can cause pain. So I'm going to start with very briefly a couple of videos. I was asked to see this particular patient regarding motor point blocks because of her severe lower extremity spasticity related to a very severe traumatic brain injury. Okay, there we go. Okay. Starting? Yeah. Okay. You might ask yourself, where do you start with motor point blocks in a patient who moves as one mass? Okay, there we go. Okay. This is how this particular patient looked at her intrathecal baclofen pump trial. You can already see a significant difference. And now what's happening, see if this plays now. What's happening now is she has had what some people are calling pain and what some people are referring to as spasticity. She's had multiple complications related to the motor vehicle crash that she was in, orthopedic issues, endocrine issues, pain issues, bowel and bladder issues. You all get the idea. Hopefully this will play. Hopefully you can hear her. And that was not. There we go. So some questions to consider as my speakers give their presentations, when is spasticity painful and when is the pain causing the spasticity? What is the source of pain and the source of the spasticity? When is it or isn't it time to mix drugs? And then again, touching on the clinical and financial considerations of the patient and the practice. And with that, I will pass the baton to Dr. Salimah and Dr. Burrell. Thank you, Cindy, for inviting me to give this part of the lecture. And we're going to talk about spasticity versus pain and using intrathecal pump programs. I am Dr. Brian Burrell. I'm an interventional pain physician, and I'm proud to say I'm also a physiatrist and mainly a physiatrist. I'm in private practice, but I'm also an adjunct professor at McGovern Medical School at University of Texas in Houston. Here are some of my disclosures. I'm currently the president of the Texas Pain Society. I do have consultant or advisory and speaker roles for the following companies. The objectives that I was given was to make sure that the participants in this presentation would be able to consider anything wrong with the pump in terms of troubleshooting, in terms of pump malfunction, and also to identify the subtle issues that might present itself to you that might make you think that there is a pump malfunction. Now, I have to say that the intrathecal therapy, you have two pumps now, and both pumps are indicated and labeled per the FDA for both pain analgesia and also baclofen. So I'm going to talk a bunch about the pumps and some differences because you're going to see different pumps now in our patients, and you need to identify how to troubleshoot these two different delivery devices. So a lot of times, if you're not used to intrathecal pump therapy, this might be jumbling around your head that it's so complicated and you might not want to do it, and if you're a pain physician, you steer away from it and you just do spinal stimulators, or if you're a physiatrist in brain injury, you might just do toxins because you're uncomfortable with the nuances of the pump. So I'd like to kind of demystify all of that in this presentation in terms of troubleshooting so you feel a little bit more comfortable about intrathecal therapy and might use it more in your practice for indicated patients. I really do want to talk about the patient because this device delivers medications, either analgesia or baclofen, into our patients, but we really have to remember the nuances of each patient and not talk about them as, oh, the one with spasticity, oh, the one with the pain, oh, the one with the pump. There's a person in there that you need to really understand and treat, not only the patient but also the caregiver. So I really love this quote from Sir William Osler and it's something to take home with you all in terms of patient care. So putting the patient in the center of our attention, I'd like to talk about a patient's journey with either spasticity or pain and we must remember that that person with a pump, with treatment for spasticity or pain, they go on life and either they're functioning and in a job or they're at home with their caregivers and comfortable and the caregivers are able to provide good optimal care because their body is in a state where it's easier for them to care for them without too much spasticity. But this is very difficult. Success is never, never a straight line for all of our patients, both pain and spasticity, and success typically goes in different directions. If you're a physiatrist treating pain, you can't forget about your physiatry background because it is really the backbone of intrathecal therapy for pain as well. So I'm going to talk about a patient quickly. This is my patient. I'm going to call him Jimmy. That's not really his name, but he hurt himself and had a spinal cord injury through a motocross accident. He has both spasticity and central pain, but he came to me for a discussion regarding intrathecal therapy and Jimmy's initial trial was 50 micrograms of baclofen and he ended up doing quite well with that trial. I implanted his pump and then life happened for him. He was doing quite well with his pump for about two years. Then he broke up with his girlfriend. He ended up going to a nursing home. He had some depression. During this time, he was suffering from also central pain and we needed to decide what to do for him. My initial dose of therapy for him when he was doing great was baclofen, 500 micrograms per mil, and I infused 100 micrograms per