Continuum Audio

Continuum Audio features conversations with the guest editors and authors of Continuum: Lifelong Learning in Neurology, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. AAN members can earn CME for listening to interviews for review articles and completing the evaluation on the AAN’s Online Learning Center.

Sleep Diagnostics and Monitoring Technology in Obstructive Sleep Apnea With Dr. Joyce K. Lee-Iannotti 08/19/2026

Sleep Diagnostics and Monitoring Technology in Obstructive Sleep Apnea With Dr. Joyce K. Lee-Iannotti Advances in sleep technology are transforming how neurologists identify and manage obstructive sleep apnea, a condition that affects up to 70% of patients with certain neurologic disorders and can negatively impact cognitive and neurologic outcomes if left untreated. In this episode, Dr. Joyce Lee-Iannotti discusses the growing role of wearable and nearable sleep-monitoring devices, when home sleep studies are appropriate, and how emerging technologies are expanding access to diagnosis and treatment. Learn practical strategies for screening patients, interpreting sleep data, and partnering with sleep specialists to improve long-term neurologic health through better sleep. In this episode, Casey S. Albin, MD, FAAN, speaks with Joyce K. Lee-Iannotti, MD, FAAN, FAASM, author of the article “Sleep Diagnostics and Monitoring Technology in Obstructive Sleep Apnea” in the Continuum® August 2026 Sleep Neurology issue. Dr. Albin is a Continuum® Audio interviewer, associate editor of media engagement, and an assistant professor of neurology and neurosurgery at Emory University School of Medicine in Atlanta, Georgia. Dr. Lee-Iannotti is a Professor of Neurology at the Barrow Neurological Institute, University of Arizona College of Medicine, and Creighton School of Medicine in Phoenix, Arizona. Additional Resources Read the article: Sleep Diagnostics and Monitoring Technology in Obstructive Sleep Apnea Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Albin: Through the neurology of sleep issue, I think we have all been convinced that we all need better sleep, both for ourselves and for our patients. And fortunately, there is an abundance of new technology that can enable us to diagnose sleep problems, and then also make sure that our patients are getting the rest that's going to give them the best chance at a good cognitive recovery, and improve their cognitive function even if they are not currently suffering from a neurologic condition. Today, I am so excited to dive deeper into this topic. Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Albin: Hello, this is Dr. Casey Albin. Today I'm interviewing Dr. Joyce Lee-Iannotti about her article on sleep diagnostics and monitoring technology in obstructive sleep apnea. This article appears in the August 2026 Continuum issue on neurology of sleep. Welcome to the podcast, I'd love to just start by having you introduce yourself to our audience. Dr Lee-Iannotti: Sure. Thank you so much for having me, Dr. Albin. I'm Joyce Lee-Iannotti. I'm a professor of neurology at Barrow Neurological Institute. I am boarded in general neurology, stroke, and sleep, but I spend most of my time in the sleep world, so I jokingly say that I get more sleep doing sleep than I certainly did in stroke. Dr Albin: Absolutely. I mean, wow, what a fascinating career, and I suspect that we're actually gonna get to some of how all of those pathophysiologies might overlap in the world of sleep. But you had the really exciting task of trying to distill this exciting, rapidly evolving field of sleep diagnostics, and I suspect it's relevant to many of the patients who end up in the neurology clinic, and I suspect that it's actually pretty relevant to many of our listeners who themselves might actually be wearing sleep tracking devices. And all of us probably wonder, well, how can we use that data to improve our own cognitive function and certainly make our patient's life even better? Before we even get into some of the meat and potatoes of this, I thought it would be really helpful for us to define some terms that come up in your article, one of which is wearables. We might figure that out, but the other is nearable. Walk us through what's a wearable, what's a nearable, how are they different? Dr Lee-Iannotti: I'm happy to do that. First of all, the article is entitled Sleep Diagnostics and Monitoring Technology, and this was a super fun article for me to write because it's very practical, and it's generalizable to everybody. So, I'm going to start with a wearable, and a wearable is really a device that is simply worn on the body. And we're all familiar with wearables like smart watches, they’re rings, they’re patches, they’re headbands, and the most validated form of a wearable that you've probably heard about is actigraphy, which we use in the sleep clinic. Dr Albin: Tell us a little bit more. So, what is actigraphy? I've heard the word before, but don't actually know what it means. Dr Lee-Iannotti: Actigraphy has been a tool that we've used in the sleep clinic for a really long time. Traditionally, we used it to monitor circadian rhythm patterns in people who are night owls or morning larks. And then more currently, we actually use it to track sleep patterns in people with suspected narcolepsy. So, before they come in for a sleep study, we actually have them wear an actigraphy for about a week just to get a sense of their sleep duration and their circadian pattern. Dr Albin: Got it. And what is it monitoring? Our movement or the patterns that we may or may not make? Dr Lee-Iannotti: It's really based on movement. You're exactly right. Dr Albin: Cool. Okay, so most of this is based on gold standard monitoring with actigraphy. What other things can be incorporated into these wearable devices? Dr Lee-Iannotti: Yeah, the technology is really advanced, and every day it changes, which is super exciting. So, on top of movement, these wearables can look at temperature. They can look at even EEG, like limited EEG, heart rate variability, and a really big word that we like to use in sleep technology, which is PPG, or photoplethysmography data, and that's really looking at heart rate variability and oxygenation, saturations, and following those levels as well. Dr Albin: Wow, so you basically can get most of the data that you might have historically needed to go to a sleep lab to get. Dr Lee-Iannotti: Most of them. They're still a surrogate. You'll hear me emphasize in the article as well that the gold standard remains the in-lab polysomnogram, but these are good surrogate markers that patients can wear long term to look at trends and patterns. Dr Albin: Absolutely. And we're gonna unpack a little bit about who specifically those are best for and, really what it gives you in the clinic. But before we jump into that, what's a nearable, and how is that different? Dr Lee-Iannotti: Yeah. Nearables are really exciting too. So, these are devices that monitor sleep but don't require direct contact on the body. So, these are devices that our patients will use, but it'll be at the bedside table. They're devices that actually go underneath the mattress, or they can be in, like, the ambient environment to detect sleep patterns. Dr Albin: Oh my gosh. How is it doing that if it's not actually something you're wearing? Dr Lee-Iannotti: I know. It seems a little Big Brother-ish, doesn't it? Dr Albin: Yes. Dr Lee-Iannotti: So, they use a technology called radio frequency signals, sometimes radar, sometimes sonar, pressure sensors, even microphones, and they're picking up things like respiration, movement, snoring, and that's how they can decipher sleep patterns. Dr Albin: Crazy. I mean, I guess the benefit of that is that it's less disruptive to the user 'cause it's not actually on them and having contact with them, and I suspect there's probably some downsides in terms of just it's a more limited data set you're getting. Dr Lee-Iannotti: Absolutely. Yeah, you're exactly right. It's more convenient because it's not touching them, so, in theory, they're gonna sleep more comfortably. But I would like to think that the most validated forms of devices that we use to track sleep have to have some form of contact with the body, and this technology is new and probably needs a few layers of more sophistication to be as accurate as the wearables. Dr Albin: Absolutely. I feel like we're going to have this conversation in five, maybe even less than that, years, and this data will have become like, oh, we all have something in our room that's monitoring everything. The world is crazy. All right. One of the places where your article really stood out to me is that sleep diagnostics have really taken off, particularly when we're thinking about obstructive sleep apnea. And I think we all might sort of scratch our heads and be like, "This is a neurology podcast. Why should I, as a neurologist, care about obstructive sleep apnea?" But I think you laid out a very convincing argument in the article. Walk us through why we should care about this. Dr Lee-Iannotti: Absolutely. So, for neurologists, sleep matters, and I hope that my article translates that. Obstructive sleep apnea, which I'm gonna call OSA, is incredibly common in all of our neurologic patients, whether you see epilepsy, Parkinson's, stroke, Alzheimer's, neuromuscular, or even chronic headache patients. The prevalence of sleep apnea is as high as 70% in these patients. Dr Albin: Wow. That's incredible. That is an incredibly high number. Dr Lee-Iannotti: And if I can add, Dr. Albin, there's growing literature in multiple studies across the literature that show that untreated sleep apnea negatively impacts neurologic outcomes in our patients. So, it is really important to ask the question about sleep, and if the red flags pop up, to then screen for sleep apnea in particular. Dr Albin: I think that that's a great point for us to drill down on, and obviously you're a sleep neurologist. You're very used to screening people in the clinic. But say someone comes in, and I'm gonna have you put your former stroke hat on, and say someone comes into the stroke clinic, and you're just making sure that they're optimized on their aspirin or dual antiplatelet therapy, and you're doing secondary risk modification. How would screening for OSA fit into that? Dr Lee-Iannotti: It would be a part of that screening process to look at preventative ways to prevent strokes, whether it be primary or secondary prevention. So, we did a survey a while back, and it actually showed that 17% of stroke neurologists are screening for sleep apnea. It has quadrupled, fortunately, in the last few years due to public awareness and a lot of education that the AAN has done, in fact. So, at this point, I would say not asking about sleep apnea to a stroke patient is similar to not asking about diabetes. Dr Albin: So, we really have to be cognizant and conscious about saying, you know, "Do you snore at night? Do you have episodes of apnea, or does someone witness you stop?" Are there things that you ask that maybe I wouldn't be aware and thinking of? Dr Lee-Iannotti: Those are the right questions, and then very practically, very easy questionnaires to implement that literally take a minute that your nurses or medical assistants can administer to the patient, and the most commonly one that is used in stroke patients is called the STOP BANG, S-T-O-P B-A-N-G, which is a validated questionnaire to screen for symptoms. Dr Albin: Absolutely. So okay, so this is easy to do. We should all be doing this. If you're not, now's the time. And I suspect if they screen positive, next steps, it can be hard to get into a sleep lab, and we're gonna talk about some workarounds, but I think some of our listeners may never have spent time in the actual sleep lab. So, let's say you refer a patient and you actually can get them in for a gold standard in-lab sleep study. What's gonna happen in that sleep study? Dr Lee-Iannotti: Yeah. And I just want to preface this by saying that my article hopefully highlights that we've come a long way where we understand that there are many neurologic populations then that can undergo home ambulatory sleep studies with just as much accuracy as an in-lab polysomnogram. But with that, I wanna say an in-lab polysomnogram is actually a highly sophisticated physiologic recording overnight, typically, unless somebody is a day sleeper. So, if I could take a minute to kinda describe the data that we're monitoring throughout the night. There is a limited EEG. We concentrate on frontal, central, occipital leads to look at sleep staging. We have eye leads. We have EMG leads on the chin and the leg. We look at EKG, flow monitors, belt, and then we also do pulse oximetry, snoring mics, and even body position sensors. So, a lot is going on. Dr Albin: This is incredible. Yeah, it truly is. I mean, this is like... I'm a neurointensivist, and so I think that you have just really outdone what I consider multimodal monitoring in your sleep study patients. I'm not even sure our neuro ICU patients accumulate that much data. All right, so tell me, they go through, and they can get this. But like you said, there's actually a lot of data that you've presented that, you know, not everyone needs to go to the in-lab sleep study. So how do you decide who actually needs to be in a sleep lab versus who can do this at home? And then how do you set them up with getting this done at home? Dr Lee-Iannotti: Yeah. The home sleep studies are really more accessible ways for us to assess for sleep apnea in our neurologic patients, especially patients who live in very rural areas and don't have access or have very long wait times for an in-lab polysomnogram. With that being said, though, Dr. Albin, I will say that there are a subset of patients who have to go into the lab, and those are patients where you suspect a sleep disorder other than obstructive sleep apnea, so like parasomnias or central sleep apnea, patients with severe cognitive or physical debilitation, like our stroke patients who are hemiplegic and won't be able to apply the home sleep study. But for the most part, I do feel like a home sleep study is a good beginner study to screen the patient. And if there are red flags, then you can always get the in-lab afterwards. Dr Albin: That's super helpful. And just from a pragmatic standpoint, will insurance cover the home sleep study? Dr Lee-Iannotti: They will, yes, and it's all about documenting. So, if I could get really practical, for neurologists, it really just requires documenting snoring, for one, whether it's noted by the patient or by their bed partner, and then any form of hypersomnia, which is daytime sleepiness or even a sense of fatigue, having low energy or napping during the day. Dr Albin: I suspect so many of our patients meet those criterias. That seems, like, wildly simple to do. Dr Lee-Iannotti: Yes. And if you wanna be the favorite referral person to your sleep neurologist or your sleep specialist, then take another step and do that STOP-Bang. And if you record a score greater than three, that automatically gets them at least a home sleep study. Dr Albin: It's amazing. And then when you get this data, again, this is really practical, pragmatic stuff, how do you get the report? Does it integrate in your electronic medical record? Does the patient bring it in? How do you get that data back? Dr Lee-Iannotti: Yeah, so this is where technology is amazing, Dr. Albin. Now we have disposable devices. Sometimes they sync to the WatchPat, or the greater Wi-Fi. So we can get them all through password-protected internet forums that transmits the data, so sometimes the patients don't even have to come back to give us the data. And then we have different forms where we can actually relay the results as well, either through the electronic medical record or through systems themselves to relay those results directly to the patient. Dr Albin: Yeah, and your article really laid out in beautiful tables, like, all the different devices that are available to patients, and it's honestly mind-blowing how many of these companies and devices exist. So, seems like the world is your oyster in terms of picking from them. Dr Lee-Iannotti: Absolutely. I think there's... The last time I counted, there was over 20 different home sleep study devices for obstructive sleep apnea. And it's a great thing to have, but sometimes too many choices can be a little bit confusing. So that's where I do say partner with your sleep specialist close by, and they will find the right type of home sleep study device for your particular patient. Dr Albin: Drilling down a little further, let's say your patient does get diagnosed with OSA. One of the things that really stuck out to me is that there's a whole range of now devices that are new that make this treatment easy so that we can actually prevent and treat neurological conditions by just improving patient sleep. So, walk us through a little bit about how that landscape has changed. Dr Lee-Iannotti: Sure. And I'll start with the gold standard of treatment, which is still CPAP, which is continuous positive airway pressure. Not only can we monitor the pressure, look at adherence, change the humidification for the patient all remotely through, again, password-protected internet forums, but we can even change the pressure with patients 300-plus miles away. Dr Albin: Wow. Dr Lee-Iannotti: It's really cool, right? It prevents patients, especially with significant neurologic debilitation, from having to come into the office for adjustments. The other thing I wanted to mention, Dr. Albin, is for patients, a lot of patients like positive feedback on a daily basis. And a lot of these companies, if you are on CPAP, have come up with a smartphone app that you can look at how many hours you used your CPAP device. They give you a score, and they even tell you how many times you had stoppage of breathing that night. Dr Albin: I think that this is what's really exciting about where we are in neurology and, like, neurologic care, is we have gotten so much better at getting patients their own data and allowing people to really see that data, integrate lifestyle changes, and see how it impacts them. And that positive feedback loop, I think, is a really powerful tool for our patients to say, "Look, this makes me better," or, "Oh, this makes me worse." I'm just really excited by how much data we can give directly to our patients. Dr Lee-Iannotti: I agree. It's so empowering. You know, as a CPAP user myself, you want that positive affirmation that all of your efforts at night and cleaning your mask and your machine paid off, and everybody likes to see an A+ on their report card. Dr Albin: I love that. Now I'm going to ask you on the flip side, I imagine, and I myself am a sleep tracker, like I have my little device and I look at, you know, the score in the morning and I kind of perseverate on like what makes it better, what makes it worse, and I can imagine that sometimes in sleep clinic, people are coming in to you and they have just pages and pages and, you know, they're flipping through all their data from the last year. And I imagine that's pretty overwhelming when you have just the insane amount of data that these devices can generate. So, from another pragmatic, practical standpoint, how are you integrating all that data when someone comes in for a sleep visit? Dr Lee-Iannotti: I love that question. So first of all, I will say myself, and I think a lot of my sleep colleagues, we love objective data, right? Because it's something that we can see.... /episode/index/show/continuumjournal/id/42038105

Obstructive Sleep Apnea With Dr. Stephanie M. Stahl 08/12/2026

Obstructive Sleep Apnea With Dr. Stephanie M. Stahl Obstructive sleep apnea affects approximately one in four adults and is especially common among patients with neurologic disorders, including stroke, Parkinson disease, dementia, epilepsy, and neuromuscular conditions. In this episode, Dr. Stephanie Stahl discusses why neurologists should routinely screen for OSA, highlights key symptoms and risk factors, reviews important considerations when interpreting sleep studies, and outlines current treatment options beyond CPAP. Learn how recognizing and treating sleep apnea can improve quality of life, optimize management of neurologic disease, and reduce long-term health risks. In this episode, Aaron L. Berkowitz, MD, PhD, FAAN, speaks with Stephanie M. Stahl, MD, FAASM, author of the article “Obstructive Sleep Apnea” in the Continuum® August 2026 Sleep Neurology issue. Dr. Berkowitz is a Continuum® Audio interviewer and a professor of neurology in the Department of Neurology at the University of California, San Francisco, in San Francisco, California. Dr. Stahl is an Associate Professor of Clinical Medicine and Sleep Medicine Fellowship Program Director at Indiana University School of Medicine in Indianapolis, Indiana, where she also serves as Sleep Laboratory Medical Director in the Division of Pulmonary, Critical Care, Sleep, and Occupational Medicine. Additional Resources Read the article: Obstructive Sleep Apnea Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Berkowitz: Obstructive sleep apnea is very common. It can cause or contribute to common neurologic symptoms, such as headache and impaired cognition, and it's a risk factor for stroke. And yet, if you're like me, you may not know too much more about sleep apnea than that. Today, I have the pleasure of talking to sleep expert Dr. Stephanie Stahl to learn what every neurologist should know about OSA. Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Berkowitz: This is Dr. Aaron Berkowitz. Today I'm interviewing Dr. Stephanie Stahl about her article on obstructive sleep apnea. This article appears in the 2026 Continuum issue on Neurology of Sleep. Welcome to the podcast, Dr. Stahl, and could you please introduce yourself to our audience? Dr Stahl: Yeah. Thank you for having me. I'm a sleep medicine physician and neurologist and medical director of the Indianapolis Sleep Lab at Indiana University Health. I serve as the director of the Sleep Medicine Fellowship program. I'm faculty advisor for our very first student interest group in sleep medicine at Indiana University School of Medicine. I'm also actively involved in some national leadership roles, including the incoming chair of the American Academy of Sleep Medicine's Education Committee and co-chair of the Academy's Inter-Scorer Reliability Gold Standard Panel. So, I really appreciate this opportunity. I look forward to our discussion. Dr Berkowitz: Me too, and we appreciate the opportunity too to get to talk to you. You have so much expertise in this area, and I certainly encourage our listeners to look at your article, which is very comprehensive and up to date, and I learned a ton from it. I didn't get much exposure to sleep neurology as a trainee, and I've always worked in academic centers where we have a sleep group and we can refer patients there. So, I have to admit, sleep may probably be the area of neurology I know the least about, and felt like I was learning something new from pretty much every line of your article, and I know our readers will too. So, your article has a lot of excellent detail for our readers on the diagnosis and treatment of this very common condition. But I'd like to keep our interview relatively high level today and focus on the essentials for the practicing general neurologist. So, to start, can you just give us a sense of what obstructive sleep apnea is, and what every neurologist should know about it? Dr Stahl: Yeah. So obstructive sleep apnea is characterized by either partial or full obstructions in the upper airway. That may sound pretty simple, but this leads to a whole bunch of issues. It leads to oxygen desaturations, arousals from sleep, leading to sleep fragmentation. This can then lead to sympathetic nervous system activation, cerebral hypoperfusion, leading to a whole bunch of symptoms or neurologic conditions. Dr Berkowitz: Great. And you mentioned this in your article, but just to emphasize, how common is obstructive sleep apnea in the general population? Dr Stahl: Yeah. So, about a quarter of the general population have obstructive sleep apnea. Much more common in many neurologic conditions. Dr Berkowitz: Yeah, so very common disorder. We are seeing patients with it quite frequently, whether that's the reason they are seeing us in neurology or not. And this leads to my next question, which is what neurologic symptoms or presenting concerns of a patient should make us think about OSA and the differential diagnosis, and what factors based on the history or the exam or the context would make you suspicious for OSA as the cause of a neurologic symptom? In other words, the patient's presenting with classic symptoms of OSA, and that's why they're seeing a neurologist or seeing a primary care doctor, but is coming for evaluation of, say, headache or other symptoms. And what symptoms would make you think of wanting to consider OSA, and then what aspects of the history or otherwise would make you want to evaluate the patient for OSA? Dr Stahl: I think a really important takeaway is for neurologists to know that obstructive sleep apnea is very common in neurologic conditions and has that potential to worsen a lot of these conditions or their associated symptoms. And so, it should be on our radar. There are certainly some basic questions and signs and symptoms that we can ask patients about or, or take a look at on exam. And so particular symptoms include snoring. Anybody that snores loudly or frequently, that's a strong risk factor for obstructive sleep apnea. If someone's seeing them stop breathing in their sleep, if they are waking up a lot throughout the night. There are some other symptoms that we may not necessarily attribute upfront to obstructive sleep apnea, such as nocturia, nocturnal reflux, night sweats. There are some daytime symptoms, of course, too, like unrefreshing sleep, daytime sleepiness, morning headaches, an important one in neurology. And then we take a look at the patient's exam. And so, some things that neurologists might want to be thinking about are people with obesity are certainly at a risk for obstructive sleep apnea. But it's also very important to know that someone does not need to have obesity in order to have obstructive sleep apnea. We look at neck size, other morphologic characteristics, such as how much that we can see in the back of their mouth. Can we see their uvula? Does their tongue size appear large in their mouth? And then some other risk factors too, such as male gender, older age, family history, post-menopausal state in women. All that being said, though, sometimes in neurologic conditions, we don't have all of those symptoms or risk factors to be thinking about. And so, in certain neurologic conditions such as stroke where obstructive sleep apnea is very common and has the potential to increase the risk of another stroke, we may need to be thinking about testing these patients even with minimal symptoms or other risk factors. Dr Berkowitz: That's very helpful. So, you mentioned their headache might be the presenting symptom, right, to a neurologist, and we should certainly be thinking about obstructive sleep apnea as a potential diagnosis, even the cause of the patient's headache, particularly you said patients with morning headache. I often try to think about in patients presenting with, for memory loss, or other cognitive concerns, and that may be due more to inattention from poor sleep, so asking about sleep and symptoms of sleep apnea in those contexts. Are there any other presenting neurologic symptoms not particularly related to sleep? I'm thinking of headache, memory loss, other symptoms that would make you think, "Oh, I should actually screen this patient for sleep apnea also." Dr Stahl: Yeah, other symptoms to think about in pediatrics, hyperactivity, people that have impaired vigilance, as you alluded to, that poor attention. Sometimes people get misdiagnosed with ADHD, and it's actually just a manifestation of obstructive sleep apnea. Dr Berkowitz: You alluded to this, Dr. Stahl, that stroke, for example, patients are at higher risk of developing sleep apnea as a result of stroke, and it's also a risk factor for stroke. What other neurologic conditions, primary neurologic diseases, put patients at a higher risk of OSA? And again, similar to the last question I asked you, what are some clues that we should evaluate for? We might be following a patient for their post-stroke care over time and not necessarily thinking about diagnosing a separate condition in them since we're following them for their stroke or their degenerative disease. What are the conditions that put patients at a higher risk of OSA as a result of the condition, and then when would you think about screening them for it? Dr Stahl: Some particular neurologic conditions where obstructive sleep apnea are very common, in addition to stroke and, and TIA, include Parkinson disease. It can worsen a lot of the motor, cognitive symptoms, sleep disruption that we can see in Parkinson disease. Very common in all causes of dementia, but in particular Alzheimer disease and Lewy body dementia. Very common in neuromuscular conditions. We should definitely have obstructive sleep apnea and all forms of sleep-disordered breathing high on our radar. In conditions like myotonic dystrophy. Charcot-Marie-Tooth is another one where obstructive sleep apnea is very common. Myasthenia gravis, it can worsen the symptoms of that. In particular, a pearl is if somebody has morning weakness in myasthenia gravis, obstructive sleep apnea should be high on your radar. And also, as you mentioned, any forms of headaches. There are some other things too. If somebody has poor seizure control, especially nocturnal seizures, you might have obstructive sleep apnea on your radar as well. Dr Berkowitz: So, I think you've covered essentially every category of neurologic disease, right? We have cerebrovascular, movement, neurodegenerative, neuromuscular, epilepsy, all conditions where either the disorder itself, such as stroke or the, correct me if I'm wrong, the neurodegenerative disease puts the patient at risk. Or the patient may be at risk for exacerbations of their disease, as you mentioned in myasthenia. I love that pearl. Not fatiguable at the end of the day, but if the patient with myasthenia is telling you they're feeling weaker at the beginning of the day, then think about obstructive sleep apnea and that obstructive sleep apnea worsening control of epilepsy due to poor sleep. So really a lot of bidirectional interactions with this common condition. Okay, so if we're concerned about obstructive sleep apnea, again, myself, a general neurologist speaking perhaps on behalf of other general neurologists, we see a patient with headache or reporting memory loss that we find to be impaired attention, or we see exacerbation of their underlying primary neurologic disease. As you mentioned, we think, "Oh, I've listened to this podcast. I've read Dr. Stahl's article. I should probably be thinking about OSA in this patient, and I should order a sleep study." Now, I admit when I get the sleep study back, I scroll to the bottom, I see they do have obstructive sleep apnea, I'm going to send them over to a sleep specialist. But for the general neurologist, what are some high-yield pearls and some pitfalls to be aware of when we get sleep studies for obstructive sleep apnea, and we are looking at the results? Dr Stahl: The first thing is to understand that there are two main types of sleep studies: in-lab polysomnography and home sleep apnea test. In-lab studies are typically what we consider the more accurate type of study. Main reason for that is that we have EEG, so we can see if someone is awake versus asleep. Most home sleep apnea tests do not utilize EEG, and so when we're looking at respiratory events, apneas or hypopneas, we're looking at over the total recording time rather than the total sleep time. So, we know we're going to capture some time where a person is awake, where we don't have sleep apnea events, and that can be a big amount of time in people with insomnia, poor sleep efficiency. And as a result of that, it can lead to an underestimation of the apnea-hypopnea index. That's really important for people to understand that that means we can end up with a false negative home sleep apnea test, or it can put them in a category of lower severity than what they actually have. And so, if you get a home sleep study report back that's negative for sleep apnea and you remain concerned, you need to go on to do an in-lab study, where about twenty to fifty percent of people will go on to have a positive in-lab study. You can also get false positives with home sleep apnea tests too, and so ideally, we should only be doing home sleep apnea tests in people that are at high risk of having obstructive sleep apnea to decrease our chance of false positive study. When we get that sleep study report, what's important to take a look at? So the main number that we look at currently is the apnea-hypopnea index. The number of apneas, which are full obstructions in that upper airway, or hypopneas, partial obstructions in the upper airway where either there's an oxygen desaturation or an arousal associated with that. Less than five is considered to be normal. Anything five or more gives them a diagnosis of obstructive sleep apnea, and then we stratify them based on the AHI. But it's important to take a look at more than just the apnea-hypopnea index. And while my eyes too on various reports like echocardiograms want to jump to the impression, it is important to take a look at that full report, see what their oxygen levels averaged and what they dipped down to. The arousal index, which is how many times a patient may have woken up briefly throughout the night. Take a look at the histogram, usually an image at the bottom of their report that shows what sleep fragmentation may have been like so that you can take that all in and make that decision. How important are these study findings, and is this a person that would benefit from treatment? Dr Berkowitz: That's a fantastic overview of sleep studies and some of the highlights to look out for, even if we won't be understanding every detail as you would to know most importantly the caveats about home sleep testing having a fairly high percentage of false negative and false positive results. So being wary if our suspicion is high, and that test is normal or inconclusive to get an in-lab sleep study. And if our suspicion is low or maybe we haven't ordered the test and the patient has had it done elsewhere, and the history doesn't really match up to know that there are false positives on the home studies as well, and again, an in-lab study to settle the diagnosis. Is that right? Dr Stahl: Yes. Dr Berkowitz: Okay. Now, for most neurologists, probably if we diagnose OSA, we will be referring the patient to a sleep specialist like yourself for treatment. I think we're all familiar with CPAP and patients being on CPAP. Your article mentions a number of treatment modalities I admit I have not heard of before or maybe heard of in passing, acknowledging most general neurologists are not going to be prescribing or knowing with the nuance that you do as an expert how to decide which treatment a patient would most benefit from or most qualify for. So, can you just give us a broad overview, again, for the general neurologist acknowledging we might see a patient whose past medical history says OSA being treated with fill in the blank. What are the different treatment modalities, and how do you think, just so we can learn from you in broad brush strokes, about particular treatments for particular patients? Dr Stahl: As you mentioned, most people are familiar with positive airway pressure or PAP therapy, and that does remain our most efficacious treatment. The way I explain it to patients is why PAP therapy is the most effective treatment is it's the only treatment that can take all of the tissues of that upper airway and open them up. Whereas all of our other treatments, we're going to target smaller spaces of that upper airway. So, our first option is if we can get somebody on PAP therapy, we know that that's going to be the best option for the majority. PAP therapy works by basically acting as an air splint to open up the air tissues. Know that masks are not interchangeable. There are masks that cover the nose and go over the nose and mouth and under the nose. Full face masks that cover the nose and mouth, they do typically require higher pressures, also tend to be less comfortable for a lot of patients as well. In addition to different PAP masks, there's different modalities of positive airway pressure therapy too. There are machines that auto-adjust, some that provide fixed pressure, bi-level PAP that provides a higher inspiratory pressure, lower expiratory pressure. Then outside of PAP therapy, there are, as you alluded to, a lot of options and more, continuing to come down the pipeline as well. Mandibular advancement devices or a form of oral appliances has been around for a while. This is device that somebody wears in their mouth. It's preferably customized for their teeth and titratable, meaning that they can make adjustments that pulls their mandible forward in relation to the maxilla in order to pull those tongue tissues further away from the back of the upper airway. That's ideally managed by a qualified sleep dentist or someone that specializes in oral appliance management. Other treatments include surgical options, including hypoglossal nerve stimulation, which is an implanted device that causes the tongue to protrude repetitively throughout their sleep period to hopefully open up the airspace. There's some other surgical options too that open up various places of the upper airway. There's a daytime treatment of obstructive sleep apnea, transoral neuromuscular electrical stimulation that changes the muscle fiber type of the tongue. And then there's some adjunctive treatments that can be helpful too, such as positional therapy, oral facial myofunctional therapy that helps a person breathe better through their nose and may help train the upper airway muscles. Dr Berkowitz: Great. Well, that's a very helpful overview, and again, I refer our listeners to your article, which talks about all of those modalities in very comprehensive detail. So, Dr. Stahl, as we wrap up our conversation, you have a captive audience of neurologists and neurology trainees here. What would you like to leave us with that every neurologist should know about obstructive sleep apnea? Dr Stahl: The most important, again, is for neurologists to know that obstructive sleep apnea is so common in your patient population, and it can have a significant negative impact on quality of life and health, including many neurologic conditions. And at the same time,... /episode/index/show/continuumjournal/id/42037995

