Continuum Audio

Lewy body dementia is a common cause of cognitive impairment in older adults but is often subject to significant delays in diagnosis and treatment, increasing the burden on patients and family caregivers. Understanding key features of the disease and use of biomarkers will improve recognition.

In this episode, Allison Weathers, MD, FAAN, speaks with James E. Galvin, MD, MPH, author of the article "Lewy Body Dementia," in the Continuum December 2024 Dementia issue.

Dr. Weathers is a Continuum® Audio interviewer associate chief medical information officer at the Cleveland Clinic in Cleveland, Ohio.

Dr. Galvin is a professor of neurology at the University of Miami Miller School of Medicine in Miami, Florida.

Additional Resources

Read the article: Lewy Body Dementia

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 James Galvin, author of Lewy body dementias from the December 2024 Continuum issue on dementia. Welcome to the podcast, Dr Galvin. Please introduce yourself to our audience.

Dr Galvin: Thank you, Allison. My name is Jim Galvin. I'm a neurologist, a professor of neurology at the University of Miami Miller School of Medicine.

Dr Weathers: We're so happy to have you with me today. Thanks, Jim, for your time. And as you highlight right from the start in your really outstanding and comprehensive overview of this really complex topic, even though Lewy body dementia is the second most common cause of neurodegenerative dementia, it often goes unrecognized in clinical practice, resulting in really potentially lengthy diagnostic delays. So, this is a really important article for a neurologist and an important topic for our listeners. So, I'm thrilled we're having this conversation today. While I traditionally start by asking the authors what they feel is the most important clinical message of their article, I would love to actually start a step earlier in this conversation with you. Can you start us off by explaining what's actually meant when we say Lewy body dementia?

Dr Galvin: Great. So, you know, I think this is a, this is an interesting concept. So, we're really talking about two diseases that have a shared common pathology. So, Parkinson's sees dementia and dementia with Lewy bodies. So, their shared pathology is a Lewy body and that's why they're often grouped together as the Lewy body dementias. And then there's arguments back and forth as to whether these are distinct diseases or sort of two ends of the same candle burning in different directions. So, Parkinson's dementia is a lot like what it sounds like. So, if someone has Parkinson's disease, then at some point later they develop a dementia. And so back in the 1800's when Parkinson's disease was like first described as an entity, we basically felt that cognition wasn't affected. But we now know that's not true. And so most patients with Parkinson's do have some cognitive symptoms and a large proportion of them will eventually develop dementia. Perhaps up to 80% of Parkinson's patients will develop a dementia. The flip side is the dementia with Lewy body picture. And these are people who present primarily with a cognitive behavioral syndrome that may or may not have parkinsonism. So, they will sometimes have bradykinesia. They rarely have a rest tremor. And so, these are the people that are very much in the delayed diagnosis group. The Parkinson's dementia is more whether the clinician is checking their cognition as part of their annual visit. The flip side is that the people with DLB are often misdiagnosed early on, but together, this is Lewy body dementia, which is the most common disease that many people have never heard of.

Dr Weathers: That's a great tagline, I think, for the whole article and for this concept. So now that that we're all on the same page about what's meant when we use that the term, what would you want our listeners to walk away with as their one key takeaway from our conversation today?

Dr Galvin: Well, I think the article makes several key points, but I think if I put those all together into a single key point, it would really be that the Lewy body dementias are underrecognized, they're underdiagnosed, yet it is very possible to make the diagnosis using the standardized clinical criteria. They're very, very, very specific. They lack a little bit in sensitivity. So, because other diseases sometimes can look like this, but they're really quite specific. So, if you're confident clinically that the person has Lewy body dementia, you're probably going to be right. And in today's world, we have tests available to help confirm our diagnosis. The world is changing. We can make these diagnosed with much more confidence and we have confirmatory diagnosis laboratory tests that can help us.

Dr Weathers: I want to talk more about the diagnosis in one minute, but first, how common actually are dementia with Lewy bodies and Parkinson's disease dementia?

Dr Galvin: That's a great question. I think one of the challenges, of course, we really don't know how many people have any disease because it's going to largely rely on how well people code the diseases in the medical record. So, if you look at the most common cause of dementia in the United States, it's really dementia not otherwise specified, right? But we believe it to be the second most common cause of dementia. The Lewy Body Dementia Association, about a decade ago, started to try to develop some estimates. So, we have an estimate about how many people roughly have Parkinson's disease and that about 80% of those individuals would go on to develop dementia. And we know from the dementia population that about 40% of those individuals coming to autopsy have Lewy bodies. So, when you start to put that all together, you can get a reasonable estimate of how many people likely have the disease. And then that can be expanded on an annual basis, just like the Alzheimer's Association uses, by extrapolating those estimates onto the census data. So, we estimate right now there are about 1.4 to 1.6 million Americans who are living with Lewy body dementia. That's less than the 6.8 million people who have Alzheimer's disease, but more than a lot of other common diseases. So, if you think about, again, I said before, it's the most common disease no one's ever heard of. You know, there are about a million people who have multiple sclerosis. There are about eight hundred thousand people who have a stroke. There are about seven hundred thousand people who have a brain tumor. There are two hundred and fifty thousand people who have muscular dystrophy. There are twelve thousand people who have ALS. But I think if you stopped clinicians or people in the street and say have you ever heard of ALS or muscular dystrophy, they would say yes. If you ask them if they've heard of Lewy body dementia, they would say no.

Dr Weathers: That's an excellent point. And I know over the years I think there's been some increased awareness. I think sadly with some of the celebrities that have been impacted, I think that did a lot to raise awareness. But I think you're right that it's still so less commonly recognized by the lay public, by non-neurologists, than so many other diseases that you mentioned. And I think that leads back well into my next question into something that we've already mentioned just a few times already in our short conversation, this unfortunate and very common delay in the diagnosis. Why? And you mentioned earlier that there are these, you know, clinical criteria, these now ancillary tests. So, what makes the diagnosis so challenging? What aspects in particular do you think that neurologists find to be the most challenging in diagnosing patients? What trips us up?

Dr Galvin: So, there's an old analogy, right, that, you know, if you'll be three blind men to an elephant and each of them are touching a different part of the elephant, they'll each think it's something different. So because Lewy body dementia has so many different diverse kind of symptoms, it would really depend on who's seeing the patient first. So, if a person presents predominantly with a memory cognitive disorder and they go see someone who specializes in memory disorders, they're highly likely to be called Alzheimer's disease. If they present predominantly with the movement problem, they're going to see a movement disorder person and be called Parkinson's disease. If they present with a behavioral disorder, they're going to go see a psychiatrist. Then they'll get diagnoses like, you know, geriatric schizophrenia or bipolar disease or major depressive disorder. If they present with the constitutional symptoms, which are very common and drive patients absolutely batty. So chronic constipation, REM sleep disorder, runny nose, you know, heat intolerance, urinary frequency, obstipation, and you know, they're going to be called all sorts of things. So, if you start thinking about this, who do you show up with first is going to guide how fast you can get a diagnosis. So, we interviewed at point over a thousand caregivers and what we found was there was about an eighteen month delay after seeing five to six doctors for the majority of patients, of which Lewy body dementia was misdiagnosed about 75% of the time for the initial diagnosis.

Dr Weathers: Wow, what a sobering statistic. And you spoke about the criteria and some of the ancillary tests. What can really help, do you think, kind of mitigate or prevent this misdiagnosis? What is your approach in your own patients?

Dr Galvin: Well, I think like every good clinician, not starting off with a preconceived notion of what the person has and trying to collect all the valuable information. So, one of the things I highlighted in the article was, while there are diagnostic criteria and people can follow diagnostic criteria, the truth is at your fingertips. You don't always sit and think about whether someone meets diagnostic criteria. So, in the first table in the article, we tried to really then put all the different common symptoms into buckets, right? Because people present like that. They say, well, I have this and I have this and I have this and I have this. Well, then you can start to think about, well, they have a cognitive symptom that's predominantly executive attention or visual perceptual in nature. And gee, they have constipation and heat intolerance and they say they can't smell quite as well as they once did, right, and they're having some disturbance in their sleep with excessive daytime sleepiness. Now you can start to say, well, even though that didn't fit the core and suggestive criteria, the fact is that spectrum of symptoms makes it much easier to begin to make a diagnosis. And so, it's investigative work. A lot of neurology is still investigative work. The old days, they used to say, we knew everything but could do nothing, but now we know everything and can do something about it. And so, I think it's really important that we try to apply this information in clinically useful ways. That was part of the gist of putting this Continuum article together was to try to present it not just as listing the diagnostic criteria, because you can get that anywhere, but how do you actually apply it in clinical practice?