day, slowly titrating that up. Then eventually, I also treated his pain on an off-label basis by including bupivacaine into his intrathecal mixture. This person is a perfect example of pain and spasticity and that this one device could potentially treat both problems pretty efficiently, but again, I have to go back to the important role of you being a physician and understanding your patient, understanding psychosocial issues and understanding that once you put a pump in, that's not the end of your treatment and the end of your constant evaluation. It is just the beginning because life happens for our patients. In terms of troubleshooting and complications, I did need to highlight that any adverse events from intrathecal therapy typically happens within the first month of implant. Most of these events are surgically related, but then in the second, third, fourth, fifth months, you don't really have surgically related complications, but you could have device-related and drug-related issues, and you have to be astute in understanding the subtleties of potential pump problems and very much understand specifically for baclofen because it could be life-threatening, the role of baclofen withdrawals as a problem. So you can have mild, moderate to severe, I'm pretty sure Dr. Salino is going to talk about this in a little bit more detail, so I'll just skip over that, but I just wanted to highlight the importance of the baclofen withdrawal syndrome in patients with intrathecal therapy. It is also important to understand this in a patient with pain, but it's much more important to understand this in terms of baclofen withdrawals. Pain, unless you're really sick and fragile or have cardiac issues, withdrawal from analgesics typically won't be too severe unless, of course, you're doing off-label use of clonidine, the opiate medications in the pump. If you're withdrawing from that, it's not likely life-threatening, but I'm pretty sure your patients will not enjoy that whole process and probably blame you in case they are withdrawing. I do want to talk about the acute troubleshooting algorithm. It's pretty similar to the non-acute troubleshooting algorithm. The difference is that you go down that algorithm much quicker in an acute situation where they're in acute baclofen withdrawal. You could also go down this pathway if you are assuming that a person is withdrawing from their pain analgesia intrathecally. In an acute problem, there are very important roles for medical management and supportive care that's listed here on the left, but we're going to go through some of this in terms of troubleshooting if you are worried about pump malfunction or the baclofen or analgesia is not getting to this spinal fluid. So loss of efficacy, and this is a troubleshooting algorithm for that. You want to know, is it pump-related? Many of you that have treated intrathecal baclofen patients probably have had the phone call from an emergency room or a phone call from a colleague asking, oh, is the pump working? Is the pump not? And it's your role as the manager or even the implanter like myself to go down this list of things to do to determine whether or not it is truly the pump that's causing the issues. But it's not always the pump, and I want to highlight that very clearly. It's not always the pump, and unfortunately, we always get a call, oh, is it the pump? But I am always concerned that, you know, if it's not the pump and everyone's putting all their eggs in that basket that, oh, it's the pump, it's the pump, it's the pump. You're delaying care and delaying diagnosis of either infection, a nauseous stimulus such as pain can increase their posturing or their spasticity or their tone. Is there a pressure sore happening, ingrown toenails? Are they constipated? Do they have a gallbladder that needs to come out? So many different things can cause a person's tone to increase or a person's pain to increase, and it's very important to, in parallel while you're going down this algorithm, to get your other medical professionals and colleagues to look at other ideologies that might be resulting in their symptom change. So anytime there is a thought of a subtle change in their function, either for pain or spasticity, you want to always look at your pump programming and interrogate it and determine if there was a programming error. I can't stress that enough that many times it's a programming error. It could have been that you changed your concentration from 500 micrograms per mil to 2,000 micrograms per mil, but somebody or you yourself forgot to enter that in, and that itself would be a problem. And also, if there's no findings, you could potentially program a bolus, either a baclofen or an analgesic pump. And if you see a difference, then it may very well be that the pump is delivering medicine into the intrathecal space. It may very well be that the pump and catheter are working just fine. If no response in tone, and I'm going to say also in pain after a bolus, you want to look at the pump reservoir volume and compare it with the actual aspirated volume, and look at the months prior and the refills prior to see if there's a pattern that you're seeing that you're always getting a discrepancy. And if there is a discrepancy, your suspicion for malfunction is going to be higher. And if that's the case, and you're seeing that pattern, then you might decide to do you might decide to do a catheter access port aspiration. And if that's the case that you find that you can't aspirate CSF from