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A pragmatic and organized approach is needed to recognize patients with symptomatic Alzheimer Disease in clinical practice, stage the level of impairment, confirm the clinical diagnosis, and apply this information to advance therapeutic decision making. In this episode, Aaron Berkowitz, MD, PhD, FAAN, speaks with Gregory S. Day, MD, MSc, MSCI, FAAN, author of the article “Diagnosing Alzheimer Disease,” in the Continuum December 2024 Dementia issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of clinical neurology at the University of California, San Francisco  Dr. Day is an associate professor in the Department of Neurology at Mayo Clinic Florida in Jacksonville, Florida. Additional Resources Read the article: Diagnosing Alzheimer Disease Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Guest: @GDay_Neuro Full episode transcript available here Dr Jones: This is Doctor Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Berkowitz: This is Dr Aaron Berkowitz, and today I have the pleasure of interviewing Dr Gregory Day about his article on Alzheimer disease, which appears in the December 2024 Continuum issue on dementia. Welcome to the podcast, Dr Day. Would you mind introducing yourself to our audience?  Dr Day: Thanks very much, Aaron. I'm Gregg Day. I'm a behavioral neurologist at Mayo Clinic in Jacksonville, Florida, which means that my primary clinical focus is in the assessment of patients presenting typically with memory concerns and dementia in particular. Dr Berkowitz: Fantastic. Well, as we were talking about before the interview, I've heard your voice many times over the Neurology podcast and Continuum podcast. I've always learned a lot from you in this rapidly changing field over the past couple of years, and very excited to have the opportunity to talk to you today and pick your brain a little bit on this very common issue of evaluating patients presenting with memory loss who may have concerns that they have dementia and specifically Alzheimer disease. So, in your article, you provide a comprehensive and practical approach to a patient presenting for evaluation for possible dementia and the question of whether they have Alzheimer disease. The article is really packed with clinical pearls, practical advice. I encourage all of our listeners to read it. In our interview today, I'd like to talk through a theoretical clinical encounter and evaluation so that I and our listeners can learn from your approach to a patient like this. Let's say we have a theoretical patient in their seventies who comes in for evaluation of memory loss and they and/or their family are concerned that this could be Alzheimer disease. How do you approach the history in a patient like that? Dr Day: It's a great way to approach this problem. And if you're reading the article, know that I wrote it really with this question in mind. What would I be doing, what do we typically do, when we're seeing patients coming with new complaints that concern the patient and typically also concern those that know the best? So be that a family member, close friend, adult child. And in your scenario here, this seventy year old individual, we're going to use all the information that we have on hand. First off, really key, if we can, we want to start that visit with someone else in the room. I often say when talking to individuals who come alone that there's a little bit of irony in somebody coming to a memory assessment alone to tell me all the things they forgot. Some patients get the joke, others not so much, but bringing someone with them really enhances the quality of the interview. Very important for us to get reliable information and a collateral source is going to provide that in most scenarios. The other thing that I'm going to start with, I'm going to make sure that I have appropriate time to address this question. We've all had that experience. We're wrapping up a clinical interview, maybe one that's already ran a little bit late and there's that one more thing that's mentioned on the way out the door: I'm really concerned about my memory or I'm concerned about mom 's memory. That's not the opportunity to begin a memory assessment. That's the opportunity to schedule a dedicated visit. So, assuming that we've got someone else in the room with us, we've got our patient of interest, I'm going to approach the history really at the beginning. Seems like an easy thing to say, but so often patients in the room and their caregivers, they've been waiting for this appointment for weeks or months. They want to get it out all out on the table. They're worried we're going to rush them through and not take time to piece it together. And so, they're going to tell you what's going on right now. But the secret to a memory assessment, and particularly getting and arriving at an accurate diagnosis that reflects on and thinks about cause of memory problems, is actually knowing how symptoms began. And so, the usual opening statement for me is going to be: Tell me why you're here, and tell me about the first time or the first symptoms that indicated there was an ongoing problem. And so, going back to the beginning can be very helpful. This article is focused on Alzheimer disease and our clinical approach to the diagnosis of Alzheimer disease. And so, what I'm going to expect in a patient who has a typical presentation of Alzheimer disease is that there may be some disagreement between the patient and the spouse or other partners sitting in the room with me about when symptoms began. If you've got two partners sitting in the room, maybe an adult child and a spouse, there may be disagreement between them. What that tells me is at the onset, those first symptoms, they're hard to pin down. Symptoms typically emerge gradually in patients with symptomatic Alzheimer disease. They may be missed early on, or attributed or contributed to other things going on in the patient's time of life, phase of life. It's okay to let them sort of duke it out a little bit to determine, but really what I'm figuring out here is, are we talking about something that's happened across weeks, months or more likely years? And then I'm going to want to listen to, how did symptoms evolve? What's been the change over time? With Alzheimer disease and most neurodegenerative diseases, we expect gradual onset and gradual progression, things becoming more apparent. And at some point, everyone in the room is going to agree that, well, as of this state, there clearly was a problem. And then we can get into talking about specific symptoms and really begin to pick that apart the way that we traditionally do in any standard neurological assessment. Dr Berkowitz: Fantastic. And so, what are some of the things you're listening for in that history that would clue you in to thinking this patient may indeed be someone who could have Alzheimer's disease and going to require a workup for that diagnosis? Dr Day: It's pretty common when I have new trainees that come to clinic, they just head into the exam room and they sort of try to approach it the way that we would any patient in the emergency department or any other clinical scenario. The challenge with that is that, you know, we're taught to let the patient speak and we're going to let the patient speak - open-ended questions are great - but there's only so many questions you need to sort out if someone has a memory problem. And memory is really only one part, one component, of a thorough cognitive evaluation. And so, I'm going to help by asking specific questions about memory. I'm going to make sure that there is memory challenges there. And whenever possible, I'm going to solicit some examples to back that up, add credibility and sort of structure to the deficits. I'm also going to choose examples that help me to understand how does this concern, or this complaint, how does that actually affect the patient in their day-to-day life? Is it simply something that they're aware of but yet hasn't manifested in a way that their partner knows about? Is it to a level where their partner’s actually had to take over their responsibility? It's causing some difficulties, disability even, associated with that. That's going to be important for me as I try to understand that. So, I'll ask questions when it comes to memory, not just, you know, do you forget things, but do you manage your own medications? You remember to take those in the morning? Do you need reminders from your partner? What about appointments; health appointments, social appointments? Are you managing that on your own? Sometimes we need a little bit of imagination here. Partnerships, and particularly those who have been together for a long time, it's natural that different people are going to assume different responsibilities. And so, might have to say, Imagine that you went away for the weekend. Would you worry about your partner remembering to take their medications over that time frame? That can help to really solidify how much of an impact are these challenges having on a day-to-day basis. I may ask questions about events, something that they maybe did a couple of weeks ago. Is the patient likely to remember that event? Are they going to forget details? Maybe the most important of all, with each of these, when there's a yes or an affirmation of a problem, we want to be clear that this represents a change from before. We all have forgetfulness. Happens on a day-to-day basis, and we all pay attention to different details, but what we're concerned about and typically the reasons patients want to come and see us as neurologists is because they've noticed a change. And so, I'm going to focus in on the things that represent a change from before. After I've discussed memory, I think it's really important to talk about the other domains. So, how is judgment affected? Decision-making?  In a practical way, we often see that borne out in financial management, paying the bills. Not just paying them on time and consistently, but making wise choices when it comes to decisions that need to be made. You're out at a restaurant. Can you pay the bill? Can you calculate a tip? Can you do that as quickly and as efficiently as before? Are we starting to see a breakdown in decision-making abilities there? We can sometimes lump in changes in behavior along with judgment as well. The patient that you know, maybe isn't making wise choices, they've picked up the phone and given their social security number out to someone that was calling, seeming to be well-meaning. Or maybe they've made donations to a few more institutions than they would have otherwise? Again, out of- out of order. Again, something that could be atypical for any individual. Looking for behavioral changes along with that as well. And then I'm going to talk about orientation. What's their ability to recognize days of the week, date of the month? Do they get lost? Is there concerns about wayfinding? Thinking about that, which is really a complex integration of some memory, visuospatial processing, judgment, problem solving, as we look to navigate our complex world and find our way from point A to B. And then I like to know, you know, what are they doing outside of the home? What are they doing in the community? How are they maintaining their engagement? Do they go to the store? Do they drive? An important topic that we may need to think about later on in this patient 's assessment. And inside the home? What responsibilities do they maintain there? Are the changes in decision making, memory problems, are they manifesting in any lost abilities inside the home? Cooking being a potentially high-risk activity, but also using typical appliances and interacting with technology, in a way that we are all increasingly, increasingly doing and increasingly reliant on. And last but not least, you know, maybe the one that everyone wants to think about, well, I can still manage all of my own personal care. Well, good news that many of our patients who have early symptoms can manage their own personal care. Their activities of daily living are not the big problem. But we do want to ask about that specifically. And it's not just about getting in the shower, getting clean, getting out, getting your teeth brushed. Do you need reminders to do that? Do you hop in the shower twice because you forgot that you'd already been in there once during the day? And so, asking some more of those probing questions there can give us a little bit more depth to the interview and really does sort of round out the overall comprehensive history taking in a patient with a memory or cognitive concern. Dr Berkowitz: Fantastic. That was a comprehensive master class on how to both sort of ask the general questions, have you noticed problems in fill in the blank memory, judgment, behavior, orientation, navigation and to sort of drill down on what might be specific examples if they're not offered by the patient or partner to try to say, well, in this domain, tell me how this is going or have you noticed any changes because the everyone's starting from a different level cognitively based on many factors. Right? So, to get a sense of really what the change is in any of these functions and how those have impacted the patient's daily life. So, let's say based on the history, the comprehensive history you've just discussed with us, you do find a number of concerning features in the history that do raise concern for dementia, specifically Alzheimer's disease. How do you approach the examination? We have the MoCA, the mini-mental. We have all of these tools that we use. How do you decide the best way to evaluate based on your history to try to get some objective measure to go along with the more subjective aspects of the history that you've ascertained? Dr Day: And you're honing in on a really good point here, that the history is one part of the interview or the assessment. We really want to build a story and potentially and hopefully a consistent story. If there are memory complaints, cognitive complaints from history, from reliable- that are supported by reliable collateral sources, we're going to expect to see deficits on tests that measure those same things. And so, I think that question about what neuropsychological measures or particular bedside tests can we integrate in our assessment is a good one. But I'll say that it's not the end-all-be-all. And so, if you've got a spouse, someone that lives with an individual for twenty or thirty years, and they're telling you that they notice a change in daily activity and it's impairing their day to day function, or where there's been some change or some concern at work, that's going to worry me more than a low score on a cognitive test with a spouse saying they haven't noticed any day-to-day impact. And so, we're going to take everything sort of in concert and take it all together. And it’s part of our job as clinicians to try to process that information. But often we're going to see corroborating history that comes from a bedside test. He named a few that our listeners are probably pretty familiar with. I think they're the most common ones that are used. The Mini-Mental State Exam, been in practice for a long time. All the points add up to thirty and seems to give a pretty good sample of various different cognitive functions. The Montreal Cognitive Assessment, another favorite; a little bit more challenging of a test, I think, if we're if we're looking at how people tend to perform on it. And like the MMSE, points add up to thirty and gives a pretty good sample. There are others that are out there as well, some that are available without copyright and easy for use in clinical practice. The Saint Louis Mental Status Exam comes to mind. All these tests that we're willing to consider kind of share that same attribute. They can be done relatively quickly. They should sample various different aspects of function. There should be some component for language reading, spoken, spoken word, naming items, something that's going to involve some kind of executive function or decision making, problem solving. Usually a memory task where you're going to remember a set of words and be asked to recall that again later. So, learn it, encode it, and recall it later on. And then a few other features, I mean, some of them, these tests, most of these tests use some sort of drawing tasks so that we can see visuospatial perception and orientation questions about date, time, location, sort of the standard format. Any of these tests can be used aptly in your practice. You're going to use the one that you're most comfortable with, that you can administer in a reasonable amount of time and that seems to fit with your patient population. And that's the nuance behind these tests. There are many factors that we have to take into account when we're picking one and when we're interpreting the test results. These tests all generally assume that patients have some level of traditional sociocultural education that is westernized for the most part. And so, not great tests for people that aren't well into integrated into the community, maybe newcomers to the United States, those that have English as a second, third, or fourth language, as many of our patients do. Statements like no ifs, ands, or buts may not be familiar to them and may not be as easy to repeat, recall and remember. And so, we want to weigh these considerations. We may need to make some adjustments to the score, but ideally, we're going to use these tests and they're going to show us what we expect and we're going to try to interpret that together with the history that we've already ascertained. When I obtain that history and I'm thinking about memory loss, I'm going to look at the specific domain scores. And so, if I'm using the mini mental state examination thirty point test, but three questions that relate to relate to recall. Apple, penny, table. And so, depending on how our patients do on that test, they could have an overall pretty good score. Twenty seven. Oh, that looks good. You're in the normal range according to many different status. But if I look at that and there's zero out of three on recall, they could not remember those three items, that may support the emergence of a memory problem. That may corroborate that same thing on the MoCA, which uses five-item recall, and other tests in those same parameters. I mentioned some other caveat cities testing. Are patients who are presenting with prominent language deficits important part of cognition. They can't get the words out. They can't frame their sentences. They may really struggle with these tests because a lot of them do require you to both understand verbal instructions and convey verbal instructions. People with prominent visual problems, either visual problems that come because of their neurodegenerative disease and so part of cognition, visual perceptual problems, or people who simply have low vision. Are there difficulties for that? These tests require many people to read and execute motor commands, to draw things, to follow lines and connect dots, all very difficult in that setting. And so, we have to be cautious about how we're interpreting test results in patients who may have some atypical features or may arrive with sort of preexisting conditions that limit our ability to interpret and apply the test to clinical practice.  Dr Berkowitz: Really fantastic overview of these tests, how to use them, how to interpret them. It's not all about the number. As you said, it depends if all the points are lost in one particular domain, that can be salient and then considering, as you said, the patient 's background, their level of education, where English falls in their first language, second, third or fourth, as you said, and then some of the aspects of the MoCA, right, are not always as culturally sensitive since it's a test designed in a particular context. So, let's say your history and exam are now concerning to you, that the patient does indeed have dementia. Tell us a little bit about the next steps in the laboratory neuroimaging evaluation of such a patient?  Dr Day: I've got a history of memory and thinking problems. I've got some corroborating evidence from bedside cognitive testing, a normal neurological exam. This is where we think about, well, what other tests do we need to send our patients for? Blood testing really can be pretty cursory for most patients with a typical presentation who have typical risk factors, and that can include a thyroid study and vitamin B12. So, measuring those in the blood to make sure that there's no other contributions from potential metabolic factors that can worsen, exacerbate cognitive function. And pretty easy to do for the most part, if patients have other things in their history, maybe they come from a high-risk community, maybe they engage in high risk behaviors, I may think about adding on other tests that associate with cognitive decline. We'll think about the role of syphilis, HIV, other infections. But generally, that's when it's driven by history, not a rule of thumb for me in my typical practice. But beyond the blood tests, neuroimaging, some form of structural brain imaging is important. A CT scan will get you by. So, if you have a patient that can't get in the scanner for one reason or another or won't get in the scanner, or you don't have easy access to an MRI, a CT scan can help us in ruling out the biggest things that we're looking for. That's strokes, hemorrhages, and brain masses. So other things that obviously would take us down a very different path, very different diagnosis and very different treatment approach. An MRI, though, is going to be preferred, not only because it gives us a much higher-resolution view, but also because it helps us to see sort of regional areas of atrophy. It's a sensitive scan to look for small vessel disease, tiny strokes, tiny bleeds, microhemorrhages that again might point towards meteorology for us. Of course, it's better at finding those small masses, whether they be metastasis or primary masses, that could give us something else to consider in our diagnostic evaluation. I get an odd question often from patients, well, can you see Alzheimer's disease on an MRI? And the true answer to that is no, you can't. Can we see the signs of Alzheimer’s disease? Sure, in some patients, but really what we see on an MRI is a reflection of neurodegeneration. And so, we see evidence of tissue loss and typically in areas that are most often involved early on in Alzheimer's disease. The hippocampus, the entorhinal areas around the hippocampus, we may see atrophy there. We may see biparietal atrophy, and of course, as the disease progresses, we're going to see atrophy distributed throughout other areas of the brain. But if you're looking for atrophy, you’ve got to have a pretty good idea what's normal for age and what you expect in that patient population. So, I do encourage clinicians who are assessing patients routinely, look at your own images, look at the images for patients with and without cognitive impairment. So we develop a pretty good sense for what can be normal for age, and of course work with our colleagues in radiology who do this for a living and generally do an excellent job at it as well.  Dr Berkowitz: Perfect. So, you're going to look for the so-called reversible causes of dementia with serum labs, structural imaging to either rule out or evaluate for potential structural causes that are not related to a neurodegenerative condition or patterns of regional atrophy suggestive of a neurodegenerative condition, and maybe that will point us in an initial direction. But the field is rapidly expanding with access to FDG-PET, amyloid PET, CSF biomarkers, genetic testing for APOE 4, probably soon to be serum biomarkers. So, patients may ask about this or a general neurologist referring to your clinic may ask, who should get these tests? When should we think about these tests? How do you think about when to send patients for advanced imaging, CSF biomarkers, genetic testing for APOE 4? Dr Day: It's not that patients may ask about this. Patients will ask about this. And you've probably experienced that in your own world as well. They're going to ask about any of these different biomarkers. Certainly, whatever they've recently read or has been covered on television is going to be common fodder for consideration in the clinic environment. It's important to know what tests you can get, what reliable tests that you can get, and to know the differences between some of these tests when making a recommendation or weighing the pros and cons of doing additional testing. I think common practice principles apply here. Let's order tests that are going to change our next steps in some way. And so, if we have a patient, particularly a patient like the one that we've been talking about: seventy something year old, presenting with memory complaints, they're concerned, the family is concerned. We've got that history, physical exam, and now we may need to really hone in on the etiology. Well, I say may need because for that patient it may be enough to know, yeah, I agree, there's a problem here. And I can say it's an amnestic, predominant, gradual-onset progressive cognitive decline. This is probably Alzheimer disease based on your age. And maybe that's all they want to hear. Maybe they're not ready to pursue additional testing or don't see the value or need for additional testing because it's not going to change their perspective on treatment. In that case, it's okay to apply an often underrated test, which is the test of time. Recognizing this is a patient I can follow. I can see them in six months or twelve months, depending on what your clinic schedule allows. If this is Alzheimer disease, I'm going to expect further gradual progression that may affirm the diagnosis. We can think about symptomatic therapies for a patient like that, perhaps Donepezil as an early, early medication that may help with symptoms somewhat and we can leave it at that for the time being. But there's many scenarios where that patient or the family member says, look, I really need to know. We really want this answer. And as you pointed out, there are good tests and increasingly good tests that we have access to.  