Dr Weathers: That's a great point. And that table that you referenced was really fantastic. And I know I say this a lot, but they're true. So, you know, many of the tables, the reference to Continuum, one I will certainly kind of come back to again, again, as an excellent point of care tool. So, I know in, in preparing for today and reading more about, about you and your areas of research that one of your particular areas of focus and expertise is in healthcare disparities, especially in the early detection of neurodegenerative dementias. What is the greatest inequity or disparity that you see in the diagnosis and treatment of patients with Lewy body dementia?

Dr Galvin: So, there's a couple things that are that are really interesting. So first, unlike Alzheimer's disease, which tends to be a little bit more female predominant, the Lewy body dementias are male predominant. It's about 1.6 men for everyone woman. So, it's going to be a different presentation. It's going to be largely men and their caregivers are largely going to be their spouses. So, you're going to see sort of a different person looking, you know, staring on the other side of the table to you. It's going to be largely a male. And the other thing that's really interesting is that almost all of the series, case series, case reports, clinical papers are in predominantly white populations. So, this lends to some interesting things. So, you know, is the disease less common in African Americans and other minority populations or are we just really bad at ascertaining the disease? You know, many of the case reports in Alzheimer's disease include African Americans. In fact, we know that African Americans may be at a twofold increased risk of developing Alzheimer's disease compared to nonHispanic whites, probably due to vascular risk factors. But in case series of Lewy body dementia, almost all the patients are non-Hispanic white. There also seems to be a higher risk in Asian populations, and in fact, some of the very earliest case reports were from Japan. Is this a case ascertainment problem or is this really a disparity in how the disease presents? And I think those are really important questions that still need to be asked. I know as researchers, we struggle to try to develop cohorts that could help us understand that. I would say in my twenty five years of seeing these patients, I would say the large percentage of them, and I've seen a lot of them, have been no-Hispanic white.

Dr Weathers: So, so definitely more research needed in this very important area. So, moving on to somewhat of a personal question, I always, this is such an honor. I always talk about that I get to have this time to sit down with the authors of these outstanding articles and learn not only more about their subjects, but about them as people. I had shared during my last interview that my paternal grandmother had Alzheimer's disease, and unfortunately also my maternal grandmother actually did as well. In preparing for this, I had listened to one of your previous interviews and learned that you also have a personal connection that led you to this subspecialty with several family members impacted. How has this connection inspired your research and your interactions with your patients?

Dr Galvin: Yeah, I mean, so my personal connection was that my maternal grandfather had Lewy body dementia. So, I grew up in a two family home in New Jersey. My grandparents lived on the second floor. We lived on the first floor. I wass very close to my grandparents. I'm still close to my grandmother, who's a hundred and three years old. But when I was a high junior in high school, my grandfather was driving me home from a swimming practice. I was thinner, fitter and more athletic at that point in my life, and he made the world 's slowest left hand turn and we were broadsided. So luckily no one was hurt. But I remember because I was sixteen at the time and just learning how to drive us, Grandpa, what happened? And he's like, oh, the car didn't react. Or, you know, he was blaming the car. And I didn't think much of it because, you know, I was sixteen years old. Sometime after that he was at work, and he was a greaser. So, he would climb through the machines at Colgate Palmolive and keep them all moving.

And so, he was at work and he fell off a ladder and then broke his ribs. And in the emergency room, when my grandmother went to pick him up, the ER doctor turned to her and said, how long has your husband had Parkinson's disease? And she's like, what are you talking about? And then that was the first time that all of us had noticed his rest tremor. And the reason he turned the wheel so slow is because he was Bradykinetic. And so then over the next few years, he progressed in his motor symptoms. And then as I got into college, he developed the cognitive symptoms. And so, by the time I had finished medical school that was doing my residency, he was no longer oriented to time. So that even though I had finished medical school, I was in my neurology residency, I was married and with children, I was still in college at that time for him. So, he would always ask me, you know, have I heard anything from getting to medical school and the like. So, I got to watch this person who I grew up with go through all of the different stages of disease. And then eventually he developed lots of hallucinations. And although he was relatively immobile, he experienced a hallucination and jumped out of his chair, fell down, and broke his hip. And so, he underwent a hip replacement, being rather severely demented, and then passed away in the rehab hospital. As I was living this with my grandparents, the one thing that my grandfather, while he could still communicate, and that my grandmother continued to say to me, you know, up until fairly recently was, you know, what are you going to do about this? You know, we're counting on you to make a difference. And so, a lot of my research is really focused on how I can make a difference for people. One, to make sure they get diagnosed properly. Two that we would have something to offer the patient and the family. And three, we can provide hope that we are actually going to come away with effective treatments to make a difference in their lives.

Dr Weathers: Well, that is really inspiring. And I think you have really done that in your work. I always like to end these conversations on a hopeful note. So, what are the developments that are on the horizon in terms of diagnosis and treatment of Lewy body dementia that you are most excited about?

Dr Galvin: Well, I think there are three things that are of great interest right now. I mean, there's lots of things, but I think three things of great interest are, one, on the diagnostic side is that we now have assays that allow us to assess synuclein in body fluids and body tissues. So, we can measure synuclein seeding assays in the spinal fluid and we can visualize Lewy bodies through skin biopsies. And that's a tremendous advance because we were really, really limited otherwise to using indirect evidence, and the only indirect evidence we had was abnormalities on DAT scanning. So, we're looking at dopamine deficiencies. But as I mentioned earlier, that's very abnormal in Parkinson's disease. But in dementia with Lewy bodies, it's a little more subtle. So, the extent of dopamine degeneration in- particularly in early DLB is limited. So, you have to look very carefully. If we're not doing quantitative DAT scan imaging, then you may miss those subtle changes. So, I think that being able to directly visualize either synuclein seeding or synuclein aggregation has really changed the game. Plasma assays, blood-based biomarkers are probably a little farther away because they're- the red blood cells have a lot of synuclein and so it interferes with the ability to get a good sensitive assay. But I do think in the next couple of years we will see PET ligands that also bind synnuclein. So, I think diagnostically we're going to be able to provide better, earlier, and more precise diagnoses. From a treatment perspective, traditionally we've just borrowed medicines from other fields to treat symptoms, but there are a number of disease-modifying trials that are ongoing. I was fortunate to be the academic PI on two very large NIH grants where we test tested disease modifying medicines. Both of those studies are fully recruited and we should get a readout toward the end of 2024 or the beginning of 2025. So very, very excited about that. I also am fortunate to be MPI an NIH grant where we're just going to be testing the first inhuman synuclein vaccine. So very, very excited about the potential to offer disease-modifying medicines and to fulfill the promise that I made to my grandma and grandpa twenty years ago. And I think the third thing is that right now there's a little bit of like an emerging controversy about developing some integrated staging paradigms between the movement disorder world and the cognitive world. And so, while those paradigms are currently published, you know, not everybody agrees with them. But I think whether I like that staging paradigm now or not, the fact that we're coming together and trying to develop some unified staging paradigms, I think, is going to make a big difference in increasing the ability for clinicians to make early diagnoses that are more precise so that we can either get people into clinical trials or into clinical treatment protocols at the earliest possible time. And that's going to make all the difference in the world for the patients and their families.

Dr Weathers: I think that was a fantastic answer. Really, all really exciting things that I think are all, I normally, I say on the horizon. I'm thinking, you know, pretty far ahead. And I think the really wonderful thing is that all of these are either here now or very, very close to being here. So, definitely a very positive way to end this discussion. Well, Jim, thank you so much for taking the time to speak with me today.

Dr Galvin: Thank you. This was wonderful. I hope the listeners found this enjoyable and interesting and read the Continuum issue. I think it's going to be the latest and greatest on what we know about the dementias.