August 2026 Sleep Neurology Issue With Dr. Karin Johnson 08/05/2026

August 2026 Sleep Neurology Issue With Dr. Karin Johnson In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Karin G. Johnson, MD, FAAN, who served as the guest editor of the August 2026 Sleep Neurology issue. They provide a preview of the issue, which publishes on August 3, 2026. 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. Johnson is a Professor in the Department of Neurology at the University of Massachusetts Chan School of Medicine–Baystate and the Sleep Medicine Division Chief at Baystate Medical Center in Springfield, Massachusetts Additional Resources Read the issue: Subscribe to Continuum®: Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about subscribing to the journal, listening to verbatim recordings of the articles, and exclusive access to interviews not featured on the podcast. Dr Albin: All right, welcome all. For the first time ever in the history of Continuum Audio, we are coming to you live from Chicago here at the AAN annual meeting. And now over to your host, the one and only editor-in-chief, Dr. Lyell Jones. Dr Jones: Welcome, everybody. My name is Lyell Jones, editor-in-chief of Continuum, and I'm here today with Dr. Karin Johnson, and we're interviewing Dr. Johnson for the upcoming and recently published issue of Continuum on Sleep Neurology. We have been doing Continuum Audio for a while, but we're doing something different this time. As our listeners online can tell, we are recording this for the first time ever with a live studio audience at the American Academy of Neurology annual meeting in Chicago, Illinois. So, this is a fun experience for us. I hope it's been fun so far for you, Dr. Johnson. Dr Johnson: Great to be here. Dr Jones: It's great to have you. So, before we get into the interview, I do wanna introduce our team here for the live recording of the podcast. You've already heard Dr. Casey Albin's voice. Dr. Casey Albin is an associate professor of neurology at Emory University. Also serves as one of our associate editors at the journal and one of our Continuum Audio interviewers. So, she's going to be working the crowd today. Let's have a round of applause for Dr. Albin. And our guest of honor today is Dr. Karin Johnson. Dr. Johnson is a professor of neurology at UMass Chan Medical School and, Baystate Medical Center in Massachusetts. She is a world-renowned expert in sleep neurology and is the guest editor for the most recent issue of Continuum on Sleep Neurology. Dr. Johnson, welcome. Why don't you introduce yourself to our audience? Dr Johnson: You did a great introduction, but I'm a clinical sleep medicine specialist. Spend my days seeing patients, taking care of people with narcolepsy, sleep apnea, restless legs, everything that comes my way. And then I have a side interest in doing sleep medicine advocacy, especially for permanent standard time. Dr Jones: And we may get to that. I mean, that might be part of our conversation today. So, you've now read all of the articles in this issue, and it's a really great issue. There's a lot of new developments in sleep neurology. There are some updates for clinicians, people who see patients with sleep disorders that I think are, are timely and important updates. You have this unique view because you have just read all of these articles, really good articles by expert authors. When you read through these, Dr. Johnson, what was the biggest, what was the biggest thing that surprised you? Dr Johnson: I think the biggest surprise for me is just so many changes in, in all of these articles. I realized how easy it was for us to make a journal that is so different from a few years ago. Whether it's Dr. Stahl's obstructive sleep apnea and new ways to think about endotyping sleep apnea that is gonna have treatment implications or the new treatments that are out there like tirzepatide, the changes that we're having with restless leg treatment. I particularly wanted to have a chapter on circadian neurology that Dr. Abbott did a great job really highlighting how if we think about the timing of when we give meds, the timing of when we eat, how that really can help neurological health, brain health, overall health, as well as mental health and cognition, especially as the AAN thinks about brain health as a whole, not just treating our patients, but how we can treat the population of people by improving sleep. I like how we hit on all these different areas in this issue. Dr Jones: And I don't know how you managed to do it. They're just a small number of articles. We cover a lot of existing territory with well-characterized diseases, with new advances. But there's a lot of new stuff in sleep, and so somehow, it's all packed in there. It's really impressive. One of the things I was gonna ask you about was an evolution, and this has been a number of years now in how we manage restless leg syndrome. When I was training, it was all about dopamine agonists, and that was your first line. And over time, the evidence has supported moving away from that, and now we have more recent guidelines that have come out, and it's really the alpha-two delta-one calcium channel antagonists. How is that transition going? Do you still see people in practice who come in on dopamine agonists? How is that going? How's the field responding to that? Dr Johnson: That's one of my most frequent restless leg consults. So even though it's been years since I have really initiated dopamine agonists in my patient, every day we get in people often on very high doses of dopamine agonists, and their doctors have just been escalating and escalating these meds over the years, and they come in with horrible augmentation. Their symptoms are much worse than they used to be, happening earlier in the day. And so, trying to get these patients off of these meds that are addictive, the way I like to teach about it is these dopamine agonists are the Fioricets of the sleep world. We know they work great, but in the long run, the patients are gonna be worse overall. And so, it's so hard to get people off these dopamine agonists, just like it's so hard to convince a headache patient that they don't need their Fioricet and that they're gonna be better off if we can get them off of it. What I think has really changed is we have more options to use. So, the alpha-delta-like agonists like gabapentin are now considered first line, but there's a lot of patients who they just don't work well enough with or they don't tolerate. And so, what do you do in that case? It's easy when that works, but and, when that doesn't work, we are being much more aggressive these days with iron replacement, potentially even trying to push ferritin levels in refractory patients up to three hundred, and using IV iron rather than just oral iron to get over the absorption issues to get the brain levels high enough. Motor stimulators, little cuffs that kind of go around the leg and stimulate the peroneal nerve in a certain way that not only can give people immediate relief, but also some data that suggests that over time it actually lessens their restless legs. We have agents like dipyridamole that work on the adenosine system in a sort of new novel pathway at addressing restless legs. And then the opiates, often meds like methadone or Suboxone can be used in some patients. But as we're getting more of these other options, often we don't need to go to those levels because we do have more to work with. Dr Jones: So, the key point is lots of options. We're not starting with dopamine agonists anymore. And I think the fact that you're still seeing a lot of patients who have been initiated on that probably tells us there's an education gap field that we need to work on. So, another thing that I noticed reading through the issue was, and this feels like a change over the last few years, is the availability and the tendency to use in-home sleep apnea testing as opposed to formal, traditional in-lab. And that feels like a great new option, and maybe that increases and improves availability for patients who need access to the test. But how do you work through that? Dr Johnson: So, I love in-home testing. We've been using it for over a decade. Other parts of the country where insurances didn't sort of mandate it are now being more mandated. I think the real change happened for a lot of places over the pandemic when labs closed down. But I think it's good because it brings a lot more patients to us. They get tested, they get tested quicker. People who would say, "I would never go into a lab. Oh, I'll do a home study." So, it just does bring more people in, and it gets them to treatment that they need that can really be life-changing. But it's not for everybody. The biggest people are people that have other bad pulmonary issues. If you're on oxygen therapy, you should not be getting a home study. That really should be a group of people that come in the lab. Similarly, if you have bad COPD, you probably should be getting a full in-lab study, so we can get more monitoring. Central sleep apnea is an interesting one. It can be very hard in some cases to differentiate the centrals and obstructive nature as well on a home study. Doesn't mean you can't do a home. So, if it's a person that just can't get an in-lab study easily, maybe you start with the home. If it looks purely obstructive, and you're all set, then you got an answer, and you can move on. But if you get back a home study that looks questionably central, they're gonna need to come into that lab. So, if you already know they're high risk because they're on narcotics, cause they have congestive heart failure, it's usually worth going straight to the lab. But again, you may consider a home study based on the patient. Patients that really cannot use the equipment can also be an issue. So, if they've had a debilitating stroke and have no one to help them put on that device, or cognitively they just can't handle the device, they're gonna be someone who's gonna benefit from coming into the lab and getting the help from the techs. So, those are the big populations that you might go starting for a home. And then the other thing that confuses a lot of people, the home is only for diagnostics. It really isn't for treatment. So, I have patients that say, "Oh, like, you can just titrate my CPAP with a home study." No. So if it's a treatment decision where they're not doing well on treatment, or I need to figure out do they need CPAP or BiPAP or IVAPS or one of these more complicated treatments, those are people that are gonna need to come into the lab to get that treatment portion of the evaluation. Dr Jones: What a great summary. That's like everything I needed to know about who do I need to bring into the lab and who do I think maybe could do an at-home study. Really great. And speaking of devices, I think all of us who see patients in the room here and our listeners out there online have experienced patients, and this feels like a very recent phenomenon to me, are coming in with their commercial at-home wearable device. And they have printouts sometimes, and they show me their phone, and they give me some numbers that I don't really know how to interpret. Reading through this issue, I learned a couple of great new words. I learned about orthosomnia, right? So, people who become so preoccupied with their sleep, it keeps them awake at night, literally, right? I mean, it's a complete paradox. I learned about nearables, so things that aren't necessarily wearables that are just in the room while the patient is sleeping that monitor proxies for sleep quality, sleep stage, and other things. And I frankly, I'm not really sure what to tell patients. So, what do you tell patients who come in with all the data? Like, or how do you tell patients to use these? Dr Johnson: I think these devices can go both ways. So, I do kind of say the pros and cons of these devices. I think for a lot of patients, they're empowering. It's getting them to think about sleep, to wanna know how good their sleep is. Are they getting enough sleep? So, if it's used in those ways, it's gonna be very helpful. I actually had a patient last week, and they noted that they're having big desats all night and could show me essentially an overnight oximetry data rather than me having to order it, and I had days of data, which sometimes can be too much. But in this case, it's like, oh, when he was on his side that night, he looked a lot better, so I can use that to give advice to the patient about particular treatments. He actually went down to Mexico, and a doctor friend gave him oxygen therapy while he was there randomly. And we could see on the nights that he had the oxygen therapy, it did really help his central sleep apnea pattern. And so that pushed us towards saying, "Let's qualify you for that up here in the States." So, I think in some cases it can give really important data. Now, I saw a posting on social media the other day of someone saying, "Can I get advice on how to improve my REM sleep? My tracker says I have no REM sleep, and I need to do something about it." There's really not data to support needing to do something about it. And so, I do think it can get some people on these wild goose chases, trying to get to a certain percentage of sleep. And these trackers, they're good in a lot of ways, but they're not perfect. He could be getting REM sleep that the tracker on him does not show. You want to relate it to what symptoms are they having. I think they can be very good for trying something out. So, let's say someone, has their tracker telling them they get five hours of sleep, and they try this intervention, and that helps them show that they got the seven hours of sleep, or they went from no REM to REM and it goes in the right direction. It can help give them that positive feedback that something they're trying, is working. But the absolutes for any given patient, it's hard to over-- What does it mean if it says you've got a 50% score versus a 70% score? That may or may not be meaningful in any given person, but again, they can compare themselves to themselves. If they were a lower score and now they're a higher sleep score because they did something that was meaningful, and that goes along with them feeling better, that can help give them that positive feedback to do something good. Dr Jones: So, a little bit of a mixed picture. Dr Johnson: Yeah. Dr Jones: Sometimes they help. Sometimes they distract. Hopefully- Dr Johnson: And as a provider, sometimes it can be overwhelming because they're like, "Come look at my year's worth of data." And you're like, "No." Dr Jones: Yeah. Dr Johnson: You know, let me see one page or two pages of data and be like, "Yep, okay, I get it." Dr Jones: Just show of hands in the audience, who in the room wears a sleep device at night, like a ring or a, some kind of sleep monitoring app? That's about half the audience. Dr Johnson: This is why they're here. Dr Jones: So that's really helpful, and I think it is. You want to be supported by the data. You want to be supported by evidence and high-quality biometric evidence. Another big trend, and this has been a number of years in the making, is the understanding, Dr. Johnson, of the relationship between sleep physiology and neurodegenerative disease. One of the things I love about neurology is there's still so much left to learn about the normal physiologic functioning of the brain. So glymphatics and other aspects of sleep physiology that we didn't know about a decade or two ago. When you think about how that relationship has developed, sleep physiology, maybe sleep disorders and neurodegenerative disease, how has that changed your approach to talking to patients? Do you counsel patients differently now because of what we understand better about that? Dr Johnson: Yeah, I mean, we are still limited with our data. We have so many studies that show the associations between whether it's not enough sleep, too much sleep, or having a sleep disorder like obstructive sleep apnea, and that being a risk factor for stroke or Alzheimer's or Parkinson's. But we still sort of lack the treatment trials that necessarily say, "If you treat obstructive sleep apnea, you're gonna have less dementia," or, "You're gonna be less likely to have that stroke." So, we have a lot of physiological studies, a lot of reasons why it makes sense, but we don't have that final, nail in the coffin to say, "If you do this, you'll definitely be better." So, we know certain groups are more at risk. If you have obstructive sleep apnea and you are symptomatic, you seem to have higher cardiovascular risk. If you have a person who's had a stroke and we find a milder case of sleep apnea, and they're someone that's totally asymptomatic. They say, "I sleep fine. I feel fine." There's not great data to say, "If you treat your sleep apnea, you're gonna be less likely to have a stroke." Now, if they come in and they're sleepy and their sleep apnea is really severe, and they have more hypoxic burden, which is also more connected with a lot of these risks, I'm going to say, "I think you are in the higher risk group of sleep apnea people who it's probably gonna be more likely to help your cardiovascular risk, your dementia risk." We can counsel them, and then it's really a personal decision. Some people are like, "No way. I'm never gonna use a CPAP machine, ever." And other people are like, "You know, my mom had a stroke. My dad had Alzheimer's. I want to do every possible thing I can to make it less likely that I have this outcome that I want to avoid." And so, you're going to take that in to, you know, do you want to try this treatment or not? It's a lot easier when you have outcomes that you can follow, like, "If I try CPAP, does my blood pressure get better? Do I stop having AFib attacks?" It's a lot harder when, will I or not get Alzheimer's ten years down the road or have that stroke? Dr Jones: It's hard to get people to do things for kind of an abstract prevention down the road, but could be important. Are there trials going on that are going to assess this data? Dr Johnson: Yeah. We currently have a big trial getting people right away, right after their stroke, on CPAP, and not only looking at prevention, but also looking at recovery outcome. It's been running for several years. Hopefully, we'll get enough data to close out the study coming up. Dr Jones: We'll look forward to that. Dr Johnson: Yeah. Dr Jones: So, I'm really excited to get to our audience here, but before we do that, I do want to ask Dr. Johnson one more question. Dr. Johnson is famous for her advocacy for sleep in general, but specifically related to Standard Time. So, let's do a little experiment here. I didn't warn Dr. Johnson about this, so we'll see how she does. She does a ton of advocacy. She's a pro. So, pretend like we're in DC, and I'm a senator, and we just got in an elevator. You're going to give me your elevator pitch on what we should do. Dr Johnson: So, you know, sleep is one of the few essential things in life. We need to eat, we need to drink, we need to have clean air, and we need to sleep and when we improve sleep, we can improve basically every outcome, whether it's academics, whether it's productivity, whether it's our physical health, our mental health. And the problem is we structure our lives in... /episode/index/show/continuumjournal/id/42037675

Unruptured Intracranial Aneurysms and Arteriovenous Malformations With Dr. Edgar A Samaneigo 07/29/2026

Unruptured Intracranial Aneurysms and Arteriovenous Malformations With Dr. Edgar A Samaneigo Unruptured intracranial aneurysms and arteriovenous malformations are frequently discovered incidentally on neuroimaging, presenting complex decisions around monitoring, referral, and treatment. This episode highlights key risk factors for rupture, the role of imaging in evaluation, and practical approaches to triage and management, including when specialist intervention is warranted. In this episode, Gordon Smith, MD, FAAN, speaks with Edgar Samaniego, MD, FAAN, authors of the article “Unruptured Intracranial Aneurysms and Arteriovenous Malformations” in the Continuum® June 2026 Cerebrovascular Disease issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Samaniego is a professor of neurology, neurosurgery, and radiology and the director of the vascular neurology fellowship at the University of Iowa in Iowa City, Iowa. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Smith: Have you ever ordered an MRI of the brain and found a coincidental unruptured aneurysm or perhaps an arteriovenous malformation? If so, are you up to speed on how to manage this common situation, how to monitor, when to refer, and how to counsel your patients? If your answers to these two questions are yes and or no, then please keep listening. Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: This is Dr. Gordon Smith. Today, I'm interviewing Dr. Edgar Samaniego about his article on unruptured intracranial aneurysms and arteriovenous malformations. This article appears in the June two thousand twenty-six Continuum issue on cerebrovascular disease. Edgar, welcome to the podcast, and maybe you can briefly introduce yourself to our listeners. Dr Samaniego: Yeah. Thank you, Gordon. So, I'm an interventional neurologist. I'm practicing at the University of Iowa. I've been in Iowa for the last ten years. I'm originally from Ecuador. Did my residency in Wisconsin, and then I went to Stanford for neuro critical care and stroke. And then I did my neurointerventional fellowship at the Baptist Cardiac and Vascular Institute in Miami. Dr Smith: You're a triple threat in the world of vascular and critical care, which I want to get to later. But your article's really great. I'll admit one of the first things I do when I read an article for Continuum Audio is I see how long it is. I saw yours was as long as the rest, and I was a little surprised because this sounded like a simple topic. But having read it, it's anything but simple. This is really important and complex stuff. I wonder if maybe you can orient our listeners to the importance of this. We frequently find unruptured aneurysms or vascular malformations on brain imaging that we order for something else. I mean, how common is that, and why do you think our listeners need to be particularly attentive to our conversation today? Dr Samaniego: It's pretty frequent that we see patients with unruptured brain aneurysms. A lot of times, you know, we do imaging like CT angiograms, or magnetic, resonance angiography. Patients come to the ER with headaches, and we find an unruptured aneurysm. And you know, the question always comes, "What should we do with this aneurysm that we found?" We know that a lot of these aneurysms will not rupture, but the caveat is that when they rupture, like fifty percent of these patients may die or have bad outcomes. So, it's always a puzzling question, you know. What should we do with the aneurysm? Dr Smith: Well, thanks, Edgar. I mean, this is certainly something that I come across. I'm glad to hear that other people struggle with this as well. What actually is the prevalence of aneurysms in the general population? How common is this? Dr Samaniego: It's more common than what we think, you know. The, the estimates talk about like one in every fifty people have a brain aneurysm, and about every eighteen minutes an aneurysm will rupture. In the United States, there's approximately thirty thousand ruptures per year. So, there's a significant number of, of patients affected by brain aneurysms. And, and the key thing is that affects usually younger patients who are in the most productive years of their lives. So that's why it shouldn't be ignored, and once we find an aneurysm, we have to have all the information for triaging and deciding on treatment of these aneurysms. Dr Smith: Well, it's a great way to begin our conversation. I mean, this is not a rare problem. It's a common problem, and there's actually a really great section of the article I'll refer people to about medical malpractice and the importance of recognizing and dealing with this thoughtfully. It's an empowering section, not a scary one, but this is important for our listeners to know about. Pretty high-stakes stuff. Maybe you can orient listeners like me or maybe simple neuromuscular people. What different types of aneurysms are there? Dr Samaniego: That's the interesting question because there's multiple types of aneurysms, and there is a whole spectrum of aneurysm. When we say aneurysm, you can be talking about a fusiform versus a saccular aneurysm. We tend to classify them based on shape, also location. But the two main classifications for brain aneurysms will be saccular, which, you know, has a sac kind of morphology shape, and then you have the fusiform aneurysms. Those are the main morphological classifications. Then on top of that, you have two other subtypes that you see quite often. The one that we see is mycotic aneurysms that is like a misnomer because it's not a fungal aneurysm. It's just an infectious aneurysm that most of the time we see on the setting of endocarditis. These behave a little bit different than the typical saccular or fusiform aneurysms. And then also you have other more rare types of aneurysms like blister aneurysms that are sometimes located in the anterior wall of the carotid artery. So, you know, within this spectrum, we have those main aneurysms. The typical aneurysms, which can be fusiform or saccular, and also the more atypical, which can be mycotic and also blister-like aneurysms. Dr Smith: I wonder if you might comment a little bit on the relevance of the type of aneurysm, fusiform, saccular, blister, and then location on rupture risk or prognosis.You have a really great figure about anatomic classification in the article actually that I encourage everyone to check out when they hopefully read it. But what do these characteristics imply for risk? Dr Samaniego: Yeah. This is very complex question because, you know, entails different characteristics of aneurysms such as shape, the location, morphology. So, we know that some locations, for example, the anterior communicating artery has a high risk of rupturing as opposed to patients such as the part of ophthalmic aneurysm, which are usually located at the origin of the ophthalmic artery in the internal carotid artery. So, by risk of rupturing, the highest risk is usually the anterior communicating. Then you have posterior communicating artery aneurysms, which are usually located in the internal carotid artery, but because of their proximity to the origin of the posterior communicating artery, they're called posterior communicating artery aneurysms. Then you have the posterior circulation aneurysms on top of risk of rupturing is the top of the basilar artery location. Those three are the highest risk for rupturing: ACOM, PCOM, and top of the basilar. In terms of morphology, I always tell my patients, you know, if it's like a nice-looking aneurysm that has this rounded shape is a benign morphology. If you have the aneurysm that's having these Mickey Mouse ears that has these blebs or daughter sacs, those are aneurysms that usually scare us because those are the ones that usually rupture. So that's another criteria, morphology. And then the other criteria would be size. There is this magnificent study called ISUIA, which was published several years ago, and basically what it demonstrated was that aneurysms that are seven millimeters or larger are more likely to rupture versus smaller aneurysms. So those are the three criteria that I'm looking into when talking to patients about morphology, location, size, and the, the shape or morphology of the aneurysm. Dr Smith: So, let's say a general neurologist or comprehensive neurologist practicing in a community setting in a rural area orders a, let's just say a CT or CTA for a patient with a TIA and finds what looks like an aneurysm. What's the next step in terms of imaging? What's the best next step? I mean, there are a bunch of different imaging modalities. Do you get an MRA? Is it time-of-flight, contrasted? You know, when do you get a DSA and so forth? Dr Samaniego: Yeah. The first thing to do is to better characterize the aneurysm. Order of more accurate imaging that we can obtain without being invasive with a diagnostic cerebral angiogram. The rest will be a magnetic resonance angiography with contrast that, you know, gives you really good detailed information about the aneurysm. Similar in terms of quality and precision will be a CT angiography. The caveat there is with CT angiography is that, you know, you use radiation, and the patient has to get iodine. And then under those two, you will have a time-of-flight magnetic resonance angiography, which doesn't use any contrast, but then you lose a little bit of quality in terms of the imaging and some morphological features you might miss. So usually what we do in my practice, I don't wanna do a diagnostic cerebral angiogram, and somebody has to refer an unruptured aneurysm. I try to do CT angiogram as a baseline, see how the aneurysm looks, and then for follow-up, I usually do magnetic resonance an- angiograms with with contrast. If there is a concern that the aneurysm has some dangerous features like it's irregular in shape, it's, it's larger, it's in one of these high-risk locations, might be better just to refer the, the patient to a specialist for a diagnostic cerebral angiography. Dr Smith: So, you know, there are these scales that you talk about in the article. There's phases in the UIATS that are used to predict rupture risk and guide decision-making. Are these scales that general neurologists or non-vascular neurologists can use to guide care? I'm thinking of like Chad-Baskin, ASBAD, which, you know, all our residents know about. Should we all be familiar with these scores? Dr Samaniego: I think they're very helpful in the sense that it will give us some guidance. Some of the characteristics of the scale might be up- outdated. For example, like ancestry. Although it's been described more in Japanese and Finnish populations, and North American, not as much as these two other populations. We do see a lot of aneurysms in people from North America and other backgrounds. For example, one of the biggest critiques for the phases is that doesn't take into account smoking history. Smoking that we know is a risk factor. And the other critiques for phases is that, for example, if you are older than seventy years old, you will score one point, which will increase your risk of aneurysm rupturing. Having said that, we do see like tons of aneurysms on younger patients, actually the most productive years of their lives that they rupture. So, it gives you some parameters like the presence of hypertension, the size, as I said, seven or larger, previous history of subarachnoid hemorrhage, and the location of the aneurysm. But it doesn't take into account other factors like smoking or morphological features of the aneurysm. Dr Smith: Now, you mentioned size. I'd like to maybe go back and talk about a case from your article, which I found really impactful. For our listeners, this is a sixty-four-year-old woman who had a five-millimeter ACOM aneurysm. She was imaged serially, didn't change over the time period, and then two years later ruptured with devastating consequence, right? And so that's a small aneurysm. Most aneurysms, I guess, are small aneurysms. I just wonder, when you see a patient like that, how do you handle the discussion regarding risk? And how do you decide when to refer them for an intervention? Dr Samaniego: Yeah. It's always puzzling when we see these smaller aneurysms. And this example is a typical example of a patient that doesn't follow the rule of seven or larger aneurysm size for rupturing. We see that quite often on aneurysms located in the anterior communicating artery. Just this last week, I treated two patients with similar characteristics, with smaller aneurysms, like average size between four and five, that rupture, and both were located in the anterior communicating artery. So, we know that there is definitely a linear relationship between size and risk and rupture, but we do see a lot of patients that have smaller aneurysms, like three, four, five millimeters that rupture, and we don't really understand very well the, biology of these aneurysms. So, when we see these aneurysms, we try to maximize the characterization of the aneurysm with better imaging, try to see the morphology. And usually when an aneurysm is discovered, what we do for follow-up is a six-month follow-up with some type of imaging, CTA, MRA with contrast, and see if there's has been any change in, on the aneurysm. Dr Smith: So, is it fair to say that a knowledgeable non-vascular neurologist can safely manage these patients, follow them over time using what they learned from reviewing your article, identify patients who have higher risk aneurysms based on the characteristics you summarize, and refer them to a tertiary center? When I get these, it's easy for me to have our vascular neurosurgeon see them or a vascular neurologist, right? But in a community where you may not have ready access to that subspecialist, is it still important to get all of these patients to a tertiary center? Are there select instances where a community-based general neurologist can follow them and then refer if there's change in size, for instance? Dr Samaniego: Yeah. I think that everything else that we do in neurology, it's important to do some type of triage in referring some of these patients for further studying and expert opinion. I think age and size of the aneurysm, age of the patient and size of the aneurysm are huge factors. For example, if we have an older patient in their nineties and has incidentally found two-millimeter aneurysm in a low-risk location like the parathalmic, that patient probably needs to be seen locally. I don't think merits a full workup. As opposed to a younger patient with a three-millimeter aneurysm located in the ACOM. I think that type of patient probably needs to be referred to a tertiary s-stroke center for workup. I mean, most of the time what's gonna happen is that if it's a small aneurysm with benign characteristics, you know, it's gonna be seen by the specialist and they're gonna determine some type of follow-up, which can be done locally. Dr Smith: So maybe we can pivot a little bit and talk about AVMs, if that's okay. What's your approach to a coincidentally discovered AVM, right? I mean, presumably, we need to think about symptomatic AVMs a little differently, I would think. So maybe we can start with the same scenario we've been talking about. You get an imaging study for something else, and, well, we find an AVM. What's the approach to that situation? Dr Samaniego: Yeah. AVMs are fascinating vascular lesions because they're very complex, they're very heterogeneous. If we're talking about the morphological features with aneurysms, this, in the case of AVMs, is way more complex in terms of location size. The complexity added to AVMs is that you have a feeding artery, you have a nidus, and then you have draining veins. So, all of these can be very heterogeneous. In case of AVMs, I think those definitely need to be referred to a tertiary center because the management of AVMs is multidisciplinary, even in the tertiary centers. You know, we don't have a magic wand that will say, you know, all these AVMs need to be treated this way. Sometimes they don't even need to be treated because we know from some studies that just watching them will be good enough. Dr Smith: You raised management of AVMs. Maybe we can go back and talk a little bit about what's the latest in management of aneurysms. You manage aneurysms from soup to nuts and as an endovascular interventional neurologist. What's the latest in management of aneurysms? Dr Samaniego: The latest is that, which falls within management, is that we have tools that they have not really been validated a hundred percent because we're still understanding the biology of some of these aneurysms. But high-resolution MRI will help us to define if there is some enhancement of the aneurysm. There is the thought that if there is enhancement after the administration of contrast, might be more of an inflammatory process. So that can be used for management, triage, and follow-up of some of these aneurysms. In terms of endovascular treatment, it has been really a revolution of how we treat these lesions. You know, we have a lot of new devices, better catheters to access the aneurysms.There is devices that you can place inside the aneurysm sac and it'll completely shut down flow into the aneurysm. There is other special stents called flow diverters that can take the flow away from the aneurysm and bypassing the aneurysm. So, all of these things have really revolutionized how we treat them. Having said that, you know, there's always a risk with any of these procedures, and that's why we gotta be mindful when we decide to treat these patients with unruptured incidentally found aneurysm. Dr Smith: I've got just one more question, Edgar, which I kind of led with. You've got training as a vascular neurologist, a neurointensivist, and an interventional neurologist. And you know, Ralph Sacco, as you probably know, used to like to talk about the neurologist, and part of the neurologist was interventional. I wonder what wisdom you have to trainees that are listening to us right now who might be interested in pursuing a career as a neuroendovascular neurologist. What wisdom do you have for them about how to go about doing that? Dr Samaniego: It has been really rewarding to be part of this process and evolution of treating a stroke and aneurysms and AVMs because I remember when I was a resident at the University of Wisconsin, we only had, like, thrombolysis and only one device for, retrieving some of these clots. But now we have, like, 10 different devices. We have two different indications or two, two different thrombolytics. So, my best advice for trainees that want to pursue neuroendovascular is to get engaged early on, understand very well the biology and the thought process because it's not only a technical field. You have to have really good judgment on when to do and when not to do the procedure, and try to find mentorship. You know, there is a lot of neurointerventional neurologists out there right now. Having a good mentor will really facilitate your career choices and getting into training. Dr Smith:... /episode/index/show/continuumjournal/id/41509840

Transitional Stroke Care and the Road to Recovery With Dr. Mona N. Bahouth 07/22/2026

Transitional Stroke Care and the Road to Recovery With Dr. Mona N. Bahouth The period immediately after hospital discharge is a critical yet often overlooked phase in stroke recovery, marked by both heightened vulnerability and opportunities for rapid brain repair. This episode explores the concept of transitional stroke care, emphasizing early specialist follow up, coordinated multidisciplinary support, and targeted interventions to improve outcomes and reduce complications. In this episode, Katie Grouse, MD, FAAN, speaks with Mona N. Bahouth, MD, PhD, FAAN, author of the article “Transitional Stroke Care and the Road to Recovery” in the Continuum® June 2026 Cerebrovascular Disease 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. Bahouth is the medical director of the Brain Rescue Unit and an associate professor of neurology at Johns Hopkins School of Medicine in Baltimore, Maryland. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Guest: Dr Grouse: A lot of attention has been paid to what happens within hours to days of a stroke, but are we missing an equally crucial time in our patient's recovery after their discharge? Today, I have the opportunity to interview Dr. Mona Bahouth about the latest issue of Continuum on cerebrovascular disease. Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Grouse: This is Dr. Katie Grouse. Today, I'm interviewing Dr. Mona Bahouth about her article on transitional stroke care and the road to recovery. This article appears in the June 2026 Continuum issue on cerebrovascular disease. Welcome to the podcast, and please introduce yourself to our audience. Dr Bahouth: Thank you for having me. I'm Mona Bahouth. I'm a stroke neurologist in Baltimore, Maryland, and I'm the medical director of our brain rescue unit at the Johns Hopkins Hospital. Great to be with you. Dr Grouse: Thank you so much. This was a very interesting article. I have to confess going into it, I really didn't know a lot about transitional stroke care and the growing sort of recognition of its importance for stroke recovery and improved outcomes. Can you tell me what the key message from this article is that you really hope that readers will take away after reading it and hopefully integrate into their own patient practices? Dr Bahouth: Yeah. I would say if there's one overarching message, it is that stroke care has come so far over the last couple of decades. We do so much wonderful life-saving work in the first couple of hours and days after stroke, but we haven't really paid as much attention to what happens once a patient leaves the hospital with this devastating acute disease. And I would just like to say that this article allows us to shine a light on providing a little bit more of a system of care, a more structured system of care that could benefit the patient for the long term, then that will benefit a large population of patients who otherwise may have complications that could cause disability longer in life. Dr Grouse: Now, Mona, could you tell us in a nutshell, what is transitional stroke care, and why are we needing to focus more of our attention on this to improve patient recovery? Dr Bahouth: Yeah. Over the last few years, we've really done a wonderful job of reducing the time that a patient spends in a hospital after stroke care. But in parallel, we have not really changed anything about what we do in the outpatient setting. So, a patient tells us that they come to the hospital with this acute and very scary and disabling disease. They feel that they're the center of the universe at our stroke centers, where we're hustling around them in groups and in interprofessional teams. But then on the day of discharge, they feel that they leave the hospital, and in some of our focus groups, that they kind of go home to a, a dark bedroom where they have to process all of this sort of on their own. It's quite a transition for both patients and their care partners. And here we've been very systematic about how we structure our care in the hospital for stroke patients, but once they leave the hospital, it's been a sort of free-for-all, or the Wild West, as some of my colleagues say. So transitional stroke care is really a way to extend the care that we deliver in the stroke unit to the patient's home or to their next phase of care. We know that stroke patients have 11 handoffs from beginning to end, in average, that they experience through the course of their acute stroke. And so, what we're really trying to do is extend the, the stroke unit to the patient's home or to their next phase of care so that they feel a bit more extension of that specialty care that they were receiving in the hospital. So, it's really a structure, a system. Dr Grouse: Now, it seems that when we're thinking about the transitional care period, that it really hinges on this idea of sort of the sensitive period of stroke recovery. What is that, and why is that so important, and why do we really need to focus on that specific time? Dr Bahouth: There are really two reasons that this is a critical period for patients. One is that we know from work in animal models as well as other sort of human early studies that the brain really has its optimal period of efficient brain repair in the first few weeks after stroke, meaning that it's recovering after this injury and figuring out how to reroute some really important brain functions. I would say it's also a critical period because the time period after stroke is a period that all the comorbid conditions that sort of conspired to cause a stroke are sometimes destabilized. And we know that sort of just putting people back on standard regimens for their hypertension, their diabetes, their heart failure doesn't always equate to sort of long-term improved outcomes at a time that the brain itself is going through changes. So, for example, we know that blood flow is critical to the brain. That's what all the hustle is about in the hyperacute period. And for the next couple of weeks after a stroke, autoregulation remains disrupted, so typical treatments of hypertension could have negative consequences for a subpopulation of patients. This management of hypertension needs to continue for a couple of days and weeks after stroke, and therefore, if a patient is discharged from the hospital, really requires a bit more specialty input. We also know that as the brain is trying to repair during the sensitive period, this high period of efficiency, we really want to inject high-intensity, high-quality activities that really improve their recovery. But in our current system in the United States, our transition to the period of rehabilitation is really quite clunky and disrupted and doesn't often happen in a seamless way. So, a true transitional stroke care program really attempts to manage the stroke itself. The comorbid conditions that conspire to cause the stroke, and the expedition of, of rehabilitation that could really jumpstart the recovery period in a more meaningful way. Dr Grouse: Now, you mentioned hypertension as being sort of a critical factor that can affect the patients during this transitional period or this sensitive period. What are some other factors that can really play a huge part in their long-term outcomes in this really sensitive time? Dr Bahouth: In our transitional stroke program, in our interprofessional group, we often talk about all of the changes that a patient is required to make at the time of stroke. Typically, they stay in the hospital several days. The patient and their care partner will receive a bolus of instructions about what their new healthier life should look like, and then they're sort of sent off to sort of self-manage without really accepting that that wasn't the perfect time to teach these things. So really, it's all about sort of lifestyle improvement. How do we get into a system of medication adherence when medications are a central portion of a patient's care? It is about managing the cognitive changes that happen after stroke, whether we acknowledge them in the hospital as a main deficit or something that people realize once they get back into the groove of their usual life, and the emotional consequences of stroke for both the patient and their care partner, who are both adjusting to this very scary moment that resulted in a brain injury. So, I think that the things that are focused on are both medical in terms of, you know, what are we doing with the diabetes? Is our glucose at a target range? Have we started wearing our sleep apnea paraphernalia? Are we managing our smoking cessation as much as we should? How have we done with our low-fat diet? Are we taking our medications as prescribed, or was there some cognitive blip that caused a mistake? But also sort of the emotional support that sometimes paralyze patients into sort of saying they cannot handle this transition into a new healthier way of brain recovery. Dr Grouse: Yes, and it sounds like when patients sort of hit that wall, they almost just give up, right? There's just so many things they have to manage. They're emotionally trying to cope, and then they may eventually get to their neurologist at some point for a follow-up, and not much has happened. Dr Bahouth: That's a really well-put statement. Like I mentioned earlier, we had several focus groups to say, "How's our stroke center doing? How is our comprehensive stroke center doing?" And we realized that we were very comprehensive while the patient was with us, but then the experience of the patient going home was really opposite of receiving comprehensive care. You know, the patient in the hospital said they felt well-supported, surrounded, quite busy all the time, but then they did go home, and this sort of set in that they've had a stroke. And many patients told us, "I just laid in bed because I couldn't quite kind of get through the thought that this has happened to me." And so, in our prior state of our comprehensive stroke system where patients weren't seen for a couple of months after their discharge, patients would tell me, "Well, I'm fine now. But those first couple of months, I sure wasn't. You know, I was laying in bed. I was crying. I wasn't taking my medicines. I had a lot of despair and fear." Care partners would say, "I wasn't sleeping myself. I was watching to see if another stroke was gonna happen every minute." So, there are a lot of elements that are going on in those first two weeks that really require a specialist to say, "This is normal. This requires more attention," and to really help people get through a lot of the changes that come with stroke and brain injury. Dr Grouse: Now, your article gave a really great, I think, example, where you had a juxtaposition of a hypothetical patient with a stroke and two very different post-discharge courses, one where they really kind of fell into that vacuum, that post-discharge vacuum, where they didn't get support and had some very disappointing outcomes versus a patient who did have a transitional care program with a lot of support post-discharge, and a lot of obstacles were overcome and problems solved such that the patient could do a lot better. And I encourage our listeners to take a look at it. If you could design and run it, how would your ideal transitional post-stroke program be structured? Like, how would you design it so that it would optimally support these patients? Dr Bahouth: Yeah, you know, we, um, tangle with this every day in our current transitional stroke program that we call the JSTEP program. We've had several chapters of what we think is ideal for a patient, and thank you for sort of acknowledging that, like, the way those cases were written were really to underscore that we can have a lot of influence for patients. And while they were sort of hypothetical juxtapositions of one another, these are things we literally see every single day for our stroke patients. And people say, "Oh, if only we had done this, we would've caught that, and we would've prevented such-and-so." Some of the indicators of success have been we've really reduced our readmission rates to the hospital. We have decreased our length of stay because the confidence people feel to go home because they're well supported. So there have been indicators of success. But if I could take our program even next level, I would probably include a few other things. So currently, some of the strengths of the program are that a stroke specialist sees a patient within days of their discharge from the hospital, a time where some of those questions are sort of raising for the patient. Maybe a complication is starting to pop up that we can address before it, uh, gets out of hand and requires a readmission. We can tackle some of the fears that patients are having to say, "I wonder if this is normal or not. I better just go to the hospital." So, some of that early touch point by a true stroke specialist is really critical. And that visit only happens because the seed is planted in the hospital, so there really has to be some initiation of the program at the time the patient is in the hospital to say, "This is what you can expect when you leave here. You have someone who's walking this with you. They're a stroke specialist. They're gonna know how to help you navigate." The second part of our program that is a success is our rapid connection to specialties. So, we know that stroke patients are gonna need connection to rehabilitation specialists, physiatrists, the therapists. We know they're gonna need connection to cardiology when atrial fibrillation or heart failure or something is really at an extreme.We know endocrinology might be a part of the patient's story going forward. And so, I think the second success of our program is really alliance with key stakeholders in a stroke patient's life and quick access to having the patient be connected to what it is they need in the moment that we realize that there is a situation at home. The third thing that I think has been really a success of our program is this interprofessional education that we schedule patients for at the time of their discharge, just as any other important healthcare visit. During this interprofessional education session, the patients get to meet dietician, pharmacist, nurse, therapist, where key discussions about healthy behaviors, avoidance of complications after stroke really happen in a group session where there can be a lot of interaction. You know, currently our education happens in a time where the brain is injured, the patient is not sleeping well in the hospital. We have a lot of stress and fear. It's not the perfect time for anyone to receive such important education. So, I think the third really most important thing has been this formalized interprofessional education to really bolster the education that started at the hospital. If I were to really take our program next level, and every day we're considering it, I really think we haven't done a couple of key things. One is we have not really found a way for the care partner to be supported, that the care partner is usually the brave one sitting there with a tight lip and nodding and very, you know, concerned about what's happening and taking close notes. But we really haven't done well to just manage the care partner's needs sort of independently of the patient themselves, sort of help them with the experience of going through this. I think that could benefit both the care partner and the patient by sort of bolstering their sort of emotional consequences of this. And they are really our key partner in the patient's success in the outpatient setting, getting the patient motivated, helping them get to appointments, helping them to adhere with medications. So, I think if we can focus a bit more on the care partner, that might really bolster the long-term effect for patients. And I think finally, behavior change is very complex. Sometimes we're taking a group of patients who may have never exercised and said, "You know, we really... You need to walk several minutes a day. You need to increase your aerobic capacity. We need you to stop smoking." And these are not behavior changes that can just happen with sort of a one-time visit. So, I think we really need to incorporate a lot more of exercise therapy and concepts of people who can sort of coach along the continuum for some of these behavior changes so that we can really promote wellness and a return to health. And I think one final thing that could be additive from a transitional stroke program is really a better way to truly measure recovery for stroke patients, some of those in between the line measures that we're not really getting by a three-month modified Rankin score. I think a transitional stroke care model would really allow us to both insert research and potential other therapies along this time period, but also measure the success of those in a more granular way. Dr Grouse: Thank you so much for that, and also it was really helpful to get a good overview of, like, what the transitional care program really means, right? Like, what is the structure? What is happening with the patient? So, I think all of that's really helpful. But I can't help but think, listening to all of that, that sounds like while certainly in an ideal state, and I don't think anyone can argue with how helpful that sounds, is it always something that's practical? Can we implement things like this, especially where access is limited, resources are dwindling as far as what patients can get and what evaluations patients can get? Do you think that this is something that can actually be implemented in programs throughout the country? And what are strategies we can consider to try to improve getting some of these resources for our patients? Dr Bahouth: I think this is such a critical topic. I think that we have, in the medical system, tried to force our healthcare practices into old models of care instead of sort of adopting new ones. And so, I think that, you know, while everyone says, "Wow, that sounds like a very resource-rich program," I would have to stop and push back and say, well, a very resource-rich situation is when a stroke patient, sometimes fifteen to twenty percent of the time, are readmitted to the hospital at a time where hospital beds are at a premium. Maybe we need to turn those dollars of savings of sort of these readmissions and extra length of stay into dollars that we put into sort of this transitional period where we help promote success. So, I think it really becomes more of a value proposition when you talk about it. But that said, of course, we have to make sure that we're a high-value, high-productivity system. So, our current transitional care program uses a telemedicine structure. We know that stroke patients cannot drive in most states after their stroke. We know that their care partners are trying to return to work and normalize. It is very difficult for patients with paralysis, cognitive changes to come back and forth to multiple appointments. In the past, we have tried to make this transitional care program an in-hospital program. I think using the technologies that we have available for telemedicine are critical, especially for this population... /episode/index/show/continuumjournal/id/41509630