Dr Berkowitz: Well, that's a very helpful overview of the landscape of more precise diagnostic testing for Alzheimer disease specifically and how you think about which tests to order and when based on your pretest probability and the patient 's candidacy for some of these new potential therapies. To close here, as you said, treatment is discussed in another podcast. There's another article in this issue. So, we won't get into that today. But let's say you have gotten to the end of the diagnostic journey here. You are now convinced the patient does have Alzheimer's disease. How do you present that diagnosis to the patient and their family? Dr Day: I think here we're going to recognize that different styles align with different patients and families, and certainly different clinicians are going to have different approaches. I do tend to take a pretty direct approach. By the time that patients are coming to see me, they've probably already seen another neurologist or at least another physician who's maybe started some of the testing, maybe even built the foundation towards this diagnosis and shared some indications. Certainly, when they look up my profile before they come to see me, they know what I specialize in and so, they may even have done their own research, which has ups and downs in terms of the questions that I'll be faced with at that point in time. The way I like to start is first acknowledging the symptoms. And the symptoms that the patients have shared with me, recognizing if those symptoms are impacting daily life, how they impacted daily life, and usually using that information to synthesize or qualify the diagnosis. Is there cognitive impairment, yes or no? And at what level is that cognitive impairment? Is this mild cognitive impairment? Is this mild dementia? Is it maybe more moderate or severe dementia? So, using those terms directly with patients and explaining the meaning of them. But I then transition in relatively quickly to the important point of not leaving it at the syndrome, but actually thinking about the cause. Because it is cause that patients come to talk about. And if they don't say that directly, they say it in their next question, which is what are we going to do about it and how are we going to treat this? And so, I will use the information I have available at that time to suggest that based on your age, based on the history, the normal physical examination, the performance and the bedside testing that we've done. And hey, that's pretty normal structural imaging or imaging that only shows a little bit of atrophy in a few areas. I think that this condition is most consistent with symptomatic Alzheimer's disease, mild cognitive impairment due to Alzheimer's disease, or mild dementia due to Alzheimer's disease. And then I'll discuss the next options in terms of testing and try to get a feel of what our patients are thinking about when it comes to treatment. Do they want to be on the cutting edge with brand-new therapies that offer potential benefits but counterbalance by pretty substantial risks that warrant individualized discussions? Are they interested in symptomatic therapies? Would that be appropriate for them? And I can usually round out the discussion with advice that works for everyone. And that's where we talk about the importance of brain health. What are the other things that I should be doing, you should be doing, and our patients and their partners should be doing as well to maintain our brain in its best possible state as we hope that we all continue to age and look towards the future where we maintain our cognition as best as possible? And that is still the goal. Even when we're talking to patients who have neurodegenerative diseases that are working against our efforts, we still want to do what we can to treat other problems, to evaluate for other problems that may be contributing to decline and may be amenable to our management as well.  Dr Berkowitz: Well, thank you so much for taking the time to speak with us today. I've learned a lot from your very nuanced and thoughtful approach to taking the history, performing the examination, making sense of cognitive tests and how they fit into the larger picture of the history and examination, and thinking about which patients might be candidates for more advanced imaging as we try to make a precise diagnosis in patients who may be candidates and interested in some of the potential novel therapies, which we both alluded to a few times, but are deferring to another podcast that we'll delve more deeply into that topic in this series. So, thank you so much again, Dr Day. Again, I've been interviewing Dr Gregory Day from the Mayo Clinic, whose article on Alzheimer's disease appears in the most recent issue of Continuum on Dementia. Be sure to check out Continuum Audio episodes from this and other issues. And thank you so much to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/AudioCME. Thank you for listening to Continuum Audio.

In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Lisa C. Silbert, MD, MCR, FAAN, who served as a guest editor of the Continuum® December 2024 Dementia issue. They provide a preview of the issue, which publishes on December 2, 2024. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Silbert is co-director at Oregon Alzheimer's Disease Research Center, a Gibbs Family Endowed professor of neurology, a professor of neurology at Oregon Health & Science University, a staff neurologist, director of Cognitive Care Clinic, and director of the Geriatric Neurology Fellowship Program at Portland Veterans Affairs Health Care System in Portland, Oregon. Additional Resources Continuum website: ContinuumJournal.com Subscribe to Continuum: shop.lww.com/Continuum More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @LyellJ Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology, clinical review and CME journal from the American Academy of Neurology.  Thank you for joining us on Continuum Audio, a companion podcast to the journal.  Continuum Audio features conversations with the guest editors and authors of Continuum who are the leading experts in their fields. Subscribers to the Continuum Journal have access to exclusive audio content not featured on the podcast. If you're not already a subscriber, we encourage you to become one. For more information, please visit the link in the show notes.  Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today I'm interviewing Dr Lisa Silbert, who recently served as Continuum's co-guest editor for our latest issue on dementia alongside Dr Lianna Apostolova. Dr Silbert is a professor in the Department of Neurology at Oregon Health and Science University of the School of Medicine in Portland, Oregon, where she's also the director of the Neuroimaging Core and now the co-director of the Alzheimer's Disease Research Center. She also serves as director of the dementia clinic at the VA Portland Healthcare System. Which, Dr Silbert, sounds like a lot of work? Anyway, welcome. I really appreciate you taking the time to join us today and co-guest editing this issue. Why don't you introduce yourself a little bit to our listeners?  Dr Silbert: Well, thank you so much for interviewing with me today and for inviting me to be the guest, co-guest editor of this issue. It's a really exciting time for dementia care and dementia research. As you already said, my name is Lisa Silbert. I'm in Oregon Health and Science University in Portland, Oregon. I've been involved in caring for dementia patients and their families for over twenty years now and been involved in a lot of really exciting research during that time. But I would say now is probably the most dynamic time in dementia research and care that I've seen. So, it's really, really exciting to be here.   Dr Jones: It really is an interesting time. So, I look back  in our last issue of Continuum focusing on dementia came out in 2022, which doesn't sound like that long ago, but a lot has changed, right? With the anti-amyloid monoclonals for Alzheimer's disease, new biomarkers and so on. And as the guest editor, you have this unique view, Dr Silbert, of the issue and the whole topic of dementia. As you were reading these really outstanding articles, what was the biggest “aha” moment for you or the biggest change in practice that you saw that's come up over the last couple of years?     Dr Silbert: I think, you know, in reading through the different manuscripts or chapters in this issue, it really struck home the advances that have been made throughout all the different areas of dementia. Not just- so, we hear a lot about Alzheimer's biomarkers and Alzheimer's treatments on the horizon, which is really exciting, but this is happening across other dementias as well. There's biomarkers on the horizon for a Lewy body disease and potentially for some of the frontaotemporal dementias. And so that to me really struck home as this is really, across the board, a change in the entire field that we're looking at.  Dr Jones: That is exciting. And I'd like to come back to some of those biomarker developments because I think that's an area where we've really been lacking in neurology as a specific way to diagnose those disorders. I think a topic which you just alluded to that a lot of our listeners and readers are thinking about are those antiamyloid monoclonal therapies for Alzheimer's disease. So, addicanumab, lecanumab and most recently the approval of donanemab. For these drugs specifically, how are you using them in your practice and how should our listeners be thinking about these drugs?  Dr Silbert: These are, you know, relatively new, really exciting new and emerging therapies for Alzheimer's disease. They are shown to remove amyloid from the brain. Patients who have clinical manifestations of Alzheimer's disease, and that is those in the stages of mild cognitive impairment or mild dementia. We are using lecanemab at Oregon Health and Science University through our therapeutics and clinical units. It's a really exciting time and it's a time where we have to be, also, cautious about who undergoes these therapies. So being really informed about the use, who's appropriate to undergo these therapies, what kind of safety tests need to be undergone, how do you assess risk in individual patients so that you can counsel them.  So, all of these factors need to be weighed in when you're making a decision about whether or not to treat a patient with a monoclonal antibody therapy. And specifically, we do neuroimaging to assess whether there are already the presence of microhemorrhages in the brain. We do genetic testing to look for APOE 4 genotypes that can increase the risk of Aria, which is amyloid-related imaging abnormalities. And all of these factors go into how we counsel patients and discuss whether or not to pursue treatment with monoclonal antibodies.    Dr Jones: So certainly a complex patient selection process and drug administration and monitoring of therapy for those patients.  And that- it brings to mind for me how we already have too few neurologists in the US. And now for a really prevalent disorder, Alzheimer's disease, we're making it a lot more complicated to deliver these new disease-modifying therapies. What do you think or what do you see as the role of the neurologists in caring for patients with dementia? And do these developments change that role?  Dr Silbert: For now, I think these developments make it even more important in a way that neurologists are involved in making a very specific clinical diagnosis of which dementia is playing a factor in the patient 's clinical presentation. I think one thing to note is with these emerging biomarkers, a lot of them can be positive before there are clinical symptoms and multiple etiologies are also very prevalent. And so just having one positive biomarker, it doesn't necessarily tell you what's going on with an individual patient. You need to take the whole picture into consideration. So, I think a really detailed evaluation by the neurologist, especially with these emerging therapies that have potential risks, is extremely important right now. Just getting a test is really not sufficient. You really have to take the entire clinical picture into account and know the ins and outs of the risks involved in these disease-modifying therapies.  Dr Jones: Which brings us back to something you mentioned earlier, right? Which is good news. We have on the horizon new potential biomarkers for other neurodegenerative causes of dementia. I can foresee and maybe I'm, you know, being an alarmist here, Dr Silbert, but if we have sensitive biomarkers for other neurodegenerative conditions, we know patients often have copathologies. Is that going to help clarify things? Is it going to confuse us? How is that going to work?  Dr Silbert: Well, I think ultimately, it's going to help clarify things. Because there are multiple pathologies that are common in age related cognitive impairment, any kind of additional specific input that we can get with different biomarkers is going to be helpful in putting the pieces together to come up with what's happening clinically with each individual patient. Ultimately, I think these biomarkers, they're not- any one biomarker isn't going to be a solution to diagnosis, but putting them together to help improve early and accurate diagnosis is really the goal here. Having a very early diagnosis, having a very accurate diagnosis will improve our ability to give prognosis and also improve effective treatment strategies moving forward. I think that these biomarkers have the promise in facilitating that for us.  Dr Jones: And progress is always a good thing. We just have to learn how to adapt and use the evidence appropriately. There have been and I think most of our listeners will be familiar with some of the controversies related to these, these new disease-modifying drugs for Alzheimer's disease. Do you want to walk us through a couple of those, and what are your thoughts about those controversies?  Dr Silbert: Yeah, these new therapies, they're very exciting for everyone in the field, but they, like you mentioned, they're not without their controversies. I think one controversy or one potential downside to these therapies is access to them. Like you already mentioned there, there's really not enough neurologists out there. There's not enough behavioral neurologists out there. There's limitations to infusion centers, sites and prescribers. Access to these therapies is is significantly limited. They are requiring infusions quite frequently. So, if you're not living near specialty care, you're not really able to feasibly undergo these kinds of treatments. Another controversy is the fact that the treatment effects are considered by some to be fairly modest when looking at the clinical data and in association with that, there are risks involved. Like I already mentioned, there's the amyloid-related imaging abnormalities, which sounds kind of like a benign thing, but they really consist of microhemorrhages that can lead to bigger hemorrhages and edema in the brain. These risks are relatively small - they are seeing more commonly in those who have a specific genotype, an APOE E 4 genotype - but they're risks nonetheless.  And so, there's controversy about the risk-benefit ratio and access to care with these new therapies.  Dr Jones: It's very exciting, but we should be cautious, right? I recall a few years ago as a program director, a neurology residency program director, interest in different areas of neurology would often follow developments in those areas, right? Lots of interest in autoimmune neurology when those developments would proceed in neuro oncology, etc. And I wonder if the therapeutic advances in in behavioral neurology and neurodegenerative cognitive disorders, I wonder if that's going to stimulate interest among our trainees to pursue behavioral neurology? Do you have a view on that or have you seen much change in interest in in this field?  Dr Silbert: You know, we are seeing a lot more interest in our trainees. The residents are very interested in these new therapies and how to apply them. And I'm really excited about that.  I'm hopeful that this will stimulate interest in the field. And we need those specialists, we need those sub specialists to undergo fellowship training in behavioral neurology and geriatric neurology so that we have more access to the subspecialty care and delivering these new therapies. So, I agree with you, I'm hopeful about it and I am seeing new interest in our trainees about these new therapies.  Dr Jones: We can hope so. And all the other fellowship directors will be anxious if neurology residents start leaving to go into behavioral neurology. But there’s certainly demand. And I know that under the best of circumstances, dementia is so common. It's something that we have to care for in partnership with primary care and community resources. And these disease-modifying therapies capture a lot of attention, but it's really a small part of the continuum of care of these patients. And Dr Silbert as an expert, you know, if we put that disease-modifying therapy to the side for a second and just said, well, what are the biggest gaps in the care for patients with dementia? What do you see as those biggest gaps and, and what can we do to fix them at not just a neurology level, but at a societal level?  Dr Silbert: That's a big question. And you know, what I see almost every day are gaps in the support mechanisms for families who are caring for patients with dementia. These caregivers are under a lot of stress and oftentimes they just don't have the resources to take care of somebody who at some point will often need twenty-four hour care and supervision. Caregivers are older, usually of older age themselves and have their medical issues as well. And then we're just not doing a good job as a nation in in supporting patients and their families with like supportive care and respite care that's really needed. So, you know, I'm not just seeing and treating patients with dementia, but I'm seeing and I'm really trying to support and care for those who are taking care of patients with dementia. To me, that's the biggest gap in our system. Dr Jones: Yeah. And as I look through this issue of Continuum, we touched on not only the conventional topics in dementia and behavioral neurology. I'm really happy in hindsight that we have invited some discussion of the psychiatric symptoms in dementia, which I think are really important and often underrecognized and maybe undermanaged or mismanaged, and really also focusing on the caregiver burden and support services. We do have an article dedicated to that as well, and I think that'll be useful to our readers and listeners when we when we publish those podcasts. We we've heard this year especially a lot of public conversation about cognitive impairment and dementia. I sometimes wonder if that public attention is helpful and constructive for the population of patients with dementia. Sometimes I wonder if that conversation is counterproductive. What's your take on that?  Dr Silbert: You know, I think it's- it can be a mixed bag, but ultimately, it's in the conversation. We're talking about it. And I think that's only a good thing. There's more public awareness of it.  There is more interest in therapies. So, I think at the end of the day, talking about it, making it more prevalent in the ether, it stimulates the conversation and discussion. And even if there's controversies about it, we're talking about it. And I think that's kind of the first step in acknowledging that we need more support, we need more therapies.  Dr Jones: Yeah, I agree. And I think often patients with neurologic disorders and their caregivers and families often appreciate being seen.   Dr Silbert: Yeah, no, absolutely true. So, I'd say in regards to the monoclonal antibody treatments, you know, despite the controversies with these new treatments, I think there's a real promise and a real hope and a real excitement across a lot of behavioral neurologists, including myself, that this is just the beginning. That even if these first line, first generation therapies maybe have downsides, that there'll be second generation and third generation variations on these kinds of treatments that are going to be more accessible, have less side effects and hopefully be more clinically effective. And, and down the line, the other real hope for the field is that these maybe second generation therapies will actually delay the onset or prevent clinical manifestation of the disease. And that's the real goal here.  Dr Jones: And that's a great segue to the to the next thing I wanted to ask you about and you, you may have already answered the question. We talked about how we have and will have new biomarkers which will help us with diagnosis. We have hopefully the first phase in increasingly effective disease modifying therapies for Alzheimer, maybe prevent Alzheimer's disease. Wouldn't that be great? Are there any other things on the horizon that you see maybe for other neurodegenerative disorders from a therapeutic perspective? What do you, what do you think the next big thing will be in that area?  Dr Silbert: Well, that's a great question. I think, you know, there's a lot of exciting research in Lewy body dementia and targeting alpha synuclein pathologies. We really need biomarkers.  So, we're ways off from therapeutics, but I think there's a lot of exciting progress in that area.  Dr Jones: So, like many areas of neurology, there are rewarding and challenging aspects to the care of these patients. What  do you- what's the most rewarding aspect of your practice, Dr Silbert?   Dr Silbert: You know, a lot of… I hear from trainees over the years that, you know, they can't imagine or it's difficult for them to think about caring for patients who have a neurodegenerative disease that has no cure. But I feel like that's a lot of what neurologists do. We don't necessarily cure all diseases, but we treat the patient throughout their disease process. And to me that is extremely satisfying. You know, I enjoy listening to patients’ stories and hearing about what they have been through over the years. And I really feel, like, appreciated for the care that I provide in giving not just an accurate diagnosis, which a lot of people come in lacking, but talking about future planning and, really, treatment throughout the course of the disease. And I was in clinic yesterday and talking to one of my patients’ caregivers, and we were talking about a particularly difficult behavioral manifestation that her husband was going through. And we were talking through how to manage it. And she said to me, you know, Dr Silbert, I really feel like I have a partner in going through this disease. And you know, that's kind of what it's all about for me. So, to me, it's extremely rewarding field. It's also a very exciting field, especially right now with all these new biomarkers and treatments. So, I just think there isn't a better area of neurology to be involved in right now.   Dr Jones: What a great place to land and end the interview. And I hope our listeners and our readers really do enjoy this issue. It's really a fantastic, not just an update, but a survey of a very dynamic aspect of the field of neurology. And Dr Silbert, I want to thank you for joining us and thank you for such a thorough and fascinating discussion on caring for patients with dementia.    Dr Silbert: It was my pleasure. Thank you.    Dr Jones: Again, we’ve been speaking with Dr Lisa Silbert, co-guest editor, alongside Dr Leanna Apostolova for Continuum 's most recent issue on dementia. Please check it out, and thank you to our listeners for joining us today.  Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. Thank you for listening to Continuum Audio. 