Dr Weathers: Again, thank you again, Dr Galvin, for joining me on Continuum Audio. Again, today I've been reviewing Dr James Galvin, his article on the Lewy body dementias, dementia with Lewy bodies, and Parkinson's disease dementia appears in the December 2024 Continuum issue on dementia. 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.

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

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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.

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 Smith: This is Dr Gordon Smith. Today, I've got the great pleasure of interviewing Dr Angelina Polsinelli about her article on care partner burden and support services in dementia. This article appears in the December 2024 Continuum issue, which is on dementia. Ange, welcome to the podcast. And maybe you can begin by just introducing yourself to our audience? 

Dr Polsinelli: Yeah. Well, thank you for having me. I'm very excited to be here. I'm Ange Polsinelli. I'm a neuropsychologist at Indiana University School of Medicine, where I work in the Department of Neurology. I also work with the Longitudinal Early Onset Alzheimer's Disease study that's led by Liana Apostolova. And I also do some work with the Outreach, Recruitment and Engagement Core of the Indiana Alzheimer's Disease Research Center. This topic that we're going to talk about today is extremely near and dear to my heart.

Dr Smith: Well, thanks for joining me. And of course, IU is a powerhouse for Alzheimer's and basketball, in that order. So, we're really excited to have you. I'd like to get right into it. I'll emphasize, we were chatting a little bit about this, Ange, before we started recording, that your topic today is so important for all of us. And I think, you know, this is a podcast that not only neurologists listen to, but students and, and I think increasingly members of the lay public.

And this conversation is going to be very important for neurologists and our neurology learners. But I lost my grandmother to Alzheimer's disease. I lost my uncle just in the last week. So, this touches all of us. So, I'm really excited. And then with that in mind, I wanted to begin with a statistic that- you can correct me if I misunderstood it, but it really blew my mind. And that is across the world, as I understand it, care partners provide one hundred and thirty three billion hours of care for people living with dementia yearly, which is pretty staggering. But what's really amazing is that by 2030 that number is expected to go to one point four trillion hours, which I couldn't grab my mind around it. So, I figured I'd try and determine how many years of person work is that and if my math is right, that's almost a hundred and sixty million person years of worth caring for people with dementia yearly across the world. One, are those numbers right? Did I get it right? And then, assuming so, can you put a human face or experience to these numbers? 

Dr Polsinelli: Yeah, unfortunately those numbers are correct. And with our increasing aging population across the world, that's why you're getting that, you know, exponential increase in care per hours, compounded by the fact that the majority of the caregiving that happens is not done by doctors, physicians, but it's done by these informal care partners, these family members, these friends, these siblings, children, who are providing these really important services and unfortunately not being trained to do this, doing it largely on their own in a lot of respect. But again, these are people who are loved ones of the person living with dementia. There are a variety of kinships, as I mentioned, siblings, children, spouses, friends; and all sorts of age ranges as well. A large majority of them being spouses, and then the second largest majority being children. So, kind of a sandwich generation of people who are caring for parents with Alzheimer's or dementia and then caring for children as well.

Dr Smith: Yeah, I was actually struck by the statistic that a quarter of caregivers or so called sandwich caregivers; in other words, they're taking care of a parent and a child. But listen to what you said. But just to call it out, two-thirds of care partners are women, which is a striking statistic.

Dr Polsinelli: Absolutely. Women are not only more likely to have dementia, but they are also more likely to be the care partners of somebody who has dementia. And so, the research shows, too, that if you're a care partner, you're at higher risk of developing dementia yourself. So, there's a lot of risk for women when it comes to dementia, development of dementia, but also that the burden and the majority of care needs that are that are supported by women as well.

Dr Smith: Right. And there's a lot to unpack in that observation, and maybe we can come back to that. But I wonder if you might talk to us a little bit about the risk of dementia in women caregivers. That's really striking. Is there any thought regarding mechanism for that? Why is that the case? Is it a shared risk factor? Is it cause and effect? What's the story? 

Dr Polsinelli: So, there are - this is kind of a dissociable or different - kind of two aspects to this, this question. There's the fact that women are at higher risk for developing dementia in general. I think the researchers feel sort of out about why exactly that is. It's not just that women are at higher risk or more likely to develop dementia because they're living longer than men, but there's probably some hormonal aspects of their higher risk factor for dementia. But then there's the other aspect of it too, is that as caregivers, caregivers are at higher risk of developing dementia. And because caregivers tend to be women, that increases or compounds the risk for women as well. We know with caregiving, particularly with someone who's living with dementia, there's more risk of developing things like depression, high stress, health problems, psychological distress, and all of these things increase somebody 's risk for developing dementia as well.

Dr Smith: So, I wonder if you might talk a little more, Ange, about what you mean by burden? I think we have in our mind what that is. But in reading your article, there's a lot of- a lot more to it than may meet the eye.

Dr Polsinelli: Yeah, it is a more complicated, I guess, topic or terminology that's gone through several iterations over the course of doing research into burden. But when we think about burden, it's really a kind of a combination of both objective experiences and subjective experiences. And these objective, subjective experiences fall into the categories of physical burden, emotional burden, psychological burden. So, there's a lot of different areas of life in which someone can experience burden. But really, it's a combination of factors of both the objective experience, lived experience, and the person 's perception of that experience or what they're dealing with. I should also mention that it appears to be more of that subjective experience or that perception that people have of their objective experience of stressors or burden. That really does determine the person's response to that, if whether they actually perceive their lived experience as being burdensome. 

Dr Smith: One of the things I found really interesting was the societal and cultural context surrounding this, that there are different cultural expectations and societal dynamics, both in the nature of the burden care partners may feel and how they're viewed. I wonder if you could talk about that? I think it's something that it would seem all of us need to be attuned to as we're working with our patients and their families. 

Dr Polsinelli: Yeah, this is a topic we could talk for a very long time on. I will try and- I will try not to kind of provide too much of a, or too lengthy of a response. But what we know now is basically that our models of stress and burden that we have typically used or historically used do not incorporate a lot of factors of cultural identity of social and structural determinants of health factors. And so, what we understand now is that stress and the way that people perceive burden is influenced by so many other factors than just kind of an experience and a perception. Because that perception is influenced by so many factors, including, as you mentioned, cultural factors that include how society's familial expectations for us, cultural expectations for us, as well as what our resources are that are determined by, again, structural and social determinants of health, what our community resources are. They're just a lot of different factors that go into how somebody perceives their ability to cope with, again, this kind of life-altering diagnosis that their loved one has received and them being the person who is caring for them through that.

Dr Smith: Your article actually goes through in some detail the types of burdens and what drives the burden. And that changes over time. And so I wonder if maybe you can talk a little bit about what the specific natures of the burden are from the caregiver perspective. I mean, what  sort of tasks there are, you know, from the many of us who take care of patients, we still don't know unless we've been in the room or in the home watching this happen. So maybe you can describe that for those of our listeners who maybe haven't lived through this? 

Dr Polsinelli: Yeah, absolutely. I will say upfront that the caregiving experience is going to be different for every single person. And again, kind of dependent on some of those factors that I mentioned before. So, it's going to look different for most people. It's also going to look different through the dementia journeys. The experiences and the requirements earlier on in dementia are going to be a vastly different than what occurs later on when dementia is in the more late stage, moderate or severe stages of the disease. Those care responsibilities absolutely change over the spectrum of that time as well. We know that early on the stage of disease, primary care partner might be spending forty plus hours a day. So, a full-time- or not a day. I'm sorry, a week. So, a full time job carrying it. But that number increases up to a hundred and fifty or so hours per week once the person is more advanced in their disease. So, I say that because the number of hours, I think, make all, like- putting that into perspective of somebody having a full time, multiple full time jobs, basically providing care, I think is really important. But the responsibilities of the care partner are going to range from everything from just helping the person early on in terms of managing finances or managing them, making sure they’re reminding them to take their medications, scheduling their medical appointments for them, maybe taking over all of the driving to get them to their appointments or to get them to family outings and things like that. They're going to be the ones that's going to be the most responsible for reminding people to do something: to eat, to maybe stay on track for a recipe or something that they are making. So, kind of being the eyes and ears for this person right away, basically right at the beginning, even early stages. And then that progresses over time to the person who is caregiving, who is doing potentially everything for this person. So that means helping them use the restroom when they need to, helping them shower. So, there's a physical component to the caregiving as well as that- sort of what we call instrumental support in terms of organizing medical appointments and things like that. They're just basically doing it all for that person. 