the port, then advanced imaging might be indicated to determine where the catheter is. Is there kinking? Is there a dislodgement? And potentially even do a bolus dose of an analgesic or baclofen, depending on what you're treating, outside of the catheter directly into the spinal fluid via an LP. And if you see an improvement in tone, all of this provides you information to potentially revise and replace the catheter. Later on, I'm going to talk about what the implanter and the surgeon and the person revising the pump might do intraoperatively to understand if there is an actual kink or a problem and what we do to fix that. So there are, again, two FDA approved delivery devices for both pain and spasticity. On the left of the screen is the Medtronic. And this is a peristalsis pump. And on the right, it's a Prometra pump from Fluonix. And that is a valve gated pump. I actually took this picture of a Medtronic pump. And this is the roller for which the catheter is placed. And that roller rolls and pushes out the medication into the catheter. In a Prometra pump, the old pump for pain but relatively new for spasticity, it's a different system. It doesn't have a roller. Rather, it has gates. And the gates open and close, open and close, and pushes your drug out of the, into the catheter stem. Both pumps come in 40 and 20 mil volumes. Both pumps are MRI safe. However, you must remove all the drug from the Fluonix pump prior to any MRI. And then replace the drug after the MRI is performed. Both pumps regardless, sorry, both pumps will require interrogation after the MRI just to make sure that it's functioning. The FDA labeled medications for both pumps include morphine and Vaplifen. Both pumps might malfunction and workup is very similar to the algorithm that I just discussed. Both pumps are programmable. Both pumps are able to provide patient boluses. The Medtronic pump, it's called a PTM, patient therapy manager, and the Fluonix is a PTC. And the implant procedure is very, very similar in implant and also catheter positioning and thinking about that as of now. Here is a picture of both the Prometra and Cincomed 2 pumps that I put side to side at one of my cases. And as you can see here, there's some differences here. They're both FDA approved for morphine and Vaplifen. However, the Medtronic pump is the only one of the two approved for Ziconotide, which is an analgesic. As you can see in the picture, the catheter stems are a little bit different for both and where the catheter attaches are different for both. And because of this, the catheter dye study, there's a different process for each that I'm going to go through very quickly. Here is a Fluonix catheter aspiration port study. I wanted to highlight this because it's different than what you might be used to if you've been using the Medtronic pump. This is the first fluoro picture of the pump under x-ray. This is not part of this person's pump, but it's very important to note that you cannot see that stem here when you take an x-ray picture of it. And once you put the needle into the stem, into the side port, it's typically right next to this, what they call the Thav valve. And you put it right in that port, but you still can't see it, but you feel it going in. And then once you are able to aspirate, and once you're very convinced that you're able to safely put contrast in that cap stem, then you can start seeing the stem highlight here. So that's a nuance and a difference for the Fluonix cap study that you might not know because this is rather new. Another difference is that in Medtronic pump, when you do an actual pump study, you do what we call a roller study. You take a picture after activating that Medtronic roller, and then you see that the roller moved. But it's different in a valve-gated pump because you won't be able to see anything move. What you do is actually activate the pump to deliver a bolus in one minute, and you have to place a stethoscope over the stem. And the way you know that this is functioning with the valves is that you actually hear the clicking of the valves. So that's a nuance and difference of a cap study when you look at the newer pump. And hopefully, all of you are familiar with doing the cap study for the Medtronic pump. So I'm going to talk about, as an implanter, what is important in implanting a pump because I think if I highlight different things in the implant, you would understand the potential complications. And so this is a way of working here, but it looks like it might not be. I'm going to fast forward this a bit, if it allows me. So patient positioning is what we were looking at earlier. Of course, we do local analgesia. Here's some floral images of us placing the catheter into the spinal space, into the fecal space, creating a pocket. So obviously, it's pretty invasive. So after implant, your patient's probably going to be a bit sore. I want to highlight the placement of anchor sutures in the pocket that we're doing here right now. If you have patients with a flipping pump or a patient with a pump that seems to not be positioned very well and moving around, it could be from the anchoring that might have been missed. This is in the spine. It's dissection of the tissue up to the lumbodorsal fascia where the catheter would be anchored. Very important to show this part is the placement of a first string suture onto that fascia. I like placing a first string around that catheter entry point because by putting a first string suture there, you make a watertight