All right, so I got 802 on my watch, so let's go ahead and get started. Welcome everyone to our October Journal Club event through the Association of Academic Physiatrists Medical Student Council. The topic for this month is pain management. So we got three great speakers and clinician expert ready to kind of talk to us about some really cool topics within the realm of pain management. So to introduce everybody here first, our clinician expert, first and foremost here is Dr. Chong Kim. He's a professor out of the Case Western University School of Medicine and the Pain Medicine Fellowship Director at the Case Western Reserve University, Metro Health Medical Campus in Cleveland, Ohio. And our first speaker today will be Dr. Alex Chorba. He is a class of 2022 candidate out of the Ohio University Heritage College of Osteopathic Medicine, currently completing his internship at Akron General Medical Center. He'll be presenting on the long-term safety and efficacy of closed-loop spinal cord stimulation to treat chronic back and leg pain. We evoke a double-blind randomized controlled trial. Take it away, Dr. Chorba. Thank you. All right. I get to present on the evoke spinal cord stimulator. Before I start on that, I wanted to give a little bit of background information on spinal cord stimulation. So spinal cord stimulators have been around for about five decades, and they try to preferentially activate a beta fibers to create a paresthesia, sort of a tingling sensation, overlapping the areas where patients feel pain, to overwhelm those pain sensations. One thing to keep in mind, that's an important part of this study, is that when the spinal cord stimulator is in place, there's a lead. It's generally implanted in the epidural space to try to activate the beta fibers in the dorsal column. And then that distance can change between that lead and the spinal cord itself in different postures. So in this picture, I have a picture of the vertebral body, the spinal column with spinal cord inside. You can imagine that as a patient leans forward, leans back, coughs, that the spinal cord can move about in that spinal canal. These spinal cord stimulators are particularly effective for neuropathic pain. They have other indications generally for chronic pains that have not been responsive to conventional therapies like medications. And for spinal cord stimulators, there's a period, basically a trial period, where you see if the patient can handle the spinal cord stimulator and if it's effective. So you want to make sure that they have a greater than 50% reduction in their baseline pain, that the patients are happy with the results of the spinal cord stimulators, and that the region of paresthesia that's generated overlaps the areas of pain. And then there's the therapeutic range that's determined essentially from the, when the patient starts feeling that paresthesia, that sort of pleasant tingling, to the point that with a certain current that is just overwhelming, that's no longer beneficial. Here's another image then. Spinal cord stimulator leads going up into the epidural space. And another one trying to give that image to, where it's close to the spinal cord, but it's not directly in contact. And that idea, again, where the space between the stimulator and the spinal cord can change. And in that idea, if it's a constant current, then sometimes the effective stimulation then will be really high and really low, depending on if the spinal cord gets closer to the lead generator or not, or lead in the epidural space. So I'm talking about the evoke trial, which has the closed loop spinal cord stimulator, in addition to the classic open loop, which I'll talk about. And overall, I wanted to give just a sense of the study. It was ultimately trying to use evoked compound action potentials, which I'll refer to as ECAPs, to have a mechanism for adjusting, ultimately the spinal cord stimulation that the patient receives, trying to keep them in that therapeutic range for as much as possible. And it's a multicenter, double blind, parallel arm, randomized controlled trial in the USA, for patients with chronic contractible pain of the back and legs. They had primary outcomes, essentially related to pain management, and then secondary outcomes, which were more quality of life measures. I'm going to just talk about the primary outcomes. And ultimately their finding was that this closed loop stimulation system was superior to open loop stimulation. And again, so these ECAPs are a way to measure the overall stimulation that the patient receives. So it gives a way to adjust the stimulation. On the left side, I don't know if you see my pointer, so if it's- You can see it, Dr. Chorba. You see it? Okay. So if you, in the fixed output then, it's just a constant charge, which that can be adjusted, but you just think, okay, it's a constant charge. And as we were saying, sometimes that lead is closer to the spinal cord, sometimes farther away, depending on postural changes, leaning back, lying down, et cetera. So sometimes that patient then receives a lot of more stimulation, sometimes a lot less. In the closed loop, they're using that ECAPs to constantly adjust the current so that the overall stimulation that the patient receives is a pretty consistent stimulation in that therapeutic range. That's essentially what I go over here. A couple of things in this study. These were the criteria for the participants. One thing I want to point out, so stable pain medications. So people weren't playing around with pain medications during this. It was patients who, you know, baseline pain medications and then assessing the response to the spinal cord stimulators in that setting, a visual analog scale and Oswestry Disability Index of certain scores. And so a visual analog scale, zero to 100, it's an idea of, and then there's usually like hash marks along and patients, you know, write down at some area on there to give a visual representation of their pain levels. That Oswestry Disability Index or ODI is Low Back Pain and Disability Questionnaire. So they had specific criteria then to meet. Patients were randomly assigned a one-to-one ratio for that closed loop or adjustable stimulation versus the open loop. And depending on the sites they were at, patients were in groups of four to six and it was blinded. So as we were talking before that pre-implantation period or that trial period, the difference then with this Evoque spinal cord stimulator was that they used those ECAPs to measure or correlate with that therapeutic range. So they had an ECAP reading of when the patient, when the current was enough to cause the paresthesia up to the point where it was overwhelming. So that's the mechanism where they were able to then adjust the total stimulation that the patient receives. And then it served as both the closed, or excuse me, the control device and investigational device. So even in the closed loop where it's adjusting, they use the ECAPs and in the fixed output where they're not adjusting, they still measure the ECAPs. And that was another measure they said to, like to correlate how often those ECAPs were in the therapeutic range for both systems. So the primary outcomes, as we said, were essentially 50% or greater pain reduction on that visual analog scale for the patients and secondary outcomes were more regarding to quality of life measures. This is the trial