Dr Smith: So, what about a busy clinician who has half an hour to see a dementia patient follow up? Kind of hard to- in these days, you know, we've got, you know, these new therapies to think about as well. What advice do you have to neurologists and other professionals caring for patients?

Dr Polsinelli: Yeah. And I think neurologists, I mean, we all have limited time. And I know neurology in particular is like primary care, has even more constrained time. I think one of the biggest things that neurologists can do is really check in with the care partner. So, take a moment to check in with the care partner who's there with the person with dementia to see how are they doing. You're looking for signs of burden or stress, so things like physical complaints like headaches or stomach ache, mentioning feeling burnt out or overwhelmed, maybe feeling depressed or something like that. There's also some short kind of questionnaires that you could give care partners prior to an appointment that they could fill out. You could kind of get a sense of where is this person at this point and then help connect them potentially to some resources that might be available. And I would refer people to that article that has a list of resources in there that you could just basically print out and give to somebody. 

Dr Smith: Yeah, I was going to make the same point, Ange. Your article is a treasure trove of information. And you know, I'm certainly, I keep all of these on file, as you might imagine, but I'm keeping it in hand for future use. One of the things you talk about that really hit home for me among many is the idea of self-care, and I think sometimes the best care partners are susceptible to burnout because they they're so dedicated. You made the airplane oxygen mask metaphor, which I love. So maybe you can talk about what airplane oxygen masks have to do with dementia care and what advice you have for us and helping our patient’s care partners take care of themselves?

Dr Polsinelli: Yeah, absolutely. Self-care is the number one thing I tell care partners to do. It's also one of the hardest things for care partners to do. Like you mentioned, there is a deep, generally speaking, a deep love and caring for the person with who is living with dementia. And the focus becomes on them. And understandably so, the care partners sort of loses focus on themselves and making sure that they're doing okay. So I oftentimes use this oxygen airplane metaphor for people, which is basically, you know, when you're in an airplane and if there's some kind of pressure change in an airplane, they always tell you, put your oxygen mask on first before you help somebody else because you're not going to be any good to anybody if you're passed out. In the airplanes, the pressure changes, you know. You need to be available. you need to be getting what you need in order to help somebody else. So, I think that metaphor, that analogy really works well in dementia care is you need to be- the care partner needs to be caring for themselves and replenishing themselves in order to be the best care partner they can be for their loved one. 

Dr Smith: Another challenge that, it strikes me as shared between people living with dementia and their care partner is that of social isolation and loneliness, right? If you're working a hundred and fifty hours a week doing anything, you don't have time to care for yourself or very hard to engage in social connections. And one of the loud messages I think I heard from your article is the power of social connectedness, both in terms of resilience and in many different ways. I wonder if you can talk a little bit about loneliness? And I just reflect that in a postpandemic world, this is probably a bigger issue than it was four years ago or four years and three months ago.

Dr Polsinelli: Yeah, absolutely. Loneliness and social isolation was a big problem before, and it's even worse now is when I'm hearing from my patients. What I'm seeing in the literature is this postpandemic time is even more has been even more isolating and more problematic for people, but this social network cannot be, as you said, it cannot be overstated in terms of the importance for people. So that social network is important for not only providing potential instrumental care - so that practically care that care partners can use can lean on other people to come into the home to do things for the person living with dementia so the care partner can go practice self-care or go do those errands that need to be done - but also the emotional support as well that social networks can provide for people. And also, you know, social networks for not just the person, the care partner, but for the person living with dementia as well. We know that social engagement in particular is really good for brain health. I mean, we don't think about it, but social engagement is a very cognitive activity. And so, it helps give the brain a bit of a workout. So that social network is important for a lot of different reasons, and understandably a lot harder to maintain in this sort of postpandemic world as well.

Dr Smith: As our time starts to come to- close to a close, we're not done yet, but I think we're probably going to have to start winding up. I wonder if we could pivot to something positive and then talk about the joy in this. And by that, I mean you describe and I think we've witnessed relationships and caring, caregiving situations that, as challenging as they are, provides fulfillment and the connection one has with a loved one or sort of that social aspect. Are there things that- predictive of that kind of positivity, and are there ways that we as professional caregivers for patients and their families can facilitate that?

Dr Polsinelli: Yeah, there are. There are a couple of things. So, one of which is basically the quality of relationship between the care partner and the person living with dementia already. So that's the quality of that relationship. The better the quality of that relationship, the more likely it is that the care partner will experience more meaning and fulfillment and joy associated with caregiving, kind of outweighing that burden. But the additional piece of that is the more resources, the more mastery they feel about their caregiving or care partnering abilities, the more competent they feel and their ability to do good by the person, their loved one, the person living with dementia, the more likely they are to find that role fulfilling and meaningful. And I think that's where neurologists and other providers can kind of come in as helping people make sure that they have those resources that they are connecting to places where they can learn skills for giving appropriate care so that they can feel confident in what they're doing. There's the preexisting relationship piece that matters a lot. But I think that there's a lot of modifiability that neurologists have, too, in making a positive impact on the care partner and the person living with dementia.

Dr Smith: That's really great advice, Ange. And I definitely will refer our listeners yet again to your article, which is a compendium of useful advice about this, both in terms of the text itself and in tables that provide lists of resources, websites, books, organizations, good case examples. It's a home run and I hope all of our listeners check it out. I'd like to wind up by talking a little bit about your work. And as I understand it, you obviously are very passionate about this topic, but you have specific interests in caregiver burden and underserved and marginalized communities. And then, we’ve touched on this, but this is a huge percentage of our population. And when you look out globally, it's even bigger than that. Tell us about what you're working on. And then maybe following that, what's the future look like? Where are we going to see advances in this in the coming years? 

Dr Polsinelli: So just a really quick kind of brief history is that I've worked in dementia for almost twenty years or so now. And what I've consistently seen is when you give care partners good supports and education and resources, there are better outcomes for them and their families. The unfortunate thing is, a lot of these really great interventions and things that we have are not necessarily really accessible by a lot of people, but particularly not accessible by those living in underserved communities. The last few years in particular, I've really shifted into wanting to better understand that and better understand how do we provide culturally and socially appropriate interventions and education for these care partners and their families. With the current research project that I'm working on, we're looking at better understanding the needs of care partners of people who have early onset Alzheimer's disease, specifically from Black and African American individuals and other underrepresented groups. Again, the idea of this is to understand the needs before building an intervention for these groups, and I'm very excited about it. I know that there are lots of really great people who are working in this area, including Dr Dilworth Anderson and Kalisha Bonds Johnson, doing really fabulous work in this area. So, and building on what they're doing as well. In terms of what the future holds, one, I think we absolutely need to, we have lots of really great care partner interventions out there that have been lots of research going on, but it's not really transitioning into the clinical sphere. It's really kind of staying in that research sphere. So, I think it's really important that we get some implementation scientists who are taking those interventions and moving them into the clinical sphere, into the sort of like everyday, how do these actually work for people sphere. And then similar to some of this conversation we're having in terms of serving, making sure our interventions and making sure that our resources are appropriate and accessible for underserved communities, we really need to be taking a look at what these communities need rather than kind of saying, this is what's available. Kind of, hopefully this works for you. Speaking with these communities, engaging stakeholders and understanding what are the needs in these groups so that we can provide the appropriate resources, the appropriate interventions, the appropriate supports for care partners and people living with dementia.

Dr Smith: And I'm just thinking, imagine what this looks like with effective treatments for Alzheimer's disease, that slow progression. And you know, that's going to make the caregiving even more important, it seems to me. But there's an opportunity to make it a better rewarding and a better-supported system as we develop these new therapies. So, this is a, like a Clarion call for learners listening that they should all become dementia neurologists and neuropsychologists like here. Thank you. That was outstanding. Say, Ange, I want to thank you a lot for a really engaging conversation. This fulfilled every hope I had coming into it. I was really excited to talk to you. I always love talking to neuropsychologists, but I think again, this is really useful for neurologists, learners, people who are nonneurologists everyone. And so, thank you very much. I've learned a lot and I really would encourage everyone to check out the article. 