Intracerebral Hemorrhage With Drs. Wendy Ziai & Vishank Shah 07/15/2026

Intracerebral Hemorrhage With Drs. Wendy Ziai & Vishank Shah Intracerebral hemorrhage carries high morbidity and mortality, but growing evidence highlights meaningful opportunities for prevention, risk reduction, and long-term recovery. This episode covers key strategies, including blood pressure management, interpretation of neuroimaging markers, and individualized decisions around antithrombotic therapy. It also emphasizes the prolonged recovery timeline and the importance of a holistic, patient-centered approach to improving outcomes. In this episode, Casey S. Albin, MD, FAAN, speaks with Wendy C. Ziai, MD, and Vishank A. Shah, MD, coauthors of the article “Intracerebral Hemorrhage” in the Continuum® June 2026 Cerebrovascular Disease issue. Dr. Albin is a Continuum® Audio interviewer, associate editor of media engagement, and an assistant professor of neurology and neurosurgery at Emory University School of Medicine in Atlanta, Georgia. Dr. Ziai is a professor of neurology and critical care medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland. Dr. Shah is an assistant professor of neurology and critical care medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Albin: A patient has suffered an intracerebral hemorrhage. They're taken to the neuro ICU, and they fortunately survive. But the journey does not end there. In fact, in some ways, the journey has just begun. Join us today as we unpack holistic care for ICH patients. Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Albin: Hello to our audience. This is Dr. Casey Albin. Today, I'm interviewing Dr. Wendy Ziai and Dr. Vishank Shah about their article on intracerebral hemorrhage. This article appears in the April 2026 Continuum issue on cerebrovascular disease. Welcome to the podcast. I am so delighted that both of you are joining. To begin, let's just do a brief introduction of who you are and, and a little bit of how you got interested in the topic. Dr Ziai: Hi, I'm Wendy Ziai. Thank you for having me on this podcast. I am a professor of neurology at Johns Hopkins. I am a neurointensivist, and I think I got primarily interested in this topic through clinical trials that I have been a part of since my fellowship days. Dr Shah: Hi, everyone. I'm, uh, Vishank Shah. I am also, uh, very thankful for being invited to be a part of this podcast. I'm also a neurointensivist at Hopkins and the fellowship program director here for neurocritical care, and I'm interested in recovery after ICH, and that's why I'm a part of this work. Dr Albin: Welcome to you both. It is such a treat for me to get to interview fellow neurointensivist, particularly those who have such a wealth of experience. So, I am delighted to dive into this. All right. So, to set the stage for our audience, intracerebral hemorrhage has long been approached with pessimism. But your article really highlights that there are meaningful advantages in prevention and risk stratification and long-term recovery for these patients. Though you both are neurointensivist, this article really emphasizes primary prevention and the holistic long-term care for the survivors. And so, to begin, Dr. Shah, can you just lay out a little bit for our listeners the scope of intracerebral hemorrhage and its community impact? Dr Shah: Yeah. So, you know, ICH is the second most common type of stroke. There are more than three million new cases of ICH globally each year, and it accounts for thirty percent of all stroke types, but it is the one that has the highest mortality, with more than forty to fifty percent of the patients dying in the first thirty days, and then continued long-term impact on both functional as well as outcomes, as well as survivorship after the early period. And it also disproportionately impacts lower socioeconomic, and then minority races like Blacks, Asians, as well as Hispanic ethnicity. And so, there's a lot of work that needs to be done to reduce the burden of this disease. Dr Albin: Absolutely. I mean, these can really be devastating for families, and I really am appreciative of your highlighting that there's a lot of disparities, and there's a lot of work to be done to really increase equity to these patients. I think a lot of this goes into really the AAN's focus on brain health and trying to improve some of what we're doing to maintain brain health. And I really wanted to kind of drill down on this because for ICH, there's a lot that can be done upfront as we think about how do we counsel patients who may walk into the office about strategies to prevent ever becoming an intracerebral hemorrhage patient. So, Dr. Shah, can you walk us through a little bit about what neurologists in the community need to be doing to make sure that no one ends up with us in the neurointensive care unit? Dr Shah: Yeah, sure. So, I think, you know, one of the most important risk factors is, of course, hypertension and long-standing uncontrolled hypertension. And so really recognizing the need for early onset screening with regular blood pressure monitoring at a very early age, particularly in the races that I discussed earlier. And then I think another big part, obesity, metabolic syndrome, and type two diabetes. And I think there's a lot of interesting new work that with the GLP-1 agonist, you know, in a large multicenter cohort studies showing that patients receiving these had a significantly lower reduction risk of ICH. And so, this might be a really important part that, you know, clinicians need to start increasingly recognizing and using in their practice. And then, of course, other risk factors that are common include smoking, diet high in sodium, exposure to air pollution, both indoor as well as outdoor. And so, mitigating all of these risk factors can also reduce the burden of ICH. Dr Albin: Absolutely. And I really want to highlight that hypertension plays such an important role and that we as neurointensivist, as community neurologists, really need to be creative about ways that we can help people meet those blood pressure target and meeting people in the community where they are, making sure that they're not suffering from side effects from their medication that would prevent them from sticking with it long term. Dr. Ziai, anything else to add about what we can do in the community? Dr Ziai: So, we really want to emphasize, even in the acute phase, that patients moving forward need to have targeted interventions to reduce blood pressure, smoking, enhance their physical activity, have a diet that is high in fruits and vegetables and low in alcohol and salt, and then promoting weight loss, of course. Dr Albin: And Dr. Ziai, I'm gonna ask you a little bit about one of the things that maybe not all of our listeners have heard about is this APOE2, APOE4 genetic risk for intracerebral hemorrhage. What's going on there and, and should clinicians be testing for that? Dr Ziai: That's a great question, and it is not one that we currently test people for at least acute ICH presentation. APOE2 and A4- E4 alleles, these give patients a two to three times higher risk of ICH by increasing cerebral amyloid deposition. And if you happen to have APOE2 carrier ship status, then along with other risk factors like white matter disease and vascular risk factors, these predict the onset of new microbleeds even during very short follow-up periods of about two years. And as we know, having cerebral microbleeds are associated with an increased risk of all strokes, ischemic and ICH, but they are one of many MRI markers of small vessel disease, which along with cortical superficial siderosis, does significantly increase future ICH risk. And so even in people who've never had an ICH, if they happen to have an MRI, it may be reasonable to look at the MRI and incorporate this burden of small vessel disease, and especially these hemorrhagic markers into, uh, decision-making about interventions. Dr Albin: That's a really excellent point. And so, I think that your article did a really beautiful job of thinking holistically about the patient, incorporating clinical markers of their risk for having ICH, but also those radiographic markers. I'm just gonna ask you to summarize those again one more time because not everyone will be familiar with these. So, when you're looking at an MRI, what are the things that you're particularly clued in on that would increase the patient's risk of future ICH? Dr Ziai: In the past, what we're looking for really is markers of cerebral amyloid angiopathy, which significantly increase a person's risk for lobar hemorrhage in particular. And so, we have a set of criteria called the Boston Criteria, and there's a new version of these, version 2.0. And these, um, incorporate a number of imaging markers that provide a very high sensitivity and specificity to diagnose CAA after an ICH. But even if someone's never had an ICH, and they evaluate that risk-benefit ratio for different cardiovascular prevention strategies. And so, the markers that we're specifically interested in are, of course, microbleeds. But not just having microbleeds, but are they lobar or are they deep? Lobar having a higher risk for lobar ICH. How many microbleeds are there? Is it greater than five, or is it just one or two? Also, cortical superficial siderosis is a marker, a hemorrhagic marker, that does portend a significant increased risk of recurrent ICH, along with having a lobar ICH. And now we have these new markers, which are the white matter hyperintensity multi spot pattern, which requires these hyperintensities on flare imaging in the subcortical area, having greater than at least ten of these multi spots, and also having enlarged perivascular spaces in the centrum semiovale, and having at least twenty of those. And finally, white matter hyperintensities, which can be measured with the physica score or just by visualizing them. We can look at white matter hyperintensities as well as being a measure of small vessel disease. Dr Albin: Got it. And so just to summarize, we're looking for small vessel disease markers because that puts our patients at higher risk of ongoing future bleeds. And then we're also looking for markers of particularly small vessel disease that's caused by cerebral amyloid angiopathy, which again, because it's having that protein deposition, that puts the patient at risk of those leptomeningeal very small vessels, putting the patient at risk of lobar ICH. Just confirming I've summarized this all correctly. Dr Ziai: Yes. That was perfect. Dr Albin: Amazing. Dr. Shah, I'm gonna go back to you. Let's say we have a patient. Let's say this is a sixty-five-year-old man who comes in and they want follow-up and they're... And you're trying to think about they've had an ICH in the past, and they are also at risk for ischemic disease. Let's say they, they have hypertension, they've had a smoking history. They have some risk for ischemic events. And you're trying to think about how do you balance those. Let's say the patient needs to be on aspirin but does have some of those high-risk features on their MRI. Is there any guidance on how we think through preventing them from having a recurrent bleed if they're a high-risk patient, also preventing them from having an ischemic event, which they might be at high risk for as well? Dr Shah: Yes. So, I think, you know, the first step is of course trying to understand what was the type of bleed. I think that has a very important role, like you mentioned. If it's a lobar hemorrhage versus a deep hemorrhage, the risk of recurrent ICH and ischemic events is very variable. So lobar hemorrhages, there's obviously a higher risk of recurrent hemorrhage events, whereas deep hemorrhage is actually at or behaves sort of like small vessel ischemic strokes and have a higher risk of recurrent arterial ischemic events. So that distinction in itself can help you gauge which patients would be safe and would benefit from these therapies. To begin, and of course, looking for some of these markers on MRI that were mentioned by Dr. Ziai for recurrence of hemorrhage risk. In terms of antiplatelet, the, there is a lot more data now to guide treatment, and we have the RESTART as well as the ESTART trial that showed that starting an, a single antiplatelet after intracerebral hemorrhage did not increase the risk of hemorrhage recurrence. They were very variable in the timing when aspirin was started, and so that remains still a question about what is the safest time point to start aspirin. For example, in the ESTART trial, they started them very early, within the first three days, whereas in the RESTART it was all the way up to two months after the hemorrhage. And so... But in general, the risk of recurrent ICH was very low with a single antiplatelet agent. And so, if it's needed for ischemic prevention, it's relatively safe broadly across all types of hemorrhages. Dr Ziai: Yeah. I would just mention that there was also a subgroup analysis of the RESTART trial using MRI. And so, this more than likely included patients with CAA, since 40% of the hemorrhages were lobar in that study, and therefore seeing that there was no increased risk of recurrent ICH in RESTART, it is thought that putting patients back on their antiplatelet therapy is safe. Dr Albin: That's a really huge takeaway pearl for our listeners, that regardless of whether it's a lobar bleed or a deep bleed, if there is a strong indication, you know, this is not just, oh, because someone gave them aspirin 81, but truly that there is a reason that they need to be on a single antiplatelet agent, it probably benefits them to be on that agent, and there's good data that there's not a huge increase in risk. Summarizing all of that? Dr Ziai: Great. Dr Albin: Now, things are gonna get a little bit tricky here, because what if the patient, what if they need to be on dual antiplatelet therapy? Or what if they need to be on anticoagulation? Dr. Ziai, I'll, I'll throw that to you. How do you tackle that patient population? Dr Ziai: Yeah, the safety of dual antiplatelet therapy hasn't really been studied in patients who've had a prior ICH. Although, in people who've had previous strokes, putting them on dual antiplatelets doesn't seem to increase the risk of ICH, but it does increase extracranial hemorrhage. And so there may be other reasons not to put patients on dual antiplatelet agents. Patients who have cancer and also cardiovascular or cerebrovascular disease, putting them on dual antiplatelet therapy does seem to increase the risk for intracranial hemorrhage. So, I think there is enough of a bias against DAPT therapy in patients who have had an ICH that we would not recommend DAPT for patients with a prior ICH. Dr Albin: Absolutely. And, and then what about, let's say they have atrial fibrillation, and you know that they have a high CHA2DS2-VASc score, and they are at very high risk of ischemic events, but they've also had a prior intracerebral hemorrhage. Walk us through a little bit, how should we approach that patient? Dr. Ziai, I'm gonna start with you again. Dr Ziai: Sure. So again, looking at the MRI, which all patients with ICH should have nowadays. If patients do have these hemorrhagic findings, a lobar ICH, evidence of CSS, cortical superficial siderosis, especially if it's disseminated, and also lobar microbleeds, especially if there are greater than five, if they're multiple, then anticoagulation should really be avoided in those patients. Dr Albin: Absolutely. So, I'm really hearing that when we have a patient with ICH, it is just critically important that we understand is this a hypertensive bleed or is this a lobar bleed that is probably related to cerebral amyloid angiopathy? And getting to that distinction is going to play a major role in our deciding whether or not the patient can be on DAPT or can be on anticoagulation. And then what are some of the strategies for patients that you're referring them to if they really cannot tolerate being on anticoagulation, but they have atrial fibrillation, and they do need some sort of ischemic stroke prevention? Dr Shah: There's still a lot of controversy, even in non-lobar hemorrhages, about resuming anticoagulation and when that would be safe. HAF trial, there was a reduction in ischemic stroke recurrence, uh, but a significantly higher increase in hemorrhage recurrences. I think that trial included both deep and lobar hemorrhages. So, we still need more data, and I think the ASPIRE trial and maybe a meta-analysis would answer that eventually. But in the meantime, if a, specifically for lobar hemorrhages, which are, uh, thought to be CAA related, if they, uh, and the patient has AFib, you know, where anticoagulation would be contraindicated, a watchman device or, you know, AFib ablation may be some of the other strategies that can be looked into for those patients specifically. Dr Albin: Right. I think that's a really important point to emphasize, that we don't just don't give up and say, "Oh, you're not a candidate for anticoagulation," but we really reach out to our cardiovascular friends and say, "Hey, what other procedures can you offer that will minimize the risk of recurrence?" You know, we don't want them to have an ischemic event, but we also know long-term that there would be a real risk of anticoagulation. Just reminder to our listeners that there are new procedures, and our cardiology colleagues are always doing new trials and new devices, and so we should really leverage their expertise here. I am in the final minutes gonna just switch gears a little bit from talking about sort of the nitty-gritty of secondary ischemic prevention and secondary hemorrhagic stroke prevention and thinking about there has been this degree of pessimism around ICH patients, and that, you know, they have a much more severe outcome than our patients with ischemic strokes. I think that that is probably a myth that we need to do some debunking around, and I think maybe we need to reframe in terms of thinking about just the trajectory. So, Dr. Shah, walk us through a little bit about what we can expect about the recovery trajectory in ICH compared to those patients who have an ischemic stroke. Dr Shah: Yes. From some newer data and studies, it is becoming clear that recovery after ICH is much slower than we expect. In general, for ischemic stroke, recovery is measured within the first few weeks to up to 90 days. But in ICH, we now know that patients can keep recovering all the way up to six months and even beyond. In general, from just a, a study of heart recovery that occurs after ischemic stroke, there's a steep recovery in the first seven days, and then sort of after that, patients still continue to recover, but it, it starts plateauing where up to 90 days. Whereas with ICH, there is not much recovery in the first 7 to 30 days, but after that, there is a recovery that occurs significantly between day 30 and day 180, and then some patients continue to recover all the way up to one year. The more severe the hemorrhage, the slower the recovery, but there's still some evidence to suggest that even severe hemorrhage patients can recover all the way up to one year... /episode/index/show/continuumjournal/id/41500450

Stroke in Children and Younger Adults With Dr. Thalia S. Field 07/08/2026

Stroke in Children and Younger Adults With Dr. Thalia S. Field Stroke in children and younger adults differs significantly from adult stroke, with varied presentations and a broader range of underlying causes such as congenital heart disease and arteriopathies. This episode highlights key diagnostic considerations and evolving approaches to treatment in these younger populations. In this episode, Aaron L. Berkowitz, MD, PhD, FAAN, speaks with Thalia S. Field, MD, FRCPC, MHSc, coauthor of the article “Stroke in Children and Younger Adults” in the Continuum® June 2026 Cerebrovascular Disease issue. Dr. Berkowitz is a Continuum® Audio interviewer and a professor of neurology in the Department of Neurology at the University of California, San Francisco, in San Francisco, California. Dr. Field is a professor at the University of British Columbia and the Sauder Family Heart and Stroke Professor of Stroke Research, and a stroke neurologist at the Vancouver Stroke Program, Vancouver Coastal Health in Vancouver, British Columbia, Canada. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Berkowitz: Most neurologists are used to evaluating and treating adults with stroke since it's one of the most common neurologic conditions. But stroke can also occur in children, in infants, and even in utero. Today, I have the privilege of interviewing Dr. Thalia Field to talk about pediatric stroke. Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Berkowitz: This is Dr. Aaron Berkowitz, and today I'm interviewing Dr. Thalia Field about her article on stroke in children and younger adults. This article appears in the June 2026 Continuum issue on cerebrovascular disease. Welcome to the podcast, Dr. Field, and could you please introduce yourself to our audience? Dr Field: Well, thanks so much. It's a pleasure to, uh, be speaking to you. I'm a stroke neurologist, and I treat adults generally. My wonderful colleague, Thivya Selvanathan, who's a neonatal neurologist, co-wrote the chapter with me. We do, unfortunately, have to treat some children with stroke collaboratively and I do advise on those cases. My practice is about one-quarter clinical, so I treat patients with acute stroke, look after them on the wards, see patients in stroke prevention clinic, and the rest of my time is mainly research and some administrative work and teaching. I run the clinical trials program for the Vancouver Stroke Program, and I do research of my own, mainly focused on stroke in younger adults. We previously did a trial and registry on cerebral venous thrombosis, and more recently, I've been running a national study looking at brain health in adults and children with congenital heart disease. Dr Berkowitz: Fantastic. Wow, that is a lot that you do, and we'll look forward to the results of some of those studies. So, when adults suffer a stroke, they typically present with sudden onset focal neurologic deficits, very common scenario we're consulted on. And one thing you and your colleague talk about in the article is that strokes can present differently in infants and in young children. Can you talk a little bit about the differing clinical presentations of stroke in the youngest young as compared to our usual experience treating the older adults? Dr Field: Sure. So, you know, speaking about this as someone who doesn't see the children directly but has had the opportunity to discuss these patients with my colleagues and, like we all do, learn about it during our training, I think one of the distinctions, especially with neonates, is that it's generally not a presentation with focal neurologic deficits. Often these babies will have seizures or encephalopathy as their main presentation, and sometimes we're only finding out after the fact if they're presenting with developmental delay or early preference for handedness and hypotonia, things like that. So, in very young children, that's a distinction. And in older children, there can be sudden onset deficits and, and unfortunately, sometimes these are mistaken for other conditions that are more common in children, like seizures. But sometimes you can have a more indolent course, say, with something like a focal cerebral arteriopathy or something like that. So, it depends on the scenario, but the big difference primarily is in neonates, as far as I understand. Dr Berkowitz: Perfect. That's very helpful. So as an adult neurologist, when I think about causes of stroke or teach sort of the categories of causes of stroke to our residents and students, when we think about the evaluation of stroke, I divide them broadly into causes related to the heart, causes related to the blood vessels, and causes related to the blood with, in the adult world, the most common things, of course, being atrial fibrillation for the heart, atherosclerosis for the blood vessels, and then risk factors for atherosclerosis in the blood, diabetes, hyperlipidemia, very rarely picking up a hypercoagulable disorder in the blood column. And reading your article, it seems that, correct me if I'm wrong, stroke in young adults, stroke in the pediatric population can basically be organized into those same broad categories, heart, blood vessels, and blood, just that there's many more conditions on the differential diagnosis that you would consider in young adults to begin with and then children and then neonates as we get into the younger and younger population. So, I'd like to talk about each of these sort of buckets of etiology in turn and ask you about some of the causes we would consider in young adults and children in each of these, and then as they come up, probably ask you more questions about how frequently we find these sorts of things, how frequently they're the cause of stroke treatment, et cetera. So, let's start with the heart. As I said, in adults, we're mostly looking for rhythm disorders, right, atrial fibrillation. Sometimes we'll pick up a patent foramen ovale or PFO or other structural abnormalities, but mostly we're thinking about atrial fibrillation. But reading your paper, I was struck by the huge variety of conditions that you might be looking for in the heart in children or infants with stroke. So, can you tell us a little more about cardiac etiologies of stroke in the young? Dr Field: Yeah. So, I'd say unlike in older adults, where it tends more often to be a rhythm disorder, in children and adults who are younger, it's primarily a structural cause, and congenital heart disease being the most common. And it changes a little bit from younger adults shifting downwards in age to younger children in terms of the fact that often if we're seeing an adult with stroke related to congenital heart disease, it can be a paradoxical embolism from a previously undiagnosed PFO. Not in all cases, but fortunately this is improving over time. You know, generally people with diagnoses of more severe congenital heart disease are followed up from childhood and people are aware of the diagnosis, and hopefully they're being managed and watched for things like premature arrhythmias or depressed heart function or other things that can develop and require their own distinct antithrombotic management, for example. In young children, however, more severe causes of congenital heart disease tend to more frequently be associated with stroke. And in many cases, those strokes can be early on in life or associated, say, with perioperative complications or other iatrogenic-related causes in, in that way. Again, congenital heart disease can be associated with stroke at, at any point in the life course. But as adult neurologists, most frequently we're seeing very simple lesions like PFO with large shunts, and in children, it tends to be the more complex causes of congenital heart disease. Dr Berkowitz: Got it. So, let's move on to the blood vessels. Again, in adults, we're usually thinking about atherosclerotic disease, be that of the cervical arteries or of the intracranial arteries. But in your paper, a lot of discussion about the various vasculopathies, arteriopathies that can be cause of stroke in younger adults and in children. Could you talk a little bit more about some of the vasculopathies and vascular conditions that are causes of stroke in the younger population? Dr Field: Sure. Before I do that, I will say that especially in older younger adults, particularly over the age of thirty-five, and you know, kind of makes me shudder that that's an older younger adult. But, um, in, in any case, certainly conventional vascular risk factors are more common in this population with stroke, especially in those who don't have PFO-associated stroke. Like conventional atherosclerosis, you know, certainly is a cause of stroke in younger adults. But that being said, certainly other vascular causes and vasculopathy in particular is a much more common cause of stroke in younger adults and, and children than it is in older adults. In particular, dissection is an extremely common cause of stroke in younger adults. Generally cervical artery dissection from non-inflammatory vasculopathy, usually on, sometimes on the FMD fibromuscular dysplasia spectrum and, and sometimes, you know, provoked by minor trauma or something post-infectious that may make the vessels a little bit more susceptible. And in younger children, this inflammatory focal cerebral arteriopathy is a distinct cause that is a common cause of stroke in, in young children. There are other causes that can affect the blood vessels, you know, rarer things like vasculitis and vasculopathies that can develop in the context, say, of sickle cell anemia. But in general, as a bucket, vessels are still very important, but the pathology tends to shift. Dr Berkowitz: Got it. And you, um, alluded to a point that I wanted to ask you about. You mentioned the sort of, there's stroke in the young, and then where do you draw the line at young? Less than sixty, less than thirty-five, and then we've also talked about strokes as young as before the age of birth. Yeah, I'm remembering, is it the Helsinki study, one of the early large series of stroke in younger individuals? I think that, was it eighteen to forty-nine in that or fifty-nine? I don't remember the exact age, but being struck reading that paper as a resident and thinking about the workup for exotic causes we do, right, and when a young patient has a stroke. And correct me if I'm wrong, the most common etiologies of stroke in that series, and I'm curious the other large series yourself have been involved with, have still been vascular risk factors and arrhythmias and things that we, even common, quote unquote, common things in the young, such as dissection or hypercoagulable states. Uh, the things that we sort of tend to think about first are actually less common. But acknowledging that that paper has folks up to the late forties when the vascular risk factors may be, um, unfortunately kicking in earlier, uh, and earlier due to dietary and lifestyle factors. So is that true, or do you have sort of an age cutoff when it's, we say stroke in the young, people sort of think, "Oh, they'd work someone up differently if they're less than sixty, and they have no vascular risk factors or few vascular risk factors." When do we start getting into the kind of younger population where atherosclerosis and cardiac arrhythmias are not number one and two? Dr Field: I'd say first of all, you and I must have trained around the same time because I was also in my training, really struck by the results of the Helsinki study going, "Wow, I, I really didn't know how much of a role these conventional vascular risk factors still play." And I think we're seeing that information reiterated, unfortunately, like even with higher prevalences and more attributable risk in some of the newer series. There are newer European series looking at stroke in younger adults, and more recently, there's been one that we mentioned in the article from the Florida Stroke Registry. And it's true that generally the burden is in the older younger adults. But what I would say overall in terms of kind of how things guide the workup, you need to look at the patient and consider things. I mean, obviously you don't want to miss things that can be treated differently and identified by tests easily. You know, things like ruling out syphilis or antiphospholipid antibody disease in, in younger patients. You really want to make sure that that's not something that, that you'd miss because, you know, obviously your treatment is going to change. However, certainly we start with the basics for stroke workup in any patient that's coming in. At my center, CT angiography. Some centers it may be MR angiography and echocardiography. We take a careful history. We look at the blood work. We look at the vascular risk factor burden. We find out if there's kind of any worrisome personal history, family history, look at their general health context. I think that really helps to guide how far we go in a particular workup, and it also helps to direct the other investigations and types of follow-up we need to do. For example, if a patient has a fairly suspicious story for dissection, let's say they're getting over a cold, and they went to the gym, and, you know, there was a sudden movement that they did that really produced headache and neck pain, and there's an obvious cervical artery dissection. I'm not going to go too far down testing them for rare infections and doing advanced cardiac imaging unless something shows up on their initial echo, for example. But I will make an effort to do more detailed vascular imaging of the rest of their body, find out careful family history. If there's additional manifestations of a non-inflammatory vasculopathy elsewhere, say consider sending them to medical genetics, or obviously, if this is, you know, a second event, your flags raise even more. So, it really depends on the patient. If I find out that there's, you know, a family history of premature cardiac disease and things like that, you know, obviously we're gonna be keeping a close eye on their cholesterol, making sure that we're not identifying, for example, familial hypercholesterolemia, which is, you know, something that comes up not infrequently where we'll see an LDL in an untreated patient of more than five. I apologize, you're gonna have to do the conversion to American units on that. But there are things we identify and, you know, again, you don't want to fall solely on heuristics and your preconceived notion of, of the patient. You do have to consider the results of the investigations that you do order. But I think you can certainly be mindful in terms of how you direct your workup and in turn, how you direct your follow-up. Dr Berkowitz: That's great to hear your approach. Yeah, as you said, our approach always begins with the same, coming back to these three categories, right? Doing some type of structural imaging of the heart, rhythm monitoring for the heart, and then vascular imaging of the head and neck. And then I was going to ask you, and you sort of began to answer this question. Yeah. What's next and how far do you go? I think most people think the expanded stroke workup in the young is at a minimum, a TEE if there's been no signal thus far on the original workup. I just mentioned and you spoke about, and then probably hypercoagulable testing and only sending arterial side if there's no shunt and venous and arterial side if there's a shunt. Is that your second pass approach or did I miss anything, or are there other nuances there that are helpful to discuss? Dr Field: No, I think that's generally in keeping with what I do. I think with TEE being very important. I mean, the first pass are arterial stuff. Really, it's antiphospholipid antibodies and, and making sure there's no cancer. Like you said, only if there's a shunt do I pursue other venous hypercoagulability testing. Again, you [chuckles] kind of reiterate, go through with the history, make sure there's kind of no red flags. And sometimes, obviously, you do your best reasonable job with the first pass workup, and you will find out when someone presents with a second event that it's something very unexpected. Maybe first manifestation, someone with no obvious history and very initially normal-looking imaging, say with, with CATASL or something like Fabry's disease or something where you would consider it if there was kind of a more classical picture. But it wouldn't be something you would do kind of on your first or even second pass workup in the absence of any sort of clinical suspicion, family history, or something along those lines. Dr Berkowitz: I'm curious just as far as rough percentage. I feel like many of these patients we see it's a patient who's young and who's had a stroke, and the initial first pass has been unremarkable, and we do our TEE, and we do our hypercoagulable workup. Again, antiphospholipid antibodies only if it's-- there's no shunt. And if there's a shunt, adding on some of the venous hypercoagulability protein C, protein S, factor five, Leiden, et cetera. A lot of the times I feel like we don't find anything. What's your sort of general gestalt? Again, as a general neurologist who does a lot of inpatient neurology, I feel like when these cases come up, it's not that common that you say, "Oh, I actually diagnosed protein S deficiency." Or every once in a while, diagnose an antiphospholipid antibody, or you'll find a PFO on TEE. You didn't find on TT. I've maybe found one fibroelastoma in many years. How often do you find something? How often is it just as an adult a cryptogenic stroke in a young adult or child? Dr Field: So much of what we see is PFO-related, dissection-related, conventional vascular risk factor-related. We do send referrals to medical genetics. Sometimes we'll do testing for rare things like Fabry's or consider other diagnoses. But I mean, those tend to be the exceptions. About one in four to one in five young adults with stroke end up with this cryptogenic label. I like to keep them on my radar for a few reasons. I think, one, it produces tremendous anxiety for them to not have a cause of stroke identified and just to kind of have a generic approach to secondary prevention. So, I think just to kind of keep an eye on them, manage their anxieties each year, make sure there's kind of no updates in, in terms of general secondary preventionAnd sometimes just things dawn on you later or there are new conditions, say things like, you know, DADA2, this, you know, adenosine deaminase deficiency. You know, there are new diagnoses that, that come on the radar. And sometimes treatments change. You know, for example, when I was starting my early career, the evidence hadn't yet been in place for PFO closure, and then all of a sudden, the paradigm completely changed. And you want to make sure that you can get in touch with those patients to reconsider your approach at the time. So I realize that not everybody has the luxury of extended follow-up with their patients, but I think often you can kind of encourage them or their healthcare team or just, you know, patient themselves to keep in touch periodically just to make sure that there haven't been any changes in treatment paradigms or just with your own awareness of particular, you know, diagnoses or, or just kind... /episode/index/show/continuumjournal/id/41500300

Thrombolysis, Thrombectomy, and Antithrombotic Therapy for Acute Ischemic Stroke With Dr. Christopher R. Leon-Guerrero 07/01/2026