breakdown from the article. Ultimately, 134 patients started. So 67 in each group, closed loop and open loop. And by the 12 month period, there were 59 in each. Anybody who withdrew was assumed to be a non-responder or in other words, did not meet those bench line 50% pain reductions. One interesting thing to point out is that the person who, or the funding source of the study had access to all information and could participate in each aspect of the study design. I didn't see that detailed in the study, but a potential source of bias. And so for the primary outcomes at three months and 12 months for that 50% or greater baseline pain reduction, both spinal cord stimulators in both modes, excuse me, were found to be effective for the majority of patients, but the closed loop or adjustable stimulation by the ECAP mechanism, 80% compared to the 60% essentially for both groups at both time periods. There were some adverse events in the study. The serious ones, including wound infection, abscess and lead breakage. And so ultimately, the ECAP controlled closed loop spinal cord stimulation was found to be superior to that fixed open loop spinal cord stimulation. Both collected real-time data from the participants. And as we discussed, then not only did the closed loop group have a greater number of participants meeting the goal baseline pain reduction, but they also had a greater amount of time in that therapeutic range, which is the proposed mechanism for the superiority or superior findings in that closed loop stimulation group. And then overall, there were some of those adverse effects, but spinal cord stimulation is generally considered safe and efficacious treatment for refractory chronic pain. And this then gave a demonstration that the adjustable stimulation can also be superior and can personalize therapy as well for those determined therapeutic ranges. And then one thing that spinal cord stimulation is particularly effective in is like neuropathic pain. So patients in like spinal cord injury or traumatic brain injury, it can be helpful for those patients, but there are all sorts of indications and it's been in use for 50 years. And this now shows like a novel mechanism that can show how spinal cord stimulators can continue to be more effective for patients with these chronic intractable pains. So yeah, thank you, everybody. I can stop sharing my screen now and see with Dr. John Kim, if he has any remarks and open it up for any questions. How about we go with anybody have any questions first? So who's actually seen a spinal cord stimulator be used yet? One and a half, maybe. So just real quick, the current technology has been on the market. I think it hit 50 years, about two years ago that it first got developed. So it's been around a relatively long time. The current stimulator, basically regardless of what anything goes on, there's a fixed output, which means there's, we program it and regardless of what the patient says, does or experiences, it basically gives you that energy. And the first landmark study probably went back to about 2005, which was the first perspective, randomized two-year follow-up data showing that there was efficacies for decades in medicine. We just do stuff because that's what we do. That's why it's a medical practice. And then they actually start studying its efficacy. So they actually, for the first time published, I think it was published in neurosurgery, which was interesting because it was a pain and neurosurgery's mixed investigative involvement. All pain studies, almost all the pain studies are usually industry funded, which I think Alexander mentioned, which is not abnormal because no one's going to spend 20 to $30 million studying something because they just have cash to waste. And last time you check, clinicians tend not to be that generous with their cash. So somebody has to sponsor. And the NIH tends to support bench work, not necessarily like clinical studies to this degree. So it is biased, but somebody has to do it. And then hopefully they do it in a manner that's appropriate. So in 2005, they first probably said it works. And it was landmark because they said, basically got 50% of people to get 50% relief at two years out. And that was actually better than anything else on the market, including surgery, conservative management, whatever you can think of. But if you really think about 50%, it's not that great. But in the research world, if you can get 30% relief, they consider that significant. In reality, anything over 50% is considered good by insurance and everything else. And it took another decade, bunch of other studies came out. Another landmark study came out in 2016, where they actually looked at non-paresthesia based, which means patients don't feel anything, it's a lot. It's kind of like animals hear sounds at a pitch that we can't hear, doesn't mean the sound doesn't exist, but we don't hear it. But in this case, instead of patients feeling something, it just blocks the pain. And that study was a big deal because it showed about 70% of patients at two years out, two years out got 50%. Still significant improvement from 50, 50 to 70% got 50%. And then if you look at this study, it's basically, it's only one year out. The two year data, I think there's follow-up to it. And there's a pre-study done in Australia only basically shows same results at 80% get about 50% relief. So we've gone from 50% to 70, now it's at 80%, which is the big deal. In the US, the common indication is failed back syndrome. Basically somebody who's had back surgery and they still have pain. Complex regional pain syndrome is another one it's been shown for, and there's other studies showing it that's level one evidence. And a lot of these conditions basically refactor to common treatment. That's why the companies are willing to sponsor these studies. And as of two months ago, they actually got FDA indication approval for treatment of diabetic peripheral neuropathy, at least one type of stimulator. They showed two year data from international studies showing that compared to conventional treatment, it's way better, much more significant to the point that FDA approved it, which means Medicare will pay for it. One thing that was mentioned from Alexander, he mentioned any kind of neuropathic pain. It tends not to do very good in terms of central neuropathic pain. So brain injury, spinal cord injury, evidence is really poor, or the results clinically haven't been that supportive yet. People do study it for various, there's case reports, but in terms of the masses, one that population is small, it's also difficult to treat, but it actually hasn't been that consistent. So keep that in mind. It's very good for certain type of neuropathic pain or nerve related pain, but anytime it becomes centralized, or it's a central cause, it's a crapshoot at best. The only background that you guys should know about the closed loop, it's novel in that it's used in different indications here, but the person who developed this actually initially studied it in cochlear implants, and basically it revolutionized how hearing aids work. Because beforehand, basically you could hear stuff, but when people start talking to them, people hearing it would either have to turn up the device or turn it down because it was so loud, or they couldn't hear it. So they're constantly adjusting it. Like it's not like me and you, where