seal around the catheter entry point to prevent a hygroma or prevent even a spinal fluid leak that would cause postural puncture headaches. In my patient population with the pain, added spinal headaches after an intrathecal pump implant is kind of devastating for them because they're so looking forward to pain control. But here I am introducing a new thing. So I really try to do that first string suture for all of my implants. I'd like to forward this, but I'm scared I'm going to jump too far. And so here is the placement of the anchoring device. Sometimes, and I've seen this in severe, severe spasticity that's still not yet very controlled. If the person is posturing, if the person potentially even had a massage, sometimes if that massage is very, very deep, it could potentially move the catheter and anchor site off the fascia. And then the catheter can be pulled out of the intrathecal space. That might be an indication to revise and the patient might not have analgesia or might not have tone control as a symptom that we identify. I'm going to forward this some more. I'm glad it ended here. This is the tunneling technique. So after the implant, this could really give a person a lot of pain. The tunneling from the pump to the catheter anchor point, we're using that tunneling device to tunnel that catheter from one side to the other. So a lot of pain from this as well. And this is probably the most barbaric part of this procedure for our patients. You might see more commonly or sort of more often now that many of the implanters are trying to put these pumps in the flank region. And this is a decision made by both the implanter and the patient. And move forward to the next slide. And as an implanter, when I'm asked to troubleshoot, because sometimes, you know, the patient is not getting the expected dose, is there a catheter tank, we do the dye study, but we can't inject dye because we can't even aspirate any CSF. Oftentimes, I go in there thinking, okay, I'm going to revise something, but we're not really sure what to revise or if I'm going to replace the entire catheter. And this is an example of a pump that's been there for three to four years. It's like this person's second or third pump. I don't remember the space in particular. But a lot of times, you're going to see a fibrous capsule in that pump pocket, and that fibrous capsule ends up looking like this. And if you can see, the catheter is just in a torturous place. And once I take out all the scar tissue and the fibrous capsule, free the catheter, a lot of times, the catheter starts leaking spinal fluid. And that point, then, okay, well, my diagnosis in intra-op diagnostic and troubleshooting is that it was kinked in this fibrous capsule mess. What I've been noticing lately with some pumps is that potentially the scar tissue, if it's this bad, can really occlude the catheter at the site of the catheter attachment to the pump. And I've seen that a few times. We've shared a few patients also with Dr. Ivanhoe that look like this. So, looking at surgical considerations, I really, really do not want patients to get infected if I'm implanting or revising a pump. And so, there's many different guidelines. What I want to highlight from this slide is that the infection rate is low. It really, truly is. But, you know, you can get meningitis from 0 to 0.5 percent. Pocket site and catheter infections range from 0.2 to 5 percent. And in patients with good pain relief with intrathecal analgesics or good tone relief with Baplifen, it's going to be very difficult for that patient if you have an infection. It's particularly more scary for patients on Baplifen therapy because if you have an infection and the person's been getting therapy for about a month or so, and you know that adverse events can happen more commonly after the first month of implant, you might consider weaning down the Baplifen. This is particularly important if you're seeing a patient who's had Baplifen therapy for the last three years, four years, or five years, and they come in with these subtle signs and somebody wants you to revise their pump, but they're on a thousand micrograms per day. You can't just go in there and revise the pump. You must wean the dose down slowly because otherwise your implanter won't ever know what dose to start that pump back on. So those are some considerations for us when we were asked to revise things. Again, staphylococcus is the most commonly reported infective bacteria. Generator pocket is a more common site. Very rarely do I see a catheter anchor point that is infected. And infections increase when the patient smokes, drinks excessively, has diabetes, rheumatoid arthritis, or on immunosuppressive medicines. So very much need to control many of those things prior to implantation. And we always follow surgical standards in terms of antibiotics given. Also in the OR, chlorhexidine is more effective than iodine, meticulous, very meticulous hemostasis. And more interestingly, you're hearing that implanters start using, have started using vancomycin powder inside the pocket and the anchor site because we don't want people to have infections. However, and I think Dr. Salino was on this study there. In retrospective review, there isn't really any evidence to support that. But also there's no big studies either. So many of us still use vancomycin powder into the pocket and into the anchor site. And this is an example of things that has gone wrong. Um, uh, this person, um, is, is a person who unfortunately