Thrombolysis, Thrombectomy, and Antithrombotic Therapy for Acute Ischemic Stroke With Dr. Christopher R. Leon-Guerrero Rapid advances in acute ischemic stroke care have expanded treatment windows and improved patient outcomes through thrombolysis, mechanical thrombectomy, and optimized antithrombotic strategies. This episode highlights evolving approaches to patient selection, the growing role of tenecteplase, and the importance of team-based systems of care in delivering timely, effective treatment. In this episode, Casey S. Albin, MD, FAAN, speaks with Christopher R. Leon Guerrero, MD, author of the article “Thrombolysis, Thrombectomy, and Antithrombotic Therapy for Acute Ischemic Stroke” in the Continuum® June 2026 Cerebrovascular Disease issue. Dr. Albin is a Continuum® Audio interviewer, associate editor of media engagement, and an assistant professor of neurology and neurosurgery at Emory University School of Medicine in Atlanta, Georgia. Dr. Leon Guerrero is an associate professor of neurology and the adult neurology residency program director at Atrium Health Carolinas Medical Center in Charlotte, North Carolina, where he also serves as outpatient stroke director. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Albin: In stroke care, every minute kills nearly two million neurons. But today, we're going to unpack all the details about the latest treatments that can give those neurons back. Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Albin: Hello and welcome. This is Dr. Casey Albin. Today, I'm interviewing Dr. Christopher Leon-Guerrero about his article on Thrombolysis, Thrombectomy, and Antithrombotic Therapy for Acute Ischemic Stroke. This article appears in the April 2026 Continuum issue on cerebrovascular disease. Welcome to the podcast. I always like to start by just having you introduce yourself so our listeners know a little bit about you. Dr Leon-Guerrero: Thanks for the introduction, Dr. Albin. Really glad to be here today. My name is Chris Leon-Guerrero. I'm a vascular neurologist at Atrium Health in Charlotte, North Carolina, at Carolinas Medical Center. I'm an associate professor in the Department of Neurology. I serve as our Neurology Residency Program Director, and I also wear the hat of an outpatient stroke director in our clinics. Dr Albin: So, you are wearing a lot of hats and balancing a lot of things, and it's a really exciting time to be talking about this. For our listeners, we are recording this right after the launch of the American Heart Association, American Stroke Association just released their new guidelines on acute ischemic care. So, no better time to kind of dive into some of this. And really, when I think about acute ischemic stroke care, it's dramatically transformed in the last two to three decades. I mean, from lengthening time windows for IV thrombolysis to expanded thrombectomy eligibility, this is really, I think, some of the most exciting stuff in neurology. And your article did a fantastic job of distilling those rapid advancements and clarifying some of the evidence behind some of these new evolving treatment selections and imaging modalities, and it's exciting. So, let's just start with thrombolysis. Where are we now with IV thrombolytics and the time windows there? Dr Leon-Guerrero: So, a lot has changed in the last decade, since that initial trial with NINDS, nearly thirty years ago. We're still giving intravenous thrombolysis in the traditional time window up to 4.5 hours, and really emphasizing we should be selecting patients for treatment early and quickly as possible. In most of those cases, a non-con head CT is sufficient to rule out bleeding and initiate treatment as quickly as possible. Where things have gotten really exciting is using advanced neuroimaging to help select patients beyond that traditional 4.5 hour window, and we're able to treat patients even up to twenty-four hours from symptom onset. Dr Albin: Which is really exciting. It has really totally shifted the paradigm here. You know, I think most listeners are going to be pretty familiar with three to four and a half hours. Like, that's sort of our standard. What can you tell us about some of the advanced imaging we're using for that later selection period? Dr Leon-Guerrero: It's around the principle of you want to be able to, uh, rescue significant salvageable tissue without a lot of core. So, this large profusion deficit and small core is really how you're trying to select out these patients. And two types of modalities are used. One is going to be MRI, and a lot of those imaging protocols, you know, are outlined in the WAKE UP trial and basically are looking for patients with DWI hyperintense lesions and FLAIR negative lesions to suggest that patients in an early time window that's treatable for thrombolysis. And then in the other category, we'll be using profusion imaging, whether that's CT profusion or MR profusion, to look for patients with large salvageable tissue. Dr Albin: Yeah. And I think that this has been one of the things that, to me, has been really impactful is I think when WAKE UP came out, it was exciting. It was fun to sort of think about, "Hey, we're going to be able to use MRI." But MRI can be very challenging to get acutely, especially in community centers where they don't have the capabilities to get someone from the emergency department into an MRI rapidly enough to make thrombolysis decisions. So, to see some of that expand to CT profusion has been really exciting. How are you going about sort of counseling patients or thinking about their risk when you're using some of those, like, advanced imaging techniques? Dr Leon-Guerrero: Yeah. I think it's similar to the conversations we've had with patients even within the traditional 4.5 hour window. The risk for intravenous thrombolysis is hemorrhage, and counseling patients on the, you know, the risk and benefits of hemorrhage and the potential clinical benefit of receiving thrombolytics is important. And then providing patients with that information to make an informed decision, so that they can make the best decision for their own care. Dr Albin: Totally. And it's, again, time sensitive, but trying to give families enough information and enough time to sort of process those, especially when it's a little bit beyond the standard that we're so used to consenting for. The other big area that's really changed is that tenecteplase has become the star of the show. It's really gained momentum, so what should clinicians understand about this? Dr Leon-Guerrero: Yeah. There's been an explosion of data over the last decade on tenecteplase supporting its use for clinical practice. You know, there was recent updates even from the neurology journal with a large meta-analysis with all of the data showing good clinical outcomes and perhaps even lower risk of bleeding. And so, I think you're seeing a lot of centers across the country switching from alteplase to tenecteplase. There's some practical advantages. So tenecteplase is a one-time bolus dose. And then biologically, it seems to have better fibrin specificity, longer half-life, which may ultimately make it a more attractive drug and may make it even more effective. But I think the practical aspects of tenecteplase are not to be understated. I think there's a lot of advantages for speed and efficiency and for centers to make that switch. Dr Albin: Yeah. I remember when our health system made the pivot from alteplase to tenecteplase. Like any changes, that obviously created some adjustments with the new workflow. But, the fact that this could be given just as a one-time dose and not with the “we got to calculate the bolus, and now we got to get the infusion on board,” like really simplified workflow. So, I think that's been pragmatically one of the nicest things we've done in stroke care. Really exciting. Dr Leon-Guerrero: Yeah. And, you know, it's a doable thing. I think you have to be, very deliberate about it at whatever center you're at to make sure that all stakeholders are aware of that change. I think that's helpful to get everybody involved and have a lot of planning to avoid wrong dosing errors or inadvertently dosing as alteplase versus tenecteplase. But it's certainly doable, and I think in the long term, centers that have switched have been pretty satisfied with tenecteplase. Dr Albin: And you know, initially when this came out, there really was sort of a debate about, is it gonna be 0.25? Was it gonna be 0.4? Where have we landed with that debate? Dr Leon-Guerrero: So, I think we found the correct dose is 0.25 milligrams per kilogram is the recommended dose with a max out of 25 milligrams. There's some within the American Heart Association guidelines that were just published. They mentioned even tier dosing based on 10 kilograms, so intervals. So, that may be an easier way for centers to do it. But that cap out dose of 25 milligrams at 0.25 milligrams per kilogram, I think, is the sweet spot. Dr Albin: Yeah. That's great, and I think that that has helped, you know, say, "This is what we're doing. There's not a debate that's happening anymore." And that really just got codified in the new ASA guidelines, so really exciting there. So, there is a lot of guidance for these patients, but I think one of the things that your article really tackled is the fact that there are some special populations, where we really still don't have a lot of guidance. And so, I think just to kind of distill those for the listeners, thinking about our pregnant patients, thinking about children, how are we approaching thrombolysis decisions in these special populations? Dr Leon-Guerrero: These are always tough cases. For example, for pregnant women, they've often been excluded in the thrombolytic trials. But there's still evidence. You know, there's some inference based on the evidence we do have, and there's a lot of registry and case reports suggesting potential safe treatment for pregnant women. And I think when you're approaching those cases, again, it's gonna be patient-centered and really should be multidisciplinary. These are the types of cases you really need to lean on your maternal fetal medicine colleagues, your high-risk OBGYNs, your obstetricians to help with that decision-making. And I think, a multidisciplinary approach is the way to go for these cases. It's the same thing with the pediatric population. We had some data. There was one trial, randomized control trial, called TIPS trial that looked at using intravenous alteplase for acute ischemic stroke in patients under the age of 18. It had difficulty with enrollment. But I think most experts would argue that patients with pediatric stroke should be considered for intravenous thrombolysis if appropriate. Again, same thing. You want to make it a multidisciplinary approach, really getting your pediatric neurologists, your pediatricians involved early to make the best decision for the patient. Dr Albin: Yeah. That's just really an important takeaway, just thinking about this as a multidisciplinary decision, because there are going to be other stakeholders to the patient's care who may have some different information than what we as neurologists are bringing to the approach. And obviously, our perspective really matters. But trying to work in everyone's unique vantage point of the patient really helps to make the most effective decision. When we talk about acute ischemic stroke care, I really don't think that you could do justice to the topic without pivoting to mechanical thrombectomy, which, you know, as we think about how the medical field as a whole, not just neurology, how the medical field has evolved. I mean, there's probably no bigger impact than mechanical thrombectomy has made in terms of reducing not just morbidity, but mortality from stroke. I mean both. So, thrombectomy has been around for a while, but just walk our listeners through what's the core that we for sure know that these are the patients that this works for? Dr Leon-Guerrero: The types of patients we should be selecting for intervention are patients with large vessel occlusions. And those initial trials that were published in 2015 really demonstrated that this is a quite an effective treatment for patients with large vessel occlusion ischemic strokes in the anterior circulation. When that smattering of publications occurred in 2015, the general consensus, we should be treating all patients up to six hours from symptom onset if they do have a large vessel occlusion. And then, Dr. Albin, as you know, the, the windows continue to expand. So, we were using advanced neuroimaging with MR selection and perfusion selection based on DAWN and DEFUSE 3 trial protocols to select patients all the way out to the 24 window, and it's even expanded beyond that over the last few years. Dr Albin: I think that when we think about trials that really, totally, changed the game, when we think about DAWN and DEFUSE 3, and we switched from that time-based window to more of that, like we talked about for thrombolysis, that tissue-based clock and, like, looking at what is salvageable and where can we make an impact on salvageable tissue, truly moved the needle in terms of just bringing this therapy for people who, you know, it's hard to get in within six hours. When we moved the needle to 24, it made a huge difference. But people were still coming in with a lot of ischemic damage already done, and they would have traditionally been excluded from being enrolled in thrombectomy trials. But that's changing too. So where are we there? Dr Leon-Guerrero: Yeah. I think there were lessons learned from DEFUSE and DAWN that we were probably over-selecting. Perhaps too stringent. You know, we had number needed to treat in the range of two to three for good outcome based on those trials. And so, I think those were lessons learned to move forward, and we, and, and people started looking at large core infarctions. And in the last few years, we've seen a multitude of randomized control trials examining large core infarctions. These are patients with ASPECT scores all the way down to zeros. A lot of the trials relied on three to six as their score, but there was at least one large core study that looked at ASPECT scores down to zero to two, and all of these studies showing benefit. Dr Albin: Yeah. And we've really moved into if there's some tissue to spare there, probably getting clot out really makes a big difference in impact. You know, it was really surprising to me as a neurointensivist looking at these trials, that the trials had such low rates of hemorrhage, and pretty low rates of dramatic cerebral edema after thrombectomy. I don't know that we've seen all of that in sort of real world applications, but again, we are still seeing some of these patients come in, that really would've been devastated having some amount of functional recovery regained, which is incredible. In terms of another patient population that I think gives a lot of people pause or stickiness, is those basilar artery occlusions, right? Another large vessel, but one that we’ve had a little bit harder of a time enrolling in trials and having well-selected trials. Where are we now on whether or not basilar artery occlusion should go to mechanical thrombectomy? Dr Leon-Guerrero: So, a lot of excitement in this area, too. There's at least two studies that were published in the last five years that were showing benefit in doing thrombectomy for patients with basilar artery occlusion up to 24 hours, and these were patients with moderate to severe deficits with NIH Stroke Scale scores greater than 10. And then making sure that they don't have large core, so using a newer scoring algorithm on the CAT scan called PC ASPECT, so basically a posterior circulation ASPECT score, to kind of make sure that patients don't have large core infarctions that are being considered for thrombectomy. All of those things collectively in those two recent studies, the ATTENTION trial and the BAOCHI trial, I think is what ended up making those studies positive, is that we were selecting the right types of patients, uh, without large core, early core, and patients with moderate to severe deficits that made the difference from previous trials. Dr Albin: Yeah. I think that that's so important. Those trials to me, and like how long it took to get those enrolled, really emphasized to me that there really was a selection bias. Like, we believed this worked, which made it hard to then do a trial. But I'm so glad to hear that we have the data now to support moving forward in a more rigorous way. Dr Leon-Guerrero: You're absolutely right. I think that was some of the challenges with the initial trials. In fact, the authors had commented on that. There's a lot of difficulties with lack of clinical equipoise, or experts wanting to take these patients anyways out of clinical trial and treat them, and so that's always been an issue. And then, you know, we all remember basilar artery occlusion cases. They can be severe, devastating cases in our career, but the reality is they're not that common. So, if you look at large vessel occlusions, they only account for about 10%, and if you look at all stroke patients presenting to most centers, they represent about 1% of cases. So really hard clinical trials to do just because there's thankfully not a lot of patients walking around with basilar artery occlusions, but certainly makes for challenges when you're trying to conduct randomized controlled trials on this subset of patients. Dr Albin: Absolutely. But we did it, and I think that, like, really if, if the listeners take nothing else, it's that the field of vascular neurology is really moving forward with evidence-based, doing very rigorously controlled clinical trials, which is, I think, is what makes this field so exciting. Finally, closing out, cause we could talk all day, but we don't have all day. You know, it seems to me that more and more we are just using dual antiplatelet therapy all the time. And maybe that is, uh, a little bit of a hyperbole, cause I don't think it's all the time, but let's walk through— when is there good evidence for dual antiplatelet therapy? Dr Leon-Guerrero: Yeah. So, there's strong evidence for early initiation of dual antiplatelet therapy or DAPT in patients with minor stroke or high-risk TIAs, and it's been studied using both clopidogrel as an add-on to aspirin and ticagrelor. Both seem like they're viable options in patients. I think one of the key things is the duration of therapy. So, in these cases with minor stroke and high-risk TIAs, we really should be confining the treatment of early DAPT for 21 days. The risk profile changes, so the risk of recurrent stroke starts to decline with time, and that risk of hemorrhage complications increases with time. And so that sweet spot of 21 days, or even some centers will do 30 days for just practical purposes, you know, really is what we should be doing in most of those cases. Other instances where DAPT can be considered, is in patients with intracranial atherosclerosis that's symptomatic, extrapolating from the SAMMPRIS trial that in the, in the medical management arm alone, used dual antiplatelet therapy with aspirin and clopidogrel for up to 90 days. So, you'll see that as well in clinical practice. Some people will opt for a 90-day... /episode/index/show/continuumjournal/id/41500155

Pregnancy and Stroke Risk With Dr. Michelle Leppert 06/24/2026

Pregnancy and Stroke Risk With Dr. Michelle Leppert Pregnancy and the postpartum period are critical windows of increased stroke risk, driven by physiologic changes such as hypercoagulability and blood pressure fluctuations. This episode highlights key warning signs, including headache and hypertension, along with practical guidance on evaluation, management, and risk reduction to improve outcomes for pregnant and postpartum patients. In this episode, Kait Nevel, MD, speaks with Michelle H. Leppert, MD, author of the article “Pregnancy and Stroke Risk” in the Continuum® June 2026 Cerebrovascular Disease issue. Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana. Dr. Leppert is an associate professor of neurology at Tufts Medical Center in Boston, Massachusetts. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Nevel: The time during and around pregnancy is often thought of as a very joyful time, full of hope. But for some, medical complications such as stroke can lead to devastating disability and sometimes even death. Today, we're going to learn about pregnancy and postpartum stroke, including stroke risk evaluation and best practices in management and risk reduction to help our pregnant and peripartum patients reduce stroke risk and achieve best possible outcomes. Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Nevel: Hello, this is Dr. Kait Nevel. Today, I'm interviewing Dr. Michelle Leppert about her article on pregnancy and stroke risk. This article appears in the June 2026 Continuum issue on cerebrovascular disease. Michelle, welcome to the podcast, and please introduce yourself to the audience. Dr Leppert: My name is Michelle Leppert. I'm a stroke neurologist, and I currently work at the Tufts Medical Center in Boston, Massachusetts. Dr Nevel: Thank you so much for being here, Michelle, and I'm looking forward to talking to you about your article. I always love starting with the question, what's the most important takeaway from your article for the practicing neurologist? Dr Leppert: I think in this article, I'm trying to highlight that during pregnancy and especially postpartum, there's a heightened risk of stroke for women, and that's important for clinical neurologists to understand that this is a particularly vulnerable time for the population that we take care of. I think that one of the few of the things that could be informing this heightened stroke risk are the physiological changes that women undergo during pregnancy. So, that includes coagability, where there's an increased likelihood of clotting, and also the cardiovascular adaptations, including increased cardiac output and having an increased cardiac volume. And all of these mechanisms all contribute to the increased risk of strokes around pregnancy and postpartum. Dr Nevel: Great. Thanks for that. What are some of the unique aspects of stroke types in etiology in pregnancy that we should be aware of? Dr Leppert: When we think of strokes overall, generally the majority of our strokes are ischemic. So, for the overall population, about eighty-seven percent of strokes are ischemic, while the remainder are hemorrhagic. However, interestingly, during pregnancy, what we're seeing is about half of our strokes become hemorrhagic strokes, and now only a half of our strokes are ischemic, and this is in contrast to what we see in the overall population. One of the reasons is because pregnancy is associated with preeclampsia, and preeclampsia increases the risk of hemorrhagic stroke during pregnancy. Dr Nevel: Can you tell us just more about headache in general in pregnancy and association of headache with secondary causes of headache and how that relates to stroke risk in this patient population? It seems like in this patient population that when somebody has a headache, we need to be very careful in our headache questions and evaluation. Dr Leppert: Yeah. And I think the most concerning symptom that we're finding in this population is headaches, and the reason is because headaches is one of the clinical signs of having preeclampsia, which dramatically increases your risk of having a stroke, and especially a hemorrhagic stroke. So just to back up, we can talk about blood pressure for a little bit and some of the pathophysiologic changes during pregnancy. What most people may not know is that there's a dramatic vascular expansion that occurs during pregnancy. And somewhere during the second trimester, your blood pressure is actually the lowest. So, it can drop below pre-pregnancy levels and make your blood pressure appear low for the baseline. However, during the third trimester, as the baby is growing, there is increased vascular volume. The blood pressure starts to increase. We're seeing some of the highest prevalence of blood pressures, which is a sign for preeclampsia, and headaches develop during that third trimester, and particularly during the time around delivery and postpartum. And one of the most concerning signs, the most common sign of preeclampsia is having a headache. So, I think that with any patient that's presenting with a headache, especially during the third trimester or after delivery, that we really need to pay attention and take their blood pressure. That's one of the easiest clinical indicators that something could be going very wrong. Some of the other red flags clinically that we look for in headaches is that acute onset of a severe headache. That headache quality is different from what they usually have. Any woman with focal neurological symptoms associated with their headache, kind of excessive nausea and vomiting that's not characteristic for them. Not getting any relief with medications, and then lastly, checking that blood pressure is very important. Dr Nevel: And what are the thoughts on blood pressure management in this patient population? I know that there is a little bit of difference in guidance in some of the obstetric societies on how we should manage blood pressure in this patient population. And then, is there anything beyond blood pressure management that we should be thinking about doing for this patient population to reduce their stroke risk? Dr Leppert: I think that's a good question, and I hadn't really understood that this could be an area of controversy, cause my practice is mostly in stroke, and for most of adult population, the guidelines for blood pressure is very clear. We treat everybody over 130/80. If you're elderly, then your blood pressure limit might be a little higher. However, there's disagreement in the OBGYN guidelines from the American guidelines to the European guidelines. So, what the current American guidelines suggests is that if you have a history of chronic hypertension, then we would want your blood pressure treated during pregnancy below 140/90. However, if you don't have a history of chronic hypertension, then we allow the blood pressure to be higher and then it's an acute intervention if it's anything over 160. One of the issues with this strategy that is concerning is we had just mentioned that the pathophysiology of a pregnancy where you have the lowest blood pressure in that second trimester, and so your blood pressure may be abnormally good. [laughs] And it appears that it's better than your baseline. And so, by the OBGYN definition, any gestational blood hypertension is considered at 20 weeks and later. Sometimes these blood pressures are masked in some women who are pregnant. I think regardless of the controversy and what the practice should be, the focus is that most of the strokes are happening actually peripartum and postpartum, right? So, the woman's no longer pregnant. It is these time periods of the highest risk that we wanna make sure that the blood pressure is controlled. So, after the woman delivers the baby, we're no longer, you know, hampered by the whatever is chronic or gestational. We should be treating that blood pressure to 140/90. I think that not focusing on the controversy until the science catches up is probably what we should do. But like, really, the message here is that we should be checking women around the time of delivery and also postpartum, that we can't forget about their blood pressures postpartum, cause it actually doesn't peak until day five after they deliver the baby. Dr Nevel: Does knowing that, that blood pressure peaks around day five, do you think that that should impact how we counsel patients in checking their blood pressure at home? Cause most women at day five are home. They're not still in the hospital. Dr Leppert: Yeah, I think that's a really good point. One of the best interventions has been having a blood pressure at home for pregnant women. So even during their pregnancy and then postpartum, allow them to check their blood pressures, cause there's... Most of the cases, to be honest, that I've seen of preeclampsia and intracranial hemorrhage has happened postpartum. And I think what's unfortunate is that the woman is at home, they're distracted cause they have a newborn baby. They have a headache. They're just taking some Tylenol. And then if you have that blood pressure cuff readily accessible, that's a, a really easy way for them to check and notice that, hey, the blood pressure's too high, they have to go into the hospital. Dr Nevel: Yeah, absolutely, and it's not just like a headache because you're sleep deprived and have a newborn. It's a headache that you need to pay attention to. Okay, maybe we could talk a little bit now about evaluation when we are suspicious of potential stroke. What do we need to know about imaging modalities and safety considerations of imaging in this patient population? Dr Leppert: Yeah, that's a great question. I think when I was training, it was fairly controversial to give a pregnant woman MR contrast with gadolinium during their pregnancy. And as I was researching for this article, actually there's not definitive evidence that that is harmful for the fetus. However, in general, for the acute evaluation of patients during pregnancy, we're recommending using the CAT scan and then a CT angiogram. And then if the acute evaluation is not necessary, then an MRI. And if we need vessel imaging, you can employ an MRA time-of-flight study. That doesn't require the gadolinium contrast. However, one thing that I learned from this article that I thought was really interesting was the use of abdominal shielding. So, you're scanning someone's brain. I always thought, "Hey, doesn't it make sense to put a lead shield over the abdomen?" It turns out the lead shield actually interferes with the automatic calibration of the CT machine, so studies have found that actually increases the dose of radiation that the fetus is exposed to. So, it's much better when we're doing acute evaluations to not shield the abdomen, and really the only thing that can help reduce the radiation dose is the duration of the study. So, what we would recommend is if you want a rapid CT angiogram, rapid CT head, go ahead and obtain it. But if you don't need extra sequences, like a delayed phase of the CT angiogram, then to avoid that and reduce the exposure. Dr Nevel: I'm so glad that you talked about that because I was shocked when I read that in your article that we shouldn't be using abdominal shielding in pregnant women. I had no clue. I thought that that was, like, something that we absolutely should do. So, I found that really interesting. Thank you for that. So, any special considerations for acute stroke intervention or management in pregnancy in the postpartum phase, especially things like thrombolysis and thrombectomy? Dr Leppert: Yeah. So, I think that as our evidence is getting better for thrombectomy, I would be more judicious about using IV thrombolysis, especially around the time of delivery, cause there is some evidence that it can be associated with postpartum hemorrhage. Patient selection, I think, is key here. So, women who have disability associated with their stroke, and then women who aren't candidates for thrombectomies are still candidates for IV thrombolysis. But understanding that this is a little bit of an unchartered territory for us, and only using IV thrombolytics when we think that there is a big benefit to be had. Dr Nevel: Can you talk a little bit more about RCVS and PRESS in pregnancy and some of the overlap that we see in this patient population and its relationship to preeclampsia? It seems like there's a lot of interconnections there, and I thought that that was pretty interesting in your article. Dr Leppert: Right now, the thinking is that RCVS and PRESS are on the same spectrum of pathology, and we think that it has something to do with the autoregulation of vascular resistance in the posterior circulation of the brain. We're not sure what triggers this, but there is something about pregnancy that classically we'll see this postpartum RCVS phenomenon. It likely has to do also with blood pressure that we're seeing. So really classically we think of this, like, thunderclap headache. You see vasospasms on imaging that is transient, that are kind of the classical signs of RCVS. But I think that we're still not completely sure what triggers it, but it's a very well-described clinical phenomenon. Dr Nevel: Great. Thank you. Could you share a little bit about migraines in pregnancy and stroke risk? [laughs] I also thought that this also a segment of your article that caught my attention because migraines are so common. What's the association of migraine, pregnancy, and stroke risk? Dr Leppert: Yeah. So that's a very complicated association. So, we know that migraines are associated independently with strokes, and especially people with migraines with aura. However, migraines are also highly associated with PFOs, right? And during pregnancy, what we see is that there is a hypercoagulability state, and so we see lots more DVTs, we see more PEs associated with women during pregnancy. So potentially, because migraineurs also are more likely to have PFOs, they could be presenting with more cardioembolic, kind of paradoxical emboli from these thrombus. But I'm not quite sure that we know why migraines in and of itself, especially with migraines with aura, lead to strokes. And especially during pregnancy, I'm not sure because we have very little understanding about pathophysiology of pregnancy while having migraines with aura also leads to more strokes, or that risk is really just associated with PFOs. So, I think that we need to think about that a lot more. The recommendation is a baby aspirin if you have some of these risk factors for preeclampsia, any vascular risk factors, and including migraines with aura during pregnancy. And we think that baby aspirin is relatively safe, especially starting around the 12 to 16-week period. Dr Nevel: So just to clarify, in a woman who's pregnant, who's 12 weeks or beyond in their pregnancy and who has migraine with aura, is that a patient that we should consider aspirin for them to reduce their stroke risk? Dr Leppert: I think you can. I am not sure that there is a specific recommendation. I think that, like, a conversation with your OBGYN is, you know, a good idea. But we do recommend that baby aspirin for women, um, above 35 years old because it's considered advanced maternal age. And then we recommend baby aspirin with women with a history of hypertension, multiple gestations, diabetes, renal disease, autoimmune disease. So, I definitely think that is something to consider. Dr Nevel: Yeah. Interesting. Okay, great. Thank you for that. When someone has a stroke and they're pregnant again, what are some strategies for secondary stroke prevention? And you mentioned some of the primary risk reduction, but are there any others that you haven't mentioned yet other than aspirin and blood pressure control for primary prevention? Dr Leppert: Yeah, absolutely. So, I think that it's important to plan ahead. So, for women who are thinking about getting pregnant after they've had a stroke, one of the tenets of stroke neurology is trying to figure out why the first stroke happened. So, I feel like before getting pregnant, it's great to have a very thorough stroke workup so that you understand what the risk factors were and that those risk factors are controlled. One of the interventions, one of the only interventions that's, has evidence in young people with strokes is PFO closure. So, if you do have a stroke from a PFO, we recommend you get that closed prior to your pregnancy because then hopefully even given the hypercoagulability of pregnancy, there's some protection against another embolic stroke. Dr Nevel: Another really interesting part of your article that I did not know before I read it was about the risk of cardiovascular disease long term in women who have had stroke during pregnancy. Could you talk a little bit more about that? Dr Leppert: What we understand is that gestational diabetes and gestational hypertension sets you up for having diabetes and hypertension later on in life, and it's really developing the actual diabetes to the hypertension that increases your risk of strokes. So, what's really an important takeaway for providers is that after women develop gestational diabetes or they have gestational hypertension or they develop preeclampsia, it's very important for their primary or their neurologist to be very vigilant of these risk factors developing so that they can be modified before the women are at higher risk for strokes. And the reason why we think this happens is because pregnancy is like a stress test for your body. And so, the fact that you've developed the gestational diabetes or the gestational hypertension kind of already suggests that you're more likely and more vulnerable to developing these traditional risk factors later on. Dr Nevel: That makes sense. Thank you for that. What do you think is a common misconception about stroke in pregnancy? Dr Leppert: When I was earlier in my training, it kind of felt like having a stroke during pregnancy was being struck by lightning. It was really random. There was nothing you could do. It just happened to people. And I think as I learned more in my career, and especially researching for this article, I'm kind of shocked and disturbed by how much of the strokes in pregnancy we can actually prevent. Through management and monitoring of blood pressure for women. And so, I do think that it does our patients a disservice if we think that these are rogue events. But really, it might be a sign of the failure of our health system where we're not taking care of women around their delivery and postpartum and being more vigilant about their blood pressure and more vigilant about the clinical signs that they're developing. Dr Nevel: Yeah, I really got that from your article, how important it is to monitor for blood pressure and other risk factors, and that that continues after the baby's born. Thank you so much for that, and thank you for talking with me today about your article about stroke and pregnancy. Again, today I've been interviewing Dr. Michelle Leppert about her article on pregnancy and stroke risk. This article appears in the June 2026 Continuum issue on cerebral vascular disease. Please be... /episode/index/show/continuumjournal/id/41499910

Stroke Prevention With Dr. Mitchell S.V. Elkind 06/17/2026

Stroke Prevention With Dr. Mitchell S.V. Elkind Primary stroke prevention is a critical opportunity for neurologists, with most stroke risk driven by modifiable factors such as hypertension and lifestyle behaviors. This episode highlights practical tools and strategies, including Life’s Essential 8 and contemporary risk calculators, while also exploring evolving approaches to shared decision making and secondary prevention. In this episode, Katie Grouse, MD, FAAN, speaks with Mitchell S. Elkind, MD, MS, FAAN, author of the article “Stroke Prevention” in the Continuum® June 2026 Cerebrovascular Disease 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. Elkind is the Chief Science Officer for Brain Health and Stroke at the American Heart Association in Dallas, Texas, and a professor of neurology and epidemiology at Columbia University in New York, New York. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Guest: Dr Grouse: Neurologists have generally been more involved in secondary stroke prevention, but primary stroke prevention is increasingly recognized as an important topic of discussion for neurologists. Today, I have the opportunity to interview Dr. Mitchell Elkind, who wrote the article on stroke prevention in the newest Continuum issue on cerebrovascular disease. Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Grouse: This is Dr. Katie Grouse. Today, I'm interviewing Dr. Mitchell Elkind about his article on stroke prevention. This article appears in the June 2026 Continuum issue on cerebrovascular disease. Welcome to the podcast, and please introduce yourself to the audience. Dr Elkind: Thank you so much, Katie. So, my name is Mitch Elkind, and I'm the Chief Science Officer for Brain Health and Stroke at the American Heart Association and a stroke neurologist by background. Dr Grouse: Well, I just want to start by saying that I really enjoyed reading this article. I think this is just a really wonderful article I recommend strongly. Such a high yield, an important topic for a lot of us who see patients who are interested in learning about their stroke risks or need help with, uh, stroke prevention after having a stroke. So, I wanted to start. What's changed in the last couple of years? You know, what are some big highlights that you really want to stress that are different from maybe the last time we reviewed this topic? Dr Elkind: Sure. Well, there's been a lot of development in the field of secondary stroke prevention, for one thing. But even beyond that, I think we increasingly appreciate how important it is to control what we call the social drivers of health on the earlier side, primordial or primary prevention. And that has been a big advance, I'd say. And I would also say, I think it's really important for neurologists to understand some of those questions about primordial and primary prevention. You know, we tend to get involved with patients after they've had a stroke or maybe a TIA, some kind of event. But sometimes we find people who are following for, you know, non-stroke related conditions who have risk factors also. And we can really play an important role in identifying those risk factors and helping to prevent a first stroke or vascular event as well. So, I think it's real important for us to be doctors even before we're neurologists. So, you know, Katie, about ninety percent of stroke risk is modifiable, so we can do a great job as neurologists in preventing stroke. And one of the most important things that we can do is to identify and treat high blood pressure. And recently, actually, the American Heart Association, American College of Cardiology guidelines on the management of hypertension have said that treatment of high blood pressure not only prevents stroke, but it can also help to prevent cognitive decline and dementia. And this is the first time that we've had a class of recommendation one and level of evidence A, the highest level of recommendation we give for the use of blood pressure treatment to prevent dementia. And that's largely based on the results of some large trials that have come out recently showing that you can prevent dementia with blood pressure control. So that's a really exciting link, I think, between cardiovascular risk factor control and subsequent brain health. It just illustrates the role that neurologists can play in, so many conditions outside of stroke as well. Dr Grouse: That's a really great point, and I want to get a little more into the idea of primordial stroke prevention. Can you tell us a little bit more about what that might be? Dr Elkind: So primordial prevention refers to addressing how we can prevent risk factors from occurring in the first place, and how can we improve the environments in which people live. You know, we know that only about twenty percent of health outcomes is dependent on what happens between the patient and their doctor in the office. About eighty percent of it is due to what happens in the environments in which we live, work, pray, and play. And so that's what we mean when we refer to the social drivers of health. What is the neighborhood like where somebody lives? Do they have access to healthy food? Do they have places where they can go to exercise? Is there air pollution in the area that may affect their health? You know, one really interesting fact that's become apparent in the last few years is that air pollution is a major risk factor for stroke. Something like a sixth of all strokes can be attributed to the quality of air. And so, what are the things we can do at the broader public policy, community level to reduce the risk of risk factors like high blood pressure and diabetes even before somebody has an event that brings them to the attention of the doctor? So that's what we're thinking about with regard to primordial prevention. It's the earliest stage in prevention. Dr Grouse: And that's really fascinating. You know, I think an area that we haven't, as neurologists, really put a lot of our time thinking about, but clearly a very important thing. I really appreciated reading your article about how you incorporated the fact that, you know, a lot of these risk factors overlap very, very closely with all the risk factors for various types of cardiovascular events. And I would imagine that the work you've done as the Chief Clinical Science Officer for the American Heart Association has informed a lot of the way you've thought about-Trying to bring all these risks together and think a little bit more holistically about the whole thing. Could you tell us a little bit more about that and the work that you've done on the American Heart Association's Life's Essential 8 score? Dr Elkind: Sure. I can't take credit for it. It's really work that was done by others at the Heart Association, particularly a cardiologist and epidemiologist named Don Lloyd-Jones. But many other volunteers participated. Life's Essential 8 is our approach to primary stroke prevention and cardiovascular prevention more broadly. We say Life's Essential 8 because it includes four health behaviors and four health factors that people can observe to reduce their risk of cardiovascular disease. The four factors are kind of things like know your numbers, your blood pressure, your blood sugar, your body mass index, right, which is a combination of weight and height, and your cholesterol level. So, know those numbers and keep them within the recommended ranges, and talk to your doctor if they're not. And then four lifestyle behaviors. So, one of them is to eat a healthy diet, and typically that means the Mediterranean diet. It means getting regular exercise, and we recommend 150 minutes a week of moderate to vigorous physical activity. Of course, it means abstinence from smoking or other tobacco products. And the last one, the eighth one, which I was so excited about when we added this, is sleep, recommending at least seven hours of sleep a night. So, I was really excited about this because we used to talk about Life's Simple 7, and then the last iteration of our recommendations included this recommendation for adequate sleep because of the mounting evidence of the importance of sleep to cardiovascular health. But sleep is really a brain function, right? And so, it was really the first, in a way, specific brain function that was added to our recommendations. So that's Life's Essential 8. People can read about it online at heart.org and recommend it to your patients as a simple way for people to understand the best approach to reducing their risk of cardiovascular disease, including stroke. Dr Grouse: I checked it out myself after reading the article. It's very accessible to patients. It's a great education tool. And they can, you know, see their own score and use that in their own way to, to think about what their risks are and how they can help mitigate and then rescore themselves down the line. There's also, though, on the kind of more the clinician side, the PREVENT calculator as well. Could you tell us a little bit more about how we could use that in approaching this patient population? Dr Elkind: Yeah. So, I think of Life's Essential 8 as being a patient-focused tool that people can use. PREVENT is really more for clinicians. Anybody can look it up online and enter your data into it. There's a risk calculator online. But the basic idea behind PREVENT and other similar risk calculators is that it's a way to estimate somebody's risk of having a cardiovascular event like stroke or a heart attack or even heart failure by entering information about your health. And we used to think, we used to use something called the ASCVD, atherosclerotic cardiovascular disease risk calculator, or the Framingham score. Framingham Heart Score, for example, was another one. PREVENT is the latest version, and it has several advantages over those earlier types of risk predictors. For one thing, it predicts risk at younger ages as well. It goes down to age 30. It predicts risk over a longer duration of time, so over 30, 10 or 30 years. It eliminates the use of race as an item to put into the calculator and substitutes for that socioeconomic status, so it's not a race base, but a measure of social disadvantage. And it also includes kidney elements, kidney measures. It includes renal function, for example, that weren't included in prior measures, and it can also be used to predict heart failure, which was not part of the original calculators. Another major advantage of the PREVENT study is that it was based on real-world data from about three million patients, many, many more than the 50,000 or so that the earlier risk calculators were based on. So, it has a much more robust data set and therefore allows a bit more precision in the ability to predict future risk of events. And typically, primary care doctors would enter their patient's data, calculate a risk, and then based on the results of the risk calculator, they can make recommendations about what type of medications a person should take or what other strategies they could use to reduce their risk. And so that's the role that PREVENT plays, is really being focused more for the clinician than the patient. Dr Grouse: Really great tool for us to be aware of. You earlier alluded to the fact that neurologists are in the situation where we sometimes are helping patients with this primary prevention. But you also make a case for why it's in the patient's best interest for us to be involved in, in these conversations when we can, when we have the opportunity. Can you tell us more about that? Dr Elkind: Shared decision-making is really important because we know that people aren't going to lead the healthiest possible lives if they're not invested in their care. And so, a doctor telling somebody what to do if the patient doesn't want to do it is gonna have limited benefit.So we emphasize the importance of shared decision-making as much as possible. And I think that where this comes up a lot is actually in the situation of, for example, atrial fibrillation, where patients will often be put on a blood thinner. And many people are fearful of blood thinners. They worry about the risk of bleeding. Maybe they know a relative who's had a bleeding complication from a blood thinner, and so they may be disinclined to try it. And so, it's really important to have these discussions about the risks and the benefits of medication and engage the patient in thinking about this. And there are even tools and visual aids that people can look to to help explain some of these complicated concepts to patients. So, these are the kinds of things that reflect implementation science as a way to improve adherence. We know what works in a clinical trial setting often, but the challenge is translating that into the real world and getting our patients to use the medications that we believe scientifically have been shown to be of benefit. I've actually been surprised sometimes at conversations I've had with people, in some cases, healthcare professionals who resist going on blood thinners because of their fear of the complications. And I feel like the evidence is there. Why don't they believe me? And that's why it's really important to have the conversation. Even our peers and colleagues can sometimes question the evidence, and it's important for us to be aware of that. Dr Grouse: Absolutely. I think that sounds very reasonable to me, and hopefully these tools will help us with making some of these decisions with our patients. Now, turning our attention a little bit to secondary prevention. So, you know, someone's already had a stroke or a TIA, sort of thinking about what we can do to optimize their risk factors for further strokes. You know, I think there has been some changes that have happened, I think, in the last few years that might be affecting some of the decisions we're making and some of the advice we're giving our patients. I wanted to talk a little bit about GLP-1 receptor agonist medications. Is the data there to support use of this either in secondary prevention or even in primary prevention in the case of stroke? Dr Elkind: There is evidence that supports the use of GLP-1s for stroke prevention. We need more data, though. We need trials that focus only on patients with stroke, for example, there have been studies in patients with cardiovascular disease broadly that include stroke patients. But if you look at the subcategory just of stroke patients alone, the data in that subgroup alone don't always show a benefit. And so, we need more data that's focused on stroke patients alone. So, I think the data are continuing to emerge, but we need more still. Dr Grouse: Is there any development in the thought about whether we should be putting patients on antiplatelet therapies for incidental, incidentally identified strokes? For instance, if you got an MRI for migraine or for other reasons and you found one, no history of any stroke-like symptoms. Should we be putting these patients on aspirin or any other types of therapies? Dr Elkind: That's a really great question. And again, it's an area where there's some controversy and really, there's really no definitive data that would support using antiplatelet therapy in people with incidentally discovered infarcts or what we call, you know, whispering strokes or silent strokes. Many stroke neurologists will use antiplatelet agents. This is one of those areas where it's so important to identify the risk factors. As we were saying before, patients who have other neurological disorders like migraine or epilepsy may turn out to have cardiovascular risk factors like diabetes and high blood pressure. That's why it's so important for neurologists to be able to treat those patients or refer them to specialists who can. Patients who have incidentally discovered lesions similarly are a group where we should be looking for risk factors. So, I don't think of it only in terms of do we put them on an antiplatelet or not, but really more holistically, can we identify their other risk factors and address those? Should the patient's information be entered into a risk calculator like PREVENT, for example, so that we can come up with a more global or holistic measure of their cardiovascular risk and address that as appropriate? Because if they are at risk for stroke, they're also at risk for cardiac events, including heart attack, heart failure, sudden cardiac arrest, and so forth. So, I think of it as a, as a great kind of teachable moment or an opportunity to catch somebody and bring them into the healthcare system more broadly and address those other potential risk factors. Dr Grouse: Speaking of, of risk factors that we often like to think about and work up when possible, in cases where it seems certainly possible the patient had an embolic stroke, but perhaps we've done a few weeks or four weeks of cardiac monitoring, have not found any evidence of atrial fibrillation. What's new and what's the current recommendations for doing further monitoring when there's high suspicion for cardioembolic stroke? Dr Elkind: This is a really active area of investigation, and guidelines suggest that we should do some cardiac monitoring for atrial fibrillation after an unexplained stroke, but it's not clear how much we should do. Studies generally show that the longer you follow somebody on a cardiac monitor after stroke, the more likely you are to detect atrial fibrillation. It could be as high as thirty percent after a few years. And that's great. And if you detect atrial fibrillation, people usually end up being recommended for a blood thinner. But how extensively we should monitor remains unknown. And I think a lot of the investigation recently has been around the question of, are there other ways to get that information rather than waiting six months or a year for the person to develop atrial fibrillation?It's a little bit funny logically to think a person has a stroke today, a year later you discover atrial fibrillation on the monitor, and you say, "Oh, now I know what caused your stroke a year ago." Right? The temporality, the causality perhaps is off in that case. And so, wouldn't it be better if we could tell what somebody's risk of having another cardioembolic stroke is, or the likelihood that they have atrial fibrillation is at the time that you first see them for the stroke, you know, in the hospital, for example. And so, there's some really new technologies that have evolved like AI or artificial intelligence interpretation of EKGs that can give a really good indication of which people are gonna go on to develop atrial fibrillation. And so, I think we need some more trials in that area to demonstrate that we can detect the risk of AFib and treat that even before it appears on one of those delayed monitors. That's an area that I think is very exciting right now. There's also a further question with regard to how to treat these patients, which is that sometimes atrial fibrillation is a consequence of the stroke itself. So, we can think about what people call known AF, meaning atrial fibrillation that's known about before the stroke even occurs, versus AF that's detected after a stroke, or AF-DAS, people... /episode/index/show/continuumjournal/id/41497570