we can kind of modulate what we hear within reason, where they were just getting either way too much or way too little. And this closed loop system basically changed them from having to turn it on, turn it off, modulate. They basically turn it on and they could basically control the sound that if it wasn't real close, they would increase what they felt. So it's basically a groundbreaker in one subset of the medical world where everyone has a closed loop system. That whole idea kind of triggers something like the diabetes treatment. And then the same two researchers that basically developed this basically said, hey, you know what? I think we can do it for pain world. And that's kind of the background behind how this company got started and why the study was done. The study hasn't published full data yet. It has been presented to the FDA, but it's actually not on the market yet, which is the interesting thing in the US at least that only time, the only people that can use it are the investigators that will participate in the study itself right now. So there's some little background, hope it's useful. Thank you, Dr. Kim. All right. And I agree. Thank you, Dr. Kim. Go ahead, Kaitlin. I was just gonna say, I'm definitely gonna have some questions for Dr. Kim regarding simulators after my presentation. Perfect. And I was gonna say, just so we can keep on track and we can circle back to previous topics if there's still time, but I wanna keep moving and kind of move in and get on to Kaitlin's presentation. So let me give Kaitlin her intro here. So we have Kaitlin Ko, fourth year med student in class of 2022 candidate, sorry, at the Stritch School of Medicine. She'll be presenting on botulinum toxin infiltrations versus local anesthetic infiltrations in pelvic floor myofascial pain, a multicenter randomized double blind study. Take it away, Kaitlin. All right. Thank you, Nathan, for the introduction. And hopefully everyone can see my screen all right. It's, yeah, they say infiltration and multicenter with the R and the E switch because this is actually a European study. So just a little disclaimer in the front, but this is coming from the Analysts of Physical Medicine Rehabilitation and we can go ahead and get started. So just a little bit of a presentation outline in terms of what I'm going to be discussing. We'll go over a little bit of a clinical context for the journal article we'll talk about. And then we'll go over some current treatments present in chronic pelvic pain patients. And then a literature review going over the article as mentioned and application to our patient. So to start off with the clinical context, we have Ms. JZ, a 38 year old Hispanic G3P2 female here at clinic for follow-up after completing eight weeks of pelvic floor physical therapy for chronic pelvic pain in the setting of a non-pathologic MRI. The patient reports the pelvic floor physical therapy moderately decreased her symptoms, but she continues to experience pain. And physical exam shows tenderness upon superficial palpation of the external right pelvic floor and then internal deep palpation of the right levator ani and obturator internus. Her medical history is significant for hypertension, migraines, TMJ, endometriosis, and then placenta accreta, status post dilation cottage. So let's go a little bit over some sources of pelvic pain. There's a lot of different reasons why pelvic pain can be a hard thing to treat. There's some visceral sources, such as the organs in the area, like the bladder, prostate, uterus, in addition to the neuropathic components of the lumbar nerve roots, the splenic nerves, both parasympathetic and sympathetic. And there's also the pelvic floor itself, which is kind of what we're gonna be focusing on in addition to other aspects of the pelvic or the pelvis, like the bones and the joints, pubic symphysis, SI joint, for example. So, oh wait, I realized it's not in presentation mode. My transitions are not going through now. So what are some common symptoms in chronic pelvic pain? I'm hoping to draw some participation from the audience for some examples. I may have given a spoiler already, but if anyone has something to contribute. I think like sacroiliac pain especially is a common one. Thank you. No worries, we can move on. And so in addition to some of the joint pain, other symptoms you can ask about when you're seeing a patient with chronic pelvic pain includes some GU issues of incontinence or retention, pain with sex or sexual dysfunction in general. Patients tend to have some gait imbalance and they can have back pain, which can present as pelvic pain, but it's coming from their back if it's the lumbar nerves. And definitely this list is not comprehensive enough. There's a lot of different aspects to what can go into it, but these are just some common symptoms we tend to see with patients. So now Ms. JZ is asking us, what are my treatment options? She's done physical therapy. It did help a little bit. She has had conservative medication management. What can we move forward with? So current treatments for chronic pelvic pain kind of are multifaceted. And of course, as physiatrists, we're going to be straying away from surgery. And so we're going to be trying to do what we can to use multiple modalities to address the patient's pain. This can include cognitive behavioral therapy, focusing on bladder training the patient or helping them with distraction techniques when they're having exacerbation, in addition to relaxation techniques. In terms of pelvic floor physical therapy, it kind of adds on to that in terms of helping the patient stretch out any muscles that are really tight to aid or facilitate relaxation, or even strengthening muscles that are unbalanced and they're weakened in the pelvic floor. Myofascial treatments will be something we're kind of discussing as well. These can include steroid injections or lidocaine injections or just other analgesics in addition to Botox injections. It also can be adjuvant therapies such as acupuncture. For some of these patients, they really are looking for a lot of different ways they can address their pain. And of course, there's medications. We have some of the central and peripheral neuromodulators, as we discussed. There could also be like gabapentin or analgesics and some patients will even use tricyclics to address the neuropathic pain. And there's a lot of different ways we can go about it. Surgical treatments actually would also include, there are some studies that are starting to look at RFA, which is radiofrequency ablation of the nerves in the area, and also peripheral stimulators, kind of what ties in with what Alexander was talking about, has been sort of in the whispers of the research world, but no official studies endorsing that yet. So what's in the literature? This is kind of when we dive into the journal article. So the study is looking to compare the efficacy of Botox combined with ropivakine, which is an analgesic injections versus ropivakine alone at two months follow-up for patients with chronic pelvic myofascial pain. So this is where they're actually treating the patient's pain by using injection of the medication to the muscles to try and facilitate the relaxation, but also give some pain relief in that sense. So this was a double-blinded multi-center study that was randomized and controlled from 2013 to 2016 in six health centers in