For certain diagnoses and patients who meet clinical criteria, neuromodulation can provide profound, long-lasting relief that significantly improves quality of life. In this episode, Aaron Berkowitz, MD, PhD, FAAN speaks with Prasad Shirvalkar, MD, PhD, author of the article “Neuromodulation for Neuropathic Pain Syndromes,” in the Continuum® October 2024 Pain Management in Neurology issue. Dr. Berkowitz is a Continuum® Audio interviewer and a professor of clinical neurology at the University of California, San Francisco Dr. Shirvalkar is an associate professor in the Departments of Anesthesia and Perioperative Care, Neurological Surgery, and Neurology at Weill Institute for Neurosciences at the University of California, San Francisco in San Francisco, California. Additional Resources Read the article: Neuromodulation for Neuropathic Pain Syndromes Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Guest: @PrasadShirvalka Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor in Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors, who are the leading experts in their fields. Subscribers to the Continuum Journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Prasad Shirvalkar about his article on neuromodulation for painful neuropathic diseases, which appears in the October 2024 Continuum issue on pain management in neurology. Welcome to the podcast, and if you wouldn't mind, please introducing yourself to our listeners.  Dr Shirvalkar: Thanks, Aaron. Yes, of course. So, my name is Prasad Shirvalkar. I'm an associate professor in anesthesiology, neurology and neurological surgery at UCSF. I am one of those rare neurologists that's actually a pain physician.  Dr Berkowitz: Fantastic. And we're excited to have you here and talk to you more about being a neurologist in in the field of pain. So, you wrote a fascinating article here about current and emerging neuromodulation devices and techniques being used to treat chronic pain. And in our interview today, I'm hoping to learn and for our listeners to learn about these devices and techniques and how to determine which patients may benefit from them. But before we get into some of the clinical aspects here, can you first just give our listeners an overview of the basic principles of how neuromodulation of various regions of the nervous system is thought to reduce pain? Dr Shirvalkar: Yeah, I would love to try. But I will promise you that I will not succeed because I think to a large extent, we don't understand how neuromodulation works to treat pain, to describe or to define neuromodulation. Neuromodulation is often described as using electrical stimuli or a chemical stimuli to alter nervous system activity to really influence local activity, but also kind of distant network activity that might be producing pain. On one level, we don't fully understand how pain arises, specifically how chronic pain arises in the nervous system. It's a huge focus of study from the NIH Heal Initiative and many labs around the world. But acute pain, which is kind of when you stub your toe or you burn your finger, is thought to be quite different from the changes over time and the kind of plasticity that produces emotional, cognitive and sensory dimensions. Really what I think is its own disease, chronic pain, of which there are multiple syndromes when we use neuromodulation, either peripheral nerve stimulation or electrical spinal cord stimulation. One common or predominant theory actually comes from a paper in science from 1967 and people still use it, foundational theory and it's called the gate control theory. Two authors, Melzack and Wall, postulated that at the spinal level, there are, there's a local inhibitory circuit or, you know, there's a local circuit where if you provide input to either peripheral nerves or either spinal cord ascending fibers that to kind of summarize it, there's only so much bandwidth, you know, that nerves can carry. And so that if you literally pass through artificial signals electrically, that you will help gate out or block natural pathological but natural pain signals that might be arising from the periphery or spinal cord. So, you know, one idea is that you are kind of interfering with activity that's arising for chemical neuromodulation. The most common is something known as intrathecal drug infusion drug delivery ITTD for that we quite literally put a catheter in the spinal fluid, you know, at the level of the dorsal horn neurons that we think are responsible for perpetuating or creating the pain. Where's the pain generator? And you really, you can infuse local anesthetic, you can infuse opioids. And what's nice is you avoid a lot of systemic side effects and toxicity because it goes right to the spinal cord, you know, by infusing in the fluid. So there's a couple of modalities, but I will say just, like maybe all of our living experience, pain is in the brain. And so, we don't really understand, I would say, what neuromodulation is doing to the higher spinal or brain levels. Dr Berkowitz: Fascinating topic. And yeah, very interesting to hear both what our current understanding is that some of our current understanding is based on data that's 60 years old and that we're actually probably learning about pain by using these modulation techniques, even though we don't really understand how they might be working. So interesting feedback loop there as well as in as in the as in this land. So, your article very nicely organizes the neuromodulation techniques from peripheral to central. So, encourage our listeners to check out your article. And first before we get into some of the clinical applications, just to give the listeners the lay of the land, can you sort of lay out the devices and techniques available for treating pain at each level of the neuroaxis? We'll get into some of the indications in patient selection in a moment, but just sort of to lay out the landscape. What's available that you and your colleagues can use or implant at different levels when we're thinking of referring patients too? Dr Shirvalkar: Absolutely. So, starting from the least invasive or you know, over the counter patients can purchase themselves a TENS machine. Many folks listening to this have probably tried a TENS machine in the past. And the idea is that you put a couple of pads, at least two. So you have like a dipole or you have a positive and a negative lead and you basically inject some current. So, the pads are attached to a battery and you can put these pads over muscle. If you have areas where myofascial pain or sore muscles, you can put them, frankly, over nerves as well and stimulate nerves that are deeper. Most TENS machines kind of use electrical pulses that occur at different rates. You change the rates, you can change the amplitude and patient can kind of have control for what works best. Then getting slightly more invasive, we can often stimulate electrically peripheral nerves. To do this we implant through a needle, a small wire that consists of anywhere from one electrical contact to four or even eight electrical contact. What I think is particularly cool, like TENS, which is transcutaneous electrical nerve stimulation that goes through the skin. Peripheral nerve stimulation aims to stimulate nerves, but you don't have to be right up against the nerve. So, yeah. We typically do this under an ultrasound and you can visualize a nerve like the sciatic nerve, peroneal nerve, or you know, even if someone has an ulnar or a neuropathy, you know, that's the compression. There's a role obviously for surgery and release, but if they have predominantly pain, it's not related to a mechanical problem per se, you could prevent a wire from a peripheral nerve stimulator as far as one centimeter from a nerve and it'll actually stimulate that that modulated and then, you know, kind of progressing even more deeply. The spinal cord stimulation, SCS, it's probably the most ubiquitous or popular form of neuromodulation for pain. People use it for all kinds of diseases. But what it roughly involves is a trial period, which is a placement of either two cylindrical wires, not directly over the spinal cord, but actually in the epidural space, right? So, it's kind of like when you get an epidural injection or doing labor and delivery, when women get epidural catheters, placing spinal cord stimulator leads in that same potential space outside the dura, and you're stimulating through the dura to actually target the ascending dorsal column fibers. And so, you do a trial period or a test drive where the patients get these wires put in. They're coming out of the skin, they're connected to a battery, and they walk around at home for about a week, take careful notes, check in with them, and they keep a diary or a log about how much it helps. Separately. I will say it's hard to distinguish this, the placebo effect often, but you know, sometimes we want to use the placebo effect in clinical practice, but it is a concern, you know, with such invasive things. But you know, if the trial works well, right, you basically can either keep the leads where they are and place a battery internally. And it's for neurologists. You're familiar with deep brain stimulation. These devices are very similar to DVS devices, but they're specifically made for spinal cord stimulation. And there's now like seven companies that offer manufacturers that offer it, each with their own proprietary algorithm or workflow. But going yet more invasive, there is intrathecal drug delivery, which I mentioned, which involves placement of the spinal catheter and infusion of drug into spinal fluid. You could do a trial for that as well. Keep a patient in the hospital for a few days. You've all probably had experience with lumbar drains. It's something real similar. It just goes the other way. You know, you're infusing drugs, and it could also target peripheral nerves or nerve roots with catheters, and that's often done. And last but not least, there's brain stimulation. Right now, it's all experimental except for some forms of TMS or transcranial magnetic stimulation, which is FDA approved for migraine with aura. There are tens machine type devices, cutaneous like stimulators where you can wear on your head like a crown or with stickers for various sorts of migraines. I don't really talk about them too much in in the article, but if there's a fast field out there for adjunctive therapy as well,  Dr Berkowitz: Fantastic. That's a phenomenal overview. Just so we have the lay on the land of these devices. So, from peripheral essentially have peripheral nerve stimulators, spinal cord stimulators, intrathecal drug delivery devices and then techniques we use in other areas of neurology emerging for pain DBS deep brain stimulation and TMS transcranial magnetic stimulation. OK let's get into some clinical applications now. Let's start with spinal cord stimulators, which - correct me if I'm wrong - seem to be probably the most commonly seen in practice. Which patients can benefit from spinal cord stimulators? When should we think about referring a patient to you and your colleagues for consideration of implantation of one of these spinal cord stimulator devices?  Dr Shirvalkar: So, you know, it's a great question. I would say it's interesting how to define which patients or diagnosis might be appropriate. Technically, spinal cord stimulators are approved for the treatment of most recently diabetic peripheral neuropathy. And so, I think that's a really great category if you have patients who have been failed by more conservative treatments, physical therapy, etcetera, but more commonly even going back, neuropathic low back pain and neuropathic leg pain. And so, you think about it and it's like, how do you define neuropathic pain. Neuropathic pain is kind of broadly defined as any pain that's caused by injury or some kind of lesion in the somatosensory nervous system. We now broaden that to be more than just somatosensory nervous system, but still, what if you can't find a lesion, but the pain still feels or seems neuropathic. Clinically, if something is neuropathic, we often use certain qualitative descriptors to describe that type of pain burning, stabbing, electric light, shooting radiates. There's often hyperpathia, like it lingers and spreads in space and time as opposed to, you know, arthritis, throbbing dull pain or as opposed to muscle pain might be myofascial pain, but sometimes it's hard to tell. So, there aren't great decision tools, I would say to help decide. One of the most common syndromes that we use spinal cord stimulation for is what used to be called failed back surgery syndrome. We never like to, we now try to shy away from explicitly saying something is someone has failed in their clinical treatment. So, the euphemism is now, you know, post-laminectomy syndrome. But in any case, if someone has had back surgery and they still have a nervy or neuropathic type pain, either shooting down their legs and often there's no evidence on MRI or even EMG that that something is wrong, they might be a good candidate, especially if they're relying on long term medications that have side effects or things like full agonist opioids, you know that that might have side effects or contraindication. So, I would say one, it's not a first line treatment. It's usually after you've gone through physical therapy for sure. So, you've gone through tried some medications. Basically, if chronic pain is still impacting your life and your function in a meaningful way that's restricting the things you want to do, then it it's totally appropriate, I think, to think about spinal cord stimulation. And importantly, I will add a huge predictor of final court stimulation success is psychological composition, you know, making sure the person doesn't have any untreated psychological illness and, and actually making sure their expectations going in are realistic. You're not going to cure anyone's pain. You may and that's, you know, a win, but it's very unlikely. And so, give folks the expectation that we hope to reduce your pain by 50% or we want you to list personally, I like functional goals where you say what is your pain preventing you from doing? We want to see if you can do X,Y, and Z during the trial period. Pharmacostimulation right now. Yeah. Biggest indication low back leg pain, Diabetic peripheral neuropathy. There is also an indication for CRPS, complex regional pain syndrome, a lesser, I'd say less common but also very debilitating pain condition. For better or worse. Tertiary quaternary care centers. You often will see spinal cord stem used off label for neuropathic type pain syndromes that are not explicitly better. That may be for example, like a nerve injury that's peripheral, you know, it's not responding. A lot of this off label use is highly variable and, you know, on the whole at a population level not very successful. And so, I think there's been a lot of mixed evidence. So, it's something to be aware about.  Dr Berkowitz: That's a very helpful framework. So, thinking about referring patients to who have most commonly probably the patients with chronic low back pain have undergone surgery, have undergone physical therapy, are on medications, have undergone treatment for any potential psychological psychiatric comorbidities, and yet remain disabled by this pain and have a reasonable expectation and goals that you think would make them a good candidate for the procedure. Are those similar principles to peripheral nerve stimulation I wasn't familiar with that technique, I'm reading your article, so are the principles similar and if so, which particular conditions would potentially benefit from referral for a trial peripheral nerve stimulation as opposed to spinal cord stimulation?  Dr Shirvalkar: Yeah, the principles are similar overall. The peripheral nerve stimulation, you know, neuropathic pain with all the characteristics you listed. Interestingly enough, just like spinal cord stim, most insurances require a psychological evaluation for peripheral nerve stim as well. And we want to make sure again that their expectations are reside, they have good social support and they understand the kind of risks of an invasive device. But also, for peripheral nerve stem, specifically, if someone has a traumatic injury of an individual peripheral nerve, often we will consider it seeing kind of super scapular stimulation. Often with folks who've had shoulder injuries or even sciatic nerve stimulation. I have done a few peroneal nerve stimulations as well as occipital nerve stimulation from migraine, so oxygen nerve stimulation has been studied a lot. So, it's still somewhat controversial, but in the right patient it can actually be really helpful. Dr Berkowitz: Very helpful. So, these are patients who have neuropathic pain, but limited to one peripheral nerve distribution as opposed to the more widespread back associated pains, spine associated pains. Dr Shirvalkar: Yeah, Yeah, that's right. And maybe there's one exception actually to this, which is brachial plexopathy. So, you know, folks who've had something like a brachial plexus avulsion or some kind of traumatic injury to their plexus, there is I think good Class 2 evidence that peripheral nerve stem can work. It falls under the indication. No one is as far as to my knowledge, No one's done an explicit trial, you know PNS randomized controlled trial. Yeah, that's, you know, another area one area where PNS or peripheral nerve stems emerging is actually, believe it or not in myofascial low back pain to actually provide muscle stimulation. There are some, there's a company or two out there that seeks to alter the physiology of the multifidus muscle, one of your spinal stabilizer muscles to really see if that can help low back pain. And they've had some interesting results.  Dr Berkowitz: Very interesting. You mentioned TENS units earlier, transcutaneous electrical nerve stimulation as something a patient could get over the counter. When would you encourage a patient to try TENS and when would you consider TENS inadequate and really be thinking about a peripheral nerve stimulator?  Dr Shirvalkar: Yeah, you know TENS we think of as really appropriate for myofascial pain. Folks who have muscular pain, have clear trigger points or taught muscle bands can often get relief from TENS If you turn a TENS machine up too high, you'll actually see muscle infection. So, there's an optimal level where you actually can turn it up to induce, like, a gentle vibration. And so folks will feel paresthesia and vibrations, and that's kind of the sweet spot. However, I would say if folks have pain that's limited or temporary in time or after a particular activity, TENS can be really helpful. The unfortunate reality is TENS often has very time-limited benefits - just while you're wearing it, you know? So, it's often not enduring. And so that's one of the limitations. Dr Berkowitz: That's helpful to understand. We've talked about the present landscape in your article, also talk a little bit about the future and you alluded to this earlier. Tell us a little bit about some off label emerging techniques that we may see in future use. Who, which types of patients, which conditions might we be referring to you and your colleagues for deep brain stimulation or transcranial magnetic stimulation or motor cortex stimulation? What's coming down the pipeline here?  Dr Shirvalkar: That's a great question. You know, one of my favorite topics is deep brain stimulation. I run the laboratory that studies intracranial signals trying to understand how pain is processed in the brain. But, believe it or not, chronic pain is probably the oldest indication for which DBS has been studied. the first paper came out in 1960, I believe, in France. And you know, the, the original pivotal trials occurred even before the Parkinson's trial and so fell out of favor because in my opinion, I think it was just too hard or too difficult or a problem or too heterogeneous. You know, many things, but there are many central pain syndromes, you know, poststroke pains, there's often pains associated with Parkinson's disease, epilepsy, or other brain disorders for which we just don't have good circuit understanding or good targets. So, I think what's coming down the pipeline is a better personalized target identification, understanding where can we stimulate to actually alleviate pain. The other big trend I think in neuromodulation is using closed loop stimulation which means in contrast to traditional electrical stimulation which is on all the time, you know it's 24/7, set it and forget it. Actually, having stimulation respond or adapt to ongoing physiological signals. So that's something that we're seeing in spinal cord stem, but also trying to develop in deep brain stimulation and noninvasive stimulation. TMS is interestingly approved for neuropathic pain in Europe, but not approved by the FDA in the US. And so I think we may see that coming out of pipeline broader indication. And finally, MR guided focused ultrasound is, is a kind of a brand new technique now. You know, focused ultrasound lesions are being used for essential tremor without even making an incision in the skull or drilling in skull. But there are ways to modulate the brain without lesioning. And, you know, I think a lot of research will be emerging on that in the next five years for, for pain and many other neuronal disorders. Dr Berkowitz: That's fascinating. I didn't know that history that DBS was first studied for pain and now we think of it mostly for Parkinson's and other movement disorders. And now the cycle is coming back around to look at it for pain again. What are some of the targets that are being studied that are thought to have benefit or are being shown by your work and that of others to have benefit as far as DBS targets for, for chronic pain? Dr Shirvalkar: You know, that's a great question. And so, the hard part is finding one target that works for all patients. So, it may actually require personalization and actually understanding what brain circuit phenotypes do you have with regards to your chronic pain and then based on that, what target might we use? But I will say the older targets. Classical targets were periaqueductal gray, which is kind of the opioid center in your brain. You know, it's thought to just release large amounts of endogenous opioids when you stimulate there and then the ventral pusher thalamus, right. So, the sensory ascending system may be through gait control theory interferes with pain, but newer targets the answer singlet there's some interest in in stimulating there again, it doesn't work for everybody. We found some interesting findings with the medial thalamus as well as aspects of the caudate and other basal ganglion nuclei that we hopefully will be publishing soon in a data science paper.  