I, uh, changed out his, uh, baclofen pump, very skinny, as you can see there. Um, and again, I worry very much about skin integrity. This is the old incision, um, that this patient had, um, that pump looks scary. That pump was about to, uh, expire. Uh, I did the pump, uh, exchange and, uh, you could see my incision looks pretty good, but the problem is the old pump, uh, scar, uh, dehisced, um, and, and then the pump started poking out. Unfortunately, this gentleman does not, uh, have this pump anymore. Um, here is a lady I just explanted a pump. She's 92 years old. She had a pain pump for, um, this is probably her third pain pump. And it's the pain pump has been there for, um, the last seven years. And it was now time to replace it, but she's 92. Um, she doesn't really complain of pain anymore. She's a little bit, uh, going down the path of dementia. Um, and we had a very long conversation because this, this is a very old, creepy skin. That's very sensitive. And any scratch was very scary for this to come out in terms of skin integrity. And, and this, this round thing right here, uh, is her catheter. Yep. The catheter is right there. So I had a talk with her and her caregivers and her, her family. And the thought was to wean down the, uh, the pump as low as we go, we could get. And, um, she didn't have any change in her pain score. So the thought would be just to explant the pump, um, rather than replacing the pump. Um, she wanted to explant it. I agreed with her because see, the skin is very, very thin. And I was very, very scared of, of a scenario like the previous slide for this 92 year old. So, um, really discuss skin, uh, skin integrity, really discuss a risk and benefits of pump therapy along that person's life, along that person's journey with interpeople therapy. Um, so that was my last, this is my last slide. I just want to highlight the, uh, women in medicine that I've had the pleasure to, um, help train in the operating room. And all of these three women here are now attending physicians, uh, in brain injury. Um, so, um, that's the end of my talk. Hello, uh, my name is Dr. Mike Salina. I want to thank both Dr. Bruel and Dr. Ivanhoe for the opportunity to participate in, uh, this virtual, uh, Academy Assembly. Uh, much of my talk will dovetail very nicely with, uh, what Dr. Bruel had talked about. And, uh, certainly a little repetition will, uh, will help with that. Um, I am a physiatrist at Moss Rehab in Philadelphia. And similarly to Brian, I consider myself a physiatrist first and a pump manager second. Uh, I think the principles of physiatry work quite well, uh, when you're dealing with individuals who have intrathecal delivery systems. My task for the, the next little bit is to really kind of highlight the similarities and differences, uh, between utilizing intrathecal drug delivery for pain and spasticity. And, uh, point out the, the highlights of why physiatrists are uniquely equipped to handle that. So again, here are my objectives, just, uh, what I talked about. Uh, these are my disclosures. I work with many of the pharmaceutical companies and, uh, device companies that are involved in targeted drug delivery, as well as the Journal of Neuromodulation, which has a focus on, uh, intrathecal drug delivery also. Um, we'll discuss some off-label issues and I'll do my best to point them out as we move along. So first as, as highlighted by both, uh, Dr. Ivanhoe and Dr. Brewell, these are the indications for intrathecal drug delivery, uh, chronic pain or severe spasticity. In generally, in general, we look at, uh, that for folks who have been, um, afforded more conservative therapies first and have failed those and are, or not getting adequately controlled, uh, having a life expectancy of more than a couple of months, uh, and, uh, no allergy to the proposed medication. Uh, you'll see one of the difference in the treatment algorithm as we go through is one difference between the pain and spasticity populations is the need for a, a more in-depth psychological evaluation. I think it's very important from the very beginning when you're dealing with a patient who you're considering for intrathecal delivery to lay out what the expectations are. Certainly, we want to see both the pain and spasticity reduced, but at times it may not be appropriate or even possible to completely eliminate, uh, the pain or spasticity. Uh, we would want to reduce or perhaps, uh, diminish the amount of oral medications or other procedures. Uh, but as Brian mentioned, it doesn't completely eliminate the totality, uh, of their approach to, uh, a comprehensive treatment. Approach to, uh, a comprehensive pain or spasticity management. We want them to have a better side effect profile and as mentioned, be part of a, of a bigger pro program. The advantages as mentioned by both of my colleagues is a higher potency compared to oral medications, the capacity to deliver unique medications, long-term pain and spasticity results, decreased healthcare utilization, and perhaps the biggest one is the ability to trial. The ability to give patients the opportunity to experience what the therapy will be like before they actually, uh, get the permanent implant. Disadvantages of the program, excuse me just a second there, there we are. Disadvantages of the program as mentioned, it is an interventional procedure requiring an implant. It is considered a palliative therapy. It does not modify the underlying disease. It does require constant and mandatory maintenance. There is both an