Social Determinants of Health and Their Impacts on Stroke Prevention and Outcomes With Dr. Nneka Ifejika 06/10/2026

Social Determinants of Health and Their Impacts on Stroke Prevention and Outcomes With Dr. Nneka Ifejika Social determinants of health, including housing, food access, insurance status, and structural inequities, significantly influence stroke prevention, recovery, and long term outcomes. These factors affect biological risk, treatment adherence, and disparities in care, even when traditional clinical measures are addressed. This episode highlights practical strategies for integrating screening, leveraging multidisciplinary teams, and identifying opportunities for advocacy to improve patient outcomes. In this episode, Teshamae Monteith, MD, FAAN, speaks with Nneka L. Ifejika, MD, MPH, author of the article “Social Determinants of Health and Their Impacts on Stroke Prevention and Outcomes” in the Continuum® June 2026 Cerebrovascular Disease 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. Ifejika is an adjunct professor of physical medicine and rehabilitation at UT Southwestern Medical Center in Dallas, Texas, and the chief scientific officer of the Division of Academics at Ochsner Health System in New Orleans, Louisiana. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Monteith: Two patients have the same stroke, but when they return, they have very different outcomes. We can look into some of their comorbidities, but something we don't spend enough time talking about is the social determinants of health. Stay tuned to this discussion. I promise you, you'll become a better neurologist. Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Monteith: This is Dr. Teshamae Monteith. Today I'm interviewing Dr. Nneka Ifejika about her article on social determinants of health and their impacts on stroke prevention and outcomes. This article appears in the June 2026 Continuum issue on cerebrovascular disease. How are you? Welcome to our podcast. Dr Ifejika: Thanks for having me. I'm doing great. Dr Monteith: Great. So, can you introduce yourself to our audience? Dr Ifejika: Sure. I'm Dr. Nneka Ifejika. I am the Chief Scientific Officer of Ochsner Health System in New Orleans, Louisiana. But I'm also a cerebrovascular rehabilitation doctor. I've been practicing for about nineteen years, and am happy and honored to be a contributor to this Continuum Neurology article. It's a really important topic. Dr Monteith: Great. So, what got you into this field, first of all? Dr Ifejika: Well, I was deciding between PM&R and neurology, and I was putting in both match lists. And I thought about it and I leaned toward PM&R, but stroke still had a grasp on my heart and my mind. And so, after I finished my residency, I joined the UT Houston stroke team, and I did a, thankfully did a two-year fellowship and became cross-trained in stroke as well as physical medicine rehab. So, I am a jack of both trades. Dr Monteith: So, you got your way in a way. Dr Ifejika: I did. Dr Monteith: You know, we have a lot of learners that are listening, so it's always, uh, nice for them to be inspired, I think, by people's career paths. So why don't we talk about the objectives of your article? Dr Ifejika: Sure. So, one of the most important things that we wanted to do was make sure that medical students, residents, faculty, and fellows understood the impact of social determinants of health on stroke recovery and stroke rehabilitation. It's not as simple as you have hypertension, hyperlipidemia, we're going to manage your stroke risk factors. Oh, you had an ischemic stroke. You presented in time for the window. We're going to give you endovascular therapy and then modified Rankin scale at hospital discharge in ninety days. No, no, no. The stroke survivor and their caregivers and their family have a lot more to deal with outside of what we look at during the acute stroke hospitalization and post-acute rehabilitation. Things like, can they afford the medication that we're prescribing? Antiplatelet agents or anticoagulation can be extremely expensive. Do they have housing insecurity? Is there food insecurity? What's going on behind the scenes that we are not addressing that can directly impact the admission rate and the readmission rate after we take care of a stroke survivor? Dr Monteith: I love the article because you took a real deep dive into social determinants of health, what they are, why they matter, and what we can do about them. And so why don't we talk a little bit about the NINDS framework for social determinants of health? I think many of us might not be familiar with the framework per se. Dr Ifejika: So, the framework consists of multiple domains specifically that relate to social determinants of health that were published in Neurology a couple of years ago. So, I do hope that people who are hearing this recording actually read them. There are interpersonal domains, there are classic medical domains, there are indeterminate domains, and there are six total domains. And health domains are the last domain. So, things like when it comes to housing insecurity, food insecurity, that's a domain of social determinants of health. When it comes to chronic racism, when it comes to biases that patients experience, those actually impact outcomes. So, there are six separate indices that we're going to get into in detail and how we address them as clinicians, whether it be at the medical student level, resident level, faculty level, to integrate the social determinants of health in our care plans, because we could be doing a much better job. And I think it'll be really important from the interpersonal perspective when we really relate to our patients and their families that we ask these questions. For example, if we're prescribing someone to have treatment for their diabetes mellitus and ha- and, and be taking insulin, if they have housing insecurity and they're in a homeless shelter, they have to leave the homeless shelter during the day. So, what happens to the insulin that we prescribe? These are variables that we are not considering on a regular basis, but they directly relate to compliance. Dr Monteith: Great. So that was one thing I wanted to bring up. We're very good at measuring blood pressure and trying to determine, uh, the association between stroke outcomes and things that we can measure, glucose, lipids, blood pressure. What is the evidence for social determinants of health and stroke outcome? Dr Ifejika: The evidence is growing, and there have been many publications that have come out that are, are going to be highlighted in this article related to structural determinants of health inequities, like structural racism, as well as disparities related to ethnicity and race. There's geographical disparities. For example, a lot of patients are, are primarily concerned about rural versus urban, whether you have access to different post-acute rehabilitation, whether you have access to secondary stroke prevention because you simply don't have the transportation from a, a rural area to get to a drugstore to get things available to you. Social status. There are actually publication related to socioeconomic status and the concerns when it comes to air pollution. So particulate matter 2.5, we know that that has a direct impact on stroke outcomes and health overall, but we don't really think about it as a structural determinant of health inequity. There's several multiple layers of research that have gone on specifically that have been cited in the literature that relate directly to social determinants of health and how we can address them moving forward. Dr Monteith: And what I found interesting in your article in that you gave at least a few examples where social factors like income, education were controlled for, and maybe in large part it is, but even when you control for some of these very obvious social risk factors, you still have inequities. Dr Ifejika: Absolutely. And I think it was really important to show that we had strong peer review evidence behind this, as it wasn't just something that we were creating or hypothesizing about. There have been studies that have been done over this over decades of time, showing the impacts of social determinants of health on outcomes. But the question and concern that we have is we know this growing body of literature continues to expand. What are we doing about it when it comes to education of the future generations of providers who will be caring for this population? Dr Monteith: Before we get into how, you know, what we're going to do about that, let's just kind of put that link, cause the evidence is there. How does it drive biology? Dr Ifejika: It's a great question. So, for example, particulate matter 2.5 in air pollution has been shown to have an existing impact on hypertension, raising your blood pressure. So that's a direct effect of a social determinant of health related to socioeconomic status because people who live in areas with higher air pollution are... They're not green spaces. They live near highways. Those are areas that unfortunately are also impacted by food deserts. Food deserts, if you're not able to get fresh fruits, vegetables, whole foods, increases your risk of developing diabetes, hyperlipidemia, also increases your sodium intake, again, increasing hypertension. These things are all connected to biological determinants. It's just that we're not asking about them necessarily within the social history when we're taking people into the hospital, but they have direct effects. Dr Monteith: Great. Neurologists tend to be busy and, you know, we're... have all of these things that we're being asked to do and chart and click and all of that stuff. And so how can we more readily integrate screening for social determinants of health and that conversation into the work we do? We recognize it's important. We recognize it's an important risk factor. There's a lot of these determinants. So, what is a good way to do so? And I, I know that in the paper you've, you've given different roles to different team players, so I want you to talk about that too, but just kind of even a regular routine office visit. Walk us through a way we can more easily integrate that kind of conversation. Dr Ifejika: It's an excellent question, and what I've recommended that we do in a standard office visit is utilize the time before the visit to send out screeners. So, for example, usually with an electronic medical record, you can send documents before the visit even starts, where people can check off whether they have any concerns regarding housing, food insecurity. They can check out their location of where they live, whether they live near a highway or not near a highway. It's specifically related to socioeconomic status. We can ask about insurance status, whether they have insurance, insured versus uninsured, but then also types of insurance, whether they have Medicaid insurance versus Medicare insurance. Then even drilling even further, type of Medicare insurance, Medicare Advantage versus traditional Medicare, cause all of those things actually play a role in this. Dr Ifejika: And evaluate these things and don't take time during your office visit. Send these screeners out beforehand. Have them be assimilated by your medical staff. Make sure you're utilizing every resource that you have at your disposal to help streamline things, so by the time the person comes in for the visit, you've primed the pump. You have this information already in your hands at your fingertips cause it was sent out in advance, and you have your medical staff already have an understanding of. If they didn't fill it out electronically, give it to them in the lobby. Make sure they have a handwritten copy in the lobby so that when they come into the office visit, you have the information at your fingertips. Dr Monteith: Are there any particular resources that you recommend for those types of screeners? Dr Ifejika: What I've used in the past, if you have patient-reported outcomes, so the PROMIS instruments, that's a good start. It doesn't get into the details of housing insecurity, food insecurity, but it's a good start to help prime questions and to start the conversation during your office visit. In my clinics, I do a PROMIS 27 on every patient, as well as a PHQ-9 for depression on everyone. And then I collect data longitudinally, and I can always drill down on factors that I noticed that could become a problem moving forward. Dr Monteith: Yeah. And then also in your article, you spoke a bit about this impact from the acute presentation in the hospital to rehab. Dr Ifejika: Yeah. Dr Monteith: So why don't you talk about these different entry points where we can really engage our patients and try and help reduce their burden? Dr Ifejika: Sure. So, healthcare can be quite fragmented, and the stroke patient, stroke survivor, and their family member have no grasp of that. They've had a stroke, and they may be going from the ER to the ICU to the stroke unit to the floor to the rehab unit, and we see it as multiple levels of care, multiple types of providers. They see it as one hospital. And the concern that we have is, at those branch points, things get dropped, and we have the opportunity to pick things up at those branch points. So, during the acute care hospitalization-Primarily, that's the establishment of what has happened, how we're gonna treat it, what are the variables that we can control for right now to address those determinants of health moving forward, and to specifically looking at whether they were taking medications before, whether they could afford medications before, what that looks like at hospital discharge. Is there any duplication of medications? If a person is taking Coreg and you prescribe metoprolol, but they still have the Coreg at home, should we have really prescribed the metoprolol? We're just spending money that they may have concerns when it comes to access to care and the cost of these prescriptions. So, it's the responsibility of the acute care physician to kind of look at that. Those are subtle things that we think are subtle, but they add up quickly for the family when it comes to having one group of medications that's the same class and having to buy another type. When it comes to post-acute rehabilitation, it's really an important time to screen for whether the caregiver can handle what's occurring. So specifically, if the caregiver is already burning out and the average length of stay for a stroke patient is five days and they've come to rehab for two weeks, what's gonna happen in the next two years or the next four years? So, during the post-acute rehabilitation phase, it's time to kind of look at that and drill down on those kind of questions. Also, the levels of care, Dr Ifejika: it's really important to look at other levels of rehabilitation, so skilled nursing facilities, making sure people have access to that if they need to, if the caregiver is burned out and they don't have the ability to go straight home. Because acute inpatient rehab, the goal of it afterwards, is to go straight home. It's not to go to another facility. So, you need to have that screener in place when it comes to whether the family can take care of this person, and whether the family can do it in an effective way to prevent them being readmitted. Dr Monteith: Great. I also like that you spoke about kind of the team approach and different roles, both for screening and for intervention, both being very important, especially the intervention. And so why don't you give us a few examples how the team could break up the responsibility and how also for the intervention component that can be done. Dr Ifejika: Sure. So, I broke up the team into several levels. So, the team medically is the medical student, resident, and faculty physician. However, the team also includes the support staff, so your case manager, your social worker, the therapist, physical therapy, occupational therapy, speech therapy, the pastoral services, all these members of the team. You know, sometimes as physicians, we don't read those notes. There's a lot of information in the notes from social work, care coordination, and the therapist. They get down to subtleties cause they're asking questions, for example, "What kind of equipment do you have at home? How many stairs do you have at home? What level of house do you have, one story, two story? If you live in an apartment, do you have an elevator access?" That's important for someone with hemiparesis. When it comes to medications, when it comes to insurance status, when it comes to your ability to have the mechanisms to pay for care as an outpatient, social workers are required to ask these questions cause they have to figure out resources for the patient and their family to help facilitate improved outcomes. So, they have to ask questions regarding these tasks. The concerns are, do we read what they're saying? So, it's really important to interact with them, and if it's not something that you're looking at in the chart, cause we're all so tied to our computers, find where they are in the hospital. Walk by their office and have a chat. Run your list with them, especially for people who you're concerned have vulnerabilities, and make sure that you're setting an example for your medical students with your faculty doing so. If you're looking at it from the medical student, resident, faculty perspective, medical students, listen. This is your opportunity to really contribute to the team as well as learn about social determinants of health and research in their fields. You are the boots on the ground for the medical team. You are the ones who should be priming the pump and asking these questions of the family members. We're sending you into the rooms to do a history and physical. Social determinants of health should be a part of your history and physical, and you should be taking what we're saying in this article and asking these questions and tying it into your resident. Now, the resident is the work person of the hospital. We all know this. Things run through the resident. Things run through the fellow. It's really important that they have this information in a manner that is negotiable. The list keeps getting longer, and a resident doesn't need to be overburdened. It needs to be synthesized in a manner that can help facilitate the resident being able to act as well as communicate any concerns to the faculty. And at the faculty level, we are the voices that can affect change. So, if there's any concerns when it comes to advocacy, research, making sure that people are accessing care in a way that makes sense, particularly when it comes to the ability for us to galvanize change on a national level, that's kind of our job. Dr Monteith: Great, and so let's talk about intervention. What are things that, let's say, the neurologist can do to deal with some of these social factors? Dr Ifejika: From the neurology perspective, I think it's really important to identify missed opportunities and making sure that we address them. For example, the conversations around the ability to have access to care related to insurance versus no insurance. There are many, many ways that neurologists are able to advocate for a person being able to get to Medicare insurance, particularly in the outpatient setting. When we see patients in clinic, it takes two years, them, to qualify for Medicare, two years at a... /episode/index/show/continuumjournal/id/41497400

June 2026 Cerebrovascular Disease Issue With Dr. Cheryl Bushnell 06/03/2026

June 2026 Cerebrovascular Disease Issue With Dr. Cheryl Bushnell In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Cheryl Bushnell, MD, MHS, who served as the guest editor of the June 2026 Cerebrovascular Disease issue. They provide a preview of the issue, which publishes on June 3, 2026. 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. Bushnell is a Professor of Neurology and Director of the Center for Transformative Stroke Care at Wake Forest University School of Medicine in Winston-Salem, North Carolina. Additional Resources Read the issue: Subscribe to Continuum®: Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Jones: One of the core tenets of our field is that we learn neurology one stroke at a time. But what do we have to learn about preventing them altogether? The science of stroke prevention, acute treatment, and recovery are evolving rapidly, and it's hard to keep up. Today, we're speaking with Dr. Cheryl Bushnell, guest editor of our latest Continuum issue on Cerebrovascular Disease, to discuss these topics and much more. Dr Jones: This is Dr. Lyell Jones, editor-in-chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about subscribing to the journal, listening to verbatim recordings of the articles, and exclusive access to interviews not featured on the podcast. Dr Jones: This is Dr. Lyell Jones, editor-in-chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr. Cheryl Bushnell, who is Continuum's guest editor for our latest issue on Cerebrovascular Disease. Dr. Bushnell is a professor of neurology and the director of the Center for Transformative Stroke Care at the Wake Forest University School of Medicine in Winston-Salem, North Carolina, where she specializes in the care of stroke patients and their social and functional determinants of recovery and health, and is an internationally recognized expert on those topics. Dr. Bushnell, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners? Dr Bushnell: Absolutely. Thank you for the invitation. It's really an honor to be here. So, as you mentioned, I am the director of the Center for Transformative Stroke Care at Wake Forest. It's a really fun transition for me to be involved with different care models for stroke, and I think a lot of the Continuum topics are directly relevant to some of the things that I'm doing now as an administrator and sort of a facilitator of new research. So, thanks again for having me. Dr Jones: Yeah, and, and you have a wonderful perspective, and we're gonna pull that out today in our interview questions, and I'm looking forward to sharing that with our listeners. But before we get to the questions, we're gonna start off today's podcast with another Continuum Audio trivia question for our listeners. Anticoagulation has played a critical role in secondary ischemic stroke prevention for a long time now. While direct oral anticoagulants have taken on a greater role in the treatment of prevention of stroke, there are still some use cases for vitamin K antagonists like warfarin. The trivia question for our listeners is this: How was warfarin discovered, and how did it get its name? Stick around and we'll share the answer to that question toward the end of our interview today. So, Dr. Bushnell, let's get right to it. You alluded to your various roles, and your leadership in the field has been exemplary. The interventions for acute ischemic stroke have really exploded over the last decade or so, and they get a lot of attention and discussion, but prevention and recovery are just as important in the care of these patients. Tell us a little more about how you approached this issue, about the article topics you chose, etc. Dr Bushnell: Well, once I was chosen to lead the guest editorship, I wanted to come up with a group of topics that were maybe a little bit different from previous issues. So, I kind of looked at the previous issues and saw, as you said, an emphasis on acute stroke, and that's really important because it has been evolving. But my thought was, how about what happens to patients after they get the intervention and they're discharged home? And because a lot of trainees may not get to see these patients ever again, or it's months before they might see them, or if they're readmitted, which is what we don't want to see, but that certainly is a lot of the exposure is in the inpatient setting. So, I thought I would kind of transport the education into the outpatient and transitional setting, as well as prevention, not only secondary, but primary prevention, with an emphasis on brain health. Some of the populations that may not get as much attention. So, sex differences, stroke in women, pregnancy, the transitions of care, and also the emphasis on holistic view of patients and their challenges, which includes the non-medical factors that drive health, otherwise known as social determinants of health. Dr Jones: I appreciate that perspective, and obviously th-this is an area of your deep expertise, and it's great to have an issue that really digs into some of those topics a little more deeply. As an educator, I'm really glad you mentioned that about the trainee's perspective. You know, especially junior neurology trainees that are in the hospital all the time. They're seeing patients in the middle of a cerebrovascular catastrophe. But there's a long tail of recovery, right? And they'll get to see that in continuity clinic, but it's a good message to share from an evidence and, um, experiential perspective in the issue. So, appreciate that perspective. You've just read all these articles and edited them. Was there anything that you ran across that was a surprise to you? Dr Bushnell: Well, I personally chose a lot of the authors based on my knowledge of their work. So, I wouldn't say that it was completely surprising, but I do think that I was just genuinely impressed with the quality of the writing and the synthesis of information. I just was incredibly proud of the work that these co-authors have put together. I'd say that that was-- it wasn't surprising so much as just a sense of pride that I had with the product that's coming out. But of course, there have been some new trials that had to be incorporated at the last minute, some of which were presented at the International Stroke Conference just a few weeks ago. Dr Jones: Yeah. We try to be as up-to-date as we can, and I will completely agree with you. We have some really good writers in our field, and it's really just a pleasure when you read an article that's by an expert, and it's a joy to read. I can tell you it's one of the best parts of this job, and you get to learn a lot. I think one of the more challenging scenarios that I hear about from colleagues in recent years has been optimal management of patients with asymptomatic extracranial atherosclerosis. The pivotal trials that inform how we manage those patients were from a long time ago, decades ago, predating a lot of the more intensive medical management tools that we have today. In that scenario, Dr. Bushnell, what's the latest on that, and what should our listeners know? Dr Bushnell: Well, obviously, the CREST 2 trial has been long awaited. It's been going on for over ten years, I believe. Of course, it's, uh, two different trials all in one, the carotid stenting and angioplasty versus intensive medical management. And of course, each of the carotid vascularization arms of the trial also had intensive medical management. And then the other trial is the carotid endarterectomy as the form of revascularization. And it interestingly did not show any benefit of carotid endarterectomy compared to intensive medical management. But of course, the somewhat surprising result was that carotid angioplasty and stenting truly was superior, although it was a small number of events in the trial overall. But that stenting plus intensive medical management was somewhat better than intensive medical management alone. And I think stenting has come a long way in terms of safety, and so I think that's been part of the evolution of the field. I do wanna say that I'm a huge fan of the intensive medical management, and I think that what the protocol does in terms of blood pressure management, cholesterol management is very much above and beyond what's done in private practice even. And the health coaching for all the other things related to diabetes and weight loss and smoking cessation and physical activity, that is what we need to be doing to actually decrease the risk of stroke, and I think that it's very effective. I can't say enough about the design of the study for that reason, that everyone gets the intensive medical management, and then you just layer on the type of revascularization on top of it. So, I wouldn't have been surprised if this was a completely negative trial overall. They just happened to have some better outcomes in the stenting arm. Dr Jones: I recall a few years ago when the series of endovascular therapy trials for acute stroke came out, and I think there was a, a period of time where the field had to adapt to that. I wonder what you think about with the CREST 2 findings on stenting. I mean, is that gonna be a big change? Because obviously atherosclerosis is highly prevalent. Is that gonna be a big change? Is the field ready for that? How much adjustment do we have in store? Dr Bushnell: I'm not sure it's gonna be a really big change. If you read the editorial that accompanied the trial in the New England Journal, just a few patients in either direction would have changed the outcome. I kind of look at it as an absolute difference that's relatively small. So, I'm not sure that it will have a huge impact on the field. I do think that the specialists who insert the stents may have some differences of opinion of who should be stented and who shouldn't. Because I think, you know, all of the specialists who do procedures were involved with the trial. But I would say there's a larger percentage of vascular surgeons who were involved, and so I'd say they may have a change of their practice. And neurologists may not even get involved at all. Dr Jones: Right. Dr Bushnell: That was one of the challenges for getting patients in the trial is that, you know, not all of us see the asymptomatic carotid stenosis, that they tend to get referred to vascular surgery. So, I think maybe in a corner of the practices of vascular surgeons is where you might see the differences. Dr Jones: Your point about the way the trial was designed or the trials were designed, that intensive medical management is really important, and we have huge gaps in that. In our specialty, it's, you know, we have probably an opportunity in primary care even to address that. And that leads me to my next question. You know, given your perspective and your expertise, what do you think is the biggest practice gap in the care of patients with stroke or with cerebrovascular disease of any kind? Dr Bushnell: I think by far the biggest gap is transitions of care and access to follow-up in a specialty clinic after discharge and continuous secondary prevention. We only call it secondary prevention because it happened to come after a stroke, but I really feel like we should just focus on prevention and call it that. There are a lot of people who are trying to kind of, get us away from primary versus secondary prevention. And, and Mitch Elkind is phenomenal and had a beautiful chapter weaving in prevention and brain health. So, I highly recommend that people, if they don't read any other chapters of the Continuum to read his, because I think that it's getting to your point about where the gaps are, and I think prevention is the biggest one. I think we could do so much more in models of care to ensure that there is a pathway once patients are discharged. We have no quality metrics. We have no measurement of how well people are doing after they're discharged. We have all of these fancy things and sophisticated acute treatments, but all of those are for naught if somebody goes home and they fall and they have a severe head injury or hip fracture because they weren't properly supervised or they didn't have the help that they needed at home. So, you got me on my soapbox here for a second, but that is definitely what I see as the gap. Dr Jones: That's an important soapbox, an important gap, and obviously, if it was a simple problem, we could solve it. But it's obviously something that education is a valuable tool for that, and that's part of why we are including so much content in this issue of Continuum. So, if we put that aside as a gap that we would love to close, when you look into the near future or distant future, Dr. Bushnell, and what's the next big thing on the horizon? New interventions, new prevention tools, or something else entirely? What do you think? Dr Bushnell: There are two things that I would mention. One is sort of the new category of anticoagulants, antithrombotics, the factor XIa inhibitors. We had an amazing presentation of the oceanic stroke trial at the International Stroke Conference, and this is probably going to be a game changer for the arsenal of antithrombotic therapies that we can offer to patients that do not have a reason for anticoagulation. So, they, they don't have atrial fibrillation, for example, or something else that requires anticoagulation. And so, the factor XI, asundexian, is the drug that they used in that trial. The safety profile is pretty amazing. There was very little bleeding complications and a great benefit in those patients with some degree of atherosclerosis, but, you know, of course, not enough to require carotid revascularization, but then also, um, small vessel disease and cryptogenic stroke. I think those are the three categories of patients, and that's a lot of the strokes that we see all benefited from this new drug. So, I think that's gonna be exciting. There, of course, it has to go through the FDA approval process, and so it might take a little bit of time before that's on the market, and we don't know how much it's gonna cost, but I think it is a, a major breakthrough. And of course, there are other similar medications in that category that are coming. And then I think the other thing is the emphasis on brain health and lifestyle factors and the things that we can do to prevent stroke and dementia because they are the same, essentially. Those are really important. And when we have someone in the hospital with a stroke or a TIA in particular, it's a great teaching opportunity for those patients to say, "Hey, here's what you can do to protect your brain." These are things that we always tell people to prevent a stroke, but just think about it as protecting your brain and keeping your brain as healthy as possible. Dr Jones: That's a great message, and one that you get to share with patients directly. You're joining us today for this interview. You're on stroke service, so you're actively involved in caring for patients with stroke. What in your practice is the most rewarding aspect of caring for these patients? What is it that you find most rewarding? Dr Bushnell: I've been involved in a clinical trial that has focused on managing blood pressure and also coaching and other aspects of stroke recovery. I think that has probably been the most rewarding aspect of my career. Until I was involved with this trial, I didn't necessarily do intensive blood pressure monitoring, but I'm seeing the benefits of having data from home, what those blood pressures are over a span of time. I see the immediate or intermediate effects of the blood pressure medication changes that I've made, and I see how the patients respond. So, I have to say that this is not part of usual practice, but I think it should be. And I think it's been incredible from the perspective of a neurologist who is really intensively trying to make the patients' lives better. And it's not just what I do, it's what the health coaches do as part of this intervention. And again, very similar to intensive medical management. So, I, I feel like I've been living it in a slightly different setting than in the CREST 2 trials. But there are other trials that have used the intensive medical management as approach as well. But I would say that's the most rewarding. I've seen people who've lost weight, who are physically fit, who are able to get off of blood pressure medications practically by the end of six months, and that's amazing. And then they continue doing it because they see the benefits. Dr Jones: You've had a front row seat to a lot of that. That's really got to feel rewarding. Dr Bushnell: It is, absolutely. Dr Jones: You know, when you put it that way, it makes me want to go home and check my blood pressure, which I haven't done in a while. But I think that's a message to all of our listeners that we do have plenty of opportunity for risk factor optimization and following the evidence that has been generated and is being generated. Huge opportunity, not only at the population level, but I think the, um, individual patient level too. Okay, so now we're back to our Continuum Audio trivia question, and I'll repeat it for our listeners. How was warfarin discovered, and how did it get its name? Dr. Bushnell and I were talking about this earlier, so I'll just go ahead and share the answer. So, in the early 20th century in the U.S. Midwest, there were epidemics of a hemorrhagic disease in cattle, of all places, and this was eventually traced to moldy cattle feed that was made from sweet clover. And in 1940, researchers at the University of Wisconsin discovered that the anticoagulant in the sweet clover was a compound that was later synthesized for therapeutic use in 1954 as warfarin. And the name came from, uh, the support for the research. The research support came from the Wisconsin Alumni Research Foundation, or WARF, and the end of the word came from the underlying compound, which was coumarin. So that was a little bit of trivia that I had never heard. It's not in the issue, everyone, so you're getting something extra here on the podcast. But been using the drug forever. It still has its uses, even though it's become less advantageous than some of the newer agents. But-- And of course, Dr. Bushnell already knew that when I brought it up, but I just thought that was an interesting bit of history. Well, Dr. Bushnell, thank you for joining us. Thank you for such a great conversation about the latest in cerebrovascular disease. I learned a lot today. I learned a lot in reading these wonderful articles. I hope our listeners learned a lot today as well. I'm really grateful for your hard work on the issue, which I think will come in handy for junior readers and subscribers, as well as our more experienced neurologists as well. Sometimes it's hard to keep up with a rapidly changing subspecialty of our field. So, thank you for joining us today. Dr Bushnell: Thank you for having me. It's been my pleasure. Dr Jones: Again, today we've been speaking with Dr. Cheryl Bushnell, guest editor of Continuum's most recent issue on cerebrovascular disease. Please check it out, and thank you to our listeners for joining today. Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for... /episode/index/show/continuumjournal/id/41494130

Family Planning in Neuroinflammatory Disease With Drs. Ruth Dobson and Kerstin Hellwig 05/27/2026

Palliative Care in Multiple Sclerosis With Drs. Penelope Smyth and Janis M. Miyasaki 05/20/2026