Dr Berkowitz: Fantastic. That's exciting to hear and encourage all of our listeners to check out your article. That goes into a lot more depth than we had time to do in this short interview, both about the science and about the clinical indications, pros and cons, risks and benefits of some of these techniques. So again, today I've been interviewing Dr Prasad Shirvalkar, whose article on neuromodulation for painful neuropathic diseases appears in the most recent issue of Continuum on pain management in neurology. Be sure to check out Continuum Audio episodes from this and other issues. And thank you again to our listeners for joining today.  Dr Shirvalkar: Thank you for having me. It was an honor. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Opioids may be considered for temporary use in patients with severe pain related to selected neuropathic pain conditions and only as part of a multimodal treatment regimen. Close follow-up when initiating or adjusting opioid therapy and frequent reevaluation during long-term opioid therapy is required. In this episode, Allison Weathers, MD, FAAN speaks with Friedhelm Sandbrink, MD, FAAN, an author of the article “Opioids and Cannabinoids in Neurology Practice,” in the Continuum® October 2024 Pain Management in Neurology issue. Dr. Weathers is a Continuum Audio interviewer and the associate chief medical information officer at the Cleveland Clinic in Cleveland, Ohio. Dr. Sandbrink is the national program director of Pain Management, Opioid Safety and Prescription Drug Monitoring Programs at the Veterans Health Administration, Uniformed Services University in Bethesda, Maryland. Additional Resources Read the article: Opioids and Cannabinoids in Neurology Practice Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media @ContinuumAAN facebook.com/continuumcme Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum Journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal and how to get CME. Dr Weathers: I'm Dr Allison Weathers. Today I'm interviewing Dr Friedhelm Sandbrink, who is one of the authors of the article Opioids and Cannabinoids for the Practicing Neurologist from the October 2024 Continuum issue on pain management Neurology. Welcome to the podcast and please introduce yourself to our audience.  Dr Sandbrink: Yeah, hi. So, I'm Friedhelm Sandbrink. I'm a neurologist and pain physician. I work at the Washington DC VA Medical Center, where I lead our intercessory pain management team, and I have a role also in the VA central office for pain management. I'm also associate professor, clinical associate professor at George Washington University and at the Uniformed Services University in Bethesda.  Dr Weathers: A lot of expertise, which you obviously brought to this article. And I do want to emphasize before we get started, although the article discusses both opioids and cannabinoids, as I said in the introduction, you worked in specifically on opioids. And so that's the part of the article where we'll focus our conversation today. Of course, I think all of our Continuum Audio topics are really fascinating. I know that some may not resonate as much, especially with our non-neurology listeners as others. Clearly not the case with your articles. I was reading it and preparing for a conversation today. I was really struck by how broadly applicable this topic is, not only to all neurologists but, really, all physicians, and even it should be to all of our listeners. Especially with what happened been going on over the last several years, what's been in the news about the opioid epidemic. And while usually like to start with this question, it feels even more pertinent in your case, what is the most important clinical message of your article? Dr Sandbrink: So, the role of the opioid, the role of opioid therapy, really, for pain care has changed dramatically over the last many years right? I mean, it's we, we still consider opioids like the most potent analgesic medication for treatment of acute pain. The benefit for chronic pain really has changed right I mean, you know, we- the understanding in that regard and they're controversial. So, they're generally not recommended for chronic treatment for neuropathic pain conditions or for headache, but there are probably situations when opioids are still indicated and may be considered especially for temporary use. So, one example is probably the patient who has severe acute post hepatic neuralgia and we know that we use other medications for that, you know, the gabapentinoids and duloxetine and but they may take several days or weeks to work, right? And we have to titrate them up. And when more acute pain relief is needed, the opioid medication may be may be an option for temporary use. But I think what we need to keep in mind is that when we use it, we need to be informed about how to mitigate the risks, right? What, what are our best ways to reduce harms? And we need to also know the regulatory, you know, situation right I mean, what is that that we have to do nowadays to stay within the frameworks, right? And so, one of the main emphasis on this article is really go through what the clinical that the CDC has now established as the standards for opiate therapy when we use opioids I think we all need to know the rules right I mean, we know what to do to mitigate risks. What is expected from us in regard to use it as safely as possible, right? And that's important for the patient. That's also important for us in our practice.  Dr Weathers: I think very important advice. And this seems so obvious, but at the same time, I think it's worth very clearly stating why is it so important for neurology clinicians and again, really all clinicians, to read this article? Dr Sandbrink: Yeah. We need to know the words regarding opiate prescribing right in the clinic. You know, the CDC has now issued their opiate practice guide, the Opiate Therapy Guideline. Really, it's a guideline for pain care in 2022. It's an update from 2016 that made some major changes in that regard. And I think we need to know really where we are nowadays in regard to expectations. I think we need to place the opiate therapy appropriately in our armamentarium regarding the many options that we have for pain care. But then when we use them, we need to know what we need to do to make it safe. Right? So, I'm thinking about the prescription drug monitoring programs and the patient education that's expected. We use in our practice an informed consent process even for patients on chronic pain, When and how to interpret urine drug screens, right? And how to issue, and maybe when to issue a naloxone comedication in order to have a rescue medication in case the patient is in a terrible situation. So, these are just things that have become nowadays standards of care and part of our practice. And we need to be familiar with it and use them as we take care of the patients. And for instance, in regard to opiate medication, we need to know about the specific rules regarding telehealth, prescribing of controlled substances, controlled Substances Act and the Ryan Hate Act that mandates in person evaluations for patients when we prescribe controlled substances. That obviously has been somewhat amended or changed or temporarily put on hold during the COVID crisis. And many states now have started developing their own guidance in regard to what's available and what's possible during telehealth. And we need to be familiar about that also.  Dr Weathers: I think those are such important and thoughtful points. I, I've mentioned it several times on this podcast before. I am a clinical informaticist and this is a topic that really lends itself to the EHR being able to help support. So, a lot of the things that you just mentioned, the consents for patients, the prescribing of naloxone, some of the support, clinical decision support can really be done in the electronic health record to help support providers. However, it's also one of those things where if people don't understand what's behind it, it can become a little bit of a crutch. And so, as I was reading the article, I was really struck by how helpful it is to really have that background. I think people can become very dependent and it becomes almost just doing it all for them and, and they lose the- then you can make this argument about probably a lot of the other clinical decision supports in there, but really understanding the why behind a lot of the support that's there around all of the, the tools that are in there to, to support safe opioid prescribing. I think it's so important for that people have that background that the article provides.  Dr Sandbrink: I think often it feels like you're going through a checklist of things to do right and, and, and you do right. But at the same time, as you said, you need to know why you're doing it right And, and I think it's very important for us to know what the rules are and the expectations in regard to standards of care. So, we also know what is the framework that we have to follow, but where can we make modifications? Where can we individualize based on the patient's need? What is really that that is still within our ability to do and how to modify that? Because in the very end, it really is about good care of the patient. We need to know what we are allowed to do, but we also need to know where the limits are right And I hope that that article provides really some information about that, especially as it outlines what the CDC expects. But then also, I think it gives - hopefully, and this is a message that the CDC also has – it really emphasizes that it's about good communication with the patient, truly informing them and about what are the range of options and the limits that we have, but also at the same time never to abandon the patient. You know, I think this is something that we need to understand. It's not really about us. The rules are there to make the care of the patients safer. The rules are not the primary goal itself. It is still patient care. So, in that regard, we need to make sure to never abandon the patient, even if the patient for instance, may come to us and maybe they took more opiates and prescribed or you know, and they ran out early and figure out what exactly was that drove the patient for that, right? I mean, you know, so that we know maybe it is actually worse than pain. Maybe there was something that happened that caused the patient to have a significant increase of it. You know, I think one of the biggest misconceptions is really also that patients who make sure some misuse of medication, that everybody has opioid abuse disorder, addiction. Common, far too common, right? And I think we've learned over the years how common it is. Clearly pain itself, intractable pain is a very strong driver of behavior. If you're in pain, if a patient is in pain, they are desperate often to seek some kind of relief. And taking extra medication in itself, while it's not at all something that we can endorse and tolerate, obviously in many ways, right, we have to still take it as a possible sign of pain control rather than opiate use disorder in itself. So, we need to be very careful of how to assess such a patient and that we guide them into the right direction in regard to the next.  Dr Weathers: That, again, is very important advice, and thinking about how chronic pain on a very different level than acute pain, right? Understanding how these patients are processing pain in a very different way than patients with acute pain. And again, also, I think a very important point that the pendulum has swung kind of back and forth over the years. You know, that they were in pain was another vital sign and it was make sure you're asking your patient about pain. And then all of a sudden it was, oh, we have to be really careful and people should not, nobody should be on these medications, which you- to your point, led to sudden abandonment. And that's not the point. That's not what we should be doing as providers. I know, though, there's very sensitive and challenging situations when you find out a patient though, perhaps taking more than expected because of chronic pain, but perhaps diversion. How have you handled those challenging cases? Dr Sandbrink: I think diversion needs to be taken obviously very, very seriously. And you know, if a patient is truly diverting medication and there are obviously multiple variations of that, right? I mean, it's like giving it to a family member, for instance. That's one thing. It's on the other hand actually selling it. I think a patient who diverts is such a situation where opioid prescribing has to stop immediately, right? I mean, this is not a patient that we would take off at this point. I mean, so I think it's one of the very, very few occasions where you'd say that you have to just stop it immediately. I think there are other situations really in general, I think the patients who have been on opioids long term, especially in higher doses, I mean the majority of patients are not different. We have to be aware of it. We have to always look out for it. That's part of our risk mitigation. But we also have to make sure that patients on long term opioid therapy, right, that we guide them appropriately. I think the guidance probably in many ways is that we want to make sure whether opioids, the opioid medications still have helps them to achieve their functional goal. Are they truly helpful for the patients in achieving what they aspire to do in regard to their work life, in regard to the family situation. I think a lot of times for patients who have been on opioids long term, it's probably not that it really helps them that much for pain anymore, but they've often made that experience and they try to stop it. Pain gets worse, which is the effect obviously, that that happens with opiates right I mean, the moment you stop them, the opposite of the effect happens right I mean, they become irritable, right? The sleep gets worse, the pain gets worse, right? And it's a temporary phenomenon. And so, when we try to talk to a patient about possibly reducing the medication, I think this is one of the most challenging aspects that we have, that we really look at the patient and try to motivate them to be part of that plan. It's not something that we want to impose on the patient, but rather that we motivate the patient to look towards in the long term, probably more efficient pain care, which is really much more comprehensive pain care using all modalities. And I think one of the things that we learned over the last years is that when we make opiate medication reductions, we have to go very slowly. I think in the past we've talked about a matter of weeks and now the guidance including from the CDC guideline is probably more- closer to 10% per month to reducing it. So, you make reductions that may take many months to a year even, right. And the patient is allowed to help us, guide us how fast we can go. And you're allowed to make pauses if needed for the patient to adjust physiologically to reduction. And we want to go slowly enough that we don't run into an acute withdrawal situation right If you do it very gradually, it's much more manageable for the patient to do that. Then they'll be much more motivated to work with you. But still, it's a challenge right I think that we do. And I think at the very end, it's really providing good patient care that allows us to build that rapport with the patient that they trust us and that they say, Hey, you know, yes, I'm, I'm willing to work with you, doc, to maybe reduce my reliance on the medication, right? So that that I don't end up on this. You know, one of the things that I sometimes do is asking patients when they come to us this first time and there are a lot of opiate medication maybe is like, what's your goal in this regard? Where do you see yourself in, in five or ten years? Are you thinking you will still be on this medication or would you want to come off? And how can we help you then if that's your goal? So, I think this is all part of our important conversation that we have to have in order to motivate the patient.  Dr Weathers: What I heard you say repeatedly through that. And what I really want to emphasize for our listeners is that the therapeutic relationship with that patient that no matter what that scenario, really keeping them and their goals at the focus and really making it a partnership, not a paternalistic relationship, not dictating to them what the plan will be, but really emphasizing shared decision-making. And I think again, that's such a key take home point for our listeners. And also, even going back to my original question about diversion, what really struck me in your response is even though you said yes, then that was one of the few cases or perhaps even the only case where you said, all right, this is where we have to cut it off immediately. It still wasn't abandoning them as a patient, although you said we have to stop the medication. It wasn't about ending that relationship with that patient necessarily, but ending that therapy option. So really critical in how we think about opioids therapy and our relationship overall with patients.  Dr Sandbrink: So, Allison, maybe I can add on, you know, I think the patient with diversion is the one aspect where we have to look at the population as a whole and the opioid that makes it to somebody else, potentially a vulnerable child, right, even you know, who could die from it, right? Another aspect of probably the patients we mentioned them earlier who have opioid use disorder, who maybe take more than prescribed and where we as a neurologist feel often quite uncomfortable dealing with that. And I think that's so important that at that point we don't abandoned the patient, right. I mean, you know, maybe we want to continue, we don't want to continue the opiate medication for the treatment of the pain. But as we diagnose and initially suspect opiate use disorder and have a conversation about it with a patient, we need to guide them to therapy. It's a treatable condition, right? It's an untreated, it's, it's actually rather lethal in many situations, right? So, we have to make sure that we provide an integrated access to the treatment or we have a warm hand off to somebody who will continue that and not abandon the patient in regard to that pain care, as we said earlier also, right? I mean, because that second condition really doesn't obviously I mean in any way that the pain is any better. No, I mean it's a common concurrent situation and we need to make sure that they still have the better pain care possible. Dr Weathers: Again, it's a really key point for our listeners as and as I emphasized at the beginning, regardless of their subspecialty or specialty or even if they're physicians, I hope for everybody listening they can take away something from this. How did you become interested in pain management? I know that this was something that that you became interested in even when still in training. What struck you about this? Dr Sandbrink: So, yeah, so my initial fellowship actually after residence was clinical neurophysiology. So, you know, a lot of the spine and different nerve conditions really was, was, but then when I began practice, clearly longitudinal care, chronic disease management, I think many of us in neurology do that right That, that became an emphasis. And I think building that accord with the patients right and, and, and that having that ability to provide pain care is something that really worked out very well. I think I love teamwork and part of teamwork pain care in in our setting is a collaborative approach right You have other disciplines, physical therapist, psychologist, right? You know, you have intervention and nonintervention provider. I think nowadays we even have integrative modalities available to us. So, I'm working together on a team, trying to optimize it here with many team members that we have with everybody bringing that personal expertise is something that I really cherish. Dr Weathers: I feel like that's such a great example and I feel like a lot of people don't necessarily think about this specialty as one that is, that is collaborative in that way. And it really is. So, I, I think that's a wonderful way to highlight it. I always like to end on a hopeful note. And I know that there hasn't been necessarily a lot of hope or positive news in regards to, to opioid use, opioid therapy in the last several years. But are there developments that give you hope that you're excited about?  Dr Sandbrink: So, you know, I think there are probably two things I would mention. On one hand, I think patients are so much more aware now about the risk of opioids. So that is actually much easier to look and get them motivated about comprehensive pain care. There's much more interest in integrative modalities. Patients nowadays would be much more willing to maybe try acupuncture or mindfulness or yoga or Tai chi. So, I think that's actually a really nice development in that regard. But if I think about opioids specifically, I think the availability of buprenorphine as a medication, it's certainly something we should mention in this interview here, right? I mean, buprenorphine is now increasingly used for pain as well, not just in the higher dosage for opiate use disorder. It really is a good choice for patients who have. pain conditions, chronic pain conditions, severe pain and to require a daily opioid, especially in regard to safety aspect when the patient has medical conditions or mental health conditions that may put them at higher risk and they have to be on an opiate anyway. This is really something that I think has changed our practice. As you know, we don't have to rely on the X waiver anymore. Anybody with a DA license can prescribe buprenorphine. Even for opiate disuse disorder, it really has become something that I think many of us integrate much more into our practice and I want to encourage the listener to really look into that direction.  Dr Weathers: Excellent advice and I'll actually refer our listeners who are subscribers of Continuum to reference, specifically, Table 4 where you dive into the buprenorphine. It's just a fantastic table, as are all the tables. It really goes into detail of the commonly prescribed opioids for pain with the special characteristics and the conversion of morphine equivalent, but especially for this one about how to prescribe the details of us. Again, when I was preparing for this, I said wow. Like for me as a neurohospitalist and thinking about when I'm on service, how to use it, when to use it, I thought it was incredibly useful for that management of patients, especially as a powerful point of care tool. Well, thank you so much for being here with me today for this great conversation.  