overdose and withdrawal perspective as Dr. Burrell talked about and one of the unique features on the pain side of the house is the development of intrathecal granuloma which I'll talk about a little bit later on in this talk. This is the treatment algorithm for both intrathecal drug delivery for pain and spasticity. It always starts with an evaluation. If you are considering it on the, for a pain patient, there is the mandate for a psychological evaluation. Both individuals then go, or both populations go through a trial phase leading on the implantation as Dr. Burrell just eloquently described, post-implant rehabilitation and then long-term management. So I'll just go through that algorithm a little bit, kind of outlining the similarities and differences. Certainly we want to review patients' histories, both with pain and spasticity, looking at what is their response to prior therapies, what are the involved body regions, and do they have constant or intermittent symptoms. In general, it is considered that constant symptoms are more adequately handled with targeted drug delivery compared to intermittent symptoms. We always want to consider their comorbidities as Dr. Burrell talked about, and this is on both groups. None of these things represent contraindications to implant or trialing, but you certainly want to have these things optimally managed prior to going ahead with a trial and perhaps even prior to, I mean, certainly for implant and certainly maybe even for trialing also. The initial evaluation, one of the hallmarks that I take a lot of time with is evaluation of the patient's social history, and do they have the resources to be an active participant in this therapy? This therapy is not a passive kind of get and forget type therapy. You need to ask questions like, what's the home situation like? How do patients get to appointments? What's their transportation considerations? And again, this is for both groups. Document a baseline musculoskeletal and neurological evaluation so that you can compare your results over time. Explain to patients the beginning, middle, and end of the program, not just giving them a taste of it, but give them the full discussion. I've received patients from other providers who didn't go through this, and some patients have said to me, no one told me that I needed to come back to clinic every couple of months to have this done. I thought I just got it put in, and it stayed there forever. So explain the entirety of the program. Certainly you want to understand what the payer coverage is for your individual patients. Recognize that payer coverage may be different for on-label and off-label medications. This is where your billing staff, your support staff is of crucial importance. Some of our patients have pretty big co-pays, and if you're using an expensive medication, 10 or 20% co-pay of an expensive number can rise up pretty fast. The big difference in the baseline evaluation between pain and spasticity is the need for psychological evaluations. It is not mandated for cancer pain, but for all non-cancer pain, for both governmental and most commercial insurances, it is required. Recognize we're not saying that a patient can't be depressed or have some degree of anxiety, but there is a psychological profile in which patients will tend to do better. This is really where you want to do some outreach to your psychologist. If you're lucky enough to have a psychologist in your clinic, this helps out a lot. Sometimes you have to use community-level psychologists, and you have to explain to them what you're looking for, that it's not just any degree of depression, but individuals who demonstrate such severe psychopathology that their ability to participate in a comprehensive program is not attainable. These are what are considered the typical psychological exclusion criterias, and most of these would be relatively recognized easily, but again, this isn't necessarily our particular area of expertise, and our psychologists can really help out with this. It is their training to maybe pick out some of these subtleties and help you make a decision on whether a patient should move forward to implant. There may even be occasions on your spasticity population that you may want to explore a psychological evaluation also. The screening trial. The concept here is you let the patient have a test drive. Before you buy the car, you get a test drive, and if you like the test drive, you buy the car. If you don't like the test drive, that doesn't mean you don't buy any car. You may buy a different car, and you may have to test drive something else. The general approach on the spasticity side is to do a single-shot lumbar puncture and give a bolus administration of liquid back with it, and that's a pretty uniform standard on the spasticity world. There are some individuals who are doing continuous trials, but I would think that would be the exception rather than the norm. On the pain side of the house, we do see that there are multiple methods that are possible. Single, multiple boluses, a continuous infusion through an external pump with an intrathecal catheter placed. Right now, there is no prospective data that supports one trialing method over another, but just recognize that there are different trialing methods out there that are more commonly used on the pain side of the house. For both the pain and spasticity populations, we may wanna wean down their oral medications. For the pain patients using opiates, this helps create a safety