Palliative Care in Multiple Sclerosis With Drs. Penelope Smyth and Janis M. Miyasaki Palliative care in multiple sclerosis spans the disease course, from early screening and support after diagnosis to symptom management and quality‑of‑life optimization in midstage disease, and end‑of‑life care in advanced MS. This episode outlines a staged approach to palliative care, highlights the roles of neurology and primary care teams, and discusses tools such as patient‑reported outcomes and symptom scales to support ongoing assessment of patients and care partners. In this episode, Katie Grouse, MD, FAAN, speaks with Penelope Smyth, MD, FRCPC and Janis M. Miyasaki, MD, MEd, FRCPC, coauthors of the article “Palliative Care in Multiple Sclerosis” in the Continuum® April 2026 Multiple Sclerosis and Related Disorders 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. Smyth is the director of the Division of Neurology in the Department of Medicine at the University of Alberta in Edmonton, Alberta, Canada. Dr. Miyasaki is a professor in the Division of Neurology in the Department of Medicine at the University of Alberta and the zone clinical department head for Clinical Neurosciences at Alberta Health Services in Edmonton, Alberta, Canada. Additional Resources Read the article: Palliative Care in Multiple Sclerosis Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Dr Grouse: With the new treatments for MS, people might be saying palliative care is not relevant at all. It's about giving up hope and hopelessness. But this article covers why palliative care is important for your patients and families throughout their illness trajectory. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Grouse: This is Dr. Katie Grouse. Today, I'm interviewing Drs Penelope Smyth and Janis Miyasaki about their article on palliative care in multiple sclerosis, which appears in the April 2026 Continuum issue on multiple sclerosis. Welcome to the podcast, and please introduce yourselves to our audience. Dr Smyth: Thank you, Katie. I'm Penny Smyth. I am a neurologist at the University of Alberta, a professor in neurology, and a clinical multiple sclerosis specialist. Dr Miyasaki: Hi, Katie. Thanks for having us. I'm Janis Miyasaki. I am a movement disorder neurologist primarily who also provides neuropalliative care at the University of Alberta in Edmonton, Canada. Dr Grouse: It's so great having you today to talk with us about your article. I thought this article was really a wonderful take on the topic. I learned a lot, and I'm really hoping all of our listeners will take advantage of this article and take advantage of all the learning they can get from reading about this topic. So, I wanted to start with a more general question, which is, what is the key message from this article that you're hoping your readers will take away? Dr Smyth: In terms of key takeaways, I think it's our hope that neurologists will come away from reading this article with, really, an expanded understanding of what palliative care is and how that might be applicable to them in their care for their patients with MS along a continuum of treating people with MS, that there can be components of palliative care and strategies that can be integrated early after diagnosis in, really, anywhere along the continuum of caring for people with MS. We've called that kind of mid-stage. And then there are particular needs for people with MS and their care partners in late-stage or severe MS and end of life that might require different palliative care strategies. I think we kind of have maybe a bit of a bias sometimes in thinking of palliative care as more directed towards those that are near end-of-life. But in fact, it's a much expanded concept. Dr Miyasaki: And I'll just add that we also discuss a palliative approach, that palliative care skills and philosophies can be used by generalists---in this case, neurologists who are providing care to people with MS---and that adopting certain skills and communication techniques can help us better address our patients' and their families' symptoms. And also to keep in mind that for most people with neurologic illness, the unit of care is not only the patient, but it's the patient and the family, however that family looks. Dr Grouse: Now, Penny, I'm curious, how are early-stage and mid-stage multiple sclerosis palliative care strategies different from, say, a typical evaluation and counseling that a neurologist would give, say, an MS specialist or even a general neurologist? Dr Smyth: Thank you, Katie. That's a great question, and something that actually I learned in writing this piece with Janice and from her as a neuropalliative care expert. I think in terms of early strategies around palliative care that can be helpful to the general neurologist in their office, palliative care is about holistic support for patients and their care providers spiritually, emotionally, physically. There are components of palliative care and symptom management and making sure that the patient is at the center of the care, as well as support for their care partners with their holistic approach of relief of suffering as well as offering hope. When I started this piece, I was thinking that many of us neurologists, I think, often informally utilize many of these components already when we're dealing with patients early on after diagnosis in terms of communication, counseling, and education; going through their fear of an uncertain future; spiritual well-being; and then connecting them with supports for adaptive coping strategies. And then as well in mid-stage, which is really around what we can do in symptom management and improving quality of life, with screening tools and patient-reported outcome measures. However, I have to say that there are many unmet needs for people with MS and their care partners that they identify that are clearly not being met by us neurologists in this day and age. So even though we may be incorporating some of these strategies, I don't think we're meeting the mark all the time and hitting the target, especially in our busy office practices, in various ways. Dr Grouse: Given that, at a high level, what are some important early-stage MS palliative care concepts that we should be keeping in mind when we are counseling patients in these stages of the disease? Dr Miyasaki: An important concept to keep in mind for neurologists dealing with early-stage MS patients is that for us, we feel successful that we have made a diagnosis. And yet for the patient, it is taking away that hope. Maybe it's not MS. Maybe I just have a numb hand and it's gonna go away. And for us to appreciate that while we make this diagnosis multiple times a week---or, for MS specialists multiple times a day---for this person, it is the first time, the first experience, and it shakes their entire foundation of who they are as a person, how they will perform all the tasks and roles that they have in society, in their professional lives, in their family structures, and in their close, intimate relationships. As physicians, we may be overwhelmed by acknowledging that. I feel that it's important for us to understand the needs that our patients have and to allow them to have their feelings. You know, feelings can feel messy and time-consuming, and yet when we fully see our patients, I feel that this is the best of medicine. And it certainly is, in terms of palliative care, the principle that we seek. We accept all of the patient, the joy and the sorrow, the anger and the frustration. We accept it all, and we try to determine what will serve this person who is suffering in front of us now. Dr Smyth: There's another piece to this, which came up as Janice and I were writing together. We were talking about offering a prognosis to a patient as to how they would do, and this was something that I thought deeply about, because I said, we always communicate how uncertain the prognosis is and how we can't predict the future. And then she said to me, well, what about offering a roadmap to a person with MS soon after diagnosis as to how you're gonna determine how they do over the next couple of years? Which are really important years in terms of determining how patients are doing on their disease-modifying therapies, whether they're having progression or not, and things. It's a pivotal time. So, if you can offer a roadmap to a person with MS and say, look, this is when we will be following you up. This is how we will be following you with MRI and biomarkers if you have that available, and this is how we will determine how responsive you are and then how we move forward from there. Dr Grouse: Really important concepts. And the roadmap certainly makes a lot of sense to me and something that, apart from just being useful to the patient for so many reasons to help set expectations, you know, is useful for us to better partner with the patient so they understand this is sort of how we do things and everyone's sort of expectations are met. So, I think those sound like really great goals and things to keep in mind. Now, we talked about early-stage MS palliative care concepts. How does that change as you get into the mid-stage of the disease? Dr Smyth: Yeah. So, this is reflecting the fact that the course of MS is so different and the experience of MS is so different person to person. And so, what do we do as neurologists when we follow these people long-term over years and decades of living with their MS as their needs evolve, as their symptoms evolve, and as their disability evolves? Well, really, this is about the time of getting into, what are the symptoms that they're struggling with, what are the causes of their suffering at various points? And then how do we identify that, maybe with use of patient-reported outcome measures, screening scales, things like that. And then how do we direct symptomatic management to the specific symptoms that are causing distress to the patient? As well as trying to improve their quality of life in various ways, treating their comorbidities, making sure to check on exercise, healthy living, and that kind of thing. Dr Grouse: Now getting into, I think, topics that we're more used to thinking about when we think about palliative care: a lot of us, I think, are really unsure of the right time to discuss advanced care directives in the course of multiple sclerosis, and I think that's not helped by the fact that many of us are just, in general, not terribly comfortable talking about those types of things in general. What is your advice to questions like this? Dr Smyth: And this is something that, again, Janice and I had to come together on, because there is no universal accepted time for when is the right time in multiple sclerosis to discuss advanced care directives and goals of care. And in fact, when they have looked at it in the literature, different things have come out. It has come out that neurologists can be uncomfortable discussing this. There's unique challenges to people with MS in that they have a diagnosis at a young age with an uncertain trajectory of how their course of disease is going to go. And many of these things lead care providers to be somewhat hesitant as to when is the right time, as well as, there were identified barriers within patients themselves as to when the right time might be to discuss. In that, you know, some of the coping strategies might be, as identified by some of the qualitative studies that have been done on this, around the fact that they would prefer to focus on the present rather than the future. In some studies expressed an ambivalence as to when they thought the right time might be, as well as some negative experiences that they might have had from providers trying to discuss these things in their previous experience. So, I went back to looking at the European guidelines for palliative care in MS, who suggested when a person might have severe MS---which they define as walking with bilateral aids for at least twenty meters or an EDSS of six or higher---or trigger-based, when there has been a change in the patient's status, when there's been a decline in some way or progression. Now, this is a little different, actually, than what we offer other people with neurologic diseases, and I don't know if that's the right answer. And this is where I'm going to turn it over to Janice, because I think we could learn something, as neurologists who treat people with MS, from our palliative care specialists. Dr Miyasaki: I think of advanced care planning in a very different way. I think what a lot of the patients were expressing in the studies was that being asked about advanced care planning signaled to them in some way that they have reached this point in their illness where things aren't going so great and I anticipate that you may run into complications. Whereas in our movement disorder clinic, one of our fellows did a study looking at capacity for decision-making. And even in people who scored normally on the Montreal Cognitive Assessment, they had impairments in some of the domains of decision-making. And so, our philosophy in movement disorders at least---and some of our patients are quite young who have multiple system atrophy, they could be in their forties---we take the philosophy that everyone over the age of decision-making capacity, which is generally eighteen, should have some goals of care established. And how I introduce it in my clinic is, you know, for the young resident, you want the full-meal deal, because the likelihood of the resident surviving the ICU admission is very high. And then when we look at me, who… I am older, the likelihood of surviving an ICU admission is considerably lower. And so, the appropriate goals of care might be that I am willing to go to the ICU, and if things go well, then they can continue. But if things are not going well, they can have a discussion with my personal directive or power of attorney to talk about what the goals of care should be. And then the other aspect is sometimes having the conversation with family is really important because most of our families in hospital express an uncertainty. Am I doing the right thing? And they want to do the right thing for their loved ones. And most people actually say, if you ask them, I don't want to burden my family with making decisions that are going to tear at their hearts. So, then we can't actually make good informed decisions for our loved ones unless we have clear conversations. I think it does speak to our superstitious beliefs that if we talk about death, it's going to happen. But I hope the listeners will take my word for it, it really doesn't. And someone had a really good saying about the advanced directive. They're kind of like evening clothes. You should take them out every once in a while and make sure they still fit. And so, when you normalize it in this way, it helps people to just say, oh, yeah, it's once a year. Dr. Miyasaki is gonna ask me about how do I feel about those goals of care. And then it doesn't have this portent of, oh, I'm not doing well. Instead, it's just, this is what we should all be doing for our sake and for our family's sake. Dr Smyth: Now, one thing that I have to add on to this is that it is important to try to establish advanced care directives before patients experience cognitive decline, because then that can make it a much more challenging conversation and brings nuances of challenge into the interactions, which, you know, are hard. Dr Grouse: And Penny, I'm glad you brought that up, because I was really struck by that point too when reading this article, how easy it is to miss the subtle signs that cognitive changes are happening. I think it's just- it's a good kind of segue into that topic in general, but it is such an important link to, you know, making sure that you get those advanced directives at a time when the patient's really able to express and understand what they're talking to you about. Now, on the topic of the cognitive screenings, what's a good way to do this type of screening, and why is this type of screening so particularly important in the case of multiple sclerosis? Dr Smyth: Yeah. Thank you, Katie. I think that it's important for our listeners to think about and recognize when we see our patients with MS because it is one of the invisible symptoms that people with MS can live with and may not be apparent on regular conversation in the office. So, it's important to deliberately ask about subjective challenges in cognition. Ask the partner about how they're doing in terms of their cognition in various ways. As well as asking them and exploring then, how are they doing in their professional roles if they're working or in their surroundings? How are they coping on a daily basis on a cognitive level in addition to a physical level? We know that cognitive issues are actually the biggest contributor for not working and are a huge driver of disability in MS in terms of functioning, even more than physical decline in many ways. So, it is important for us neurologists to keep top of mind and to think about and deliberately attend to. There are screening tests that we can do in the office. The easiest for us, which measures the verbal processing speed, is the SDMT test, which is a ninety-second test matching symbols and numbers. It's easy to do. You can train a MOA to do it before you see the patient and things like that, and it just gives you an idea as to where the patient is at. And usually they're having difficulties if they're greater than two standard deviations below the norm for their age, or if there's a significant drop of four or eight points, and that might signal to you that there might be more going on. You can explore it, and then if you do have this available, the ability to refer for neuropsychological testing if there's questions. But often we can't get it with the MoCA score, unfortunately. Dr Grouse: Talking about all these concepts, I think they all sound great. I think a lot of us hearing this will naturally say, "Yes, these are absolutely things we should be incorporating in the care of these patients." What I wondered about was, certainly we're all very busy, it is really hard to find time for a lot of these things. We don't always have access to specialists who can help us with some of these conversations. How can we find time, and how can we work this into the care of our patients effectively and still make time for all the other things we have to talk about, and make sure that we're seeing all of our other patients and staying on time and all of those things? Dr Miyasaki: Yes. I think that's the challenges of dealing with people who actually, over time, their care needs increase, is huge in neurology. I can't think of a single subspecialty where care actually gets easier. It's constantly getting harder. You know, having come from private practice, I completely understand my colleagues' challenges in the community. Some of the ways that other groups have managed this when they don't have government or university support in their center is actually to look at not-for-profits. There are a lot of not-for-profits that can help in terms of wayfinding for social services, explaining to the patients and the family... /episode/index/show/continuumjournal/id/40685405

Infection Risk and Vaccine Considerations in Multiple Sclerosis and Related Disorders With Dr. Avindra Nath 05/13/2026

Infection Risk and Vaccine Considerations in Multiple Sclerosis and Related Disorders With Dr. Avindra Nath Advances in immunotherapies for multiple sclerosis and related disorders have increased the risk of infections and raised important questions about vaccination efficacy. This episode reviews infection risks across treatment classes, emphasizes the importance of monitoring and patient education, and discusses optimal vaccine timing to preserve protective immune responses. In this episode, Aaron L. Berkowitz, MD, PhD, FAAN, speaks with Avindra Nath, MBBS, FAAN, coauthor of the article “Infection Risk and Vaccine Considerations in Multiple Sclerosis and Related Disorders” in the Continuum® April 2026 Multiple Sclerosis and Related Disorders issue. Dr. Berkowitz is a Continuum® Audio interviewer and a professor of neurology in the Department of Neurology at the University of California, San Francisco, in San Francisco, California. Dr. Nath is the chief of the Section of Infections of the Nervous System at the National Institute of Neurological Disorders and Stroke, National Institutes of Health, in Bethesda, Maryland Additional Resources Read the article: Infection Risk and Vaccine Considerations in Multiple Sclerosis and Related Disorders Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Berkowitz: Over the last decades, there has been a revolution in the treatment of multiple sclerosis, neuromyelitis optica spectrum disorder, and other immune-mediated neurologic conditions with countless new, highly effective medications. However, with every new treatment comes new risks; and in the case of immunomodulatory therapy, many of those risks relate to infection. Today, I have the privilege of talking with an expert on this topic, Dr Avindra Nath, about the infectious risks of treatments for multiple sclerosis and other immune-mediated neurologic disorders. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Avi Nath about his article on vaccine considerations and infection risk in multiple sclerosis and related disorders, which he coauthored with Dr Amit Bar-Or. This article appears in the April 2026 Continuum issue on multiple sclerosis. Welcome to the podcast, Dr Nath, and could you please introduce yourself to our audience? Dr Nath: Thanks very much for inviting me to this podcast. I'm absolutely delighted to have the opportunity to discuss our areas of interest and expertise related to infections and vaccinations for MS patients. My area has been studying the infections of the nervous system since the beginning of the AIDS pandemic, and over the years and decades, we've developed expertise related to various types of CNS infections. That includes ones that are developing in individuals who have immune compromise due to a variety of different reasons. Dr Berkowitz: Fantastic. Well, glad to have the opportunity to speak with you today. When I was in medical school---and you were my attending, actually, we were just reminiscing, which we probably think was not that long ago, but is now over twenty years ago---there were just two medications for MS, right? Beta interferon and glatiramer acetate. And now we have over a dozen, and it's amazing to think of all the progress in these last two decades, as well as for related diseases like NMO. I don't think we even had the aquaporin-four biomarker, right, when I was working with you as a med student in the early 2000s. Dr Nath: And that certainly dates me a lot. Dr Berkowitz: Both of us. Dr Nath: Yeah. Dr Berkowitz: Of course, with all these new treatments, these have been amazing advances for our patients, right? But these come with new treatment-related risks to monitor for with the immunomodulatory medications for MS and related disorders. And one of those most important risks is that of infection. So, your article reviews the potential infectious complications of medications used to treat MS, NMO, etc, and also covers considerations related to thinking about vaccines in this patient population. So, as the MS treatment landscape grows, I can say as a general neurologist, keeping up with all these medications and what to screen for and what to worry about and when to vaccinate just becomes more challenging every year. And your article has so many helpful tables, some organized by medicine, some organized by- sorry, medication, some organized by infection, some by vaccines. So, this is gonna be a great resource for our providers to print out and tape up in their clinic rooms. We won't be able to get into all the depth and detail that you have in this article today, but I do want to focus on some of the key points here related to the common medications we use for MS and which infections to think about and which vaccine considerations we might need to keep in mind for these medications. But before we delve into the drugs, I just wanna ask you more broadly, you talk in the article about the challenge of patients with immune-mediated diseases who are on immunomodulatory therapy being at risk for both flares of their disease and for infections; and these infections can present somewhat atypically, right, in immunomodulated hosts, to maybe coin a term you can correct me on, because they can't mount the full inflammatory response. So how do you approach new symptoms in patients on these immunomodulatory medicines as far as distinguishing disease flare from a treatment-related infection? Dr Nath: So, I have to say that although a lot of new treatments have come along for MS, and they've really, you know, improved the outcome tremendously and there are so many different options, it has also kept people like me relevant because they cause a lot of various types of infections, and so keeps me in business all the same. But just as you mentioned, there's so many of them, even I have difficulty keeping track of what does what. So, you do need to be able to refer back to published literature, and the tables, I hope, will be quite useful in that regard. You're absolutely right, and you can get new infections, you can get reactivation of existing infections, and you can get atypical presentations of various types of infections that you may not normally think of. So that presents multiple challenges to the treating physician. The other interesting thing about MS is, just as you mentioned, that you already have CNS lesions to begin with. Now, on top of it, you have an infection, so now how to sort out what is the existing disease and what is the infection, it can again become challenging. But one thing is for sure: all these infections are caused by an organism. So, what you really need to do is, the underlying diagnostic is to demonstrate the presence of the organism. Whether you demonstrate it depending on the infection in the spinal fluid or in the brain or, you know, some peripheral organ system, that is going to be key to making the diagnosis. So, all your clinical acumen is good, but that alone may not be sufficient. Dr Berkowitz: Very good. So, when you see a, a patient now who has a new neurologic symptom in the context of an immune-mediated disease who's on immunomodulatory therapy, what goes through your mind? Are you thinking this disease and this drug, and sort of what are the infections, and does the syndrome match? Or are you thinking, you know, you can't always rely on the imaging to distinguish between, say, a flare of an MS and PML because white matter lesions could look similar? How do you sort of approach this scenario when it comes up? Dr Nath: So, you're right. You have to keep an open mind so that even though you know some infections are more likely to occur with certain types of medications, that doesn't mean that others cannot occur. So, I think when you first see the patient, you should not jump to conclusions, but rather have an open mind. But yes, for example, your patient is on natalizumab, the chances of PML are going to be high. It's a very interesting drug. It does not cause immune compromise in the periphery, but what it's doing is preventing these cells from getting into the brain. So, because then it's acting at the blood-brain barrier. So that means that organisms that are already present in the brain have an opportunity to get reactivated. Turns out you don't have a lot of organisms in the brain, except JC virus seems to be one of them that does somehow, in some individuals, manage to reside out there. And so that can get reactivated. It can get reactivated in the periphery and then enter the brain, too. So, where the very specific mutations have to occur in that virus in order to take residence in the brain. That would be a suspicion that you might have, and MRI can be useful in, again, helping you think about that possibility. If you have typical lesions involving the U fibers, they're demyelinating, usually you do not have much edema around them because patient is immune compromised, but certainly within the brain in these individuals. And so, then you need to demonstrate the organism. The demonstration of the organism should be in the spinal fluid and not in the blood because in the virus, it can-- is reservoir in the kidneys and in the lymph nodes, and periodically it'll shed into the blood. Detection of the organism in the blood can be a false positive, but in the spinal fluid, it shouldn't be there unless you have an infection. Or if you cause a traumatic tap, I guess, if a patient is viremic, that's a possibility, but those are extremely rare. So at least for PML, that's the way that you would diagnose it. Now, you can develop, for example, if an individual is on fingolimod, you can get a wide variety of infections. Here it's a totally different type of mechanism of action. Here the cells are trapped within the lymph nodes, so that means now your entire periphery is immune compromised, right? So here you can get viral infections, bacterial infections, fungal infections. So here, if a patient presents with new neurological symptoms, you have to have a really open mind for all these possibilities. Now, let's say a patient was on dimethyl fumarate, and dimethyl fumarate causes neutropenia early on. So here you have to worry about an individual developing bacterial infections, so latent tuberculosis or bacterial meningitis can occur in these individuals. That's something to keep in mind. It's not that other infections cannot occur with dimethyl fumarate, you can see PML and other things too, but the chances of bacterial infections are greater. So, you got to make sure that you draw all the cultures for that purpose. Similarly, if you're on a complement inhibitor, like a C5 inhibitor or the thing that I could use in NMO, there are the chances of meningococcal meningitis. So, these patients, you need to prevaccinate them before you start these kinds of treatments and look for that possibility. When you suspect bacterial infections, particularly acute bacterial meningitis, there time is of essence. Also, in some of the acute viral infections, for example---herpes encephalitis is another one---you have to be so careful, and if you suspect any of them, even if they're with possibly atypical manifestations, you treat first and then diagnose later, and draw all your cultures, whatever you need to, and just treat them. And these infections can also cause cerebral edema, so one has to be careful about doing spinal taps in these individuals. You want some kind of neuroimaging before you do them. In the days when we didn't have neuroimaging, we used to say, "Okay, if your patient has focal neurological signs or is comatose, you don't do it." But these days, you can get imaging very quickly and very easily. All the-- Because of our stroke management, we've learned how to do them so quickly. So, I think there's little excuse not to do imaging and prevent herniation from occurring. Dr Berkowitz: That's very helpful. So, using the information we know about the drug, and we're going to rapid-fire review some of that in a bit to know what infections the patient is susceptible to, but acknowledging that any patient can get any infection, right? Whether they're on particular medications or not. And then if you're not sure, based on the neuroimaging, which as you said, is helpful, but not always helpful in distinguishing between infections and flares or, as you said, in the case of meningitis, encephalitis, early on at least, especially in immunocompromised or immunomodulated, quote unquote, patient might not see the typical imaging. So really, when safe, getting CSF or cultures, PCRs, and other infectious studies too is really gonna be the definitive diagnostic maneuver here. Is that fair summary across the board? Dr Nath: I think you said that absolutely right. And you summarized that correctly. And, you know, thing about infection, a lot of neurological diseases are, you know, diagnosed by clinical acumen, like your Parkinson's and Alzheimer's and others. Think about infections is caused by an organism, demonstrate the organism, right? That should be your goal. It doesn't mean that clinical acumen is not important, but here you have an opportunity to demonstrate the organism, so you should depend upon that. Dr Berkowitz: Okay. Well, you gave us a nice segue by talking about some of the infections to worry about with some of the medications. So what I'd like to do now for the sort of second half of our interview here is to go through some of the more common medications used for MS, and if we have time, for NMO, and just sort of go kind of rapid fire here, and for each medication, if you can tell us the kind of top infectious concerns and whether when to consider them or what screening needs to take place before or during administration of the medication, and then any vaccine considerations we should be aware of. Some of these will obviously be quite short depending on the medicine. So, going back to the two medications I alluded to earlier that were the only ones in play when you and I last saw each other on the wards when I was a medical student, beta interferon, glatiramer acetate, any infections or vaccine considerations with these medications? Dr Nath: No, I think they're probably your safest medications now as far as immunomodulatory therapies are concerned. These two, and IVIG, if you ever use them, are probably the safest, do not require any vaccine considerations, per se. Dr Berkowitz: Perfect. Okay. So, moving on to fingolimod and others in the sphingosine-one phosphate receptor modulator family, what are the infectious considerations? Any prescreening or vaccination considerations? Dr Nath: I think all your patients should be prescreened for antibodies to JC virus, because there is a risk for PML, and those who are positive should be closely monitored. So, it's not an absolute contraindication for using these medications, but they just require closer monitoring. With this class of drugs, PML is of consideration. Also, these varicella-zoster virus infection, yeah, with that you can develop zoster encephalitis or myelitis. It can present with motor symptoms as well, which can be atypical. You don't usually see them otherwise in immune-competent individuals. So, varicella-zoster, sometimes you can develop encephalitis, also vasculitis with varicella-zoster, so one has to be careful. So, getting the shingles vaccine can be actually very helpful to prevent these things. And then some patients can even develop herpes simplex encephalitis also, and that can be extremely atypical. So, they don't- they can involve the basal ganglia, can involve the brain stem and cerebellum. So again, your index of suspicion should be very high. Interestingly, although HSV encephalitis has been associated with NMDA receptor encephalitis, those reports of NMDA receptor encephalitis have not been published yet with NMS patients. Not sure why, maybe they just have been missed. But that doesn't seem to be a major concern. And then there are a whole host of other infections that can occur with this class of drugs, and that can include toxo; fungal infections, particularly crypto. There's a case report of histoplasmosis; hepatitis virus, particularly hepatitis C; and then the poxvirus is a good example. You can get molluscum contagiosum; warts with papillomavirus; you can get atypical mycobacteria; and even Kaposi sarcoma, which is HHV8. So, there's a huge variety of infections with the sphingosine one phosphate receptor modulators. Dr Berkowitz: And any- aside from screening for JC virus before initiating these, any- and then continuing to monitor for JC antibody index, any other considerations as far as labs to send, monitoring before or on the drug or vaccine considerations for patients on fingolimod and the others in this category, siponimod, etcetera? Dr Nath: Yeah, there are a lot of things to consider. All the details are really available in the chapter if you look at them. But briefly, all the things that one could potentially vaccinate patients for, all these infections I mentioned, one should do so. The timing is critical so that if you can do it before treatment, I think, before starting treatment, that is absolutely important. And you got to give them at least, you know, two to three weeks for these vaccines to take effect before starting your medication. If your patient already arrives on a medication, then you got to play this game of you know, before the next dose, give them again two to three weeks before the next dose and start vaccinating them and get all the vaccines in. Broadly, about the things to worry about the vaccines are you have live vaccines, and you've got the inactivated vaccines or the subunit vaccines. You have to be careful with live vaccines, because if your patient is immunocompromised, that virus can sometimes itself cause harm. For example, you know, yellow fever is one, and there you can develop encephalitis from it. Measles, mumps, rubella, these are all live vaccines. Now, the good thing is that a lot of us have been immunized very early in childhood, but that may not be the case any longer. And so, these things, one has to be very careful with when you're giving live vaccines, that we want to avoid them as much as possible, and individuals are gonna be immune-compromised. But all the others, meningococcus, for example, you should- the HPV vaccines, the varicella zoster vaccines, all these things, you've got to pre-vaccinate and make sure that they have an antibody response to them before starting immunocompromising therapy. Dr Berkowitz: Perfect. Okay, moving on to some of the other orals. What infectious and/or vaccine considerations do we have with teriflunomide? Dr Nath: Okay, yeah. Teriflunomide is a very interesting drug. It's relatively safe. There is concern about the possibility of varicella zoster infection, people have reported that, and also tuberculosis. But PML is extremely rare, if not at all, and we haven't seen herpes encephalitis quite yet. Dr Berkowitz: Got it. How about dimethyl fumarate? Dr Nath: Yeah. So dimethyl fumarate is... as I mentioned earlier, it's interesting because it causes this neutropenia. It's transient, but it occurs early on, and these patients can be at risk of PML, although small. They can develop varicella zoster virus infection, herpes encephalitis, and also fungal infections. For example, cryptococcal infection has been... /episode/index/show/continuumjournal/id/40685260

Treatment of Multiple Sclerosis With Drs. Ellen M. Mowry and Daniel Ontaneda 05/06/2026

Treatment of Multiple Sclerosis With Drs. Ellen M. Mowry and Daniel Ontaneda There are many treatment options for people with relapsing MS. Patients should be carefully monitored to assess treatment response, and a change in treatment approach should be considered if safety concerns emerge. In this episode, Teshamae Monteith, MD, FAAN, speaks with Ellen M. Mowry, MD, MCR, and Daniel Ontaneda, MD, PhD, coauthors of the article “Treatment of Multiple Sclerosis” in the Continuum® April 2026 Multiple Sclerosis and Related Disorders 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. Mowry is the director of the Multiple Sclerosis Experimental Therapeutics Program and a professor of neurology at The Johns Hopkins University School of Medicine in Baltimore, Maryland. Dr. Ontaneda is the director of research at the Mellen Center for Multiple Sclerosis and a professor of neurology at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in Cleveland, Ohio. Additional Resources Read the article: Treatment of Multiple Sclerosis Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr. Monteith: There are so many new treatment strategies for multiple sclerosis, which is a blessing, but it does come with the complexity of really just trying to nail down the approach. I just got finished talking to Drs Ellen Mowry and Daniel Ontaneda about their article on treatment of multiple sclerosis. We discussed relapses, weighing escalation versus early high-effective treatment and progressive disease. This is a must-listen-to podcast. I hope you enjoy it as much as I enjoyed talking to them. Dr. Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr. Monteith: This is Dr. Teshamae Monteith. Today, I'm interviewing Ds Ellen Mowry and Daniel Ontaneda about their article on treatment of multiple sclerosis, which they wrote with Dr. Darin Okuda. This article appears in the April 2026 Continuum issue on multiple sclerosis. Welcome, both of you. How are you? Dr. Mowry: Great. And thank you so much for having us. Dr. Monteith: Absolutely. So, why don't you both introduce yourself? Dr. Ontaneda: All right. My name is Daniel Ontaneda. I'm a neurologist at the Cleveland Clinic. I spend the majority of my time doing research, but I still dedicate about a day a week to seeing people with MS in clinic. Dr. Mowry: I'm Ellen Mowry. I'm also a neurologist, but practice at the Johns Hopkins University. And similar to Dan, I mostly work on research, but also have an active clinical care component, taking care of people with MS. Dr. Monteith: Well, thank both of you for writing this article and being on our podcast. I assume you guys have probably known each other for quite a while now. Dr. Mowry: Yes. Dr. Ontaneda: Yes. Dr. Monteith: What inspired you to get into multiple sclerosis research and then clinical care? Dr. Ontaneda: I always loved neurology, and I think a lot of us who go into neurology are attracted to the complexity of the human brain and how the nervous system works. But what really hit home to me was a family member of mine who had multiple sclerosis, and he was being treated in a time where we really didn't have super effective disease-modifying medications. And so, as I went through my medical career, I always kind of kept an eye on what was happening with multiple sclerosis, and I started my training at a time where it was really flourishing in terms of the medications available, so that's what inspired me to go into MS. It's a disease that we can definitely treat, and you can change outcomes for people. So, that was it. Dr. Monteith: Yeah, that personal experience can be very impactful. Dr. Mowry: My journey started, actually, because I was thinking about whether I wanted to be a physician at all, and I happened to land, just after high school, a position with a neurologist who happened to mostly focus on multiple sclerosis and taking care of folks with multiple sclerosis. And by the end of the summer, I knew I wanted to go to med school and I wanted to be a neurologist and I wanted to work with people with MS. I thought I would be a clinician exclusively, but I think as time went on and I started to hear the consistent questions that people I served were asking in the clinic and realizing that those questions could be turned into research projects that could address their concerns, I moved more and more towards research. Dr. Monteith: Great. There are a lot of really detailed information in the article, so I think that research mind is very useful, and I see that in the writing. Why don't we talk about the goal of the article? Dr. Ontaneda: So, I think the goal of the article was to set out kind of what the large view of what treatment for multiple sclerosis looks like. And, you know, many times we divide the treatment of multiple sclerosis into these large pillars, and I think that's what we did in the article. The first was, you know, what do you do with a person who has an MS attack or relapse? The second is, what medications do we use to treat the relapsing forms of multiple sclerosis where there is a lot of acute inflammation, focal inflammatory lesions that are occurring? And then the final one is, what do you do with individuals who have a more progressive form of the disease where they're accruing disability slowly and gradually? Dr. Monteith: And what were some of the main points? Dr. Mowry: Dr. Okuda provided a really nice section on the treatment of acute relapses in multiple sclerosis, and it's important to understand what we talk about when we are saying “relapse”. For people with MS, many symptoms can fluctuate and occur and then get better over time, and sometimes people with MS use the same term of “relapse” to describe those symptom fluctuations. As neurologists, when we're thinking about relapse, we're really trying to think about symptoms that can be attributed to new focal inflammatory events somewhere in the central nervous system. Typically, these are accompanied---if you were to get an MRI at the same time---by a new lesion or MS spot, as I like to call them, on MRI scan. And so, it's important to distinguish when somebody is talking about symptoms, whether they are true new symptoms that could be mapped to a place in the central nervous system. Because alternatively, a lot of people who've had attacks or relapses in the past can have what we call pseudo-relapses, and these are essentially recrudescence of old symptoms, typically in a similar pattern as what had occurred in the past. And these can be brought out by things like fever or infection, sometimes stress. And pseudo-relapses are not thought to be due to new development of immune system-induced injury and therefore would be less likely to respond to treatment; and in fact, treatment may be contraindicated for those events. We also talked a little bit in that article about how relapses are treated, talking about the use of high-dose steroids for true new relapses, but also kind of cautioning that those are not necessarily free of concerns, especially if you have a pseudo-relapse or there could be an infection going on. And that ultimately, the decision as to whether to treat a relapse really is a shared decision-making because it's thought that although the steroids can speed up recovery from a relapse, they may not have a major impact on ultimate recovery. And so, a lot of the shared decision-making comes in here because for a mild relapse, you might choose to forego a course of high-dose steroids. Dr. Monteith: Daniel, any other main points? Dr. Ontaneda: Yeah. On the side of treating relapses, I think one of the other things that probably has changed a lot, at least during the course of my training, is that in the past, whenever we had identified a relapse, as Dr. Mowry has clearly defined, we would typically treat with intravenous high-dose corticosteroids, typically with methylprednisolone. And that was kind of our go-to. We would either do it in an infusion center or we would set it up with home care. And I think one of the things that our field learned over, I would say, the last five or ten years is there's an abundance of studies that show that you can give that same dose of methylprednisolone. Rather than giving it IV, you can give it orally. No pun intended, as I tell my patients, a lot of pills to swallow because we use fifty-milligram prednisone pills, and they have to take 1,250 a day. The pharmacy always pushes back on that many pills, but really the advantage of being able to take steroids orally that way for three to five days is really, I think, one, better for people with MS because they can do it in the comfort of their own home, and two, I think also when you look at the costs associated with that treatment, it is the most cost-effective option. Dr. Monteith: And what are some of the latest developments that you're really excited about that weren't in the article? Dr. Mowry: A lot of the article focused on the approach to treatment of people with what we've traditionally called relapsing/remitting multiple sclerosis. So, this is the kind of MS that traditionally presents with a relapse or an attack initially, although some of that nomenclature is changing, actually. And the article focused a lot on the strategies surrounding treatment of somebody with newly diagnosed relapsing MS, and thinking about this vast number of disease-modifying therapies that are available to people with MS and their clinicians, and how to think about the strategy with respect to largely centered around the efficacy class of the medication, whether people should take an approach of using a higher-efficacy therapy---meaning a medicine that in clinical trials was more likely on average to suppress relapses as well as new lesions---or whether there's still a good argument for the case of using an escalation approach, using some of the more modest efficacy medications that also probably in general have lower risks, monitoring for response to treatment and changing if the medication isn't working. And so, there's still a lot of debate in the field, I would say, even though many people have moved towards a one-size-fits-all kind of approach. I think there's still a lot of debate in the field about the evidence underlying that. And, you know, full disclosure, Dr. Ontaneda and I are each running parallel and very complementary clinical trial programs to address this very question, the results of which should be available within the next year, year and a half. Dr. Monteith: Well, we can't wait that long. Give me some clinical pearls to how we initiate these modifying therapies. Like, what are the pearls that we need to have in our mind? Dr. Ontaneda: Yeah. I think when we think about starting the disease-modifying therapy in an individual who has an active form of multiple sclerosis, I think, you know, one of the cornerstones I would say of making that decision is shared decision-making. I think we tend to sit down with the patient and analyze the data that we have at hand, what we know about their multiple sclerosis, and we use several factors to inform how likely we think their disease is gonna be active or potentially might not respond to the initial treatment you give. And we look heavily at the MRI. The MRI is really a useful marker because it shows us, one, how many lesions a person might have---both, you know, where those lesions are and also kind of the amount of lesions. Lesions, certainly, that are in the spinal cord, a very large burden of diseases. A lot of active lesions, which we determine by the presence of contrast-enhancing lesions, really helps us inform on disease severity. I would say that was our number one tool that we use to decide and help us decide how we think that person's MS is gonna do over time. And then the second thing that we put into the equation also is, you know, how well do we think this person is going to tolerate our medications? All our disease-modifying medications act through suppression of the immune system, and we know that that carries some risks associated with it. Some of those risks are stuff like infections. Some of those can be simple infections that really don't have major consequences, but some of them can be quite serious, including the need for hospitalizations or prolonged antibiotic treatment courses. And so, we also look at what, you know, the underlying risk of a person has for infection. This kind of is determined by, one, A, how many infections they've had up to date, and also how much disability they had. I would say in our average patient who when we see them, they're probably typically pretty young, in their twenties, thirties, forties, they typically don't have a lot of infectious risks. And therefore, I think there's kind of a move to saying, "Well, actually their risk of infections is quite low." And we put that together with, you know, also what the preference of the patient might want. So, do they prefer to take a pill, for example? Do they prefer a medication where they receive that via infusion every six months and they don't really have to think about it? There are some people that don't like going into a hospital, and they might prefer an injection type of those medications. And so, after a complex discussion of all those factors, we take into consideration how much risk the patient wants to take as well, and we come up with a rational choice of a couple of medication options. So, I think it's challenging sometimes because we have over two dozen medications. There's the risk of you saying, "There are these twenty-four medications, you can pick one." And I think our job as neurologists is to kind of pare those down, talk about, in a person like yourself, these are the two or three medications that I would recommend using. Why don't you review them? And then we bring them back, and we kind of make a final decision with, one of the key factors that I think is important to remind people is that you're gonna start this medication, and we are gonna monitor to make sure it's working. We're gonna monitor to make sure you're tolerating it well. And although it's an important, the first decision you make, I think one key theme that we tell people is, we can revise our strategy whenever we like. We just have to think about it and do it in a way that we think is gonna make sure that their MS is under the best control. And then we think about the ultimate goal of treatment, which, in multiple sclerosis, is the absence of any attacks and also the absence of any new lesions on MRI. And that's where whether you are offering more of the high-effective medications or more moderate- or low-efficacy medications, that's where there's a little bit of controversy still in our field, and that's what our trials are trying to answer. Dr. Monteith: Excellent. So now we've selected a particular option- and I love those points with shared decision-making, using the MRI to guide and then kind of risk tolerance related to infection. But now a patient's still having relapses, and I know the goal is zero, but, you know, there's some margin. What are the pearls to advance to more high-efficacy therapies? Dr. Mowry: Yeah, that's a great question. Dr. Ontaneda in the article actually talked about the literature surrounding monitoring for breakthrough disease and when to say this much is too much, and there's actually not a definite right answer. It's clear that more active disease early in the course is probably more of concern than, say, developing, you know, a new spot in your fifties or something to that effect. So, different people have different thresholds. I know at our center, we tend to be pretty on top of making changes for breakthrough disease. So, what we typically do is reimage people about six months after they start a medication to establish a new baseline. And sometimes, because of delays in starting or because the medications take a while to kick in, there might be a new spot or two. So, if that's the case, I really only get concerned if the spots are also taking up the dye or enhancing to indicate they're really quite recent, and I think, "Ugh, that's not something I'd like to see six months after starting a medication." And so that otherwise is sort of the reference scan, moving forward, to evaluate the medication, and I have a very low threshold for changing, particularly if somebody is on a moderate-efficacy therapy. To me, I think, well, our goal of trying the moderate efficacy therapy is essentially to see if we could get away with a medicine that is probably, on average, safer and that will still work for your MS. But if the answer is no, I personally don't like to stick around too much on them. One caveat I would say is that if somebody develops what appears to be a new lesion or spot on higher-efficacy therapy, before presuming that that new area of activity is a definite new MS event, I always like to rethink carefully, did I get the diagnosis correct? Or could this be an early infection such as, you know, progressive multifocal leukoencephalopathy in people on natalizumab in particular? Because I see breakthrough activity so rarely in people on higher-efficacy therapies that I just like to rethink my diagnosis and the differential prior to making switches to, typically, another higher-efficacy therapy in that case. But that, again, is a little bit of shared decision-making. It's sometimes contextual. If a person is using a self-administered medication and they have a little breakthrough, sometimes you can solicit some history, saying, "Oh, I actually kind of stopped taking it for a few weeks because something was going on, and I really want to retry." And that's very reasonable as well. Dan, do you have any other thoughts? Dr. Ontaneda: No, I think I agree. That's really close to how I practice myself as well, and the majority of people at my center. I think that we are learning that when you start a treatment, many times---depending on how deeply you look---you can find evidence of ongoing disease, and that's something that we struggle with. It's almost like we have tools to treat inflammation in terms of new MS lesions and new relapses. And so, when those are present, it's pretty clear that you probably have to switch medication. I think a slightly trickier issue is when, for example, you have a person who might be stable. They don't have an attack. But you notice that they're worsening, and they tell you they're worsening. I think our ability and tools for that is a little bit harder, and we recognize that that can actually happen fairly early in the disease. And that's why we're trying to rethink this mantra that we've had for many years, where we kind of divide MS up into relapsing and progressive, and we see people develop progressive MS 10 to 15 years after they've had a relapsing form of the disease. So, I think that's just a reality of clinical practice. And we don't have as many tools to treat that gradual worsening, which is kind of what the rest of our article spent some time talking about. Dr. Monteith: You've also written about the clinical trial long-term extension studies. And what are the few points that you take away from the emergence of these types of... /episode/index/show/continuumjournal/id/40685055