Dr Polsinelli: Well, thank you so much for having me on and giving me the opportunity to talk about the stuff that is really important to me and, I think, to most of us out there. So, hopefully people find the article and the resources in there useful and, and thanks again for having me. 

Dr Smith: I'm sure they will. Again, today I've been interviewing Dr Angelina Polsinelli, whose article on care partner burden and support service in dementia appears in the most recent issue of Continuum, which is on dementia. Be sure to check out Continuum audio episodes from this and other issues. And thanks to you, 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. 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.

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

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More about the American Academy of Neurology: aan.com

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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

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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

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Social Media

facebook.com/continuumcme

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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.

Peripheral neuropathic pain is primarily influenced by the biology and pathophysiology of the underlying structures, peripheral sensory nerves, and their central pathways.

In this episode, Kait Nevel, MD speaks with Miroslav Bačkonja, MD, an author of the article "Peripheral Neuropathic Pain," in the Continuum October 2024 Pain Management in Neurology issue.

Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana.

Dr. Bačkonja is the clinical director in the Division of Intramural Research at the National Institutes of Health in Bethesda, Maryland.

Additional Resources

Read the article: Peripheral Neuropathic Pain

Subscribe to Continuum: shop.lww.com/Continuum

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Host: @IUneurodocmom

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 Nevel: Hello, this is Dr Kait Nevel. Today I'm interviewing Dr Miroslav Backonja about his article on peripheral neuropathic pain, which appears in the October 2024 Continuum issue on pain management and neurology. Welcome to the podcast.

Dr Backonja: Thank you.

Dr Nevel: Misha, can you please introduce yourself to the audience?

Dr Backonja: Yes, I'm Miroslav Backonja, but everybody calls me Misha. So everybody knows me by that. I'm a training neurologist, and I also have training as well as certification in pain management. And most of my practice has been where neurology meets the pain, which is neuropathic pain. I spend some time basic science lab and then transition into clinical research. And I was in academia for a couple of decades and was most recently recruited by NCCIH National Center for Complementary and Integrated Health and have been there for two and a half years now.

Dr Nevel: That's wonderful. I would love to hear more about your career at the NCCIH, a little bit and what you do in your role now, and how that came to be.

Dr Backonja: Yeah, I was recruited to help and provide clinical support to efforts at NCCIH in the phenotyping of pain and neurologists who've done research in quantitative sensory assessment and other quantitative means of assessment of pain. Coming to NIH was very rewarding and quite of a learning experience. After six months being there, I've discovered that NIH is the biggest secret in plain sight. They say in the plain sight because it's public institution and everything is open to public and it's a secret because we don't think about it. This is in particular in reference to biomedical research training, including clinical trainings. So, I would encourage everybody to think of NIH as a place to spend some time and learn. There are wonderful research opportunities as well as educational opportunities. Vast library of presentations, green rounds and different other types of courses - some of them open to public, and some of them are up to FAS, which is a foundation of advances in science education by discovering. I feel like being back in school and having fun.

Dr Nevel: That's wonderful. Can you share with us a little bit about how you became interested in peripheral neuropathy and pain management of peripheral neuropathic pain?

Dr Backonja: It actually goes back to my residency and fellowship. And actually, you know, I had the luck of being exposed to a couple of clinicians who actually became my mentors. First was Jose Ochoa, who was one of the first people to quote from a small fiber, C fiber specifically, and he also was pioneered in quantitative sensory testing. And the other one was Charles Cleland, who was a psychologist and who pioneered assessment of patient symptoms, developing the Brief Pain Inventory is one of the tools. That actually peaked my interest in the topic of pain and once when I started learning about pain, what is the kind of mysterious experience of humans' pain, turns out that we have learned a lot of science about the pain and can make the pain very accessible. And I hope some of this will come to the chapter that we've provided.

Dr Nevel: Thank you for sharing that. I think of peripheral neuropathy and I think most neurologists think of peripheral neuropathy as one of the bread-and-butter diagnosis within our field. For the practicing neurologist out there who might be listening, what do you think is the most important takeaway from your article that maybe they don't already know about peripheral neuropathic pain?

Dr Backonja: When it comes to peripheral neuropathy and peripheral neuropathic pain, it goes back to my early experience and still holds the truth. Neuropathies don't kill people, they just maim them. They create- cause lots of disability and if you add a pain to it, it can be quite disabling. In some regards, it has been neglected the area of development in neurology in terms of scientific discoveries, although things are changing quite rapidly as of recently. Main take home messages, and especially when it comes to a sensory neuropathies and painful neuropathies, is that it's one of the skills that has not been well researched and then not well communicated to the vaccine neurologist in terms of what to do with it. But most neurologist sensory symptoms are just like a noise because, especially when it comes to pain and prosthesias and allodynia and hyperalgesias, like, what is that like? It's just not knowing what to make of it. Frequently associated also with emotional components in terms of the people are either depressed because of persistence of pain or anxious, not knowing what's going on. And that really can create quite a bit of a challenge in terms of what to do with it. But once anybody who's interested learns the fact that sensory neuropathies and fever neuropathies as well could be as well and is easily diagnosed by a neurologist who pays a little bit of attention and gains some skills in assessing not only negative sensory phenomena, because that's what he as a neurologist get trained to detect and quantify sensory deficits as well as motor deficits and loss reflexes. Also, if you pay attention to positive sensory phenomena, which is part of the repertoire of symptoms that patients with neuropathic pain experience, it's not whether patients would have either positive sensory phenomena like prosthesia and pain or negative sensory phenomena. Actually, they have all of them. And that's kind of puzzling for many patients. And lots of times, very patients say, like, how can I hurt when I don't feel like, let's say, like most commonly it's lower extremities. Like I don't feel my feet, but it hurts. I mean, how come? Oh, that's a cardinal feature of neuropathic pain, neuropathic painful neuropathy.

Dr Nevel: Yeah, thanks for that. You know, I really thought that your Table 3-1 was really nice. It kind of lists through the common causes of peripheral neuropathic pain and just demonstrates the diversity of the different etiologies or other conditions that can cause neuropathic pain. And so, I encourage the listeners to review that table. But, on that topic, can you share with us what you think are the most important components of evaluating patients with neuropathic pain to maybe come to a diagnosis, to find what the underlying etiology or driver is?

Dr Backonja: When it comes to painful neuropathies, there are actually two problems you have to solve. So, don't forget that part. The first one is finding a pathological theology. Why a person has a neuropathy, what kind of neuropathy. And then second is, what's the nature of the sensory problems? What's the nature of the sensory symptoms, specifically pain, levodenia and hypogesia. So, figuring out the theology of the B12 deficiency or diabetic painful neuropathy, you can relatively quickly or hopefully one would relatively quickly come to that at theological diagnosis. But then the second part is the diagnosis of symptoms. What's the underlying metaphysiology of that. And again, just reminding colleagues that the specific sensory phenomena such as thermal hyperalgesia is now well established to be due to what's called peripheral sensitization of C fibers, which are the small unmyelinated fibers, expressed TP 1 receptors. So, patients who will report that taking a hot shower is very painful. An example of that or when conducting sensory exam and applying if you come to the point of examining the perception of warm and hot and patient affords the pain. That's just the hallmark of the C hurtful sensitizations to C fibrous sensitization. On the other hand, if somebody has mechanical ordinia like putting the shirt on hurts, putting the socks hurts. Well, that's evident to central sensitization. These are the simple, relatively simple but symptoms or signs that could have implication if those patients with central sensitization are more than likely to benefit from medications that restore descending inhibition, such as tricyclic antidepressants or SNRI's. And so just paying attention to that, it gives a clinician being a clinician or a neurologist, like, let me consider prescribing medication that have central A acting properties. Or if it's purpose sensitization, something we have like a sodium channel blocking property, things of that sort. Actually, there are some other strategies such as antagonist TRPV1receptors, the capsaicin base. Those are the kind of things that can help a neurologist kind of take the evaluation of painful neuropathies to the next level.