margin. For the spasticity patient, it may help you define the efficacy of your bolus trial. You may also wanna consider when you do neurolytic and chemodenervation procedures so as not to confound your results. This is some of the pros and cons of bolus versus continuous trials. I won't read them to you. There is a little bit more technical difficulty with placing a catheter. Most individuals who have trained a little bit in medical school or in residency can do a single-shot lumbar puncture without too much difficulty. You probably do need a little bit of specialized training to place an intrathecal catheter. The trial assessments. Again, this will be different in the two populations. There are the classic spasticity evaluations, the Azuret scale, a spasm frequency scale, a TARDU scale. But that doesn't mean that you can't use similar things like a visual analog scale, both for pain or spasticity. You are also doing functional assessments. I'm a very big believer that doing a trial either for pain or spasticity has to include some sort of rehabilitative assessment, getting a handle on what patients are capable of doing, and hopefully seeing a change in their... Between the two populations. For both groups, you are assessing if any adverse events occur and what's the intensity or frequency of those adverse events. Sometimes adverse events represent a relative contraindication in moving forward. Other times it just gives you a hint of what you may be dealing with with a long-term implant and long-term infusion. A good example of that is spasticity patients and neurogenic bladder. Certainly conceivable that intrathecal baclofen delivery could alter an individual's spasticity presentation or neurogenic bladder presentation. And you may pick that up during the trial and give you a heads up as to what you're gonna need to keep an eye on during the post-implant phase. This slide is worth a little bit of discussion. On the spasticity side, there is only one medication that is FDA approved, and that is baclofen. Recognize there's a couple of different brands of baclofen that do have FDA approval, but it's still baclofen, no matter what the trade name might be. There are several other medications that are used on the pain side of the house, but only two are approved for, formerly FDA approved for pain. One is morphine, and the other is ziconotide or Preyalt. The other medications, including hydromorphone, fentanyl, sufentanyl, clonidine, and bupivacaine are all off-label, and any combination is also considered off-label. The vast, vast, vast majority of spasticity patients are treated with baclofen monotherapy. Combination therapy is very common on the pain side of the house. This is another area where you wanna pay attention to payer coverage. Some payers will only approve FDA approved products, and you should know that ahead of time as you make a decision as to what drug you're gonna utilize. Dr. Burrell did a terrific job in describing what implantation would be, and they are similar for both groups. Perhaps the biggest controversy in targeted drug delivery at the moment is where do you place the catheter tip to get what effect? Both on the pain and spasticity populations, this is a challenging question that truly no one has a clear-cut answer to. Do you place it closer to the suspected pain generator? Do you place it lower in the thecal sac where there may be a little bit more CSF to avoid granuloma formation? Do you put it more cephalad if you're dealing with upper extremity coverage? This is probably the area that is the greatest unknown in targeted drug delivery. Post-implantation is similar for both groups. You are adjusting the pump to optimal levels. You are weaning folks off of oral medications. You're managing any adverse effects that may be occurring during that titration phase. And this is really where you wanna do that functional retraining. And I'm a huge believer in immediate post-implantation rehabilitation for both groups. This really gives you the advantage for patients to truly experience the benefit of this therapy and to experience a functional improvement. Sometimes we can get this covered as an inpatient, but certainly a comprehensive outpatient program is appropriate during this phase. With some of the drug issues, as Dr. Bruel mentioned, some medications have very significant withdrawal. Baclofen has a very significant withdrawal syndrome. So does clonidine as well as the opiates, bupivacaine and ziconotide a little bit less so. The causes for withdrawal are listed there on your screen for you. Sometimes these are man-made issues. Other times it is a mechanical issue. Sometimes these things are easy to pick up and other times there's not. And this is truly where we earn our stripes as pump managers to be able to evaluate these situations and develop their underlying cause. It's also important to recognize in moderate to severe withdrawal presentations that the first step in the process is always to treat the underlying withdrawal while you're concomitantly doing your diagnostic workup. They run in parallel courses, as Dr. Bruel mentioned. You don't have to do all your diagnostic studies and then begin the treatment. Overdose, again, very commonly due to human error, but could also be due to some other mechanical issues. On the pain side of the house, there are reversal agents, including naloxone and naltrexone. There truly is not reversing agents for baclofen. Some older literature did support that. It's been shown that that's