France. So inclusion criteria includes chronic pelvic pain inherent greater than six months, at least one trigger point on pelvic exam, a specialist consultation, which is limited or not limited to a proctologist or a gynecologist, a urologist or a gynecologist, and then some imaging that just shows there's no organic pathology, such as a tumor growing in the area, anything compressing from the disc, from the lumbar plexus into the pain, and then some other things that they wanted were the patients to have a five-day pain diary prior to inclusion of the study. So their max score was between four and nine out of 10. Exclusion criteria would, of course, include the things I listed of other organic pathologies for pain, the history of Botox in the last three months, intolerance to any of the medications used, NO being nitrous oxide during the procedure, and pregnancy. That would be a good reason to exclude them. So here's a table of the demographics for these patients. And some of the things when I was initially looking at this paper was I noticed that the age tends to difference for average between the two treatment groups, in addition to a couple of other factors and females being more predominant in this group, medication quantification scale score, which kind of takes into point of what else do they need to take in addition to this intervention for pain management and social functioning. As you can see, I don't know if you can see my cursor, but if you looked at the P values, none of them are statistically significant. So they're not huge differences technically, but it's something I just noticed on my own. And so looking at the randomization and outcomes measured, it did an electronic randomization to ensure that the procedure remained double-blinded. And so patients were put in either the control group, which had Repivacaine only or the intervention group, which included Botox in addition to the Repivacaine. They likely use the Repivacaine for analgesic because it's a long acting one versus Bupivacaine, which is sometimes used, which is more short acting. Repivacaine though is a little less lipophilic. And so, you know, you could argue that it may not like penetrate large myelinated fibers just as well. But anyway, so only the pharmacy dispenser giving out the medications in pre-filled syringes knew which patient was in which group. So the doctor and the patient was blinded. There was a standardized injection procedure where the patient was in dorsal decubitus. They were given the injection transperineally. And then they were also, you know, given the option if they wanted nitrous oxide per patient request. And then the injection procedure confirmed along with ultrasound guidance and sometimes EMG or Neurostim to make sure they're in the right spots. So the outcomes, the primary outcome would be this PGII, the patient global impression of improvement score. And they measured that at day 60 follow-up. And then secondary outcomes would have been the percentage of improvement or worsening of their symptoms based on the patient report of their diary score and then follow-up patient scores. Medication quantification scale as needed or as explained earlier is the additional drugs given. And then the quality of life improvement, adverse effects and trigger points present at each visit. The scale is one to four, only so that it would only include levator ani and obturator internus and bilaterally would give you a max of four trigger points. So what are the results? So the study kind of looked at using chi-squared tests for assessing primary outcome in addition to the categorical secondary outcomes. And then quantitative outcomes were assessed using student T-test and Wilcoxon, ring-thumb and a linear regression. Obviously the P had to be less than 0.05 for statistical significance. And they had groups of 40 in each so that the effect size was 80% with, or the power was 80% with attrition rate of I believe 10%. So the results of this study showed that there was actually no difference between the two groups, between the primary and the secondary outcomes. So they saw that the Botox and the Rupivacaine led to a decrease in pain on the day of injection and at 60-day follow-up. And there was no statistical difference between the two groups. So as a result, they concluded that Botox is not really a justifiable first-line treatments for patients, especially considering the cost of Botox compared to Rupivacaine. I think it's a great win for everyone here. And so some of the other things to note were that some of the secondary outcomes, there were no differences detected either, including quality of life, amount, or number of adverse effects, and in addition to percentage of improvement symptoms. The one thing I think they did kind of point out was that the number of trigger points tended to be decreased in the Botox group at long-term follow-up, but it wasn't statistically significant. So in the discussion section of our paper, they kind of really talked about why did they believe that Botox and the analgesic kind of had the same effects? And they came to the same theory that it's because myofascial pain is more of a reaction to chronic pain than the cause of chronic pain. And so that's something they talk a lot about in terms of why patients were still experiencing relief from both. And at the top on figure two, on the top left, you can see how the PGI-I kind of tended to get distributed at 60 days with the x-axis showing one and two being very much improved and much improved in the categorical scale. On the bottom figure, you can see how the numerical pain rating score of zero to 10 changed over time, and you can see a significant decrease between follow-ups and also that there wasn't this huge statistical difference between the two groups at day 60. As you can see, the standard deviations tend to overlap. Okay, one other thing, sorry, really quick. They did note that after 60 days, the pain did continue to decrease in intensity for the patients, but it stabilized around 90 days. So it was kind of giving us a good measure of how long are these treatments really lasting for our patients. So what are the study limitations? One of the things that I kind of talked about earlier was my concern of patient heterogeneity. Ideally, the population would be a more homogeneous sample in terms of like age, what are their impairments in function at this point when they're receiving treatment, but I also recognize that it can be difficult to find and control numerous confounding factors when concerning patients. So one of my thoughts would have just been to increase the sample size and make sure that it was enough to control confounding factors, but also find it an adequate sample of the population. And then one of the other things I also was really interested in was how did they pick these measurements for their outcomes? And so after doing a little more digging, I found that the PGII, which is the measurement for their primary outcome, wasn't actually validated for chronic pelvic pain. It has been shown to be validated for urinary incontinence in both males and females, and also pelvic organ prolapse, but I wouldn't have necessarily thought it would completely translate over to the study since many of the patients didn't have urinary incontinence as their primary source of pain, and you can't widely apply such a scale and hope for the