Neuromyelitis Optica Spectrum Disorder With Dr. Sara Mariotto 04/29/2026

Neuromyelitis Optica Spectrum Disorder With Dr. Sara Mariotto Although rare, recognizing NMOSD is crucial for improving patient outcomes through correct diagnostic and treatment approaches. Reports of atypical forms and increasing knowledge of clinical, imaging, and laboratory-specific features are fundamental for the accurate recognition of this condition. Research on targeted therapies and biomarkers measuring and predicting disease activity will improve NMOSD management. In this episode, Gordon Smith, MD, FAAN, speaks with Sara Mariotto, MD, PhD, coauthor of the article “Neuromyelitis Optica Spectrum Disorder” in the Continuum® April 2026 Multiple Sclerosis and Related Disorders issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Mariotto is a neurologist in the Neurology Unit in the Department of Neurosciences, Biomedicine, and Movement Sciences at the University of Verona in Verona, Italy. Additional Resources Read the article: Neuromyelitis Optica Spectrum Disorder Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Smith: Neurology is an increasingly therapeutic specialty, and across many of our subspecialty areas, lots of new drugs are being approved. Are you interested in learning more about a historically disabling disorder for which we now have a spectrum of new therapies that, if used appropriately and promptly in the right clinical situation, promise to dramatically improve patient outcomes? If so, keep listening. My name's Dr Gordon Smith. Today I'll be talking with Dr Sara Mariotto about her article on neuromyelitis optica spectrum disorder or NMOSD, which she wrote with Dr Romain Marignier. This article appears in the April 2026 Continuum issue on multiple sclerosis. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: This is Dr Gordon Smith. Today, I'm interviewing Dr Sara Mariotto about her article on neuromyelitis optica spectrum disorder or NMOSD, which she wrote with Dr Romain Marignier. This article appears in the April 2026 Continuum issue on multiple sclerosis. Sara, welcome to the podcast, and maybe you can start by introducing yourself to our audience. Dr Mariotto: Yes. Thanks, Gordon. I'm Sara Mariotto. I'm a neurologist, and I work at the Neurology Unit, University of Verona, where I do both clinical diagnosis and research into neuroimmunology---so, in particular, autoimmune encephalitis, NMOSD, and MOGAD. Dr Smith: Well, this is a super exciting area. Whenever I hear about NMOSD, I think of one specific patient I had, and I always think of her when I come across something like your article, which is really fantastic. So, before we dive into the details, I wonder if maybe you can just explain to our listeners who aren't up to speed on what NMOSD is, what the disorder is, and maybe why it's so important that all of our listeners learn how to recognize it quickly and get people started on therapy. Dr Mariotto: Yes, sure. So, neuromyelitis optica is an inflammatory autoimmune CNS disorder usually associated with aquaporin-4 antibodies, although there are a few cases, around 10%, who can be antibody-negative. And I think it's very much important to have in mind this disease and recognize it because it can be severe, as you pointed out; can present with very severe optic neuritis, myelitis, the brain stem, or area postrema syndrome. So, it can be really severe, affect quite young people around 40 years of age---although it can affect also the pediatric population and elderly people---and, importantly, it can be treated. It's very much important to treat this patient in the acute stage very quickly with steroids or plasma exchange in addition, and then to start a chronic treatment. So, we have treatment for this condition. So, it's very much important to, to recognize it quickly and treat the patient properly. Dr Smith: So, I wonder if we can talk a little bit about the diagnostic criteria and boundaries of NMOSD, right? So, someone who comes in with bilateral op- severe long segment optic neuritis or long segment myelitis, we think about it. But what are the boundaries? Should we be looking for this, for instance, in someone who comes in with a unilateral optic neuritis or looks like typical multiple sclerosis? Is it important to get aquaporin-4 antibodies in those patients? What do the diagnostic criteria say about this? Dr Mariotto: So, I wouldn't test aquaporin-4 antibodies in all patients with demyelinating conditions because although aquaporin-4 antibody assay is very specific, as for all assay and all antibody testing---also for MOG antibodies, for example---some false positive results can come out. So, I would suggest to test aquaporin-4 antibodies not in typical MS cases but in those who could be suggestive for not being MS, so in all those cases with atypical optic neuritis and myelitis or other syndromes. For those cases, it's important to test aquaporin-4 antibodies, but I wouldn't test them in all typical, classical MS cases. As I said, it's quite specific, the assay, so it's uncommon to have false positive results, but it can be. Dr Smith: Serum, CSF, both? Dr Mariotto: So, for aquaporin-4 antibodies, they're usually present in serum. They can be positive also in the CSF. And there are a few reports of isolated CSF positivity. But if we analyze larger samples volume, then it becomes clear that isolated CSF positivity is so, so rare that it's not recommended to test them in the CSF when serum is negative. So, for aquaporin-4 antibodies, the recommended matrix of testing is serum, which is different for MOG, which is not the topic of our article but is important to mention because MOG antibodies should be tested in serum and CSF. But aquaporin-4, I would recommend to test serum. Dr Smith: What are the boundaries between MOGAD and NMOSD? And you talked about the differential testing of antibodies, which I was going to ask about. But when should we think of NMOSD relative to MOG? Dr Mariotto: Yeah. There are aspects which are the one mentioned in the criteria, highly suggestive for NMOSD. But the clinical spectrum can be similar to that of MOGAD. Usually, although there are some clinical aspect---like, for example cortical encephalitis or ADEM, which is more typical for MOGAD, or others like area postrema syndrome, which are more typical of NMOSD. The spectrum can be similar among the two conditions, so that's why in our clinical experience, usually they ask both aquaporin-4 and MOG antibodies in patients. It's- for experts, it can be easy to differentiate the two conditions, but for nonexperts can not be so easy. Dr Smith: Can you define area postrema syndrome? I think not all of our listeners see that every day. Dr Mariotto: Yeah, sure. This is a syndrome which is highly suggestive of NMOSD. That's why I mention it. And it's characterized by nausea, vomiting, hiccups are known as the syndrome. And it is very, very suggestive because of the expression of aquaporin-4 in that area of NMOSD. That's why I strongly recommend for all patients who comes out to have this syndrome to test for aquaporin-4 antibodies. MOGAD is hardly ever positive for that, so I think that whenever you see a patient with that syndrome, you should think about NMOSD. Dr Smith: I'm just curious, aquaporin-4 is a water channel, which is kind of an interesting concept. Our conversation, I really want to make sure we give clinically important information to folks, but it's so curious to me at least, how does this actually result in a inflammatory demyelinating syndrome? For a simple neuromuscular guy, what's the immunopathogenesis of this? Dr Mariotto: Yeah, the immunopathogenesis is quite complicated, as in all CNS disorders. And of course, aquaporin-4 antibodies are the main focus, but they are not the only one. As you said, aquaporin-4 antibodies have a target, this water channel, which is at the basis of the disease, and they are produced by the interplay between T cells, B cells, and plasma cells. But then also eosinophils, macrophages, cytokines, and chemokines are involved, enter the CNS, and then another important component is complement, which is highly activated in this disease. At the end, we have astrocyte damage because astrocytes are the main target of the disease, but also axon and myelin are involved. So, it's a quite complex pathogenesis based on the antibodies, but not only on that. Dr Smith: And this will become important when we start talking about treatment. There seems to be a recurring theme of long segment demyelination, right? Optic neuritis is typically a large percentage of the length of the optic nerve, and obviously the myelitis se- more than three segments. Do you see other long segment areas of CNS demyelination, corpus callosum or things like that? Any ideas why that is, if that's true? Dr Mariotto: Of note, this is quite interesting because usually when we have NMOSD, we have a longitudinal involvement, especially of the optic nerve and spinal cord, while brain lesions are quite different. Like, we usually do not have the typical Dawsen fingers-like lesions that we have in MS, for example, or the classical periventricular or subcortical extensive lesions that we can see and we have in mind when we think about MS. In some cases with NMOSD, the brain is completely negative, so we do not see anything. And Dawsen lesion’s quite suggestive of NMOSD. So, you're right. I mean, this is related partially to the expression of aquaporin-4, and that's why we have this typical involvement also for area postrema, for example, and maybe also our other examples of clinical aspect that we can see in these conditions. But it's basically linked with the expression of aquaporin-4, which is the main target of the disease. And that's why usually the brain doesn't show so much involvement as we can see in MS, for example. Dr Smith: I was actually really interested in some of the unusual manifestations or phenotypes, and I don't want to get into arcadia, really, but which of these should our listeners be familiar with that would really suggest that they should be thinking about NMOSD beyond the area postrema and other features that we've already talked about that are part of the core criteria? Dr Mariotto: Yeah. I mean, I think that the encephalic syndromes or also ADEM, which is most typical of MOGAD but can be observed also in NMOSD or PRES, for example, are syndromes that can be considered in patients with NMOSD. There are the typical ones, which are the ones showed in the criteria, but whenever we have a brainstem involvement or, like, these encephalic syndromes or also PRES, we should think about NMOSD also. Dr Smith: Another area I was interested in are red flags. In your article, you talk about red flags that might suggest an alternative diagnosis, right? And then this presumably is particularly important in seronegative patients, which 10% is not a reasonably high number, I suppose. What are red flags we should be thinking about for some other diagnosis? Dr Mariotto: Yeah. I would here mention two very important red flags. The first one is a very hyperacute onset. Usually these conditions, these inflammatory conditions have a subacute onset, so whenever you have a very, very acute onset, you should think about something else. This can occur sometimes also in NMOSD, but hardly ever occur. Like, a very acute myelitis, the first thing we should think about is a vascular origin, for example, with a lot of pain and not about NMOSD, although sometimes the differential diagnosis is not so easy. The second thing is a progression independently of relapses, which hardly ever occur in NMOSD. Usually in NMOSD, we have the onset, and then we have a relapsing disease course. That's why we have to treat patients always and not to stop treatment. But we do not have progression in the meanwhile, while we can have, for example, this in MS. Same thing is for MOGAD. So, these are two things that I think is very much important to keep in mind. Dr Smith: I want to pivot to talk about treatment because that's been super exciting. But rumor has it there are new diagnostic criteria coming for NMOSD in the next year. I bet you know a bit about those. Can you give our listeners any indication about kind of where the puck is going on this? Not so much what the criteria are specifically, but what sort of diagnostic challenges are the new criteria going to help us with once they come out? Dr Mariotto: Yeah. So basically, we are working on that, so you will read them in the next future. This is the good point of the conversation on the new criteria. And we work a lot on the definition, on the new definition and nomenclature of NMOSD; on the definition of seronegative NMOSD, which is also quite tricky; and then on the assay we should use to test aquaporin-4 antibodies, and also on potentially new syndromes which should be included into the main feature of the disease. But hopefully you will read about this very soon. Dr Smith: Looking forward to it. And Continuum Audio listeners, you heard it here first, so thank you. Let's pivot to treatment. This has been super exciting, and I wonder if the way to approach this is to start with acute management and then sort of chronic management. Would that make sense? Dr Mariotto: Sure. Dr Smith: Let's say I go on service on Friday, and I have a patient who comes in with positive aquaporin-4 and bilateral optic neuritis. What's the acute approach to managing that patient? Dr Mariotto: So, the first approach is to administer intravenous steroids, but I would not wait to escalate to plasma exchange. There is quite good evidence that we should treat the patient with additional plasma exchange very quickly, and every day of delay of plasma exchange can cause increased disability. So, we should treat patients with steroids first, and then if we are not satisfied by the recovery, soon start with a plasma exchange. There is also some evidence, although less, for IVIG, but it's important to try to treat them very quickly, even if it's Friday, you know, there is the weekend and so on. But I think it's very much important to start with steroids after excluding other infectious causes or so on, and then to start quickly with plasma exchange. The main problem could be that we do not have the results of the antibody yet. Dr Smith: Right. So, let me ask that question. You know, let's say my patient comes in on Friday, and clinical syndrome that really looks like NMOSD, and we're waiting for the aquaporin-4. There are many places where it's hard to get plasma exchange over weekends. And so, in that setting, are you better off doing the steroids over the weekend then PLEX on Monday, or should we just give IVIG because maybe it's as good as PLEX? What's your advice there? I'm trying to get ready for Friday because I know one's coming in. Dr Mariotto: That's true, that's true. Usually they come on Friday or Saturday. I think it's acceptable to have three days of steroids and see how the patient improves, and then after three days to start with plasma exchange. Actually, we have a very good improvement if we start between three and five days after onset. So, I think waiting for three days is acceptable just because we can see if the steroids work properly or not, and then we can quickly start to plasma exchange. But I would not wait, like, 10 days, you know, before starting with a plasma exchange, and I would not wait for antibody results. Dr Smith: Got it. Super helpful. And I'm actually not joking around, I learned recently that I have a reputation among our residents for having lots of optic neuritis when I'm on service, which I think is sort of karmic justice for being a peripheral nerve expert. But let me ask another question. So, let's say we do that, and the patient gets three or five days of pulse methylprednisolone and five courses of PLEX, and they're not doing well. Do you then just move right along into another agent B cell depletion therapy? I mean, what's your next step in escalation in the acute setting? Dr Mariotto: I would for sure start to, as you said, with steroids, plasma exchange, and in case IVIG, and then quickly move to chronic treatment. And for patients who are not recovering well, I would think of something which has a quick effect so we can really start treating patients very quickly. There are different options. And all over the world, there are different rules for using immunosuppression in NMOSD. Like in Italy, for example, it's different from US or other countries, Germany, for example. There are different approved treatments and different rules of using them before or after rituximab, for example. We all know that there are treatments approved for NMOSD all over the world. But in some countries, like for example in Italy, we should use rituximab first, and then if it doesn't work, escalate to the approved treatment. I know in the US it's different. But anyway, for a patient who does not improve quickly, I would start with something which has a quick effect on the disease. Dr Smith: And then rituximab versus inebilizumab, you know, CD20, CD19, what's your advice there? Is one preferable to the other, you know, if we have options to do either? Dr Mariotto: Yeah. So, between rituximab and inebilizumab, we know that the target, well, is different, but is anyway B cells, so CD19 and CD20. With CD19, we can affect both plasma blast, plasma cells, and B cells. That's why the target is broader. And of note, this is an approved drug, while rituximab is, in most countries, used as off-label treatment. Dr Smith: So inebilizumab would probably be preferable if we're able to do that. Dr Mariotto: Unfortunately, there are not so many studies comparing rituximab with the approved drug, which is, of course, a pity, but that's the case. While we have clinical trials for all the approved drugs, and although the trials were designed differently, as we mentioned in the Continuum paper, we can argue something of the comparison between the approved drugs. But it is not so clear the comparison between rituximab and the new drugs, which is also something that we should work on. Dr Smith: And then for chronic suppressive management, what other options are there? Dr Mariotto: So, in addition to B cells, target can be interleukin-6, as we know with tocilizumab or satralizumab, and then complement with eculizumab. These drugs are both based on the pathogenesis of the disease. That's why we also discuss it in the paper, which shows a clear involvement of complement, and among cytokines of interleukin-6. So, targeting these made clear that could improve the disease quite well, and that's why they designed some clinical trials on these drugs, which are now approved, as we said, for NMOSD. Dr Smith: Wow, so many options, and a lot of questions, but limited time. Let me just ask a couple of more. I see a lot of myasthenia patients, and there's a lot of variability, as you know, in patients with myasthenia, the extent to which complement is an important mechanism versus other, you know, important mechanisms. To what extent is response to a complement... /episode/index/show/continuumjournal/id/40684785

Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease With Dr. Eoin P. Flanagan 04/22/2026

Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease With Dr. Eoin P. Flanagan Familiarity with the clinical, MRI, CSF, and serologic features of MOGAD can help neurologists recognize this condition in clinical practice. Awareness of the utility and pitfalls of the MOG antibody test is critical. The current therapeutic approach is guided by retrospective studies and the application of immunotherapies used in other autoimmune neurologic disorders. In this episode, Gordon Smith, MD, FAAN, speaks with Eoin P. Flanagan, MBBCh, coauthor of the article “Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease” in the Continuum® April 2026 Multiple Sclerosis and Related Disorders issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Flanagan is a professor of neurology and the division chair of the Division of Multiple Sclerosis and Autoimmune Neurology in the Department of Neurology at Mayo Clinic in Rochester, Minnesota. Additional Resources Read the article: Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Smith: So, what neurological disorder can cause bilateral optic neuritis, transverse myelitis, ADEM, or can mimic acute flaccid myelitis, intracranial hypertension, viral encephalitis, or cause seizures? Sounds like the great imitator, perhaps. If you want to know and learn more about this syndrome and how you can treat it---and it is very treatable---keep listening. My name is Gordon Smith, and today I have the great opportunity to talk with Dr Eoin Flanagan from the Mayo Clinic on his article on myelin oligodendrocyte glycoprotein antibody associated disease, or MOGAD, which is in the April 2026 issue of Continuum on Multiple Sclerosis and Related Disorders. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: This is Dr Gordon Smith. Today I'm interviewing Dr Eoin Flanagan about his article on myelin oligodendrocyte glycoprotein associated disease, or MOGAD, which appears in the April 2026 Continuum issue on multiple sclerosis and related disorders. Eoin, welcome to the podcast, and please introduce yourself to our audience. Dr Flanagan: Yeah, thanks so much. I'm Eoin Flanagan. I'm a neurologist at the Mayo Clinic. I'm originally from Ireland. I work in the neuroimmunology lab at the Mayo Clinic, and work and see patients with MS, MOG, and autoimmune disorders here in Rochester, Minnesota. Dr Smith: Your article is super interesting, I think, and this has been a really rapidly evolving area over the last, you know, many years. We have many more antibodies, and MOG is something that's been around for a while, but we've certainly learned a lot more about it. This is a topic that I think will be familiar to most of our listeners, but I wonder if maybe you can just begin by laying the foundation. Like, what is MOG? What's its typical presentation? Dr Flanagan: So, MOG is a protein on the surface of the oligodendrocyte or its CNS myelin, and it was always of interest as a potential antibody target, and initially it was investigated in multiple sclerosis. But subsequently, we recognized that the antibodies to MOG have a specific syndrome, of which about a quarter of patients are pediatric and then the remainder are adults. And they can present with a variety of syndromes, probably most commonly optic neuritis, but also acute disseminated encephalomyelitis, or ADEM. Transverse myelitis can also occur, and then some other unusual brain and brainstem cerebellar syndromes can also occur. Dr Smith: I was really impressed in the very broad phenotypic spectrum of MOG. We'll talk more about that, of course. But I wonder if maybe you can tell us when we should be ordering MOG antibody? Given this broad variability, does anyone who has a CNS demyelinating disease need a MOG assay, only specific phenotypes? What guidance do you have for our listeners? Dr Flanagan: Yeah. It's a great question. So, I think you have to be a little bit careful because the MOG antibody test is a little bit sticky. So sometimes we can see some low-positive false positives. So, we don't wanna order it in every single patient with classical MS. So, I suppose we'll start with who not to order it in. I think it's also a very optic nerve- and optic neuritis-central disease, so I think you really need to be considering this in a patient with optic neuritis who does not have lesions in the brain suggestive of multiple sclerosis. And then we think about some of the features: if the lesion, the enhancement along the optic nerve is long, if it's bilateral, if there's a lot of optic disc edema accompanying that, we tend to think about MOG antibodies. And then children with demyelinating disease, MOG is over-represented in that cohort, so it accounts for about a third of those. So, if you have a child with CNS demyelinating disease, particularly if they're under twelve, with ADEM presentations or other presentations, you probably want to be ordering the MOG antibody test. And then a longitudinally extensive transverse myelitis in adults, certain types of cerebral phenotypes that we can get into, you would want to consider ordering MOG antibodies too. Dr Smith: Now, you point out in the article that it's really important that laboratories use the cell-based assay for MOG as opposed to an ELISA, for instance. Is this something folks need to be very attentive to, or are all of the commercial laboratories now using a cell-based assay? Dr Flanagan: Yeah. I think all of the commercial labs are using cell-based assays, so we don't really get into much of an issue. There are some differences between serum and CSF, so really, serum is the optimal sample to order. There is also some differences between the live cell-based assay and the fixed cell-based assay, where the live cell-based assay may have some advantages in terms of sensitivity. And then CSF is kind of still under evaluation about its role in the condition. So in general, it's a serum test. And then we have to remember that the antibody tends to be highest at the onset, and then it goes down over time. So, if you delay your testing or you're testing a patient long after the condition, it can go negative, for example. So it tends to be highest both around the relapses and particularly at the onset of the condition. Dr Smith: You mentioned earlier that the test is sticky, which I take to mean that there is some risk for low-titer false positives. How do you navigate that situation? When should we be suspicious about a false positive? Dr Flanagan: Yeah. I think there's some very useful features that can help you. You know, the main differential diagnosis is going to be multiple sclerosis, particularly in the US, in regions of the northern US where MS is particularly common. So, you really wanna be making sure that if you get a positive result, low positive, that it's not multiple sclerosis. And some of the best discriminating features are CSF oligoclonal bands. They're about 85% in MS and about 15% in MOG, so an easy number to remember, 85 and 15. And then the lesions in MOG, the brain lesions, tend to disappear over time. So, if you have the advantage of that follow-up MRI a year down the line, about 70% of lesions in MOGAD will resolve, while in MS, as we know, the term means multiple scars, so the MS lesions tend to persist over time. So, they are two quite useful features that can help discriminate. Dr Smith: And how about specific phenotypes or areas of involvement or imaging abnormalities that suggest MOG? One of the things I found really interesting in your article is there are a host of different syndromes that I think had largely been previously described, many of them, that became clear later that these were really tied to MOG antibodies. Presumably, that's helpful in interpreting the antibody assay in that patients who have, perhaps, a borderline low titer, for instance, but have a very typical phenotype are more likely to have MOG than those who have a more clearly MS-type phenotype. Dr Flanagan: Yeah, absolutely right. Yes. So, there's certain phenotypes that we don't tend to see with MS. The acute disseminated encephalomyelitis, or ADEM, is one that's particularly common in children. And about half of people that have ADEM will be positive for the MOG antibody. So that's a syndrome you need to look out for, which would be often in children, encephalopathy, and they would have multifocal white matter lesions, sometimes involving the gray matter. A second syndrome that was an interesting discovery from a Japanese group was this unilateral cerebral cortical encephalitis, where patients can have this swelling and T2 hyperintensity, often just on one side of the brain. And it's in the cortex, and some of those patients won't have any white matter lesions. And in that situation, it's important to order the MOG antibody, and that seems to be a specific phenotype of MOGAD. But sometimes people don't think about it because the white matter is not involved. So, if you see these patients, they often present with seizures, sometimes they even have fever accompanied by it. And if you see those patients and see this radiological feature, then you really want to consider ordering the MOG antibody too. Dr Smith: Yeah, I found that really interesting. And I- actually, my next question is perhaps a good follow-up on that, is, what are the diagnostic pitfalls? You give a lot of examples of situations and I think some cases where it's easy to get tripped up and misdiagnose someone who has MOG with another fairly common neurological problem. Dr Flanagan: Yeah, I think some of the things that can help you when you're determining if the MOG is a true positive or false positive is the level of the antibodies. The super high titers, if it's a clear positive or very strong positive, the likelihood is that that is much more likely to be MOGAD than those low positives just above the cutoff. So that can be useful to help you discriminate from false positives. Those lesions, again, if all the lesions persist over time, that's going to be more suggestive of multiple sclerosis. Other diagnostic pitfalls, I suppose, if it's a syndrome that's not really associated with MOG, like peripheral neuropathy or other syndromes where we'll see some case reports, but usually I would be very cautious about those kind of presentations. So usually, having the antibody at a high level, and then also if they've had other symptoms suggestive of MOGAD, like if a patient has had recurrent optic neuritis and then they have an unusual brain syndrome, or they start out with an unusual brain syndrome and then have recurrent optic neuritis. You know, there are situations that make it more likely if they're having other typical phenotypes of the MOGAD where we can kind of expand the spectrum, but we have to be careful. Dr Smith: I was really curious about the dynamic imaging findings. And you point this out both in terms of the resolution of imaging findings, but also in that patients who have an acute MOG syndrome often have very rapid evolution of the imaging abnormalities. I'm just curious, you know, why is that, and what do you make of it? Does it have a mechanistic implication, do you think? Dr Flanagan: I don't think we know for sure. I think there's probably a lot more happening than we see on MRIs sometimes. What sometimes can happen in about 10% of patients is the initial MRI can be normal. We don't tend to see that with multiple sclerosis or NMOSD. Then what we see is it evolving over time. So, at that time, if you do a CSF, you'll often see inflammation, but we don't see the lesions. Now, that might be because the MRI is not very good at picking up cortical involvement. That can be difficult to see in MRI. Or there could be other factors. It could be a functional effect on the MOG but without frank demyelination yet, for example. Or there could be edema that you- myelin edema that you can't see as a lesion yet on MRI. But we do see that if you repeat the MRI, sometimes it'll change a lot. So, you may go from one or two lesions on the first MRI to twenty lesions on the second MRI a week later. So, it does tend to change a lot. And then over time, those lesions also resolve. So, what I say is if it's a very suspicious situation---like a child comes in with new-onset encephalitis, has inflammatory CSF---you might wanna consider repeating that MRI down the line and seeing if it's changing. And then over time, you know, a repeat MRI a year after the onset when there's brain or spinal cord lesions can be very helpful just to make sure you're on the right track, because lots of those lesions will then disappear, and that's a very clear discriminator from multiple sclerosis. Dr Smith: Yeah, thanks. I mean, I was wondering the same thing about whether that particular feature might imply, you know, a functional abnormality as opposed to more of a structural abnormality. So probably a lot more to learn as we move forward. There are now consensus diagnostic criteria that were published a couple of years ago. I think you've already touched on kind of the general approach, but do you want to speak to those? I found your summary pretty helpful. Dr Flanagan: Yeah, I think that those criteria are quite useful. They have three main parts to them. The first part is having a characteristic clinical syndrome. So, we talked about ADEM, we talked about cerebral cortical encephalitis, transverse myelitis that's often longitudinally extensive, and optic neuritis being the main syndromes, but sometimes other brainstem or cerebellar involvement can be seen. And then the second part is having a positive MOG antibody. And then there's some caveats there. So, if you have a high positive, then you don't really need any additional supportive criteria. On the other hand, if you're low positive, to get at those sticky antibodies that make sure it's not a false positive, you need some additional supportive clinical or MRI criteria. Or if you're only positive in CSF, you need that additional criteria. You also need to be negative for the aquaporin-4 antibody, because they can overlap clinically. And some of those supportive criteria are things that we talked about a little bit earlier, longer lesions within the optic nerve, bilateral involvement, involvement of the nerve sheath or optic disc edema. This is a situation, MOG antibody disease, where your fundoscope is useful and looking in the back of the eye and seeing swelling, because we don't tend to see that quite as often. It's less common in multiple sclerosis, but we often see prominent edema in MOGAD. And then in the spinal cord, the lesions tend to be central in the cord. Sometimes they form this H sign where it's restricted to the gray matter, and they tend to be longer, sometimes involving the conus. Patients will often have neurogenic bowel or bladder. And then in the brain, deep gray involvement, those large lesions along the cortex with swelling are some of the typical features. And then the final step is exclusion of another diagnosis. Just like with any test that we do in neurology, our final step is going to be to put that into context. So that's just a normal thing that we will always do when we get a group of test results back that we don't know what it means. We have to put it into context. So, make sure it's not multiple sclerosis, everything else does not look like multiple sclerosis, and then you can be on your way to make a diagnosis. Dr Smith: Definitely encourage listeners to read your article. I guess I say that with every time I- or with everyone I talk to for Continuum Audio, but the images are really fantastic and the cases are fantastic. So, everything you've described is well-illustrated, including really nice schematic sort of diagrams that help differentiate NMO from MOG and MS. So, if you like MRI scans and good imaging frameworks, then this is the article for you. Dr Flanagan: I think that's true, and the other thing is that the imaging is quite helpful because it takes a while for that antibody to come back. We're lucky at Mayo Clinic, if you work here, it, it comes back faster for you. But for many places, that time of sending it in, so a lot of times you don't know right away. So, looking at scrutinizing that MRI can be very helpful to guide you on your way and to know what you're dealing with and how to approach both the acute treatment and plans to have potentially a steroid taper after the acute treatment and those kind of things that can help guide you in that regard. Dr Smith: Yeah. So, let's talk about treatment. You know, what's your approach to treating a patient who has an acute demyelinating syndrome related to MOG? Dr Flanagan: So similar to other things, MOG is very steroid responsive. So, we use high-dose IV methylprednisolone in adults. That would be one gram IV for five days. And then we also will sometimes use oral steroids, twelve hundred and fifty milligrams. That's a bit of a hassle because it's twenty-five fifty-milligram tablets, it doesn't come in a larger tablet version. But it's very helpful to patients because they can get started on it right away. You don't have to set up an infusion center. So, we have used those oral steroids often in people who don't have access to an infusion center, are not in the hospital. And particularly as it's often optic neuritis, some of those patients are seen in the outpatient setting, so we can get in with treatment quickly. In patients where it's more severe, it doesn't recover quickly with steroids, then we would consider escalating to plasma exchange as our second-line treatment, and there's some retrospective data that suggests that plasma exchange can be useful. That's gonna be particularly for those people who don't have that quick response to steroids, or maybe more severe phenotypes like that brain involvement with ADEM or cerebral cortical encephalitis, where those patients might be in the hospital and quite unwell. I will say, we might get on to this, that sometimes MOG can be very, very severe and even fulminant, where there can be increased intracranial pressure, and these patients can be in the ICU, and it can be life-threatening. And so, it's really important to treat those patients aggressively, and some patients have even required hemicraniectomy or additional treatment. Sometimes IL-6 blocking medications have been used in that situation. So, monitoring and treating increased intracranial pressure in those rare patients, probably 2 or 3% that have the very severe attack, is important. Dr Smith: I think one of the things I found interesting, and then I'd love to get your feedback on this, is that most patients with MOG seem to have a very readily treatable disorder that's monophasic, right? You treat them with steroids, and they do well. On the other extreme, there are these patients that have a much more malignant presentation, and there are some that sound like they benefit from prophylactic or some chronic therapy. What's your approach, right? In MS, we do serial scans to monitor, and obviously, our patients are on, you know, chronic disease-modifying therapy. How do... /episode/index/show/continuumjournal/id/40684590

Adult-Onset Leukodystrophies Mimicking Multiple Sclerosis With Dr. Roberta La Piana 04/15/2026