Dr Sandbrink: Yeah, thank you. That was my pleasure. Dr Weathers: Again, today I've been interviewing Dr Friedhelm Sandbrink, whose article on opioids and cannabinoids for the practicing neurologist, written with Dr Nathaniel Schuster, appears in the most recent issue of Continuum on Pain Management and Neurology. To learn more about the topics of opioids and cannabinoids, be sure to read the full article. And don't forget to listen to Continuum audio episodes from this and other issues. Thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Orofacial pain comprises many disorders with different etiologies and pathophysiologies. A multidisciplinary approach combining medication, physical therapy, and procedural and psychological strategies is essential in treating patients with orofacial pain. In this episode, Teshamae Monteith, MD, FAAN, speaks with Meredith Barad, MD; Marcela Romero-Reyes, DDS, PhD, authors of the article “Orofacial Pain,” in the Continuum® October 2024 Pain Management in Neurology issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Barad is a clinical associate professor of anesthesiology, perioperative and pain medicine, and neurology and neurological sciences and codirector of the Stanford Facial Pain Program at Stanford Medicine in Stanford, California. Dr. Romero-Reyes is a clinical professor and director of the Brotman Facial Pain Clinic and Department of Neural and Pain Sciences at the University of Maryland in Baltimore, Maryland. Additional Resources Read the article: Orofacial Pain Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media @ContinuumAAN Host: @headacheMD Guest: @meredith_barad facebook.com/continuumcme Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum 's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum Journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. Today I'm interviewing Drs Meredith Barad and Marcela Romero-Reyes about their article on oralfacial pain, which appears in the October 2024 Continuum issue on pain management and neurology. Welcome to the podcast, ladies. How are you?  Dr Barad: Excellent.  Dr Romero-Reyes: Fine, happy to be here.  Dr Monteith: I am so happy to see you. I mean, I think both of you I've known for like ten years. Dr Romero-Reyes: Yeah.  Dr Barad: Yes.  Dr Monteith: So why don't you introduce yourselves? While I know you, our audience, some of them, may not know you.  Dr Romero-Reyes: I'm Dr Marcella Romero Reyes. I am a neuropathial pain specialist, clinical professor, and director of the Provident Special Pain Clinic here in the University of Maryland School of Dentist. Dr Monteith: Excellent.  Dr Barad: My name is Meredith Barad. I'm a clinical associate professor at Stanford and I work- I'm the codirector of our headache and facial pain clinic in the Stanford pain management clinic. Dr Monteith: Well, first of all, thank you for writing this article. It is extremely detailed and up-to-date and very informative. And in neurology, I think we don't get enough pain management. I'm interested in both of your backgrounds and, you know, what led you even to become an expert in this area? And both of you have complementary areas. I think we can see in the quality of this article. But why don't we start with you, Dr Romero-Reyes? Dr Romero-Reyes: Well, for me to get interested in orofacial pain, I will say more than an interest was like a calling that I wanted to take care of this patient population. So, as you know, my background is dentistry and at that time I was very interested in patients with complex medical issues. And was the time I was- I started to be interested in temporomandibular disorders. But what really picked completely my attention was the first time I saw a patient with trigeminal neuralgia. This was my last year in dental school. This patient already had, like, almost a full upper quadrant of teeth extracted where pain was not resolved. So when the patient came to us and I did my exam and, you know, and I triggered the pain, the sharp shoot electrical pain, that really broke my heart. And I took an x-ray and I didn't find anything that will explain it was something wrong until I talked to my professor and he said, no, this is medical. There's nothing wrong with it, with that tooth and needs to be, you know, followed with proper management and medication. And for me, that was like, wow, what a proper diagnosis and proper management can take care of these of these patients. And when the patient got better, that really said, oh, you know, I want to do this.  Dr Monteith: That's a crazy story. It's always that last patient of the day.  Dr Romero-Reyes: And you know, think about it, at least in dentistry at that time, I learned about trigeminal neuralgia from a book, right, my classes. But when you see the patient, this is it. That completely, you know, made me say yes, I want to study this.  Dr Monteith: Yeah. And unfortunately, that's not an uncommon scenario where patients with trigeminal neuralgia get, you know, their extractions and pain can sometimes be more complicated. What about you, Dr Barad? Dr Barad: Well, I guess I'm sort of like the opposite. So as a neurologist and a trained pain physician, I saw a lot of patients with neuralgic pain and headache pain, but I also saw many patients who would say, I have TMJ. And as, as Dr Romero has educated us, that's like saying I have shoulder or I have knee. But I quickly realized that I needed to work with a multidisciplinary team to really understand more about orofacial pain. It's not just neuralgic. There are other ideologies. And so that's how we started working together and that's how we practice in our clinic at Stanford. Dr Monteith: So, why don't you tell us about the objectives of this article? Dr Barad: I think our objectives were to help the neurologist broaden the differential diagnosis on facial pain to encompass below the nose, the oral cavity, the temporal mandibular joint. And to just think more broadly about facial pain and to understand some of the more recent diagnostic criteria that have been developed for facial pain and to- how to diagnose properly and how to begin treatment for some of the other conditions that are non-neurologic.  Dr Romero-Reyes: And I think I will ask about what Dr Barad say that also to bring awareness to the neurologist about the vast classification of oral facial pain disorder, craniofacial and orofacial. I think that was also a key thing too. And also, to show how well we can work together, you know, the multi-disciplinary management that is indicated for these cases. Dr Monteith: Cool. And you mentioned some of the new diagnostic criteria. I want to talk just briefly about the new international classification of orofacial pain, ICOP. When did that come out and what was the process there in really fine-tuning the diagnosis of orofacial pain disorders? Dr Romero-Reyes: So, in 2019 the orofacial head pain especially interest group of the International Association for the Study of Pain, the International Network for Orofacial Pain and Related Disorders methodology and the American Academy of Orofacial Pain and the International Headache Society. They partnered together to develop to develop this international classification of orofacial pain. And these, I think- it's such a great effort, you know, all the main people doing pain about this area, and goes very well together with the international classification of headache disorders. So, for example, you know, some disorders that International Classification of Headache Disorders doesn't present such as and the ICOP, International Classification of Orofacial Pain, presents, like the persistent idiopathic dental Viola pain. You have it in the ICOP. It's not, you know, mentioned in the in the International Classification of Headache Disorders, as well as, also we have the- I think it’s item number five, the orofacial representations headache disorder or primary headache disorder. The ICOP gives you a nice, clean diagnostic criteria.  Dr Monteith: So, I guess I would ask Dr Barad with this classification in mind, how useful is it in neurology practice? And I know obviously you see patients with pain, but how useful even in managing patients with headache? Dr Barad: I think it's great because I've had a lot of dentists and ENT doctors who have started referring patients to me because they've realized that they've increased their awareness about orofacial pain and realized that pain in the sinuses, for example, accompanied by light sensitivity and sound sensitivity and rhinorrhea, may not be a recurrent monthly sinus infection. And so that kind of broadens our awareness of these of these disorders. And it's been, it's brought new patients into my clinic that we can help and treat. So that's been exciting.  Dr Monteith: And what about in the world of dentistry? Obviously, I think people in orofacial pain worlds are highly attuned to this, but I would hope this would hopefully have been disseminated into dentists and regular practice at C patients with trigeminal neuralgia. Dr Romero-Reyes: Going back for the, what you were discussing about the ICOP. So, it's what we're trying now as a new specialty. Well that we have been for the last four years, but finally in 2020 we have been recognized by the American Mental Association to disseminate this knowledge. But also, you know, can you imagine in in the realm in orofacial pain or dentistry have a patient with this recurrent pain, phonophobia, photophobia, throbbing dental pain is throbbing, but it's nothing wrong with your tooth. And that did they tell you that actually you have an orofacial or facial migraine or a neurovascular or facial pain. How crazy, right? And that is managed with migraines therapy. So it really, you know, to make you think like that. Wow, so these weird tooth things that used to come every week or these with facial pain, it's nothing to deal with, you know, with my teeth or any structure, you know, inside my mouth. Dr Barad: It sounds to me like what you're saying is that we've, this has encouraged patient education as well, not only interdisciplinary education, but really helping provide an explanation for the patient about what is going on with them. So rather than just getting sent away to another tertiary specialist, the patient is getting a more robust understanding of what's going on.  Dr Romero-Reyes: And going back to what you were saying about trigeminal neuralgia, you know, at least in dentistry also we're teaching now a new awareness like for two things, right? What about from the neurology setting? The patient has captured electrical pain. The trigger is intraoral. If it's pain inside your mouth, the first practitioner you're going to see who will be maybe the dentist that the dentist knows that could be a possibility of a disorder that doesn't deal with teeth, but also, it's important and we discussed that in our paper. What about that actually that weird trigger actually, it's not a general. What about if it's a cracked tooth has that singing sensation too. So, you see, it's two ways; one, to teach dentist to learn about this disorder and you know, we have learned, but you know, it's much more awareness now that this is great that, you know, these disorders you're not going to treat with dental procedures. Right? It's medical and vice versa, that the neurologist also has the awareness that oh, central trigger. Have you gone to the to the dentist? Have you checked that out? Dr Monteith: So what should neurologist know about dental sources of pain? Dr Barad: Well, maybe they should read the paper?  Dr Romero-Reyes: Yeah. Yeah, you need to read the paper. Yeah.  Dr Monteith: Top three, don't treat this with gabapentin.  Dr Romero-Reyes: Like well, dental pain is not going to be resolved with gabapentin. That would need to make a diagnosis if and you know it's that examination that come comes with a radiographic evidence that shows that maybe could be a cavity or could be a problem. You know in the in the practical tissues of the tooth that is given a symptomatology. Not only dental could be a lot of different disorders inside there now that can produce pain that also the readers can check our paper and learn about and see the wonderful interesting pictures that we have added there. Dr Monteith: Yeah. And so why don't we talk a little bit about TMD disorders and what is the new thinking around these conditions? Dr Romero-Reyes: Well, I will say for the last decade, maybe a little bit more has been a change in the evidence. They evidence based understanding of the theologia pathophysiologist and for mandibular disorders. Imagine that what's the shift in the in the paradigm that in dentistry prevails for a long, long time. That is that really focus and I will call it the pathological mechanistic point of view. What I mean by that I was focusing your bite, your occlusion, how the relation between in your maxilla mandible. That was the only issues that would create in temporomandibular disorders. So now we know that temporomandibular disorders are complex, are multifactorial and you need to understand them and see them within a biopsychosocial framework. And this dictate the main way to management for the primary way that we start will be conservative, reversible and basing evidence that the best evidence available that we have. Dr Monteith: And what about for trigeminal neuralgia? Is there newer kind of classification around trigeminal neuralgia? and what are some key points that we should consider when diagnosing these patients and treating these patients, Dr Barad?  Dr Barad: There haven't been any new diagnostic criteria, but I would say that there's been an increased awareness that classical trigeminal neuralgia is more likely than not related to neurovascular compression or we should say, maybe I should say neurovascular contact or compression. There is a developing grading system of that. That's an evolution as we speak. I think it's an exciting time for facial neuralgia because it's opened the door for us to look at other neuralgia also as vascular compressions and to think about how we can treat them with decompression or possibly with peripheral nerve stimulation or medicine or Botox. Or who knows what's the future is going to hold? But it is I think a change in the way we are thinking about the definition of neuralgia of, of trigeminal neuralgia in that is caused by a compression which is different than other neuralgia in other parts of the body. I should, I just want to classify there's about maybe ten twelve percent of people who present with classical trigeminal neuralgia who there is not evidence on imaging of a vascular contact or compression. But the majority of cases do seem to have some somewhere in the spectrum from contact to compression.  Dr Monteith: Even contact I find to be a bit vague sometimes say, well, thanks for letting me know that they're touching. But and then some of the neurosurgeons have different perspective when you open the patient up. So, I didn't know about the grading.  Dr Barad: Yeah, I think you've hit on it exactly like that is a big problem in the field right now. How do we understand what patients will be the best patients for surgery? And it used to be that you have the classical trigeminal neurologist symptomology plus some imaging that shows something versus nothing. And now we're getting into parsing out the imaging and trying to understand who's the best candidate for that with the imaging.  Dr Monteith: Dr Romero, anything to add?  Dr Romero-Reyes: No, that I agree about that, you know, and I think now maybe for the patients that I have seen with that, because under partial pain settings, sometimes we're the ones that, oh, actually what you have is trigeminal neuralgia idea, you know, so we start to have our small disciplinary management, but you know, when they come out, I already have an MRI doctor, but, and they say that these are compression, but what degree? And some patients that they don't have symptoms can have a compression. And I'm thinking maybe right that later on when we have more time and maybe nicer imaging, we're going to really find out or if it's the development angle is the measurement has some other characteristics, who knows. So, I think for trigeminal neuralgia, the things is still evolving, right? For our understanding. I have to help us to make a more- I will not say definitive diagnosis, but maybe some parameters will change in the future. Dr Monteith: So now we have a lot of people listening, international folks listening, and they always want some treatment, a tip, some clinical tips. So, can you give us a little bit of clinical insight to how to treat patients with trigeminal neuralgia and when you're seeing patients for second and third opinions, what might you see that may explain why their pain is not well controlled? We all get into interdisciplinary care, but in terms of pharmacology? Dr Barad: I think people are a little reluctant to use some of these medications that neuromodulating medications because, in general, it's an older population and they're rightly worried about falls and dizziness and confusion and low sodium. And so, I think they hesitate to go to the doses that are needed to help with pain control. So, a lot of our, my initial management is gingerly and gently titrating that to try to get to see if we can get control of the pain. Dr Monteith: Dr Romero?  Dr Romero-Reyes: I could add, for example, one thing that I in the realm of facial pain addition to pharmacology. Let's say that we have a patient with that intraoral trigger and we were able to localize that intraoral trigger. Sometimes we can even also use topical medication. And in the topical medication we can use, for example, an anticonvulsant, let's say gabapentin, oxcarbazepine for example, to add in the cream. And we use, we call it a neurosensory stent in my looks like a Nygard, but it's not a Nygard that can cover that area. So, the patient can add that cream very delimited in that area. And that helps, you know, can help with the pain sometimes. What we can find is that, at least in my, in my experience, and that when we add a topical, maybe we don't need to increase as much. The systemic medication, of course, depends from case to case.  Dr Monteith: So those are two great tips. Not being afraid to push those doses up in a safe manner and maybe with monitoring as well as of maybe utilizing more topicals. And I think we could probably hear a lot more from you on topicals at some other point. But thank you also for the table. I think it's, it's really nice the way all the treatments are laid out. So what other cranial neuralgia advances have there been? Dr Barad: I would say the main advancements have been in applying the knowledge that neurosurgeons have learned from microvascular decompression of the trigeminal nerve, to the glossopharyngeal nerve, to the geniculate nerve, and really trying to optimize imaging and optimize neurosurgical techniques to try to treat these neuralgias. If the patient has failed medicine, if the patient is a good candidate for surgery and if the patient desires that. Dr Monteith: Great. So now let's talk about multidisciplinary approaches. I know both of you are big fans of that, and you may do things a little bit differently at your institution, especially with your background. So maybe Dr Romero, do you want to tell us about your experience? And then we'll have Dr Brad. Dr Romero-Reyes: But in my experience from study management, let's say depend, of course, also the started we're talking about. But let's say for example about temporomandibular disorders, you know that for TMD is one of these overlapping pain conditions and we know that TMD is common with primary headache disorders, especially migraine. So, if we're able to utilize, you know, the expertise of neurologist specializing headache. With me, for example, or a facial pain person that is that is helping you manage a patient with this comorbidity. This is super effective because we know the presence of TMD in a migraineur can help the disorder to, to progress some more chronic form. So, you see, this is super important and effective to provide, you know, optimal care for the patient. For example, in the patients that I do see with neuralgias, like in addition to trigeminal neuralgia, let's say nervous intermediates neuralgia, that sometimes they can come to me like, oh, the pain is in my ear and my EMT or, or I think maybe it's my TMJ and for the pain is charged shooting inside the ear doesn't follow the for the diagnosis of temporomandibular disorders. And I can maybe help the patient to get a proper imaging or already penalize it with a neurologist to make sure. And maybe at least my way will be maybe I'm the one that can catch those disorders and help, you know, the patient to go for the next step. Dr Barad: I think Marcella, Dr Romero-Reyes, hit on a nice point that maybe this group is not as familiar with and that is that temporal mandibular dysfunction TMD is a, is one of the disorders that we call chronic overlapping pain conditions or COCPs. And those include headache. it's not, it's not specified fibromyalgia, irritable bowel syndrome, chronic pelvic pain and several other chronic pain syndromes. And they suggest a central sensitization to one's pain. And the way that we treat centrally sensitized pain is not just through medications, it's in a biopsychosocial framework because we see much higher rates of depression and anxiety in this group. And so, using a pain psychologist to help the patient develop coping strategies to help them manage their pain, using a physical therapist to help them learn this, the stretching exercises and using medications to help with not only with their pain syndrome, but also sometimes with their psych comorbidities. And then additionally, procedures sometimes play a role in the process to help usually turn down the pain. Interestingly, when we look at trigeminal neuralgia, we see much less overlapping pain disorders. It's much rarer to see somebody with TN who has other COCPs or the kind of chronic levels of depression and anxiety that we see in these patients. So, the approach is very different, and I think it requires the use of a multidisciplinary team to help guide the treatment pathways for these patients. Dr Monteith: Today, I've been interviewing Drs Meredith Barad and Marcelo Romero-Reyes, whose article on orofacial pain appears in the most recent issue of Continuum on pain management and neurology. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/AudioCME. Thank you for listening to Continuum Audio.