similar outcomes. One of the studies also showed that they were looking for a correlation between that measurement and the quality of life survey, and the two measurements actually differ greatly when you've put them together. So that was one of the things I looked at, and then I think I kind of alluded to the rapivacaine use as well in terms of it being not as lipophilic. But yes, those are some of my assessments. And so how do we apply this to our patient, Ms. Jay-Z? After her exhaustive treatment with medication and physical therapy, in addition to the hopefully cognitive behavioral therapy teaching that we can give with her, it would be reasonable to move forward with trigger point injections, but local anesthetic should be the first line, and Botox may be considered in the future, given patient preference, and these anesthetic injections can be repeated. You know, I would think, I think insurance covers about six times a year, but patients tend to see decline after three months out. So, all right, thank you everyone, and I'm open up for questions. Thank you, Caitlin. I had a quick one. Was it sterilized? Because I know you can look at trigger points in terms of muscle and anatomy, right? But then with myofascial, it kind of throws in another wrinkle in things where they might not be in generic location in terms of trigger points. So did they talk about that in terms of how they were looking, or like a sterilized exam, or? Yeah, so I think they were going by, when you're doing the pelvic exam for pelvic pain, there is a standardized like order in a clockwise fashion that you do go in. And similar to how you would do externally, you'd do like superficial to deep palpation. And so you can assess the different, there's technically three, but sometimes people just say two layers of the pelvic floor muscles. And so that's a way they were able to isolate it. But I do agree with you that trigger points can be tough in that they can be, they're definitely up to patient subjectiveness, how they defined it in the paper was more just the areas of increased analgesic, or not analgesic, hypersensitivity, I suppose. I'm looking for a different word in terms of like increased pain, but. Yeah, that's how they were kind of defining it. It was definitely more patient subjective in that way. Gotcha, thank you. Nice presentation, Caitlin. I was wondering, we, my understanding is that with botulinum toxin, patients can develop tolerance with repeat injections for its general use. Is there a reason to believe that with the local anesthetic, it would actually maintain its efficacy based trigger point injections on repeat use? Yeah, so I think with the botulinum toxin, it was, because you're definitely right, they can build increased tolerance. There's several theories out there about that, I think about whether it's increased tolerance, or if the body tends to build up, correct me if I'm wrong, Dr. Kim, about this, like immunity almost in a way to the different proteins included around the Botox. So they made a point to specify that the Botox they use in this didn't have accessory proteins because there's three different types of Botox on the market, I think, and only one doesn't have that. And so my belief is they were trying to control for it by using that specific type of Botox. I don't know if that answers your question. That's pretty correct, yeah. So there's theories on like, you know, when Botox came out and then there's Dysport, there's other companies that's saying it's Botox AB and why it's better, but it is a potential risk for majority of them that the more you use it, it may not work as well. But in terms of the bigger picture, the study really looked at, it's conditions really tough. If you see these patients, I mean, they struggle and there's usually multifactorial causes for why they have it. But a couple of things you should keep in mind is in the U.S. Botox is approved for migraines, overactive bladder, spasticity like torticollis and basically excessive sweating. It's not approved for trigger point. And the reason is if you look at the Cochrane reviews and they quit doing reviews on Botox for trigger point because there's no evidence supporting for it. The last one was in, I think 2014, before that they do it 2012 and basically between 2012, 2014, they were like, no one's doing any studies. We're gonna quit doing it until a new study comes of any value. And if you actually just look at the treatment of trigger points itself, just sticking a needle into the muscle is what seems to work. The only one that makes a difference is putting a little lidocaine because that may decrease the procedural pain initially. So what local anesthetic you use or what you inject doesn't seem to matter. If you look at the background data that already exists, you shouldn't be surprised that this study basically said that there was no real difference. The study also looked at two months out, right? How long does Botox typically last? Six months. Right? That's the max, but I average you're talking three to four months. What's the average duration of a Pivocaine? I think it's like three weeks. No, it's like three to four hours is the duration of a Pivocaine. So when they use Ropivacaine, it's because it has less of a motor block than Bupivacaine, but it's basically the same thing. It's basically a trendy medication a lot of people use because it's more expensive. So Lidocaine's the shortest acting, but it's the most dense. Bupivacaine's the longer acting, but you can get a motor block, which in this case doesn't really matter. Ropivacaine is a, like a S anomer of Bupivacaine. And it's, if you're doing a Epidural or a Intrafecal block, especially the Epidural block, it has a less motor block, which is very useful. So basically you decrease sensation without them having to not be able to move. But otherwise people use it for joints. There's a big market for it because it's more expensive and it was basically a brand name, but it's basically shown not to be anything that's significantly different in all the studies. And then if you look at the studies for just doing anything, 60 days is such a short thing because most interventions, the placebo rates are almost 30% that you'll get some relief short term. So at this point, you can't tell it's doing nothing versus sticking saline versus local anesthetic versus Botox makes a difference. But if you go back to the initial stuff, we know trigger points, doesn't matter what you do. If it's a muscle band, you put something in it, it helps. So they did that, both of them. They've shown Botox doesn't really help trigger points any more than anything else. This study doesn't really show anything. And that might be why the FDA still hasn't approved some of these medications for the treatment of these conditions. So keep that in mind. Some of these studies are really interesting, but it's not a surprise results to a lot of people when you actually look at the background info. Why they did that, it's actually still useful because they're hoping to find something that works, but it wouldn't really been a surprise if it actually was because other studies that have used it in similar conditions haven't shown it either. Yeah, I definitely agree. I've seen a couple of patients who have gone through multiple rounds of the anesthetic and then they want the Botox like desperately because it's not working, but it