Dr Nevel: Yeah, the- by getting a careful history and exam, that can influence what treatment you prescribe to patients. Understanding whether it's central or peripheral. On the topic of treating patients and talking with patients and evaluating them, what do you think is most important to counsel our patients about who we are treating for neuropathic pain?

Dr Backonja: Number one: by getting good history and exam. Well, really in the coming to specific diagnosis is huge relief to the patients who thinks many themselves that they're just going nuts are crazy because nobody else understands these symptoms. So, validation in terms they have a real problem. Second important step is that for the most patients, there is probably reasonable degree of therapeutic interventions that can lead to relief of pain. And also, with applying the integrative approaches with complementary medicine is that patients are given tools to deal with what is otherwise underlying problem. Those two steps make a huge difference.

Dr Nevel: Absolutely. What's the most challenging aspect about managing patients with peripheral neuropathic pain?

Dr Backonja: Actually, there are a couple. Number one thus far: we do not have a cure for any other neuropathies or painful neuropathies. So that's one of the big disappointing things one would need to communicate to the patient. The second challenge is actually the therapies that actually for neuropathic pain. There's a half a dozen- yeah, half a dozen FDA approved treatment. One thing that's interesting characteristic that all of them prove proven efficacy in clinical trials. If you scratch the surface, you find out that only 40% of patients obtain 30% pain relief. So, it's a rare patient that gets 100% pain relief, and even those, too, get what we call clinically significant, and then in studies, basically significant benefit. It's only partial penalty. But for the most those who do get the benefit, pain goes down probably enough for them to get some a semblance of normality in terms of having some control over the symptoms and their function. It's then the third challenge is really working through those available therapies to find what works for individual patients because we're not at the point yet where for example, other fields like oncology, you can quickly through the means of biomedical and other evaluation come to the patient specific therapy. So, at this point in time you're far from that. What we end up doing with when it comes to management for painful neuropathies is a trial. Sometimes patients say, well, trial and error. I would say, well, it's a treatment trials. We try one thing at a time, assess the risks and benefits and then there was many treatments that carry the benefit. If you carry it on when once, when they don't or if there's adverse events, side effects, we discontinue them. And then most of the patients end up with a combination of pharmacological and now pharmacological treatments and most of them can get some semblance of symptoms control.

Dr Nevel: I really appreciate your point on preparing our patients and you know, expectations and things like that and working with them and looking for things that may help. But also having an understanding that the likelihood of complete pain relief is maybe not a super high chance of complete pain relief.

Dr Backonja: But if you're going back to the kind of preparing patients, it's a good to acknowledge or give a chance to express themselves because many times they patients are confused because they have symptoms that are confusing to them. And so just to have them express it. And for example, my alma mater, we developed the color paint drawing where the different sensory qualities are presented by different colors. And then on the body diagram, patients draw where they have symptoms. And this is probably one of the rare examples where you can literally see a pain because these neurologists can recognize the patterns. You can see the pattern of the motor, right, is multiplex or radiculopathy or the list goes on and on. So, this is one of the kind of tools that's very simple, but gives the patients another way to communicate because lots of times they really have difficulties expressing themselves.

Dr Nevel: Right. So, the opposite of the most challenging, can you share with the listeners what you find the most rewarding about taking care of patients with peripheral neuropathic pain?

Dr Backonja: What is rewarding is that with some work- and again, it's not easy work because it does require multiple visits and multiple assessments and the reassessments, most patients can get control over their symptoms to the point of coming to beginning some of the functional improvement and aspects of quality of life like sleep and work, they are definitely rewarding and most of the time it's fairly obvious. And again, pain management is definitely a team sport where really, it's important to gauge colleagues. Most of the places don't have what I have had when I was in academic institutions, easy access to health psychologist or physical therapist. Most communities do have those specialties. And many patients actually benefit from things that are what's considered a complementary medicine, such as Tai chi or yoga. And actually, in my practice, Tai chi was probably most common prescription for my patients because, as I tell them, there are multiple benefits. Number one: one of the risks of patients, especially prophyl neuropathies and lower extremities, is a loss of proprioception. Again, even those who have a reasonable preserved proprioception over welding, noise of pain actually makes the problem walking the at risk of falling. Actually, Tai chi one gets improvement in balance. There's also medicating component to it. So, mindfulness medication is kind of built in it and that all kind of gives the patients a better control of symptoms. So, some of those interventions are easily accessible in community. So, it's, again, it's a patient education that really takes important part.

Dr Nevel: Yeah. And that Tai chi is maybe one of the answers to the next question that I have for you. But as the clinical director of the Division of Intramural Research at the National Center for Complementary and Integrative Health, I have to ask you, Misha, what sort of integrative and complementary type interventions do you counsel your patients about, maybe beyond Tai chi, and which ones do you think are the most helpful?

Dr Backonja: To clarify, the NIH patients I see are all admitted per protocol. Actually, NIH has the largest research hospitals called clinical NIH Clinical Centre, which has a hospital and clinics. All the patients that come to our program, they come per protocol for the most part.

They come for specific investigations. At the moment, we do not have intramural treatment protocols, although in near future one of my goals is to establish that. The NIH funds- 90% of funding from NIH goes extramurally to academic institutions and other healthcare organizations and so on, and only 10% goes for intermural research. So, what we do is much smaller in scope, much more focused. So, what do we support NCCIH actually support extramurally full range of anything from probiotics, research in microbiome related to health and pain all the way to interventions such as mindfulness meditation? Intramurally, once when patients come for protocol, we evaluated and it's unavoidable to be a question. So, what do we do now? What recommendations do we make? Again, we don't- with the present time, we have treatment protocols and then, most of the time, what I can do is provide recommendations to the patients when they go back to the treating community, to the treating providers. It's usually a fairly comprehensive list including pharmacological and non-pharmacological accommodations for those who have had experience with pharmacology. Sometimes I can just say yes, continue or change or whatever. But then when it comes to additional complementary accommodations, they always provide information. For example, why do I recommend Tai chi? Or, what's the benefit of yoga and why would one want to try to learn trying to behavioral therapy or mindfulness meditation? What's the benefit of turmeric and some other components of what's called anti-inflammatory diet and what's the rationale behind all of that? So rather than just giving a list of recommendations and leaving it that, I try to engage patients in terms of having to understand why something is recommended, whether the fits with their expectations and what fits with their lifestyle and so on.

Dr Nevel: Yeah. So, what's coming up, what's next in painful peripheral neuropathy? What do you think is exciting? Where do you foresee some breakthroughs in this field?

Dr Backonja: Probably what will make the most difference is application of some of the really molecular biology tools that are being applied to peripheral neuropathy. So hopefully one of these days you'll have a cure for neuropathy and pain and anything would come to that will be probably interaction between a nervous system and an immune system, in particular neuroinflammation. That's kind of my bias. They're probably that's- well, the answer will be, but many painful neuropathies - actually every painful neuropathy, because they come from, as a result, specific pathologies - are different in a sense of trajectory natural course that will have to be first addressed. And again, depending on the underlying disease and molecular biology of that and genetics of it will determine that. But on the other hand, there are some common denominators, as we talked, when it comes to painful neuropathies, which is drivers of peripheral and central sensitization. And maybe one of these days, we'll find what are those drivers and how to change the system so it does not produce pain and other associated symptoms.

Dr Nevel: So once again, today I've been interviewing Dr Miroslav Misha Backonja, whose article on peripheral neuropathic pain 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 to our listeners for joining us today. And thank you, Misha, so much for talking with me today about your article. I encourage all of the listeners to read it. It was very comprehensive and just really wonderful to read.

Dr Backonja: Thank you. Enjoyed it.

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.

Spine pain is one of the most common presenting concerns in health care settings. It is important for neurologists to understand strategies for evaluating and managing patients with spine pain.

In this episode, Katie Grouse, MD, FAAN, speaks with Vernon B. Williams, MD, FAAN, author of the article "Spine Pain," in the Continuum October 2024 Pain Management in Neurology issue.

Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California.

Dr. Williams is the director of the Center for Sports Neurology and Pain Medicine at Cedars-Sinai Kerlan-Jobe Institute in Los Angeles, California.