In the patient populations treated by neurologists, central neuropathic pain develops most frequently following spinal cord injury, multiple sclerosis, or stroke. To optimize pain relief, neurologists should have a multimodal and individualized approach to manage central neuropathic pain. In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Charles E. Argoff, MD, author of the article “Central Neuropathic Pain,” in the Continuum October 2024 Pain Management in Neurology issue. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Argoff is a professor of neurology and vice chair of the department of neurology, director of the Comprehensive Pain Management Center, and director of the Pain Management Fellowship at Albany Medical College in Albany, New York. Additional Resources Read the article: Central Neuropathic Pain Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @LyellJ Full episode transcript available here Dr Jones: This is Doctor Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum Journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Jones: This is Doctor Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today I'm interviewing Dr Charles Argoff, who recently authored an article on central neuropathic pain in the latest issue of Continuum covering pain management. Dr Argoff is a neurologist at Albany Medical College where he's a professor of Neurology, and he serves as vice chair of the Department of Neurology and program director of the Pain Medicine Fellowship Program there. Dr Argoff, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners?  Dr Argoff: I'm Charles Argoff. It's a pleasure to be here and thank you so much for that kind introduction. Dr Jones: I've read your article. Many of our listeners are going to read your article. Wonderful article, extremely helpful. Closes a lot of gaps, I think, that exist in our field about understanding central neuropathic pain, treating central neuropathic pain. You now, Doctor Argoff, you have the attention of a huge audience of mostly neurologists. What's the biggest point you would like to make to them, or the most important practice-changing advice that you would give to them? Dr Argoff: I think it's at least twofold. One is that central neuropathic pain is not as uncommon as you think it might be, and it occurs in a variety of settings that are near and dear to a neurologist's heart, so to speak. And secondly, although we live in an evidence-based world and we want to practice evidence-based medicine - and I'm proud to have formerly been a member of the Quality Standard subcommittee, which I think has changed its name over time. And so, I understand the importance of, you know, treatment based upon evidence - the true definition of evidence-based medicine is using the best available evidence in making decisions about individual patients. And so, I would urge those who are listening that, although there might not be as robust evidence currently as you’d like, please don't not take the time to try to treat the patient in front of you o r at least acknowledge the need for treatment and work with your colleagues to address the significant neuropathic pain associated with that central neurological disorder. Because it can be life-changing in a positive way to make even a dent and to really work with somebody, even though not clear-cut always what's going to work for an individual patient. Dr Jones: Well said. I'm glad you brought that up. So, to put it a different way, absence of evidence is not an excuse for absence of treatment. Right? Dr Argoff: Exactly. And I think that, I hope that we would agree that especially in neurology, what we do is about as far from, ‘Yep, you've got strep throat, here’s that antibiotic that's going to work for you and all you have to do is take the medicine.’ I mean, most of what we do is nowhere near that.  Dr Jones: It's complicated stuff. And this is a complicated topic. And I'll tell you, I learned a lot reading your article. I think most of us in neurology and medicine, when we hear the term neuropathic pain, it feels roughly synonymous with peripheral generators of that pain, such as diabetic neuropathy or posttraumatic neuralgia. But as you mentioned, there's central mechanisms for pain generation. How is it defined? What is central neuropathic pain? Dr Argoff: It's defined as pain caused by a lesion or disease of the central somatosensory system . Though neuropathic pain in general is pain associated with the lesion of the somatosensory system; and to your point, that can be peripheral, which of course is outside the spinal cord, or brain or central, which is within the spinal cord or brain. And central neuropathic pain is defined specifically as pain caused by a lesion or disease of the central somatosensory system. That's either brain or spinal cord. But there's an interesting follow-up, and I'm going to ask if you could remind me because I know we're talking about definitions now, but I'll just bring something up and we can come back to it. What's interesting about that is that my - whoever 's listening, that's not to say that they're not connected. And in fact, they are very much connected. And there's very new work, which I included in the article, down at Washington University in Saint Louis, that suggests you can actually affect central neuropathic pain by addressing peripheral input to the central nervous system. If you remember Ken Casey at the University of Michigan at the World Pain Congress in Vancouver, British Columbia many years ago, he ended his talk on pain with a limerick, of which the last line was, Remember, there ain't no such thing as pain without a brain. And so that kind of summarizes that. Dr Jones: Well, and it goes both ways too, right? We know that there's some central sensitization that can happen with peripheral generators, right? So we really have to think about the whole circuit. Dr Argoff: Yes. And that's been sometimes the bane of my existence as a colleague of others and a sometimes debater. Is the pain central? Is it peripheral? Well, it's everything. And it's important to know as many of the mechanisms and many of the targets that you could use for treatment so that you can affect the best outcome for your patients. Dr Jones: Yeah, so - and you mentioned in your article what some of the common causes of central neuropathic pain are. What are the big ones in your experience?  Dr Argoff: So, the biggest ones are spinal cord injury-related pain, MS-related pain - and I'd like to come back to a point and just if I do the third one - and central poststroke pain. And what struck me, I think Tim Vollmer published a survey about the incidence, the prevalence of ongoing pain in patients with multiple sclerosis. And it blew my mind several years ago because it was incredibly high. Like in this survey of MS patients who, you never hear about pain, you hear about these modifying treatments, all the wonderful expanses that have been made. I mean, like seventy something percent of people say they have moderate to severe pain. And when you think about how sensory processing occurs, it makes perfect sense that a demyelinating disorder is going to interrupt the flow of information for a person to feel normal.  Dr Jones: Yeah, I think it's a good example of, there are things that we tend to focus on as clinicians where we worry about deficit and function and capacity. But if we're patient-centered and we ask patients what they care about, pain usually moves up higher on the list. And so, I think that's why we, it's maybe underrecognized with some of those central disorders, right? Dr Argoff: I think so, and I and I think you hit the nail on the head that - and we're also trained that way. I tell this to my patients very often so that they are reassured when I examine them and I say, and I tell them that everything looked pretty OK. It's not a medical term, I understand that. Because what we do in a typical neurological exam, even if it's detailed, doesn't really address all the intricacies of the nervous system. So it's really a big picture and sensory processing and especially picking up sensory deficits; you know, we use quantitative sensory testing and research studies and things like that, but bedside testing may not reveal the subtle changes. And when we don't see overt changes, we often think - that can lead someone to think that everything is OK and it's not. Dr Jones: So, when you when you see a patient who you've diagnosed with a central mechanism, so central neuropathic pain, how do you approach the management of those patients, Dr Argoff? Dr Argoff: I always review what treatments and what approaches have been addressed already. And I see if - a handful of time, we actually just submitted a paper for publication regarding this in a group of patients with pelvic pain who had untreated, difficult-to-treat chronic pelvic pain, seen all the urological kinds, gynecological things. Look, we picked up two patients who had unknown MS. So, it's just interesting when it comes down to that level. And we also picked up some patients who had subacute combined degeneration. So that's another central kind of disorder as well. Again, the neurologist in us says to make sure that we have specific diagnosis that underlies the central neuropathic pain. And so interestingly, of course, for somebody with MS - or even though it's uncommon, it could be more than one. Somebody with MS might have a stroke, somebody with MS might have a cord injury due to cervical, you know, joint disc disease. Not to overcomplicate things. Know the lay of the land, know the conditions, know what you're battling and lay out so that you can treat the treatable; you want to treat whatever you can correct? So, for MS you simply want to have the best disease-modifying treatment on board, tolerable and appropriate for that person, and so on. And then you really want to take a history of past treatments - and your treatments can be everything and anything, including behavioral modification, physical rehabilitative approaches, as well as pharmacologic management. That's - as I think I put in my article, we concentrated in the article on pharmacologic management because honestly, that's what most patients are looking for, is ‘what can we, what can you do to help me now, in addition to what I can do myself.’ And that's what we typically think of. There are also some more interventional approaches, invasive options, that have developed over time. And of course, those are the ones, some of them, especially in neuromodulation, that we have the least information about, but it appears somewhat promising.  Dr Jones: No, that's exactly what we need to hear. And you also mentioned something that I think is important. This is a common theme throughout the issue because I think it's true for the management of many different types of pain and interdisciplinary approach. In other words, not just honing in on pharmacotherapy or neuromodulation as a one-size-fits-all magic pill, right? So, that - tell us a little bit more about that interdisciplinary approach and how that's important for these patients. Dr Argoff: So, let me back up and give an example. Let's look at Botox for chronic migraine. So, the pre-M studies that led to the approval of Botox for chronic migraine: two treatment sessions versus two random, two placebo session in different patients. The mean headache frequency was, let's say, fifteen to twenty in each group. It was like seventeen, eighteen, something like that. But the mean pain headache day reduction was somewhere between four and five after two treatments compared to a lesser, a lower number in the placebo group. So, if you think about that, that means that you went from nineteen, let's say, to fourteen, thirteen, or twelve. Want to be generous, eleven or ten. But that means that person, everyone 's happy. We use treatment. We have better data than that because the longer you use it, the better it gets in general, but it means that people are still going to be symptomatic. So that drives home in a different painful disorder the importance of yes, treatment can be effective, but it's not the only treatment that a person is going to likely need. And so, I think that's what's so important about multidisciplinary approach. I- we may affect positive changes, reduction in pain intensity with a particular pharmacologic agent, but we don't anticipate it's like taking an antibiotic or a strep throat, not curative. And so, we want to, early on, to explain that logically, methodically, step by step. There are many options for you and we're going to, you know, systematically go through them. And I may need to call in some colleagues to help because I don't do everything. No one does everything, right? But don't feel as if there isn't any hope because there is. If we were to use intraspinal Baclofen for someone who has painful spasticity following a stroke or a spinal cord injury, combining that with physical therapy might give more effect, maybe synergistic. Some targeted muscles, some local muscles may not respond as well to the intraspinal Baclofen, so is that - what can we do? Well, we could use oral agents or we might be able to target that with botulinum toxin, and so on and so forth. So it's limitless, virtually, in what you can do. Dr Jones: There's kind of setting expectations and letting people know that you, you're going to need a lot of different approaches, right? To sort of get them the best possible outcome. Dr Argoff: Yeah, I think that's so important. And of course, no matter what we try to set out, there are going to be individuals - for those of you who are listening, we all know - who expect to be cured yesterday. That might be challenging for us not only to actually complete, but also, it's challenging for some individuals to appreciate that we're with them, we're going to work with them. It’ll be a process, but we've got your back. Dr Jones: Great. And you know, this is a question that I get all the time from patients and from other clinicians is, you know, what about cannabinoids? What's the role of cannabinoids for the management of central neuropathic pain? Dr Argoff: First, I'll say that the short answer to that is we don't know. The second part of my response would be, there is new evidence that it might be helpful in the acute treatment of migraine. And I'm happy to say that the editor of this edition of Continuum is the person who developed that evidence, and it's been recently presented at the American Headache Society. But the challenge and the conundrum that we all face is, everywhere within our nervous system where there's pain being processed, there are endocannabinoid receptors. There also happen to be opioid receptors, but that's a separate issue. And the endocannabinoid system, the peripheral or central, you know, CB1, CB2, is very, very important, but we haven't figured out a way of harnessing that knowledge in developing an analgesic, an effective analgesic. And part of that is that there are so many chemical agents that have cannabinoid properties and there are different… the right balance has not yet been found. But even the legalization, the available of medical cannabis, hasn't led to a standardized approach to evaluating if a preparation does help. And that's part of the conundrum. It's like saying, ‘does medicine work?’Well, yeah, sometimes. But which medicine? Which receptor? How do you harness the right ratio between TBD, THC, other active agents, et cetera? And I think maybe as we go forward in the future, we’ll be able to do that with - more precise. I mentioned Dr Schuster's study in which he had defined ratios of THC effect and CBD and was able to clearly show effect based upon that. But the average person going into a dispensary doesn't really get that. We don't get to study that. Each person's an NF1  and it's not very helpful to understand how to do that. I would say, as I'm sure you remember, there was a practice parameter that was published probably over a decade ago about using cannabis symptomatically in different neurological disorders. And I believe that it was what they studied or what they reviewed was helpful in MS-related urinary discomfort and spasticity, but not necessarily pain.  Dr Jones: And we're still in the early days of studying it, right? Dr Argoff: Yes.  Dr Jones: That's part of the point, as we got started late and we're still waiting for high-quality evidence. And I guess, if you look at the horizon, Dr Argoff, or the future of management of central neuropathic pain, what's going to be the next big thing?  Dr Argoff: One of the joys of being asked to get involved in a project like this is that inevitably we learn so many new things because, you know, that's when anyone says, oh, you must be an expert, I say, I don't know anything because I'm always learning something new. One of the reasons why I moved to Albany Medical College about seventeen years ago was to be able to further my interest in studying why people benefit from topical analgesics by working with a scientist at Albany Med who studied keratinocyte neurochemistry and its impact on pain transmission. And that's a separate issue, but it indicates my love for the peripheral nervous system. And one of my thoughts historically, that is, what the central nervous system processes is what it processes and it might get input, as you mentioned earlier, from the peripheral nervous system, so that topical agents could be dampening central mechanisms. And lo and behold, as I was doing research for this article, I learned that people doing peripheral nerve blocks - so blocking peripheral input at the into the spinal cord - at Washington University, Simon Guterian and colleagues, demonstrate that they could give prolonged benefit from central pain by blocking peripheral input. And that's wild because certainly the nervous system is a two-way street. It's an understatement. What I really found amazing was that, again, blocking input helped the injured central nervous system to behave better.  Dr Jones: That is kind of cool to think about. And I'll tell you, as editor of the journal, one of the funnest things is getting to learn all about neurology, including pain and including central neuropathic pain, when in the end you're doing all the work, I just get to sit here and enjoy it. And you're a program director of a pain fellowship. What's the pipeline look like? Are neurologists more interested in pain than they used to be?  Dr Argoff: I'm happy for this. We are seeing more and more applicants from neurology into our pain management programs. I would say… I was going to say tragically. If I say tragically, it's because what specialty better understands how to diagnose, figure out, assess, come to a conclusion? You can't have pain without your brain. It's always amazed me that more neurologists weren't interested, and I understand the background and such. Just like in migraine, it's only advances in understanding mechanisms of migraine that allow neuroscientific advances that are leading to great therapeutics - that's happening and increasing in ‘pain.’ Today, as program director, we had our fellowship interviews earlier today and three of the nine applicants that we interviewed were neurologists. Last week, I think we interviewed two or three also. That would not have happened five years ago or six years ago. And if you think about it, we can not only diagnose, quote-unquote figure out what's happening, but we now, with pain management training, we can offer people a variety of both invasive and noninvasive options, all while understanding what we're doing with respect to the nervous system in a way that's different than the other specialties that typically go into pain med. And that's such - for me, it's a beautiful experience and something I really enjoy doing. There isn't a neurological condition in the most part that either doesn't have pain associated with it or doesn't have mechanisms that overlap. If you think about epilepsy, and please don't think I'm crazy, but epilepsy is associated with disinhibited hyper-excitatory behavior, just to put it loosely, among certain neurons. That's what pain and neuropathic pain is about too. And you, in fact, we know that several mechanisms since now what medicines are used for both. But what was interesting since, if I may just go back to another point, one of the advances since I brought up the migraine that's very exciting is the whole story about sodium channels. Dr Harouthounian at WashU and his group used lidocaine injection. Lidocaine's a more generalized sodium channel blocker, but some of the newest treatments for treating neuropathic pain. Our NAV specific sodium channel blocker’s trying to match up mechanism to treatment. Not exactly the way that we do with migraine, but still a step forward to not just generally treat but really target different neuronal mechanisms. It's an exciting time.  Dr Jones: So, the pipeline is doing better because we're getting better understanding of disease, and hopefully that pulls in more interest because obviously there are big gaps in caring for patients with pain. And again, thank you, Dr Argoff, for an amazing article. Thank you for joining us and thank you for such a fascinating discussion. I enjoyed the article. I read the article, I learned from our conversation today. So, thank you for joining us to talk about central neuropathic pain. Dr Argoff: Thank you for having me. Dr Jones: Again, we've been speaking with Dr Charles Argoff, author of an article on central neuropathic pain in Continuum 's most recent issue on pain management. Please check it out, and thank you to our listeners for joining today. Dr Monteith: This is Doctor Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Dr. Miroslav Bačkonja, clinical director at the NIH, dives deep into the world of peripheral neuropathic pain. He uncovers the intricate biology of peripheral sensory nerves and discusses the emotional toll of chronic pain on patients. The conversation emphasizes the importance of accurate diagnosis and personalized treatment strategies. Innovative therapies like Tai Chi and mindfulness are highlighted as valuable complements to traditional approaches, promising exciting future breakthroughs by exploring molecular biology and the nervous system's interplay.