really just comes down to what you're explaining that the dry needling itself of it would be more or less beneficial than even injecting lidocaine into these areas for pelvic pain. And so, yeah, if anyone has any more on that, that'd be good because I think one of the things I talked about too is I had heard, I don't know if there's even trials out there for it, but people considering peripheral stimulators for pelvic pain, I don't even know necessarily how it works just because it's such a mobile joint or it has many mobile joints. And so, I can't really visualize how they would fixate the stimulators. And so, I didn't know if you had any thoughts or had heard anything about it. So, they've done dorsal root column stimulation or they basically target the S1 roots, sacral roots, except they put in the sacral frame. And so, if you actually look at the anatomy of where the dorsal root sits in the sacral, it actually sits in the epidural space. It doesn't sit in the neuroframing. So, they're actually basically doing a nerve root stim. But again, it's a case reports at best. Peripheral nerve, they've tried to stim the pedundal various plexus, but it's not the technical difficulty. It's the fact that most people can't reproduce it consistently. So, for pelvic pain, especially if it's muscular in nature, you wouldn't expect neuromodulation to help it because it tends to help neuropathic pain. So, if they have a big neuropathic component, it may be beneficial, but a lot of these areas, it's poor results at best, or it's case studies, or poor quality studies, if you can call it studies. So, is it worth pursuing down the road? I think it is. People have RFA'd all these kinds of nerves. They do cryo. They've done all kinds of ablations to target some of these nerves. There are more sensory. But again, it's a complex condition that nothing's really been consistent. That's why if you look at the treatment algorithm you went over, it's multimodal. You go through all these treatments that are non-invasive. There's a lot of psych involved with it. But in terms of a consensus guideline that's evidence supported, it's weak. Thank you. Yeah, that's definitely a really good wrap up for it. Thank you, Dr. Kim and Kaitlin. Just because we got one more great speaker coming up next. I'm gonna introduce her and get her rocking, but love the discussion. We can always circle back to these same topics at the end if we got time. So, next up we have Colette Viasecki-Masters. She's a third year medical student and class of 2023 candidate at a SUNY Upstate School of Medicine. She'll be presenting on a randomized trial of epidural glucocorticoid injections for spinal stenosis. Take it away, Colette. Thank you for the intro. Let me just share my screen. Okay, you can see and you can hear me? Yep, yep. Okay, great. So yes, I'm from the University of Michigan, so yes, I'm presenting on a different type of injection, randomized trial of epidural glucocorticoid injections for spinal stenosis. So just up for a background, lumbar spinal stenosis is the leading reason for spinal surgery in older adults. The stenosis is a narrowing of the spinal canal, which most commonly is from degenerative arthritis in the older population and can result in nerve compression and significant pain. Symptoms include back and leg pain, lower extremity paresthesias and weakness. At the time of this study in 2014, epidural glucocorticoid injections were widely used to treat symptoms of lumbar spinal stenosis. And in fact, in the Medicare population, it's estimated that more than 2.2 million lumbar epidural glucocorticoid injections are performed per year. I have a question for you all, and you can either unmute or type it in the chat. How are epidural glucocorticoid injections thought to reduce symptoms in lumbar stenosis? I actually can't see the chat, but I don't think we have anything. Oh, there we go. So Wally says, dampen inflammatory cytokines. Yeah, yeah. So it's definitely thought to reduce the nerve root inflammation, absolutely, and possibly the ischemia that's caused by mechanical compression, though the analgesic mechanism of action of steroids has not clearly been explained or accepted. So great, great job. Thank you. Uncontrolled studies suggest that these injections provide short-term pain relief for these patients, for some patients, but data from randomized controlled trials is really lacking regarding the effectiveness and safety of these injections. So the purpose of this study was to compare the effectiveness of epidural injections of glucocorticoids plus anesthetic with injections of anesthetic alone, which would just be lidocaine alone. This study is a double-blind randomized controlled trial conducted at 16 sites in the United States. Its inclusion criteria are patients with evidence of central lumbar spinal stenosis on MRI or CT and moderate to severe leg pain and disability as measured by the pain intensity scale and a pain-related functional disability scale, which I will talk about further. So these patients are greater than 50 years old. They have the average pain rating of more than four on a scale of one to 10, and the score of greater than six on the Roland Morris disability questionnaire. And for now, I'll explain it more later, but just remember that the higher the score, the greater the pain-related functional disability these patients have. Exclusion criteria include having a prior back surgery or receiving epidural glucocorticoids in the past six months. So of the 400 patients enrolled in this study, they received epidural injections of glucocorticoids plus lidocaine or lidocaine alone. My last question, sorry, what are two methods used in this study to inject within the epidural space and it's transforaminal and interlaminar. These study physicians were trained to administer the injections in a standardized manner with fluoroscopic guidance. So just a quick anatomy throwback, which is interlaminar and which is transforaminal. I believe the transforaminal is the top image. Yep, exactly. So patients received one or two injections at their initial evaluation and an option of one three weeks later. And the primary outcome evaluation was performed at six weeks after randomization and the first injection. One of the primary outcomes is the Roland Morris disability questionnaire or the RMDQ. And this evaluates the extent of patient's pain, the limitations that the pain causes on the day that they take that evaluation. So an example question is, I have trouble putting on my socks because of the pain in my back or because of the pain in my back, buttocks or hip, I'm more irritable and bad tempered with people. So the higher the scores, the greater the pain related disability is. So another primary outcome is the intensity of pain on average in the previous week that these patients experienced on a scale of one to 10. And I was a little confused about this in the beginning. So when I say one or two injections at the initial evaluation, they were all administered one injection and that at a three week follow-up period to evaluate them, they were offered another injection, which we can talk about further at a later slide. So just a quick outline for my results section. First, I'll discuss the primary outcomes, which include the RMDQ scale and the intensity of pain. I'll also discuss the secondary outcomes, which include patients with clinically