Additional Resources

Read the article: Spine Pain

Subscribe to Continuum: shop.lww.com/Continuum

Earn CME (available only to AAN members): continpub.com/AudioCME

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More about the American Academy of Neurology: aan.com

Social Media

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@ContinuumAAN

Guest: @VernWilliamsMD

Transcript

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 Grouse: This is Dr Katie Grouse. Today I'm interviewing Dr Vernon Williams about his article on spine pain, which appears in the October 2024 Continuum issue on pain management in neurology. Welcome to the podcast, and please introduce yourself to our audience.

Dr Williams: Oh, well, thanks for having me. My name is Vernon Williams and I'm a neurologist here in Southern California.

Dr Grouse: So, I want to start off today by asking, what do you feel is the key message from your article?

Dr Williams: So, I think the key message is that we want to make sure people understand that there's really a distinction between abnormal imaging, tissue damage, nociception, and this experience of spine pain. So, the concept is that nociception is different from the clinical experience of pain; nociception, meaning the electrical signaling from these, quote unquote, pain generators and that kind of thing. But it's really an incomplete framing. We really want people to understand that the experience of pain is colored by a number of other things, things like genetics, biochemical factors, behavior and psychological factors, social factors, those kinds of things. So that's one of the big messages, this distinction between nociception and this clinical experience of pain.

Dr Grouse: Why do you think it's important for neurology clinicians to read this article?

Dr Williams: Well, I think, you know, for one thing, spine pain is very common. So, it is likely that neurologists will encounter patients who come to see them because of that chief complaint.

But I think that if we want to really be successful at treating spine-related pain, then we really have to know all of that basic information, the basic knowledge that we came to learn as residents and medical students or what have you. But it's also important to know that that knowledge is necessary, but it's insufficient. You really also have to confront pain from the standpoint of these other things, these other behavioral factors, psychological factors, social factors, and you got to kind of combine those things to be the most successful in treating this very common condition.

Dr Grouse: You know, you mentioned earlier about the difference between tissue damage pain and nociception. I find this to be, you know, a really great lens thinking about these concepts to view this topic and your article specifically. Can you go a little more into what the difference between, specifically, pain and nociception really is?

Dr Williams: Yeah. I mean, so when we talk about nociception, in many ways we're talking about the electrical activity. And so, there's the stimulation of these nerves, in the periphery typically, and that electrical signal is transmitted, you know, from those nociceptive fibers into the spinal cord. And it's headed from the first-order neuron to the second-order neuron and axons in the spinal cord and eventually reaches the brain. But essentially the concept is that it's not pain at that point. It's not pain until those signals reach the cortex and they are experienced in some context. And that context really colors whether or not, and to what extent, people experience pain or suffer pain as a result. So, when we think about nociception, we tend to think about kind of tissue damage or the threat of tissue damage. And in clinic, we tend to kind of focus on that and we look for relationships between abnormalities on imaging studies that could be causing those kinds of electrical signals. And we tend to focus less on that second but critical aspect of things, and that's that individual 's personal experience, which is colored by a number of different things: their attention, their expectation, colored by how we interact with them, our verbal and non-verbal communication with them. And again, like we talked about: their history, who are they, their genetics, their behavioral history, their psychological history and those kinds of things. So, it's really this combination of things that we have to be aware of when we're treating spine pain. And I think the tendency is for us to focus on the first half and less on the second half.

Dr Grouse: Absolutely. I certainly think our training and our focus on localizing the lesion may in some ways hurt us in that sense because we really focus so much on the first and not so much the second. Would you say that's probably right?

Dr Williams: Yeah, I mean, that's part of our heritage as clinicians, particularly neurologists. It's, where's the lesion? And so, what happens when there is no, quote unquote, lesion? What happens if there are multiple potential lesions? And so, these kinds of concepts, I think, become really important, and the context in which you're examining and evaluating that patient becomes important. And I think they are at least as important as the potential pain generator or the nociceptive signal.

Dr Grouse: Now, you mentioned earlier something about sort of how we approach the patient and the language we're putting out, the body language. I found the concept of nocebo and maladaptive pain-related neuroplasticity to be absolutely fascinating when I was reading your article, and I was really surprised to learn that clinicians can really contribute to this effect unknowingly through their body language, verbal language, nonverbal messaging, and even how they're interpreting the test results? When a patient comes to see you with chronic back pain, how do you approach the whole process to minimize this effect and, really, to set the stage for more constructive and therapeutic evaluation?

Dr Williams: Yeah, Katie, I think that's… it's tough because our culture is so, you know, it's so ingrained in our culture to look for a structural abnormality as an explanation for an individual 's symptoms. And so, I find myself struggling with that all the time, not only discussing why we're ordering an imaging study, but, if that person comes back and I'm describing to them the abnormalities on that imaging study, I've got to be very careful about describing them in the context of what we expect. And so, I'll typically try to use words like, well, you've got some wear-and-tear changes that we all get, as compared to saying, well, you've got a disc herniation abnormality at L five S one that's causing your pain. That statement could have a negative effect on that individual's framing of what's going on. Maybe that L five S one disc is contributing to their symptoms and maybe it isn't. Maybe it's been there or for years and maybe it's new. And even if it is new, does that mean, in that patient's mind, that now they've got an abnormality that has to be fixed or else they will continue to have pain? And so, kind of trying to keep all of those things in mind is why we want to kind of color that interaction. And I mentioned both verbal and nonverbal interaction and communication with the patient, because I think that they are picking up on all of these signals. Some of them are very obvious and some of them are very subtle. But keep in mind their brains, their nervous systems are primed to interpret all of these signals, both verbal and nonverbal. And that's going to have a downstream - or upstream, I would say - effect on their framing and how they interpret the interaction and what they think it means for them and their future. So, you know, it's kind of a big thing to think about when you- every time you walk in a room, but it's an important thing to think about when we're communicating with patients.

Dr Grouse: It's absolutely fascinating and has really made me go back and think about, gosh, are there ways that I could have done things better to really message this in a more helpful way? And on that note, do you have any tips or tricks on how to put out that that messaging, both verbal and nonverbal; to be, you know, to avoid those pitfalls of kind of reinforcing the wrong message about tissue damage?

Dr Williams: Yeah. I mean, so one of the main things is trying to be very purposeful about educating people on the difference between tissue damage or potential tissue damage and pain. And so being careful not to use statements like, well, I think your pain is coming from this disc or this structural abnormality because again, we want to try to separate those things.

They are different. I think that, you know, how we discuss imaging studies is very important because you want people to understand that an imaging study is just that. It's anatomy and it doesn't equal function, it doesn't equal what they experience in terms of sensory symptoms and pain. But I think the goal is to try to be very purposeful and maybe even reexamine how we discuss those things or when we discuss those things. One of the things I've found helpful is kind of the order in which I perform my clinical assessment. So traditionally, I was taught, like many, take the history, do the physical examination, and then start to discuss and educate patients. Right? Here's the test I want to order, here's what I think may be going on, so on and so forth. I think in some cases it's more beneficial to take the history and, before the physical examination, discuss what I'm thinking, taking that opportunity to discuss the differences between nociception, tissue damage, the experience of pain, the importance of movement, so on and so forth. And then do the physical examination so that that person has some idea of what is it that he's looking for. How is this going to inform his opinions and recommendations and so on and so forth. But also provide them with the concept that movement, for instance, is safe unless they have certain kinds of red flags on their history. I'm encouraging movement and I'm encouraging them to recognize that some of these movements they may have predicted would have been painful for them actually aren't painful, and they may start to internalize the concept that they can do it once without paying, that probably means that they're not damaging themselves every time they perform that movement. And if they can do one pain-free rep, that's important, and that may counteract the concept that they are damaging themselves every time they move and every time they feel pain, that means that there's tissue damage. So, what we talk about, how we talk about it and even when we talk about it during the course of that evaluation may have some negative or positive effects. And it may be beneficial to kind of think about those things and whether or not our typical approach might be the best or maybe we can improve on that or adjust that, particularly in certain situations and with certain patients.