Dr. Vernon Williams, Director of the Center for Sports Neurology and Pain Medicine, shares insights on the complexities of spine pain. He emphasizes that pain perception is influenced by genetics, behavior, and social factors. The conversation explores a holistic approach to treatment, integrating medical, behavioral, and social aspects while highlighting the importance of communication in care. Williams discusses innovative pain management strategies, including neuromodulation and advanced technologies, and addresses health inequities affecting patient access to treatment.

Neurologists bring special skills to pain evaluation and management and are well equipped to appreciate both the focal and diffuse nature of pain. By using expert knowledge of the nervous system and implementing relevant therapies, neurologists can succeed at and find meaning in optimizing patient outcomes. In this episode, Allison Weathers, MD, FAAN, speaks with Beth B. Hogans, MD, PhD, author of the article “Principles of Pain Management,” in the Continuum October 2024 Pain Management in Neurology issue. Dr. Weathers is a Continuum® Audio interviewer associate chief medical information officer at the Cleveland Clinic in Cleveland, Ohio. Dr. Hogans is an associate professor in the department of neurology at Johns Hopkins School of Medicine and an associate director for education and evaluation at the Geriatric Research Education and Clinical Center at the VA Maryland Health Care System in Baltimore, Maryland. Additional Resources Read the article: Principles of Pain Management Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum Journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME.   Dr Weathers: This is Dr Allison Weathers. Today I'm interviewing Dr Beth Hogans, author of Principles of Pain Assessment, Diagnosis, and Management from the October 2024 Continuum issue on pain management and neurology. Welcome to the podcast, and please introduce yourself to our audience.   Dr Hogans: Good afternoon. My name is Beth Hogans. I'm a neurologist. My faculty appointment is at Johns Hopkins School of Medicine in the Department of Neurology, where I'm an assistant professor. I also serve at the Baltimore VA Medical Center, where I'm the Associate Director of Education and Evaluation for the Geriatric Research, Education and Clinical Center, as well as a neurologist.   Dr Weathers: Thank you so much for, again, being with us today and taking the time to speak with me. I was really struck by how broadly applicable this topic is, not only to all neurologists, but to all physicians and even to all of our listeners, given how prevalent these conditions are. Nearly all physicians involved in direct patient care treat some type of pain disorders, and we all experience pain at some point, though hopefully not chronic pain. Well, usually like to start with a question - again, it feels especially pertinent here in getting to speak with you - what is the most important clinical message of your article? Dr Hogans: So, I'm going to say there's two key messages. The first one is that all pain has a differential diagnosis, and the second one is that all meds work better with non-pharmacological and whole-health comprehensive management incorporated. So that's why I structured the article around the ideas of assessment, diagnosis and management. It's a pretty sort of traditional, basic approach to how we look at clinical problems, but we definitely want to start with proper assessment, go on to a thoughtful differential diagnosis, and then move towards a management plan that is not just, you know, one stop shop, but actually kind of brings several aspects together. Because pain is so multidimensional; you know, it's represented in multiple places in the brain as well as other levels of the nervous system. And so, I think we're still in an era, and we may stay in an era, of, you know, needing something to go along with medication in many cases.   Dr Weathers: I think those are two absolutely critical points for our listeners to keep in mind, both, again, keeping that broad differential, and - we'll get more into management in a bit, but again - that dual strategy of both the pharmacologic and the non-pharmacologic. And again, going down a little bit more there on that management track, a really recurring theme that I picked up in your article is the importance of interprofessional collaboration in the assessment and the management of patients with pain. In the abstract, you actually use the phrase “remarkable” for the diversity of health professions, which I really loved. What other clinicians do you work with in diagnosing and managing pain conditions, and what are their roles in the care of these patients? Dr Hogans: So, something you hear over and over again at pain meetings is, “there is no I in team.” They say that all the time. And it's one of the things I really love about pain, is that we get to work with great colleagues who have their own perspectives, approaches and therapies for pain. So, in my particular practice, which I do focus kind of more at the interface between neurological and musculoskeletal pain because of my passion and interest for spinal pain, you know, ranging from neck to tailbone, but most especially in the lower back. Physical therapy, clinical psychology, sleep sedicine, nursing, pharmacy, rehab… Podiatry is something that people don't often think of, but is really important for getting spine mechanics correct… Ergonomics. But I want to just say something about clinical psychology because there may not be enough clinical psychologists in the United States, but we as neurologists are also brain doctors. You know, we have to stay within our scope of practice. But there's a move now to talk about psychologically informed physical therapy. So why don't we talk about psychologically informed neurology? I think we could do an even better job of kind of leveraging our knowledge of the brain and how it works to kind of bring that into our practice. And so, people with pain often need a lot of empathetic support, for example, as well as knowledge about their condition. So, I would encourage people to build local networks of folks that they refer to and work with. Because when I was a younger doctor, physical therapists taught me a lot of what I know now - because I didn't get it at med school, although by the time I got to residency, I had some really great teachers. But clinical psychology, PT, sleep medicine, those are, like, almost all-the-time collaborators for me. And then like I said, nursing, pharmacy, rehab, podiatry, et cetera, et cetera, prosthetics… those things are all important for pain. Dr Weathers: I was struck by the quote, “one of the things I really love about pain.” That's a great line, and understand how it was meant, but I think - again, a really great quote, but I think you make such important points and, really, it is such a critical team approach. And I love all of those roles you called out. And I was struck in listening to your really thoughtful answer about how I've spoken with several other authors of actually very different topics, but about how we're thinking now about a trauma-informed care approach to many neurological conditions and the similarities with this patient population, how it likely informs very much the approach to this patient population as well and probably the significant potential.   Dr Hogans: A hundred percent! And so, for example, one of the things that probably does factor in for chronic pain - not in everyone, but in, let's say, many cases - is a prior exposure to trauma, whether it's PTSD or adverse childhood events. And so that's why, you know, clinical psychology is, like, very high up on my list of collaborators. And one of the things that I really like - you could say love - about working in the BA system is the ready availability of mental health co-management. So, I would say about a third of my patients in neurology are co-managed by mental health. And what it does is it sort of defuses a lot of what would otherwise come into the visit and be my job as a neurologist to manage, if not treat, right? I still have to manage, you know, someone who comes in with untreated mental trauma or mental health conditions if they're coming into that visit, and I'm trying to open the topic of whether mental health co-management could be helpful. That can sometimes, strangely enough, antagonize people. We’re still in an era of substantial stigma. But I can just say the practice of neurology, together with appropriate mental health co-management, is far superior than going alone. Dr Weathers: Absolutely. And how fortunate that for a lot of your practice, your patients do have those resources available to them. And I think it speaks to the importance of those resources, that all of our patients should really have that availability, and the importance of access. Dr Hogans: Right. So, at Johns Hopkins, we also have exceptional access to, you know, some of the world 's best clinical psychologists. And I've been really privileged to work with my colleagues in clinical psychology. The challenges that - in some of my roles, I interact with trainees and learners who are in clinics that are not as well resourced. And therein lies just tremendous heartache and difficulty. We've been trying to build some resources. There are federal resources that can help to open those conversations and maybe take some of the initial steps towards things like cognitive behavioral therapy, acceptance commitment therapy, mindfulness-based stress reduction. There's many of these psychological therapies that are proven to be effective for pain and chronic pain, and yet we haven't really had that conversation as a society about, how do we get people connected with those therapies? Many of them can be delivered on a larger scale. And I think we just need to think a lot more thoughtfully about, how can we have more of a public health approach to chronic pain and wellness? Dr Weathers: Absolutely. Such really important points. So, we've talked about the really kind of important, obvious points for what we very much kind of know to be accurate. I want to talk now about, what are the most common misconceptions that you've encountered in treating patients with pain disorders?   Dr Hogans: Yeah. So, this is where, you know, physician as advocate for the patient really comes into play. So, I think the number one misconception that I and many of my colleagues encounter: that pain is the patient 's problem, or that that pain reflects an excessive sensitivity. I think one analogy that I use with students that helps to kind of piece this apart is the immune system, right? There are people who have immunodeficiencies that they're not sufficiently protected from the environment, and then there are - lots of people have allergies where their immune system is sort of hyper-alerted to things that are not a true threat. And the pain system is exquisitely regulated. The neurology of the pain system is fascinating and compelling, and once you learn a little bit about it, you can apply it at the bedside, time after time after time. So, number one: pain is real. And there is an association between strong pain and increased risk for chronic pain. And then sort of the flip side of that is that malingering or, you know, fictitious pain is probably a lot like other functional disorders in that it's part of a complex. So, I think we need to do a lot more work to discover, you know, quote, what is pain that people think is amplified or manufactured and how can we frame that in a clinical context rather than just casting blame or- we already mentioned stigma. You know, stigmatizing people does not help. And there are people who have real pain problems that are really severe and disabling, and neurologists can actually help support those people as they encounter their environment. Dr Weathers: I really love that response. And I think you're right in that we do so often, in the medical system, tend to stigmatize these patients, even as we say the right things and we, I think, talk about it and we recognize… and yet, still, it's almost these unconscious biases. I think, as good as we've gotten in some areas, it's still hard to separate them. It's almost kind of one of the last unspoken, still-acceptable ones in some ways that oh, they must be drug-seeking or, you know, to your point, you use the word, kind of malingering, that they’re somehow, you know, either at fault or that there's some nefarious behavior going on there. And I think you made such really important points that we have to change our way of thinking that it is such a common and, frankly, wrong misconception that a lot of us really carry around and it's really hard to break. We have to kind of recognize these biases in ourself and really fight against them when we encounter these patients. Dr Hogans: I think part of how we got there is the opioid crisis. Dr Weathers: Yes. Dr Hogans: You know, unfortunately we still do not have a fantastic understanding of opioid durability. Like, how long does opioid analgesia last? Not from, like, hour to hour, but, like, from month to month. Roger Cho has done some awesome work looking at long-term efficacy of opioids, and it's surprisingly modest. And yet, opioids have this profound kind of behavioral impact, that they really are highly reinforcing. And so, once they're in the conversation, you find yourself in, like, almost this life-or-death struggle between, you know, am I going to get opioids at this visit? How many? You know, if not, why not; are you going to decrease? And so those of us who are working today, you know, and have been working for the last five years, have been through this terrible struggle. And that struggle is not yet resolved. But once opioids are kind of off the table or neutralized, then we actually have a conversation that is really, you know, A: how good of a clinician are we? Do we really understand what our patient is going through? And how can we bring, like Hippocrates said, you know, get the system to bear on the problem and not just, you know, try to throw drugs at it. So I think that, really, pain challenges us to be our best selves and to, you know, really be clever and kind and helpful. And it is a really great opportunity to help. And as I said, the mechanisms of pain are fascinating neurologically. So, it kind of satisfies some of what we come to work for, but I think it's not all done yet. One of my challenges has been, I wrote an article in 2011 with one of my trainees where we counted up the number of hours documented in the double AMC database for med schools, and we found that the modal value for US medical schools at that time was four. So out of four thousand curricular hours, there were four pain hours. And when you think about the prevalence of pain, that's just a drop in the bucket. So, you know, it's getting better, but we need to come up with some new strategies. So I wrote, I've written three books now. The latest one is really designed to give that intro-level knowledge of pain. But also, obviously, the Continuum article, I wanted to kind of set the table, lay the foundation, and give people some core knowledge to get started with. Dr Weathers: And again, a fantastic article. If our listeners haven't read it, I strongly encourage them to go back because I think you did just that. And as you were just talking, I was thinking about that, especially for those of us who, you know, depending on when in your training was, you know, mine started in the early 2000s. We've kind of lived through that era with the pendulum swinging. Where was, you know, the signs were posted in each clinic room. You know, don't forget to ask, you know, your provider about your pain meds, and it was the sixth vital sign, and all of that. And then the pendulum swung very quickly and very severely the other way, where it was, you have now created this problem, right? We have all caused this epidemic and we're supposed to immediately take these meds away, right? And now to your point, you know, we've all been in these situations with opioids where that was all that was talked about, right? So, you know, we've all been on call and now you're getting the call overnight from people trying to get their opioids filled when, you know, not their prescriber because they knew if they called - or family members, as soon as you got prescribing rights, were now calling and asking. And we've all been in these very hard situations. Dr Hogans: Just because you have a hammer doesn’t mean that everything is a nail. Dr Weathers: I know. So, in trying to negotiate and navigate, you know, these very rough situations… And I think now we're reaching kind of this new era where, to your excellent point, realizing that there are a lot of other solutions. And I love how you framed it, that this is really where we can be our best selves as providers. And actually, to that point, so - as I've mentioned on this podcast many times, clinically, I'm a neuro-hospitalist and I actually wanted to get your opinion as one of the foremost experts. So, a challenging situation I'm also often faced with in my clinical role is when a patient with a chronic pain condition such as diabetic neuropathy or lumbar radiculopathy is admitted to the hospital, often with a totally unrelated condition that either results in a new acute pain, but often also exacerbates their underlying chronic pain, what's your approach to the assessment and management of similar cases? I know our listeners will return again and again to that fantastic approach you laid out in Figure 1.1 with the coordination of the pharmacologic and non-pharmacologic therapies, as we've talked about several times just throughout our conversation, how important both of those approaches are. But a lot of those options are unfortunately limited in the in-patient setting. So how do you balance those? Dr Hogans: So, there's a whole other toolkit that comes into play for acute pain or sort of pain palliation. And you actually have some important allies in the hospital. It turns out that nurses, generally speaking, have some more education than do most physicians about pain. And the nurses that I encounter really see themselves as genuine, sincere advocates for the patient 's interest. They're at the bedside, they're working very closely, and their training actually does, I think, give them a number of tools and a set of inspirational ideas that build towards patient comfort. So, if you communicate with nursing staff about your desire to provide more comfort for the patient, whether it's padding, positioning, activities such as, you know, having them participate in something, you know, whether it's just having a family member, you know, take them for a walk, whether it's in a wheelchair or having an older adult sit by the nurse's station just to give some form of distraction. Ice, you know, cool packs and hot packs, you know, supportive toweling or pillows, all of that can really help. Years ago, nurses used to actually be trained in giving massages, and that can provide some comfort. You know, supportive touch is kind of how we frame that nowadays. But the other piece that you have is, in many cases, PT is getting involved much earlier in the patient, you know, rehabilitation course. And remember that motion is lotion. So, our endogenous analgesia system, which actually involves both endogenous opioids and endogenous cannabinoids, can be activated through many forms of motion, as well as immobility is actually a cause of pain itself. So, you just, you break out your in-patient tool kit and, you know, there are other tools and there's other allies that you want to think about in that context. Dr Weathers: Those are all really great tips, many of which, I know, as you said, a lot of us tend in our thinking to go right to pharmacologic strategy, so wouldn't even be considered, but I think really thoughtful, and that we do have at our fingertips. So- Dr Hogans: I wish I had thought to put them in the article. Dr Weathers: No, they were fantas- but again, why we podcast, agree for complimenting the article… we encourage people to take advantage of both. Well, this has been wonderful, and I know I have learned so much, even more than was in the article. I always like to end on a hopeful note, so I would love to hear what developments in the field of pain that you're most excited about. What do you think is coming down the pipe? Dr Hogans: Well, I think, like a lot of people, I've been waiting for the opportunity that's happening right now, which is, there's a massive investment in pain science being made by the NIH. Finally. You know, we've moved from, you know, just like, little things here or there, commercial kind of entities, to, we now have large NIH dollars flowing into pain. I'd like to see not only a focus on small molecule development, which will ultimately lead to better pharmacological agents, but I'd also like to see a thoughtful approach to non-pharmacological therapies, whole health approaches. Things like healthy communities, safe exercise spaces for all ages, more nutritious food, yoga, Tai chi. We know from Skelly and Cho's article in 2020 that there are many, many non-pharmacological therapies that actually work for chronic pain. There’re some things we still don't know. Like, do older adults respond as well as middle-aged adults? And how can we get NPTs - non-pharmacological therapies - more accessible to people who are subject to disparities? I think part of what happened during the opioid era is that you could get, you know, a bottle of pills for a four-to-ten dollar co-pay and physical therapy was twenty dollars a shot. And we know PT will get you to a better place, but that person that you're talking to may not have three hundred dollars to go to a course of PT. And we need to figure out, you know, how do we do this better, safer, more healthfully. Dr Weathers: And, I think, forgetting even the co-pay; it's the coordination, the time off work, all of it, right? So it's, I think, all of those challenges, but I think all of that are such important points about - and I think, that's really where I'm hopeful. Right? The emphasis, we talked a little bit about trauma-informed care earlier in our conversation, but the focus now on addressing the underlying social disparities of health and overall healthcare disparities, I think, is so promising. Dr Hogans: We need to think about the long-term consequences for human health; and pain has a terrible impact on human health for many reasons, and, I hope, will continue to be the focus of effort for years to come. Dr Weathers: Absolutely. Well, that is such an important statement to end on. Thank you again, Dr Hogans, for such a fantastic conversation and again, such an overall excellent article. Dr Hogans: Thank you, Dr Weathers, it was great to speak with you today again. Dr Weathers: Today I've been interviewing Dr Beth Hogans, whose article on principles of pain assessment, diagnosis, and management appears in the most recent issue of Continuum on pain management and neurology. To learn more about the topics of pain assessment and other topics of pain management, don't forget to listen to Continuum Audio episodes from this and other issues. Thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/AudioCME. Thank you for listening to Continuum Audio.