meaningful improvement, which is a greater than 30% or greater than 50% change from baseline to the six weeks primary outcome evaluation. And also multiple other scores from questionnaires and the 30% being considered minimal clinical improvement and the 50% being considered substantial clinical improvement. There's also going to be a subgroup analysis that the authors did about transforaminal versus interlaminar method. So at six weeks, both treatment groups had improvement in the disability questionnaire score as compared with the baseline score. So in this table two, you can see that at the top of the RMDQ score, and you can see that P value of less than 0.05 is considered to indicate significance. We have at the three week mark, there's a small between group difference in the RMDQ score and intensity of leg pain where I have highlighted, but at six weeks, the significance was lost. Additionally, the two groups were similar with respect to baseline characteristics, except for the duration of pain, which was slightly longer in the glucocorticoid and lidocaine group. And adjustment for this imbalance resulted in a statistically significant, but small improvement in the RMDQ score at six weeks in the glucocorticoid and lidocaine group, but there was still no significance between group difference in the intensity of leg pain. There was also no significant difference according to type of injection in the primary outcomes. For secondary outcomes at six weeks, there's no significant differences between treatment groups with respect to the brief pain inventory interference score, which is just a way to measure pain interference in their lives. The symptoms and physical function questionnaire, the quality of life questionnaire, or generalized anxiety scores. And you can see at the bottom, I just pasted them there for your reference, but you can tell that there's no deviation in the lines between them. So there's no significance in these questionnaires specifically. But on the patient health questionnaire, interestingly, the glucocorticoid and lidocaine group had more improvement with respect to symptoms of depression. And satisfaction scale measured on a stenosis questionnaire showed that 67% in the glucocorticoid and lidocaine group reported being very, or somewhat satisfied with their treatment as compared to 54 of those in the group with lidocaine, just lidocaine. So it's not a significant difference, but it's there. And this was all at six weeks. The subgroup analysis for patients that received the interlaminar injection, those assigned to the glucocorticoid and lidocaine group reported better physical function on the RMDQ scale and less leg pain at three weeks. And here you can see those significant values. However, there's no significant differences between treatment groups at any outcome at six weeks. And then for the patients who received transforaminal injections, there was no significant differences between groups in any outcome at three or six weeks. Adverse events like fever, infection, excessive pain, and other symptoms were reported for both groups. Because obviously this is important to see how your patients are doing with both treatments. And the proportion of patients reporting one or more adverse events was 21%, as you can see here in the glucocorticoid and lidocaine group, and 15.5% in the lidocaine alone group. And there was also more adverse events on average per person in the glucocorticoid and lidocaine group. And there was a, at both, sorry, there's a significantly higher proportion of patients in the glucocorticoid and lidocaine group with cortisol suppression. And at both three and six weeks, significantly higher proportion of patients in the glucocorticoid lidocaine group had morning serum cortisol levels that were less than three micrograms. And this makes sense, right? It's consistent with systemic absorption of the steroid. And exogenous administration of glucocorticoids have systemic effects, as we all know, which includes suppression of the HPA access and reduced bone mineral density with increased risk of fracture. In summary, there are no significant differences between treatment groups in pain-related functional disability or pain intensity at six weeks. The greater reported treatment satisfaction in reductions in depressive symptoms in the glucocorticoid and lidocaine group was really interesting. And the study didn't really explore that as much as to why there would be less depressive symptoms in the glucocorticoid group. The transforaminal injections showed no significant benefit over interlaminar. And as expected, there's more adverse events reported in the glucocorticoid and lidocaine group. What I found to be very interesting is that both treatment groups had decreased pain and improved function when compared to their baseline. Potential explanations for this could be the placebo effects, which we talked about in the last presentation, and regression to the mean. But there are also other factors, which I'll talk about in the next slide, that are present in the study that are not counted for. This paper concludes that for the treatment of lumbar spinal stenosis, epidural injection of glucocorticoids plus lidocaine offer minimal to no short-term benefit as compared with epidural injection of lidocaine alone. So there's significant limitations to the study that are valuable to discuss. There's an inconsistent methodology between and within treatment groups. As one example, one or two injections are administered prior to the primary outcome evaluation, which is the one at six weeks. And there's also bilateral and multilevel transforaminal injections allowed. There's also, similar to the last presentation, there's heterogeneity in the symptoms and the constellation of symptoms that patients experience, meaning that the patients describe many different symptoms, and it's hard to assess which symptoms directly are caused by lumbar spinal stenosis. And that's not just a flaw in this study, but in patient reporting, which happens quite frequently in many studies, it's very hard to tease out which symptoms are caused by the disease that you're studying. There's also no untreated or what they call a sham group. So you can't compare the effect of lidocaine versus no treatment at all. And as we discussed previously, lidocaine does have its short-term effects. There's other systemic reviews and meta-analysis that showed that lidocaine alone may have an effect in epidural injections for stenosis. So this study, we can't really draw conclusions from that because there's no untreated group. And this brings me to my last limitation that I'll note, and that's that the outcomes were measured at the six-week mark, but I would like to know how long these improvements from baseline lasted for both treatment groups. For clinical implications, a top chief complaint in the primary care setting in the world of physiatry is low back pain and the associated symptoms such as like radicular pain, numbness, tingling, weakness. And many of these patients are also diagnosed with lumbar spinal stenosis. According to the American Academy of Orthopedic Surgery, spinal stenosis affects 8 to 11% of the U.S. population with an estimated 2.4 million Americans affected each year. So this condition clearly imposes a large burden on the healthcare community and the patient population, significantly affecting many