Dr Grouse: That's absolutely fascinating, and great tips I think that all of our listeners will want to incorporate as we're approaching this patient population. You know, in your article, I also wanted to talk about, you mentioned some really interesting treatments for pain is that I think would include, or would, fall under the category of neuromodulation. Can you summarize some of these options for us?

Dr Williams: Yeah. I mean, so I think that the concept of neuromodulation, I tend to think of it in a very holistic sense. And so not only focusing on the application of external stimuli and that could be, you know, electrical stimuli, magnetic stimuli, cryo, analgesia, those kinds of things in order to turn up or down nervous system activity, electrical signals, what have you.

I think of neuromodulation in a global sense. I think in a way, cognitive restructuring and education, in a way, is a form of neuromodulation. It's affecting how that individual frames the concept of their pain, structural changes versus experience, so on and so forth.

But generally, I'm talking about these kinds of things. So, there are some very interesting approaches with electrical stimulation and it doesn't necessarily have to be permanent implantation of a stimulator as we tend to think about with spinal cord stimulation, but there are some interesting temporary peripheral nerve stimulators that that can be very helpful for various kinds of spinal pain. And then there's also these technologies that I find fascinating. Some of them are in the wearables category. So, combining the education and framing and cognitive restructuring with things like virtual reality, there are some interesting programs that combine some predictive modeling with virtual reality, such that an individual has goggles on,

they are participating in some activity that requires them to move in a certain direction and move to a certain extent that may or may not match what they are seeing visually in the goggles.

So, you can kind of begin to kind of dissociate their expectation of when they may experience pain as a function of their movement from what actually happens. So, these kinds of things, I think, are really interesting ways to augment our traditional approaches to pain, physical therapy, rehabilitation, medications, some kinds of injections, with these additional approaches that really have an effect on the nervous system as opposed to just focusing on what I would call kind of the mechanical anatomy, the joints and the discs and what have you, with traditional approaches.

Dr Grouse: It's really exciting to hear about some of these new options that can be tried to help with this neuromodulation and sort of cognitive restructuring. Of course, understanding that there's some things that we do ourselves that do this in the clinic encounter, which I think is a great reminder. I wanted to touch on, in your article, you had mentioned that we really have to be aware as clinicians, that health inequities and disparities and even the social determinants of health have inevitable effects on spine pain. How can our listeners better recognize and ensure equitable care for this patient population, particularly in light of the fact that many of these therapies that we've just been talking about can be difficult to access even in the best circumstances?

Dr Williams: Well, you know, thanks for asking that question. I think that's a great question. I think from the standpoint of, you know, health equity and addressing, you know, disparities and that kind of thing, the first thing is to just acknowledge and recognize that these things are present. And even, you know, though we may have the best intentions, there may be scenarios where our practices are affected and our patients are affected by these kinds of things.

So, I think the first thing is the acknowledgement. And then the second thing is kind of trying to figure out if there are things that we can do as individual practitioners, or our offices can do or the entities that we interact with, maybe that's a hospital system or what have you to address these kinds of things. So, we know, for instance, from the standpoint of race and ethnicity, there's disparities with respect to African Americans, with Hispanics and other ethnic minorities and the kind of care they receive. We know that access resulting from insurance coverage and geographical limitations, that kind of thing can be significant. And interestingly, it doesn't necessarily mean that the person is uninsured. So, for instance, we will often see individuals who've had work injuries and who are covered by the workers' compensation system have certain limitations placed on what they have access to, often resulting in lots of frustration from those patients. And that's a reality that we sometimes have to work really hard to overcome. Socioeconomic status, provider bias. And again, this is something that we have to kind of do some internal searching to say, hey, am I approaching these individuals on a on a more equal and equitable basis, or am I also subject to some of the biases that that I've been exposed to and trying to overcome that? So, I think that's a huge part of the context. And when we talk about how we learn, whether we're talking about spine pain or anything else, I'm a believer in that kind of cycle of pedagogy that includes content-based information, which is kind of the very basic foundational information, that includes things we can memorize and definitions we can memorize. And that may include things like what we've talked about relative to kind of the nociception and pain pathways, so on and so forth. But then there are concepts, and we've talked about the concept of verbal communication and nonverbal communication, the concept of cognitive restructuring and neuromodulation as an approach. But then context is kind of that last level, probably the most significant level in terms of how we can integrate all this information and really master information. And that context has to do with things like social determinants and disparities and the reality that these things have an effect on how we evaluate and manage patients and the success with which patients can be managed. And so, I appreciate that question, I think it's a great question, because it gets that kind of the reality of what does this look like in real life as opposed to just on the page or just in a textbook.

Dr Grouse: Well, that's really helpful and certainly something that we can all keep in mind as we try to be more aware of this, and I like the idea of just acknowledging it and just having it there, knowing that this exists and helping that inform how we approach these patients.

I wanted to ask you, what do you think the biggest controversy is currently in the evaluation and management of spine pain?

Dr Williams: You know, I think that there's a couple of controversies that are interesting. Nowadays, one of them has to do with the utility of some of the things that have been performed and done most frequently for spine pain, and that's things like epidural injections, facet injections, some of the interventional procedures. There's some controversy among some as to whether or not these things are effective, you know, what role they have in treatment because some people will say, oh, is there any long-term effect from these kinds of procedures? Even patients will sometimes say, hey, listen, I'm not sure if I want an injection because isn't that just temporary, or, isn't that just a band aid? But I think that when we talk about pain from the perspective of it potentially being a progressive disorder and trying to be aggressive with managing pain so that we are less likely to see some of the chronic manifestations that occur with maladaptive neuroplasticity it's important to be aggressive with stopping no subceptive signals, reducing an individual 's experience of pain, optimizing their function, and having a positive effect on the ability to treat and eliminate pain, even if that means with epidural injections or blocks or what have you, as long as they're safe and effective. I think that there are some controversies evolving related to some of the regenerative procedures that have been done for other kinds of musculoskeletal pain. So, for instance, PRP and stem cells, you know, people have been doing those for knees and muscle tears and what have you. And of course, that technology has kind of evolved into potential approaches for spine pain. People are often interested in whether PRP or stem cells may help their spine pain. And so, I think that's another area of potential controversy because there hasn't been a ton of, you know, high-level evidence, although there are some, you know, there's some studies out there and there's some evidence that they may be of benefit. And I think the role of stimulators and implants for axial pain is another area of potential controversy. Those are probably the biggest things in this area of spine pain that are topics of controversy. There are things that have people talked about for years in terms of chiropractic care versus traditional medical care. But I think right now it's the utility of these kinds of interventional procedures, the role of regenerative procedures and injections, and then the role of more aggressive interventions like permanent implantation of stimulators and that kind.

Dr Grouse: Is there anything coming on the horizon in the field of managing spine pain that we should be looking out for?

Dr Williams: Well, you know, I am still bullish on the concept of neuromodulation and we've talked about that peripheral nerve stimulation, spinal cord stimulation, and then other wearables, VR, so on and so forth. I think that those things will continue to evolve, and I think that technologies continue to evolve that are likely to help with spine related pain. Some of them are very interestingly related to the ability to strengthen multifidus muscles and improve muscular function in individuals with spine pain. But I think that's one area - neuromodulation - that we'll continue to see evolution. I think that- I'm interested to see what the role of regenerative injections and regenerative procedures may play. And then just like every other field of human endeavor, artificial intelligence, machine learning, those kinds of things are likely to have a significant effect on how we diagnose an individuals, on treatment options for various individuals, and even a predicting outcome from various treatment. So those, I think, are examples of areas that we'll see continued growth and evolution with respect to spine pain.

Dr Grouse: Well, I'm very excited to see what comes down the pipeline and both vastly more to come, I'm sure. So, thank you so much, Vernon, for joining us. I really enjoyed reading your article. I really enjoyed talking about this topic. I think I've learned a lot and I hope that our listeners will take the time to read this article. It's really, really helpful.

Dr Williams: Well, I appreciate the opportunity. I really enjoy participating in this process. The interview was fun, so thanks a lot for having me. I really appreciate it.

Dr Grouse: Again, today I've been interviewing Dr Vernon Williams, whose article on spine pain 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 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 Continnpub.com/AudioCME. Thank you for listening to Continuum Audio.