In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Nathaniel M. Schuster, MD who served as the guest editor of the Continuum® October 2024 Pain Management in Neurology issue. They provide a preview of the issue, which publishes on October 2, 2024.  Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Schuster is an associate professor and associate clinic director in the Center for Pain Medicine and Department of Anesthesiology at the University of California, San Diego in La Jolla, California. Additional Resources Continuum website: ContinuumJournal.com Subscribe to Continuum: shop.lww.com/Continuum More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @LyellJ Guest: @NatSchuster Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME Journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal have access to exclusive audio content not featured on the podcast. If you're not already a subscriber, we encourage you to become one. For more information, please visit the link in the show notes.   Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr Nathaniel Schuster, who recently served as Continuum’s guest editor for our latest issue on pain management and neurology. Dr Schuster is a pain neurologist at the University of California, San Diego, where he is an Associate Professor of Anesthesia. Dr Schuster, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners?   Dr Schuster: Thank you so much, Dr Jones, for having me. My name is Nat Schuster. I am a pain and headache neurologist at UC San Diego, in the Department of Anesthesiology. I do research, clinical practice, and of course, education of med students through pain fellows, and it's been a pleasure to be the guest editor for this forthcoming issue of Continuum.   Dr Jones: Well, I want to thank you for editing the issue. I want to thank you for putting together, really, an incredible list of topics and, really, expert authors. It's been a long time since Continuum has dedicated significant space in an issue to pain management, which is obviously a hugely prevalent, major problem in society, and I think a big gap for many of us – I know it is for me in my practice, so I've enjoyed learning about it – so I want to congratulate you on the issue and thank you for doing it.   Dr Schuster: Yeah. I was just at AAN a few weeks ago. I was chatting with the person who edited one nearly 20 years ago, a prior pain Continuum issue - so, really glad that for another generation of neurologists that we're going to have this as a reference, and hopefully, it'll serve them in their care of so many patients, because this is just such a ubiquitous problem facing Americans and people around the world.   Dr Jones: Yeah, and a lot's changed in 20 years, so let's get into it. And I will say, you know, now that with our open podcast model, we're interviewing the guest editors, you have, really, an incredible view of the entire field at the moment. And with your reading of the issue and your experience as a pain expert, Dr Schuster, what do you think is the biggest controversy in pain medicine right now?   Dr Schuster: Yes, certainly. I think the most controversial thing facing our practicing neurologists is the opioid issue and how things have been changing with national guidelines since 2016, and, fortunately, we are going to have an article by Dr Friedhelm Sandbrink - who is not only a neurologist, but he is the national director for the VA system - on pain management, opioid safety, and prescription drug monitoring programs. So, it's really wonderful that we have him as an author, and I hope that all the neurologists take an opportunity to read his really important manuscript, because it's dizzying, and, you know, if you're not reading the latest things from people like Dr Sandbrink pretty much every couple of years, you're probably falling behind when it comes to what are current attitudes, what is necessary to be, you know, most responsibly continuing your patients who have been on opioids for so long (many of whom have really debilitating neurologic conditions, nothing else is helpful for them), how are you able to best treat them, best monitor them in the appropriate ways to be doing things in compliance with guidelines.   Dr Jones: And I think monitoring is one of the things that, for neurologists who are uncomfortable with pain management, uncomfortable with the modern role of opioids, I think part of it is, well, what are my accountabilities? What are my responsibilities for doing that? That article will have great insights for our readers. Cannabinoids - that's another one I hear a lot of questions about, and it's obviously evolving. The science is relatively less mature there. From your perspective, what's the role of cannabinoids in a modern pain practice?   Dr Schuster: Yeah. Once again, so much controversy there and so much variability across the US, of course, between institutions, between states - hugely different. And as we speak, it's looking like cannabis will very likely be recategorized as being schedule III, so things are changing, you know, even between right now, probably, and when people are going to be reading the forthcoming Continuum and listening to this podcast. At UC San Diego, we certainly have been on the forefront of doing clinical trials, looking at these clinical trials. They're academic studies using the NIDA drug supply. So, they're not the size and scope of so many of the things that we use that have had industry-funded, large, multicenter studies done, but the research that we've done has shown promise for quite a few different neurologic conditions, ranging from my most recent research was in the migraine space, looking at acute migraine (and I just had the pleasure of presenting that data at AAN a few weeks ago), looking at other things over the years, looking at spasticity pain and multiple sclerosis, spinal cord injury pain, diabetic peripheral neuropathy, other peripheral neuropathies. So, in the conditions that we as neurologists so often do treat, that does seem like there is a lot of promise. It's something that in our practice, some of our doctors are more comfortable with it, others are less comfortable. I know, myself, I'm very conservative when I discuss it with patients, because there is, you know, addiction concerns, misuse concerns, abuse concerns - I don't believe that it's to the degree of opioids, and I don't think that the risks are anywhere close to what they are with opioids - and while it's less in opioids, we have other things, fortunately, in this field that don't carry those concerns, and so, I certainly try to use those other options as much as possible before having the discussions about cannabinoids. That said, so many people are using them, and so I'm able to guide them towards, you know, telling that very often, doses that are lower than what they might need to get intoxicated might actually be the doses that are therapeutic, and recommending using high CBD and low THC is probably going to have less side effects, and there's some evidence towards, hopefully, having more therapeutic benefit, especially in our most recent study looking at acute migraine that you want to have that CBD component with the THC.   Dr Jones: That's outstanding. So, we know more than we used to. It still feels like a relatively understudied area (and that's partly been the regulatory barriers to doing science on cannabinoids), so we'll look forward to hearing the latest and greatest in the issue. When we think about in neurology - and I'm thinking here as a clinician - when we think about pain and neurology, we often think about neuropathic pain. And, personally, you know, I see a lot of patients who have peripheral generators for those symptoms of neuropathic pain, but central neuropathic pain is an issue, too - and we have articles on both of those, one on peripheral neuropathic pain, one on central neuropathic pain. For our listeners, what should they know about the differences between those two and the treatment approaches to those?   Dr Schuster: Yeah. So, we fortunately have two wonderful articles - one of them from Dr Charles Argoff looking at central neuropathic pain, another one looking at peripheral neuropathic pain from Drs Misha Bačkonja and Victor Wang. And one thing that I think is really interesting about central neuropathic pain is that for these same patients, we don't need to only be thinking about the central neuropathic pain alone, and not everything that they're experiencing is going to be central neuropathic pain, because they can have “frozen shoulder” - post-stroke shoulder pain is actually a really big deal. Of course, you need to be concerned about things like sacral decubitus ulcers in so many of these patients. And so, they can have nociceptive components in those same patients, and us as neurologists, taking care of these very complicated patients, need to have our eyes open for the central neuropathic components, but also in those same patients, the other pain generators that we can do a lot for.   Dr Jones: So, the musculoskeletal and other generators of pain are relevant. I think that's something that many of us have experienced. Certainly, when I trained, Dr Schuster, the general construct around pain was that it was a really biological phenomenon, and it's an adaptive phenomenon, but it becomes a clinical problem when the pain is unmanageable or out of proportion to the patient's coping skills, and it seems to have evolved - at least in terms of our understanding of it, how it impacts people's lives. It's not just a physical or biological process, right? There are psychological factors here, there are social factors here. How does that inform your thinking about management of pain?   Dr Schuster: Yeah, so, I think that that's one of the most important running themes throughout this issue of Continuum that readers will find, is that there's a movement away from the biomedical model towards the biopsychosocial model in thinking about patients. And, at least for myself, when I was coming out of neurology residency, my training was much more on the biomedical model and on medication treatments. And throughout this issue, what you'll find is discussions of the importance of the biopsychosocial model, having pain psychology as being a component of the treatment for so many of these patients. That medications alone (for many of our most challenging patients) won't be the answer by themselves - that you'll need to have involvement of physical therapy, of pain psychology. And we have an article written by the pain psychologist who I work with at UCSD, Dr Mirsad Serdarevic, which I think will be very interesting for so many neurologists. It's also wonderful that we have an article on facial pain that's written by a neurologist, Dr Meredith Barad, together with a dentist, Dr Marcela Romero-Reyes. So, it really takes a team to treat so many of these very challenging patients who we are treating in our neurological practices.   Dr Jones: Yeah, thanks for that. I realize that with a complex problem, a lot of times you need more than one area of expertise, right? It's a team process and a team effort. When you think about your own practice, Dr Schuster, when do you bring in other specialists or other perspectives in the management of patients with pain?   Dr Schuster: So, one of the articles that I really enjoyed reading in this forthcoming issue of Continuum is the one from Dr Narayan Kissoon on widespread pain syndromes. These patients who have widespread pain syndromes very often are the patients that I'm referring to our pain psychologist. Neurologists can do so much for these patients by making the right diagnosis. So often, these patients might be treated by one specialist for one organ system, another specialist for another organ system, and they can have so many different specialists, and they can be going from institution to institution. And a neurologist is in a really good position to be able to take the full history, put everything together and say, “I think you have a chronic overlapping pain condition. I think you have central sensitivity syndromes” - to be able to talk to them about their central nervous system being amped up, and that there are treatments that we can give them to help to treat these conditions, fibromyalgia and others, that affect so many of our patients who we encounter in neurologic practice. So, the International Association for the Study of Pain now has this term, nociplastic, and some people use the term neuroplastic to talk about these central sensitivity syndromes, and while not all neurologists maybe are hearing those terms used yet in clinical practice, I think it gives us a good framework - and between Dr Kissoon's article, as well as Dr Beth Hogans’ article on general principles of pain, I think that those will give the practicing neurologist a lot of good updates as to how our thinking about these patients has evolved.   Dr Jones: I know, as clinicians, we have a very cause-and-effect kind of component to our training, right? Here is the problem, here is the lesion, here is the result, and what do I do about it. I think patients also want to know what is the cause of the pain, and I think it's, maybe, historically been frustrating when someone clearly has pain and there's not a single factor, especially a removable factor, that causes it. So, I think, hopefully, having this language that we can use to communicate it with our better understanding of pain, hopefully that will help. Does that help you in your practice when you're talking to patients, when you explain what's going on? Is that well-received in general?   Dr Schuster: Yeah, you know, I think a lot of doctors are afraid to talk about fibromyalgia, for example, with patients. And what I'm finding in my practice, actually, is that a lot of patients are liberated when they can receive a diagnosis, such as fibromyalgia, that they can read about, they can learn about treatments for it, they can join support groups online and find that they're not alone - indeed, this condition affects 2 to 4% of people, and that very well could be a underdiagnosis. It keeps them from looking to different specialists for each painful body part and potentially having unneeded surgeries - and surgeries that might make things worse. So, I think physicians are understandably concerned because there is stigma - there's stigma around a lot of painful conditions, and there's stigma around some of the treatments that we use to treat these patients - and I think that physicians who are sensitive to that can sometimes be hesitant, but I'm really surprised how often patients are just really appreciative to get the right diagnosis.   Dr Jones: And you mentioned a minute ago that things have changed even since you came out of training, and, obviously, training is really important to know how to manage these problems. In my own world, I've seen, I think, an increase in the interest in pain management as a subspecialty among neurology trainees. There's obviously something that grabbed you, something that pulled you into this field. What's been your path to being a pain specialist?   Dr Schuster: Yeah, so I was a neurology resident at Ronald Reagan UCLA Medical Center, and fortunately, there, they have a few pain neurologists - and also, in the community, we have a few other pain neurologists as well that I had the great fortune to work with. And I was so impressed, especially those who are doing both pain and headache treatment, that you were able to help so many people treating very high-prevalence conditions - very often, younger patients, people who are going through school, building families - and being able to really reduce their disability, improve their quality of life and the quality of lives of their families is very gratifying. So, I encountered that as a neurology resident. I had their mentorship. And then, I applied for both headache and pain fellowships, and I did both a headache fellowship and a pain fellowship - and I think that that's been a wonderful combination for my career. To have that mix of patients has been really wonderful for preventing burnout. I think having a combination of slightly different patient populations between the headache population and the pain population, as well as, of course, those who have comorbid headache and pain conditions, has been very gratifying to treat people with these conditions. Not that many neurology residents think about doing a pain fellowship, and I wrote, together with my good friend and colleague Jacob Hascalovici, back in 2018 (that was published in the Green Journal), an article on pain neurology as an emerging subspecialty within neurology - and certainly, I would encourage any neurology residents who are interested in potentially pursuing a pain fellowship to read this article. There's such a need for neurologists in the pain field.   Dr Jones: It can be a little bit of a self-fulfilling prophecy, right? So, obviously, role modeling was important to you, right? You could see the practice when you were in training, when you could still make the decision, and if there aren't enough pain neurologists (which I think we can agree that there aren't), there are probably a lot of trainees who don't have that window into what that practice can be like, which, again, makes it kind of a barrier to folks entering the field - so, hopefully, being more comfortable with it will help our listeners and our readers, you know, integrate this into their practice and see it as a path forward for their own careers if they're interested. One last question for you, Dr Schuster, is - you know, looking into the future, obviously, when we have more options to treat these patients, it's rewarding and engaging and exciting - what do you think the next big thing in pain management is going to be? What should our listeners know that's coming down the road for these patients?   Dr Schuster: Yeah, so the interventional segment and the neuromodulation treatments are really changing a lot these last few years, and I believe are going to keep on evolving with new treatments coming down the pathway. And so, we have two wonderful and really nicely balanced articles on these topics: one of them from one of my former mentors from my UCLA days, Dr Vernon Williams, wrote one on spine pain, and he talks about the interventional pain treatments; and another from Dr Prasad Shirvalkar on neuromodulation for painful neuropathic diseases. And these are really wonderful articles for the neurologist who wants to learn about what treatments are available that, they might not personally be doing these, but that they can refer to colleagues - and these are changing a lot. Epidural steroid injections, for example: helpful for a lot of patients, but there's so much more to the interventional pain field than just that, and I think our practicing neurologists will learn a lot about, “Oh, what can neuromodulation be useful for within the pain field?” And, of course, because there's industry involvement in neuromodulation research, you need somebody who's really good at being very balanced, and I think Dr Shirvalkar did an incredible job about writing a really balanced article about the neuromodulation options that we have for patients with neuropathic pain disorders.   Dr Jones: It's exciting stuff. I think there's a lot to look forward to. I think the update that our readers and listeners will have from this issue will be extremely helpful for themselves in their practice and for their patients. For people who are audiophiles, each of these articles will have a corresponding podcast, so we'll refer people to that. And with that, Dr Schuster, I want to thank you for joining us for a really thorough, fascinating discussion on the field of pain neurology and our brand-new issue on pain neurology. And again, we've been speaking with Dr Nat Schuster, Guest Editor for Continuum’s most recent issue on pain neurology. Please check it out. And thank you to our listeners for joining today.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information, important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. Thank you for listening to Continuum Audio.