actually more harmful than good. But first you wanna stop the infusion, perhaps even access the side port of the pump and remove some CSF, hydrate the patient. And the target is to get the CSF drug concentration down as quickly as possible. Tolerance. Again, this is a relatively controversial topic. Do patients actually develop tolerance to these medications? Is it a mechanical issue? Is it a new pain generator? Is it paradoxical pain, hyperalgesia, et cetera, disease progression? This can be quite a daunting challenge. I would say that it's a little bit easier in the spasticity population to tease this out. The pain patient who describes more pain is certainly a challenging clinical entity to deal with. I think this is where good history and physical examination comes into play with you. An individual who was previously well-controlled and then all of a sudden develops poorly controlled symptoms deserves attention. This is not just a chronic pain patient saying that they're in more pain. The treatment for this, in addition to doing the diagnostic workup, may include dose escalation, being aware that that may result in a higher risk of drug precipitation or granuloma, a drug holiday, switching, opioid rotation, or perhaps bolus dosing. Both groups have a very similar pathway in terms of chronic management. They come in for scheduled refills. They come in for medication adjustments and changes, adding or subtracting adjuvant agents, changing of their dosing regimens, including patient-directed or patient-activated delivery, as Dr. Burrell mentioned. They both get their battery replaces replaced at different times, depending on what manufacturer. And as Dr. Burrell mentioned, there is coordination involved if individuals have MRI. So you can treat both populations simultaneously with a similar program. I do wanna highlight a little bit about intrathecal granuloma. If it exists in baclofen, it is extraordinarily rare. My personal opinion is that it does not exist in baclofen monotherapy. Some people might disagree with me with that. But it can occur in individuals who are treated with intrathecal opiates. It appears to be both a dose and concentration-dependent phenomena. Higher doses and higher concentrations appear to be more prone to granuloma development. There may also be some protection if delivered with bolus delivery rather than simple continuous delivery. That's a little bit of a hypothesis and not completely proven. But any individual being treated with intrathecal opiates who describes any kind of new neurologic symptoms or perhaps even a new pain syndrome is worthy of investigation. This is a photomicrograph of what a granuloma looks like. You could see that it actually does not arrive from neural tissue per se, but actually arises from the meningeal layer, an arachnoid layer laminating itself around the catheter. And once the encapsulation gets big enough, it will begin to compress the spinal cord and if left unchecked, will result in neurologic difficulties. There is a number of papers that describe the management of granulomas. Obviously, for rapid neurologic deterioration, surgical resection is required. For stable or minimal neurologic symptoms, there are conservative management strategies that are outlined there for you. It does not represent a complete contraindication to continued or repeated intrathecal drug delivery, but you certainly wanna have a very learned conversation with your patients in terms of management. Lastly, I'd like to finish up with what the future might hold for intrathecal drug delivery. Intrathecal baclofen is not a novel therapy. It's in its third decade of utilization now, but yet we still only have one molecule. Pain has been, morphine's been around for a similar amount of time, ziconotide less so. But again, we have a relative paucity of molecules that are available for us. The technology hopefully will improve, including longer battery life and perhaps even rechargeable systems. I would find it a very intriguing idea, especially given the current environment with COVID, the idea of having some remote access to our patients, the ability to titrate or wean patients without them physically coming into the office is very intriguing. Other potentials include some disease-modifying therapies, meaning not just controlling a symptom, but help controlling the underlying disease and things like interleukin-10 and antisense oligonucleotides may be a possibility. Hopefully the future will be bright with this, although given the current COVID environment, some of the investigation into this has slowed, obviously as research investigation by the industry partners has slowed a bit. And that's the end of my presentation. Again, I wanna thank both Dr. Ivanhoe and Dr. Burwell for giving me the opportunity to share some of my thoughts. It's always a privilege to share the podium with both of them. And at this point, I'll turn it back to Cindy. I don't know if she wants to ask either of us any questions. Well, that concludes this course on pain and spasticity and intrathecal drug delivery. As always, I also enjoy sharing the podium with Dr. Salino and Dr. Burwell. I'd like to thank them and the Academy for all that has gone into pulling together a virtual Academy meeting. And next year, may we all be healthy and meet in person and network. Thank you.

intrathecal drug delivery

spasticity

pain management

evaluation

medication adjustment

post-implant rehabilitation

complications

psychological factors

future developments