patients' quality of life. With the frequency of these debilitating symptoms, safe and effective treatments for this condition are in high demand. Since 2014, when this study was published, there's been multiple papers both in agreement with and contradicting the paper's findings. So I was hard to read all of them and tease out all of their arguments, but I read one that discussed just limitations to this. Like it was a paper in response to this paper discussing all of the limitations in each study section from the beginning to the discussion about how it's needed for them to tweak certain things to make this study more relevant to lumbar spinal stenosis specifically. But in consensus with this paper and my external reading, many sources no longer recommend the epidural glucocorticoid injections for this patient population, but the clinical reality is very different and epidural injections are still offered to many patients. In fact, I was in clinic today and I saw a patient who was just administered an injection for stenosis. And in speaking with the attending physician who saw them, it seems that this willingness to keep doing these injections is due to limited alternative treatments. For example, physical therapy and other medications that come with like limited efficacy and significant side effects, especially for this population, which are generally older than 50, at least in this study. So physicians want to offer something to their patients because obviously we want to make them feel better, even if there's not the best guarantee that it will. And we want to make sure that we can optimize their treatment. And if this is out here to give to patients and it has a chance of improving their quality of life, it's still offered prior to considering surgery. And surgery is a topic for another day. So with that, thank you. And do you have any questions or comments? Awesome. Thanks, Collette. And then can you un-share your screen so we can see everybody? Yes. Awesome. And any questions? All right. Dr. Kim, what are your thoughts? So this is, yeah, this was a kind of a landmark study in theory, except for people that actually do this for a living. So the background behind the spinal stenosis, it's a mechanical issue, right? There's not enough space. So when you're even sitting, the reason it's asymptomatic or less symptomatic is because you actually create space in the spinal canal. When you stand, they actually decrease the canal. Like that's basically what it's a mechanical problem, which means unless you create space, there's nothing that you're going to be able to, to improve it. So that's the ideology behind why some of these treatments don't work is, you know, if you're out of shape, you can get in shape with therapy. If it's a strength and flexibility, you can improve physical therapy, but physical therapy cannot mechanically improve your canal diameters. Nobody's shown that. Medications can't improve your canal diameters, neither can injections, right? The only patient population that tends to benefit from injections are those that have enough narrowing that are worsened by inflammation that you may be able to decrease with putting in some medication or some volume to, you know, disperse that inflammation component of it. So as a result, all these treatments that exist, unless you physically create space, doesn't work, which is why now you have the endoscopic treatments where they go and create space. You have the spacers, which decrease your ability to extend your back, make any canal diameter or physically go in and remove bone to create space. So that's, that's not a surprise. The interesting part is that there's been studies that have been published that are relatively well done showing that if you stick saline in, it works placebo rate, but if you just put in local anesthetic, it actually works significantly better than that. So the argument has been, and they've been looking at those studies for years going, hey, what's the right volume of steroids? Because clearly consistently it seems to do better than local anesthetic. So do nothing. There's no improvement put in saline. Doesn't seem to help much beyond placebo, but you put a local anesthetic, it helps. And you put in a little bit of steroid or a lot of steroid. It still works a little better. So if you go back to just the literature where we exist, you're talking 20 MLs or 20 milligrams of dex to 16 to 12, eight to four and out standard basis as you should put something in, but probably shouldn't put more than four MLs in, four milligrams in, and then you weigh the risk and pros and cons. One thing you mentioned, I think that was interesting when you said there was a decrease in depression and some of those other psych symptoms. Keep in mind, there's plenty of studies that shown if you get epidural steroids, there's a short-term effect of euphoria or even manic like in normal patients that get hyperactive. So if you have a depression condition, it may bump you out of that a little bit temporarily. So that may be what they're seeing, although it's not proven, it's theoretical. And then in terms of actual FDA approval though, and Medicare, so FDA, there's no FDA approval for epidural steroids at all. It's just being done mainstream. It's never been studied, which why the FDA approval doesn't exist. The only thing that's been approved is local anesthetic, clonidine, and there's some other medications that are used intrathecally that are approved, but the steroids have never been approved. It's just accepted because no one's going to study, do a study to say it's safe because that's what basically FDA does. But if you look at Medicare coverage, which basically dictates what physicians do, it still covers patients with neurodentic clonication, which means if you have symptoms from spinal stenosis, that when you stand and try to walk, you get leg pain, it's still covered by insurance. It's a mainstream approval, which means they clearly know that, you know what, it's probably worth trying once because it's safe enough. Some practitioners tend to basically go, you know what, here's a risk to the patients, try without much steroids and no steroids, because six weeks is probably not worth repeating, but if somebody gets four to six months, it may be worth it. And so again, it's a placebo, but it doesn't matter if it's placebo. And then, you know, ultimately there's no, there's not a whole lot of simple treatments and that usually seems to dictate why mainstream does what we do. And you'll be surprised the more literature you read, the less impressed you'll be with medicine. Thank you, Dr. Kim. Thank you. Questions from the rest of the audience before we wrap up here? All right. Well, it's a late night, so I appreciate everyone logging on to share our time with our great speakers and our clinician expert. Thanks again to Dr. Kim, Alex, Collette, and Caitlin for all the great presentations and great discussions. Next month, we have our spinal cord injury-based month of Journal Club, so feel free to tune into that. And thank you all for the great session. Have a good night. Thank you. Thanks, everyone. Thanks for having me.

Journal Club

pain management

closed-loop spinal cord stimulation

chronic back pain

leg pain

botulinum toxin infiltrations

local anesthetic infiltrations

pelvic floor myofascial pain

epidural glucocorticoid injections

spinal stenosis