Adult-Onset Leukodystrophies Mimicking Multiple Sclerosis With Dr. Roberta La Piana Adult‑onset leukodystrophies, though rare, can closely mimic MS on both clinical presentation and neuroimaging, posing a significant diagnostic challenge. This episode highlights key clinical and radiologic red flags that can help distinguish these disorders from MS, preventing misdiagnosis and avoiding inappropriate treatment while enabling timely genetic counseling and targeted therapies. In this episode, Teshamae Monteith, MD, FAAN, speaks with Roberta La Piana, MD, PhD, coauthor of the article “Adult-Onset Leukodystrophies Mimicking Multiple Sclerosis” in the Continuum® April 2026 Multiple Sclerosis and Related Disorders 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. La Piana is an associate professor in the Department of Neurology and Neurosurgery at the Montreal Neurological Institute, McGill University, and an associate member of the Department of Diagnostic Radiology at McGill University in Montreal, Quebec, Canada. Additional Resources Read the article: Adult-Onset Leukodystrophies Mimicking Multiple Sclerosis Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Monteith: You just saw a patient in clinic. And you're clear, the diagnosis is multiple sclerosis. Not everything fits, but it kind of looks like multiple sclerosis. You see the patient back years later. There’re some treatment issues, the patient’s not responding to treatment, and things look different. Have you thought about a genetic inherited problem like leukodystrophy or a genetic white matter disorder? Listen to this podcast. We're going to help you figure it out. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Monteith: This is Dr Teshamae Monteith. Today I'm interviewing Dr Roberta La Piana about her article on adult-onset leukodystrophies mimicking multiple sclerosis, which she wrote with Dr Gabrielle Macaron. This article appears in the April 2026 Continuum issue on multiple sclerosis. Welcome to our podcast. Dr La Piana: Thank you. Thank you for having me. Dr Monteith: Absolutely. Why don't we start off with you introducing yourself? Dr La Piana: So, my name is Roberta La Piana. I'm a pediatric neurologist. I trained in Italy, I did my medical school, I did my residency in pediatric neurology there. And then I moved here to Montreal, to the Montreal Neurological Institute, to do a PhD in neuroscience. And that's where I specialized in adult-onset genetic white matter diseases. And after my PhD, I was recruited as an assistant professor here. So, that's where I got into this field. Dr Monteith: This big field, highly specialized; lots of disorders, but highly specialized. And what got you into this? Neuroscience is huge. So, was it a mentor, or…? Dr La Piana: No, actually, it was because of my background, because I trained as a pediatric neurologist and I loved the genetic white matter disorders in the pediatric population. So, when I came to the Montreal Neurological Institute, initially it was mainly to have a better expertise in imaging. And being at an adult neurology institute, I started seeing patients with adult genetic white matter diseases, and I was immediately fascinated by how different they were from their pediatric counterparts. Because in pediatric genetic white matter diseases, pediatric leukodystrophies look very diffuse, look very confluentous, so it's difficult to mistake them. But in adults, in the adult forms, I was initially driven by how often they can be misdiagnosed as multiple sclerosis or as other acquired white matter disorders. So that's why I got really interested in in this field. Dr Monteith: You're, like, literally the perfect person for this discussion. Dr La Piana: I'm not sure- *laughs* Dr Monteith: Why don't we start off with what your objectives were when writing this article? Dr La Piana: With writing this article, the goal is what I have been, actually, doing for the past ten years or so. So, really try to get more attention into the field because of the high rate of potential misdiagnosis of patients. So, that's exactly the reason why I really would like to raise the interest of neurologists for these disorders, because they are not considered enough in the differential diagnosis of patients, of adult patients presenting with white matter disorders. They are considered rare---which are, they are rare, definitely. But collectively, while each single form is rare, collectively they are not as rare. So- and thus, the risk of misdiagnosis and the potential impact of misdiagnosis on them with, you know, you can imagine giving patients inappropriate treatment or missing the possibility of a prenatal genetic diagnosis is so high that I really would like people to keep these disorders in the differential. Dr Monteith: And it sounds like more than ever, this is really important because some of the newer developments in the field. Dr La Piana: Yes. Specifically, we have now tools that will allow to diagnose these patients quite quickly. All the genetic techniques that are available nowadays can really, with one single shot, we can now sequence hundreds of genes so we can have a quicker diagnosis. And this thing was impossible up until ten years ago. So that's definitely the first huge improvement that makes these disorders now easily diagnosed. Dr Monteith: Yeah. So why don't we talk a little bit about how common is this misdiagnosis for these rare subtypes? Dr La Piana: Yeah, the misdiagnosis, it depends on the cohorts. Generally speaking, I would say that the rate of that misdiagnosis for these forms is up to 25% or even more in some other cohorts. And it really depends on the forms. Like, there are clearly some forms, especially those that present with multifocal white matter diseases, that present with nonspecific clinical presentations like migraines, image---and especially for female patients, and for which migraine is so common, having multifocal with other abnormalities is so common, the rate of diagnosis increases even further. So, these are all things that we need to keep in mind. I know these are rare, but still, we need to always have them on the back of our minds. Dr Monteith: Are there any particular disorders that are more often misdiagnosed? And you spoke about progressive forms of multiple sclerosis being a common kind of misdiagnosis. Dr La Piana: Yeah. So, there are definitely forms that are more commonly misdiagnosed. And these are those that, as I probably repeated already too many times, is the word multifocal, which is key. So, all those genetic white matter disorders that present with multifocal white matter abnormalities are not initially considered as genetic. So, I'm thinking about all of the leukovasculopathies, so, the small vessel diseases which are genetic in origin. For example, CADASIL; for example, the disorders related to collagen-4; so, the COL4 A1 or A2-related disorders. Those are clearly more commonly misdiagnosed initially. Another big group, unfortunately, is the CSF1R-related disorders. I know I'm saying a lot of gene names, but due to the fact that they start with multifocal abnormalities and they start with quite nonspecific, slowly progressive symptoms, the rate of misdiagnosis is definitely higher. Dr Monteith: And can you discuss some of the clinical challenges when seeing patients that might lead to this misdiagnosis? Dr La Piana: There are multiple clinical challenges. One is definitely the presence of nonspecific or initially mild clinical symptoms that sometimes don't raise initially the red flag of something, degenerative or progressive or genetic. One category that I would mention are psychiatric disturbances, especially in the form of depression, anxiety, or apathy. This is quite common in patients with some forms of genetic white matter disorders, and they are initially misdirected to psychiatrists and taken care in that domain. But it's only when some even mild neurological symptoms like a gait disturbance or hyperreflexia, or we had patients with, like, a urinary incontinence. It's only at that time, but maybe years have passed meanwhile, that these patients are finally referred to the neurologist Dr Monteith: You spoke about some of these clinical symptoms. Can you give us some other clinical red flags? Dr La Piana: Well, some other clinical red flags can be, for example, the extraneurological involvement. So, we have patients where- and there's a reason immediately to some specific disorders. For example, infertility. The presence of infertility in a female patient with white matter disorders should immediately form the consideration of the specific genetic white matter diseases that are associated with these forms. And this is not something that neurologists tend to ask about in the collection of the clinical history. And this is something that can make the difference and can accelerate the diagnosis. Dr Monteith: What are some other things? I mean, I know we can think about treatment, lack of a common treatment response, maybe, to steroids. You gave a great example of optic neuritis, for example. Give us some other things that we should say, hey, this doesn't fit the picture. Red flag. Dr La Piana: In this case, I think we want to talk more about the specific misdiagnosis of MS. Because these patients are often misdiagnosed with MS, but they might sometimes be misdiagnosed with other forms of acquired white matter diseases. When we consider MS, definitely the presence of being treatment resistant: so, patients that are not responsive to the common MS-targeting treatment should be always a red flag. The evolution as well. So, for example, the presence of a more slowly progressive course is another red flag. The presence of optic neuritis. Sometimes it's tricky because it's not common in the genetic white matter disorders, it's used as a criterion to orient correctly towards a multiple sclerosis. But we need to keep in mind that there are forms, genetic forms, especially the mitochondrial forms, that can present with optic neuritis and are really at the overlap with the multiple sclerosis spectrum. Then, if we want to move forward beyond the clinical side and go into the laboratory, of course a negative lumbar puncture with no oligoclonal bands should be a major red flag. Dr Monteith: What about some of the radiographic features? Dr La Piana: So, the radiographic features is something we are really working on in the field, especially with the new criteria used in MS. So, for example the paramagnetic rim lesions or the central vein sign, they are considered the specific forms. But it's true- and don't have an answer for that. I want to be clear, but it's true that they haven't been assessed yet extensively in patients with genetic white matter disorders. Anecdotally, I can say, because I have already reported this at conferences, that we have seen patients with genetic white matter conditions reaching a threshold for a central vein sign that can be considered diagnostic for MS. And we have seen that in some patients. Again, no study has been carried out extensively to date, but I think we should consider that with a grain of salt. But yeah, the paramagnetic rim in lesions is probably more accurate to distinguish between genetic and acquired white matter disorders. Dr Monteith: And what about some of the genetic white matter disorders that mimic MS? You spoke about things like CADASIL; what are other things that we should keep in the back of our mind? And you have great charts, to our listeners, and they're going to have to review those charts, because they're excellent. I think maybe they need to find a way to make that a little bookmark you walk around with on the ward. But what are some other conditions that kind of commonly mischaracterized? Dr La Piana: Two of the main groups are the one that you mentioned. So, leukovasculopathy is- so, CADASIL, is definitely one of the most common misdiagnoses of MS. And the presence, as we said, of some clinical features like migraine, especially when it's complicated migraine with visual aura, we all know that. But especially in the context of a positive family history for either a psychiatry condition or migraine as well, or strokes, these are all factors that should prompt the consideration of these disorders in the differential of a patient with white matter disorders. Another category are definitely mitochondrial disorders, which I think are more neglected than others because we don't think about mitochondrial disorders when we see white matter disease; we tend to consider that mitochondrial disorders are a problem of the gray matter, but they are not. There are white matter diseases that have definitely mitochondrial. And the third category are probably microgliocytes, which are represented by the CSF1R-related disorder. And this is also something that is clearly quite prevalent, relatively prevalent, in the field of genetic white matter disorders misdiagnosed as MS. Dr Monteith: Yeah. Why don't we go through some of the, kind of, key history, you know, some of the key questions you would ask in the history to try and differentiate? You mentioned kind of subtle symptoms, longstanding progressive symptoms. I know things that we look at like relapsing/remitting and some trigger factors can actually be associated with some of these genetic disorders. So how do you approach a patient? What are some of the key questions? You talked about family history and you talked about medical history, but why don't you kind of give us a nice way to kind of hone in on to the patient? Dr La Piana: There are a couple of questions that we usually ask. I should make a disclaimer, though, that I work very closely with the MS clinics, so we are ready to receive patients that are prescreened. So, these are already patients that people working on acquired white matter disorders feel like they are atypical, so they want our opinion. But usually, there are two groups of questions that we always ask. One is about the family history. And by saying family history, I really dig into the family history. I don't just want to know whether there are family members with neurological disorders. I ask specifically about migraine. I ask specifically about infertility issues. I ask specifically about psychiatric issues. These three things are always on the top of my mind when asking about family history. The other thing is a family history for neurodevelopmental disorder, because you know that some people might not remember that some genetic white matter diseases can present at different ages. So, in the same family, there might be cases with a pediatric-onset leukodystrophy, and that can manifest at a later age in other family members. So, this is something that we always explore. In terms of the clinical history, one question that I recommend always to ask is really about more subtle symptoms. So, for example, many of our patients present with progressive balance problems or progressive mobility issues that have been going on for a while. So, we always ask how they were when they were in their teenage years, for instance. And it's frequent that they say, actually, I was a bit clumsy. Actually, I was not the first being picked in school at phys-ed sports. And these are all interesting aspects. Maybe they are totally incidental, and sometimes they suggest that there was probably something going on for a long time. The other thing is the presence, for example, of learning difficulties. Again, these are things that are subtle but testify that there was probably a process that was more longstanding. Dr Monteith: You talked about things like rim lesions. Are there other types of sequences that might be useful to better characterize demyelinating diseases that are genetic in origin? I assume higher levels of MRI might be better at differentiating. Dr La Piana: Yeah. So, in the clinical setting, there are a couple of sequences that are very useful. One is the diffusion, because as opposed to multiple sclerosis, the presence of persistently restricted areas of diffusion can point immediately towards some genetic white matter diseases. One is CSF1R-related disorders. But there are also some other, more rare tremor and ataxia syndrome that present with persistent areas of restricted diffusion as well as others. The presence of calcification. So, adding an SWI, susceptibility weighted imaging, to check not just for calcifications that can immediately orient towards some disorders, but can also identify areas of microhemorrhages that, if we are going back to the leukovasculopathies, to the genetic leukovasculopathies, can tell us that we are on the right track for excluding those type of diseases. Basically, these are the two that are available in every scanner without even going into fancy, more advanced techniques. Dr Monteith: I was going to ask you that question, how often should we think about this next-generation sequencing when you're kind of on the fence, allowing for some negative results to come back in the abundance of caution? Dr La Piana: The problem with the panel, of course, is that you run a panel and you don't know what's coming back. So, then having to deal with variants of unknown significance in genes, then you have to deal with them, and then you have to deal with results that maybe are not as black or white as you would expect initially. So, I'll answer to your question when to do that, our recommendation would be to do that every time you are presented with a patient that presents those atypical features that we summarized in the paper, and that basically raise multiple red flags for an atypical white matter disease that is not multiple sclerosis. And then what to do when you have results? I still believe that having access, of course, to genetic counselors, to neurogeneticists, is critical, but also having access and being in contact with the network of people working on this. Because we are a network; we put the website address on the paper of the white matter rounds because this is an international network that we built over the years, and we connect monthly, on a monthly basis, with meetings to discuss exactly this type of patient. So, we are all learning together, and it's very frequent that people ask us to present cases at the white matter rounds because they have a presented with unusual or atypical genetic findings and they want the opinion of experts. Dr Monteith: Great. Well, I'm really glad that resource is available. And I'm also really glad that you wrote that article with your colleague. Thank you so much. Dr La Piana: Thank you so much, Tesha. Dr Monteith: Today I have been interviewing Dr Roberta La Piana about her article on adult-onset leukodystrophies mimicking multiple sclerosis, which she wrote with Dr Gabrielle Macaron. This article appears in the April 2026 Continuum issue on multiple sclerosis. 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/index/show/continuumjournal/id/40684390

Diagnostic Neuroimaging Biomarkers for Multiple Sclerosis With Dr. Jiwon Oh 04/08/2026

Diagnostic Neuroimaging Biomarkers for Multiple Sclerosis With Dr. Jiwon Oh Novel MRI biomarkers, including cortical lesions, the central vein sign, and paramagnetic rim lesions, are highly specific for MS and can aid diagnosis in select clinical scenarios, particularly early in the disease course or in atypical presentations. When used with appropriate MRI sequences, these markers can improve diagnostic sensitivity while helping prevent misdiagnosis. In this episode, Casey Albin, MD, speaks with Jiwon Oh, MD, PhD, FRCPC, FAAN, author of the article “Diagnostic Neuroimaging Biomarkers for Multiple Sclerosis” in the Continuum® April 2026 Multiple Sclerosis and Related Disorders issue. Dr. Albin is a Continuum® Audio interviewer, associate editor of media engagement, and an assistant professor of neurology and neurosurgery at Emory University School of Medicine in Atlanta, Georgia. Dr. Oh is the medical director of the Barlo Multiple Sclerosis Program at St. Michael’s Hospital and an associate professor at the University of Toronto in Toronto, Ontario, Canada. Additional Resources Read the article: Diagnostic Neuroimaging Biomarkers for Multiple Sclerosis Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Albin: Spend any time in a neurology conference, and you are certain to hear about the new central vein sign, which, as I learn, is not actually all that new. But have you heard about cortical lesions or these paramagnetic rim lesions? Because today I have the privilege of talking to Dr Jiwon Oh about her article, and we're going to unpack all these new biomarkers in MS. Dr Jones: This is Dr Lyell Jones, editor in chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Albin: Hello, this is Dr Casey Albin. Today I'm interviewing Dr Jiwon Oh about her article on diagnostic neuroimaging biomarkers for Multiple Sclerosis, which appears in the April 2026 Continuum issue on multiple sclerosis. Welcome to the podcast. Thank you so much for being here. I'd love to start by having you introduce yourself to our listeners. Dr Oh: Thanks, Casey. Hi, everybody. My name is Jiwon Oh and I'm a neurologist, mainly an MS specialist at Saint Michael's Hospital at the University of Toronto, and I'm the medical director of our MS program. Dr Albin: And you have written a really fantastic article that dives deep into some of the nitty gritty about these new diagnostic biomarkers that we find on the MRI that we're getting for our patients with multiple sclerosis. And I think we are going to get into a lot of that nitty gritty. How do we look for them? How do they improve our diagnostic specificity? This is really come a long way in shaping the advances for multiple sclerosis. And I'd kind of like to just start with the big picture. Like why do we need these more specific biomarkers? Dr Oh: This set of diagnostic criteria in MS, it's actually a huge change in the field, and particularly for people like me who are really interested in developing new MRI measures, we're really, really excited because it's actually the first time since MRI was officially incorporated into the MS Diagnostic criteria, which was way back in 2001. It's the first time that we've actually been able to get newer, more advanced imaging measures beyond just simply detecting, new T2 lesions in the MS diagnostic criteria. So, it's a big moment in the field, and many of us are really excited about it in terms of why we need some of these newer, more specific imaging measures. Well, you know, diagnostic criteria always evolve over time for any disease state, and MS is one that we've recognized over the years. By the time someone actually presents with typical clinical symptoms and has diagnosed, whatever has been happening from a patho-biological standpoint has been happening probably for almost 5 to 10 years before that individual actually presents. And so, because of this recognition in the field and the fact that we're recognizing how important it is to first diagnose MS and then treat MS earlier and earlier, because we know that early treatment helps prevent more clinical outcomes. Diagnostic criteria over time have become much more permissive, meaning that we're doing everything that we can to try to facilitate a diagnosis of MS when we know that someone biologically has MS. But the problem with making diagnostic criteria more permissive, and it's obviously a good thing because you want to capture as many people with MS as early on as possible. The problem with making it permissive is there is this terrible risk of misdiagnosis. As clinicians, we all think we never make mistakes. But it turns out when you actually do studies, you do. And even at MS specialty centers, when studies have been done, 10% to 20% of people with MS are misdiagnosed. So, this is exactly why we need in diagnostic criteria that really help to facilitate a diagnosis. We need things that help us prevent misdiagnosis as well. And these are these specific imaging measures that have now been incorporated into the diagnostic criteria in many settings that will help to facilitate a diagnosis. But the really big perk is if you use them, you can help to prevent misdiagnosis as well. Dr Albin: Yeah, that really shone through in your article that this was such a big step in towards being more specific about who were diagnosing. Also capturing more people, right? Trying to get those people that we, we don't want to miss because of all the things you say, you know, that allows them to accumulate more disability, have worse outcomes. Early diagnosis is so important. But I really did take away from your article just how critical these are and sharping our diagnostic acumen. And so just to jump right in, and you describe these three new biomarkers, these cortical lesions the central vein sign and paramagnetic rim lesions. And so just to kick things off let's start with cortical lesions I sort of conceptualize multiple sclerosis a disease of white matter. So, what's going on here? Dr Oh: Yes. MS classically has always been described as a white matter disease. But it turns out when you look at brain and spinal cord tissue, as well as when you use kind of better sequences to actually look for lesions in the gray matter, it actually turns out there's a ton of lesions in the gray matter as well. And in fact, what's interesting is that regardless of whether it's the cortex or the deep gray matter, it's lesions within these areas that seem to have the highest relevance for clinical disability in MS. So, all this to say, of course, MS is a lesion that does affect white matter, but it also affects gray matter a lot. And maybe pathology within the gray matter is even more relevant to clinical disability. So, this is why we're really interested in being able to develop methods using MRI to more accurately visualize the gray matter, particularly the cortex, as well as deep gray matter structures like the thalamus. I should add the caveat that cortical lesions were actually included in the 2017 diagnostic criteria revisions, but they were included together with juxtacortical lesions, which are a typical area that MS lesions form. And so, this imaging measure, despite the fact that it is relatively novel and we consider it advanced, it hasn't been used that much only because it's not that easy to detect lesions within the cortex. And reasons for this include that you usually need higher field magnet platforms. And so, the typical clinical MRI scanners that are available kind of widely, regardless of whether you're at an academic center or a community center, are 1.5 Tesla magnets. And cortical lesions are actually really difficult to detect on those typical scanners. But when you get to like, say, three Tesla or seven Tesla, they're a lot easier to detect. But obviously that's a big hindrance to widespread use. And then you actually need very specialized sequences to adequately visualize cortical lesions. And these are not sequences that are usually collected for clinical purposes. So, it kind of requires convincing your radiologists that you need this additional sequence. And then it actually takes a lot of time and training to be able to adequately, accurately detect cortical lesions. So, despite the fact that it's actually very useful when you do have the appropriate MRI sequences and scanners to detect cortical lesions, even though they were incorporated into the 2017 criteria outside of specialty centers, they're not actually widely used. But when you do have the appropriate sequences, cortical lesions are actually pretty specific for MS. So, very helpful for a diagnosis in certain settings. But there's all these practical limitations that have really limited its widespread use. Dr Albin: That is a beautiful summary. So, it sounds like once we kind of get up to speed in terms of like the protocols for this, having the magnet strength for this, this will be really a game changer in terms of increasing the specificity and also maybe finding things that impact patient's clinical presentation and therefore quite meaningful. But it sounds like for most of us, this is probably not something that they're going to be adopting right away. Is that a fair assessment? Dr Oh: Yes. And you know, they were included in the last diagnostic criteria revisions. And it really hasn't changed things very much, only because of these difficulties with, you know, requiring higher field magnet strengths and these specialized sequences and then needing training to kind of figure out how you can adequately detect cortical lesions. Dr Albin: Totally. So, the other thing we've heard a lot about, and I have to say, I was in the AAN fall conference not too long ago, and this came up quite a bit, was the central vein sign and the fascination with that, because it tells us a lot about the MS pathophysiology and again, increasing that specificity. And it seems like maybe this is one that we can more easily adopt in clinical practice. So, tell our listeners about what that is, how they detect it. How many do you need to find? Dr Oh: Sure. And so, this is one of the imaging measures I'm really excited about. So, the central vein sign heard about it recently. And probably in the last ten years particularly in the MS field we're talking about it all the time. But just wanted to emphasize that the central vein sign is not something that is new. Even back in the 1800s, when Charcot described MS lesions in these ancient textbooks, he actually very clearly described that MS lesions form around the central vein. And that makes sense, because we know that these waves of peripherally mediated inflammation somehow get through the blood-brain barrier and cause this cascade of events leading to inflammation in the brain and spinal cord, which is what MS is. But we know that B cells in T cells require veins to get into the central nervous system. And so, it's no surprise, really, that MS lesions form around veins. And so, this is something that's been known pathologically. But the reason we're so excited about it now is because we actually have good enough iron-sensitive MRI sequences that allow us to see a central vein when it is present within a white matter lesion. As a neurologist, we know that there's probably hundreds and hundreds of different things that can cause white matter lesions in the brain. But when you use an appropriate iron-sensitive sequence and you see that many of them, if not most of them, actually have visible central veins, that tells you that this person very likely has MS. And so that's why we're so excited about it, because there have been many studies done in the last ten years. In fact, so much evidence generated in the last ten years that there have been I think it's now four systematic reviews and meta analyzes. Looking at the diagnostic properties of the central vein sign. And, you know, it turns out that when you look at people with MS, most of them have a pretty high proportion of white matter lesions that have visible central veins. And there's a lot of questions about, you know, how to best use the central vein sign. But when 40% or more of the white matter lesions that you see have visible central veins, then the likelihood of a diagnosis of MS is very high. So, this is why we're so excited about it in the MS field because it's a really useful diagnostic tool. You know, again when you have appropriate ion sensitive sequences, if you see someone with white matter lesions and you see that 40% or more of them have visible central veins, this tells you that this person very likely has MS. Dr Albin: So, Dr Oh, I hear you say, you know, 40% of the lesions. Does that mean the neuro radiologist needs to look at every single lesion and then count how many have the central veins, or is there an easier way to do this? Dr Oh: Great question. Casey, there is definitely an easier way because our neuro radiologists would not be our friends anymore if we made them look at every white matter lesion and make sure that 40% of them had the central vein sign. So, because it's so time-consuming to use that 40% threshold, there's an easier criterion that has actually made it into the diagnostic criteria. And it's called Select Six. And what this means is when you have more than ten lesions, as long as you show that six of them have a visible central vein, you just have to count six with the central vein. Then you're done. So that means you're Select Six positive or central veins nine positive. However, if you have ten or fewer lesions, as long as you show that more than 50% of them show a visible central vein, then you are select six positive, and then you're done. So, as you can see, it's a much simpler criterion to apply, and it seems to perform almost as well as that 40% threshold, which is why that is the criterion that's made it into the new diagnostic criteria. Dr Albin: Perfect. I love that we definitely do not want to make enemies with our neuro radiology colleagues, but yet they do so much for us. So perfect. I'm glad that we can, make their jobs a little easier without losing any specificity there, or just losing a touch of specificity there. All right. If I am working with a, you know, in a center that maybe doesn't do this all the time, am I just getting a run of the mill SWI sequence? Do I need to ask my radiologist for a special sequence? Or is this just, you know, you can get it from the typical array of what our patients are getting. Dr Oh: You know, SWI is a widely available commercial sequence that's iron-sensitive, the ones that are typically commercially available, they can detect central veins, but there actually are little tweaks that you can do to make it a little more optimal. With the recent diagnostic criteria publication, which was, led by Xavier Montalban and recently published in Lancet Neurology. There's actually a companion MRI paper that was led by Frederick Barkov and Danny Wright. And the reason I'm specifically citing those papers is in that companion MRI paper, there's a table that has kind of optimal sequence parameters that you can use even with a conventional SWI sequence, to try to best detect the central vein sign. And then there's a wide range of different iron-sensitive sequences, and SWI is one of them, but the one that seems to have emerged as most sensitive to detect the central vein sign is something called the 3D T2*-EPI sequence. But the bottom line is there's a whole bunch of different iron-sensitive sequences that you can use, little tweaks that you can do to make them optimal, to be able to visualize central veins when they're present within white matter lesions. Dr Albin: Incredible. So like partner with your neuro radiologist, there is a great sounds like a field guide almost to this. So, it makes it easy to pick up in your standard of care so that you can make sure that you are detecting them at the optimal level to see that more specific diagnostic biomarker. Dr Oh: Yes. And you know, in contrast to what we were talking about with cortical lesions, you can actually detect central veins when you use these iron-sensitive sequences at any field magnet. So even at 1.5 Tesla, particularly when you use contrast, which is often given with the diagnostic scan anyway, you can very easily detect a central vein. So that's a huge benefit because it allows for widespread use. As long as you work with your radiologist to get the right iron-sensitive sequences in. Dr Albin: Yeah, that's incredible. I mean, I think that it really will be practice-changing. And then the last one that I think was honestly new to me, I feel like I had heard a lot about the central vein sign, but the whole new to me term was this paramagnetic rim lesion. So, what does that tell us about the underlying biology of MS? And are there any other things that might also have this finding that we should sort of be aware of? And how specific is it? Dr Oh: You know, the central vein sign is kind of the main, really new imaging measure that's made it into every part of the MS diagnostic criteria. And then together with that paramagnetic rim lesions or we call them PRL or pearls for short, they've made it as well, but in a much more limited way only because there's not as much evidence that has accumulated over time to support the diagnostic utility of pearls. But first of all, what are pearls? So, people in the MS field are really excited about pearls, because we know that they capture a subset of what we call chronic active lesions. So, MS lesions will form acutely and over time, some of them will become inactive. And then some of them are chronic active lesions, meaning that they have this rim of activated microglia around them. Over time, they continue to slowly expand. And it's almost like this slow burn. And the reason why we focus a lot on chronic active lesions is because we know that they're a driver of progressive disease biology and MS, meaning that in people who have progressive MS or who have pretty severe disability, global disability or cognitive disability, we know that they have a high burden of pearls. And so that's why there's so much excitement in MS about being able to image chronic active lesions. It's because we're always looking for an imaging measure that allows us to accurately predict progression or to, measure progression over time. So that's why there's so much excitement in MS about pearls. But as kind of an added bonus, it turns out pearls are also really specific for MS. And so, when you use the same iron-sensitive sequences, by the way, that's used to detect the central vein sign when you use appropriate iron‑sensitive sequence. And if you see that someone has a pearl, the likelihood of a diagnosis of MS is very high. The one exception to that is Susac syndrome, where pearls have been observed. But other than that, with many other white matter diseases like neuro rheumatology disease, NMOSD, MOGAD, you really don't see pearls. And so, this is why it's made it into the new diagnostic criteria. In contrast to the central vein sign, though, not everybody with MS has a pearl, so the sensitivity isn't as high. However, it's really, really specific in the range of, you know, 90 to 95%. So, this is why it's been added as, an imaging measure in certain settings. It can help facilitate a diagnosis. But the real utility, again, is when you use it, it helps you to prevent misdiagnosis. Dr Albin: It's fantastic. And hearing you talk about that, this one stands out to me as a biomarker that not only helps... /episode/index/show/continuumjournal/id/40684210

April 2026 Multiple Sclerosis and Related Disorders Issue With Dr. Andrew J. Solomon 04/01/2026

April 2026 Multiple Sclerosis and Related Disorders Issue With Dr. Andrew J. Solomon In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Andrew J. Solomon, MD, FAAN, who served as the guest editor of the April 2026 Multiple Sclerosis and Related Disorders issue. They provide a preview of the issue, which publishes on April 2, 2026. 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. Solomon is the Division Chief of Multiple Sclerosis and a Professor in the Larner College of Medicine at the University of Vermont in Burlington, Vermont. Additional Resources Read the issue: Subscribe to Continuum®: Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Jones: It's been more than 150 years since Jean-Martin Charcot first described the disease that we now know as multiple sclerosis. Since then, the tools we have to diagnose and treat this disorder have expanded enormously. So why are the diagnostic criteria for MS. still evolving? Today we're speaking with Dr Andrew Solomon, guest editor of our latest issue of Continuum on MS and related disorders. To learn more about this question and much more. Dr Jones: This is Dr Lyell Jones, editor in chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about subscribing to the journal, listening to verbatim recordings of the articles, and exclusive access to interviews not featured on the podcast. Dr Jones: This is Dr Lyell Jones, editor in chief of Continuum, Lifelong Learning in Neurology. Today I'm interviewing Dr Andrew Solomon, who is Continuums guest editor for our latest issue of Continuum on multiple sclerosis and related disorders. Dr Solomon is a professor of neurological sciences at the University of Vermont, where he also serves as the division chief of multiple sclerosis. Dr Solomon is an internationally recognized authority on MS, particularly on the diagnostic approach to this complex disorder. Dr Solomon, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners? Dr Solomon: Hi, everyone. This is Andy Solomon. It's a pleasure to be here with you. And I feel honored to have helped this collaborative effort that created this important tool for trainees and clinicians in practice, the Continuum issue on multiple sclerosis and related disorders. Dr Jones: Obviously, we're grateful that you've taken us on. A lot has happened in the world of MS and other neuroinflammatory disorders in the last few years, so lots to update. But as we've done over the last few podcasts, I'm going to start off the interview today, Dr Solomon, with a trivia question. And then we'll come back at the end of the podcast and give the answer. So, the trivia question is this. There are now more than 20 drugs approved by the FDA for the treatment of MS. What was the first disease-modifying therapy approved for MS? And when was it approved? So, don't answer because I know you know the answer. But we'll come back to it at the end of the interview. And our listeners can think about that question. So, let's get right to it. As many of our listeners know, the diagnostic criteria for MS. were recently revised. And you were involved with that revision. So, you're the perfect person to ask what were the major changes in the 2024 McDonald criteria, and why did we need to update them in the first place? Dr Solomon: I'm very excited about the 2024 McDonald criteria, and it was an honor to be part of that process that resulted in that manuscript. When we revise the diagnostic criteria for MS usually it's driven by accumulating data that suggests some changes or revisions might help us diagnose patients either earlier or with more accuracy. And that's certainly the case with this criteria. There was accumulating data that suggested some particular changes were important. You know, there's a lot of expert opinion involved as well. You know, there's many experts who are involved in the collaborative decisions that go into these revisions. And some of the changes in our field also pushed some of the revisions to where maybe there's not as much evidence, but where we felt it would improve care for patients with MS. This criteria, I would argue, is probably one of the most substantial revisions in over 20 years. There's multiple changes that are potentially impactful for the diagnosis of MS. Some very important changes involve the incorporation of new paraclinical tools that we can use to assess the visual pathway, as well as, imaging tools that provide high specificity for MS that we can use to substitute or dissemination in time, for instance, as well as other tools that may allow us to diagnose patients earlier than we would have in prior criteria. There's also some opportunities with the new criteria to potentially provide access in regions where some tools are more available than others. For instance, the incorporation of Kappa Free Light Chains as a substitute for oligoclonal bands may open up opportunities in regions where expertise for oligoclonal band testing are not available. That's a very qualitative test, whereas Kappa Free Light Chain index is more quantitative, less expensive and may allow CSF testing to be performed to aid the diagnosis of MS in some regions where it wasn't available previously. This criteria provides multiple pathways to the diagnosis of MS, many more than we've had in prior criteria. So, it's important to emphasize that while there's all these new tools and changes that have been incorporated, not every pathway needs to be available where you practice. What it incorporates as flexibility. It is a bit more complex looking at all of these different possibilities, but the point is this flexibility allows clinicians or providers to diagnose MS early with high accuracy based on the tools they have available. Dr Jones: I think it will be a learning curve, right? I think any time we make a change in how clinicians get accustomed to approaching a diagnosis of a disorder, it will take some time for folks to incorporate it. And I see what you mean about the complexity, but I think that's a really great point, that emphasizing the different pathways to the diagnosis is really a strength of the revision, right? Dr Solomon: I agree, I think, you know, in other disorders, particularly if you think about rheumatologic disorders, systemic rheumatologic disorders or inflammatory disorders, where over time we've not had very highly specific and sensitive biomarkers. And we've incorporated a variety of clinical and prior clinical findings, testing, laboratory testing and biopsy and other things to confirm a diagnosis. These approaches to these disorders are sort of a checklist. And I think that clinicians became familiar with that approach and were able to make diagnoses accurately this way. And I think of the new criteria in a similar way. It's not quite amenable to a checklist, but the pathways are sort of simplified with multiple options. Hopefully, using the figures, clinicians can look at the paper and see what tools they have available to help them confirm a diagnosis of MS. I think it's really important to emphasize that the diagnostic criteria for MS still does not discriminate MS from other disorders. Everyone who's listening here, you do, the clinicians do. So, to enter the diagnostic criteria and these pathways, we first have to feel confident that the patient has a clinical presentation and an MRI presentation or MRI findings that are highly suggestive of MS. That aspect of the criteria hasn't changed since, the Schumacher criteria in the 1960s. This concept of no better explanation. So, we still need to know what's typical for MS. And we need to know what signs or symptoms or findings are that might suggest another disorder, because the criteria are really only validated and tested in patients who have these presentations to start with that are typical for MS. A major change in this particular criteria is that we can now diagnose patients who are asymptomatic. Previously just called radiological isolated syndrome. Not every patient with an MRI finding concerning for MS and now being diagnosed with MS. There's other features that, must be present, but even more than before, knowing what the typical appearance of MRI lesions suggestive of MS, it is even more critical now than it was before, because in those patients who have either no symptoms or a nonspecific presentation, if we have an MRI that's highly convincing for MS and some other prior clinical findings, we can make the diagnosis. But we first need to know with some confidence what that MRI should look like. Dr Jones: So, there is a little circularity when we do these diagnostic criteria. I think our listeners who see patients will be reassured that the clinician is still in the loop. We haven't been automated out of the process yet. Dr Solomon: We need a highly sensitive and specific biomarker or a set of biomarkers for MS. We're getting closer with some of these advanced imaging findings like central vein sign and paramagnetic rim lesions. But not every patient can be diagnosed with those. And they're not required for the diagnostic criteria. In lieu of a highly sensitive and specific test. Our clinical acumen, for what we find a neurologic exam. And what we see on imaging in particular, is quite critical for ensuring that the criteria perform as well as we hope they will. Dr Jones: So, you've had the opportunity, the vantage point, to review all of these articles covering a wide variety of topics, MS, other neuroinflammatory disorders like aquaporin‑4–positive neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease, MOGAD. Anything that surprised you in these articles as you were reading through them? Dr Solomon: I think maybe for listeners, what may be surprising to some of them is that despite guidelines surrounding the use of some of our disease modifying therapies in pregnancy and breastfeeding that are published by regulatory authorities in the United States or Europe or other places, we are making other decisions for patients based on the data we have, the best data we have. Thinking about family planning is really important for us with patients who are newly diagnosed with MS, as well as through the course of their disease. This is a conversation we should be having shortly after diagnosis, because there are strategies we can take to minimize the risk of exposure of DMT around conception and to make plans for how we're going to think about DMT surrounding breastfeeding, to ensure the health of mom and the baby, and reduce risks as much as we can with the knowledge we have. I think in medicine it's quite common for us to use medications off label, right? I mean, so medications are often FDA approved for one indication. And in neurology, for instance, we find a lot of medications after their approval were quite effective for migraine prophylaxis for instance. Right? And so, it's not unusual for us to prescribe medications beyond the label. And I'm not suggesting that we necessarily ignore the advice of our regulatory authorities. But sometimes the data is accumulating really fast around some of these therapies after they’re approved. Sometimes we can look towards experts and how we can navigate pregnancy and breastfeeding in MS. Dr Jones: I think that's a great point about the importance of family planning and having to use judgment. I do want to highlight to our listeners and our subscribers a fantastic article in the issue on family planning and MS and other neuroinflammatory disorders. This was written by Dr Ruth Dobson and Dr Kersten Hellwig, and I think it covers a lot of that gray area where we have to use our clinical judgment to manage these diseases in the absence of a regulatory approval. And I think, again, that's an important gap that the issue fills. And really, that's just a wonderfully written article that I think is a must-read. So, we cover lots of topics in this issue. And one of them is again a relatively newly characterized disorder, MOGAD. What's the latest in the world of MOGAD, what should our listeners be aware of? Dr Solomon: I agree, I think we're in an exciting time in CNS inflammatory disease. And this is a recently described disorder. You know, and the diagnostic criteria now is only a few years old. So, I think importantly, readers should be aware of the diagnostic criteria. This is something that, really will help us distinguish this disorder from NO spectrum disorder and MS. There's a key overlap between the MS diagnostic criteria and MOGAD. Two decades ago we saw a pediatric MS included somewhat atypical presentations like bilateral optic neuritis or acute disseminated encephalomyelitis. And we had caveats in our approaches to pediatric presentations of presumed MS, suggesting that there could be something very different than adult MS. Subsequently, we've realized that pediatric MS presents quite similarly to adult MS in terms of its clinical syndromes and MRI appearance, and many of those pediatric patients who had initially been diagnosed with MS and MOGAD. MOGAD is actually probably more common demyelinating syndrome in patients who are under 12 years old. So, the MS diagnostic criteria requires testing for MOG-IgG with a good assay, a cell-based assay, any patient being evaluated under the age of 12 or with a demyelinating syndrome to avoid misdiagnosis. Dr Jones: Thanks for that. Obviously, MOGAD is one of several disorders that have been more recently characterized and, something that our readers need to be familiar with, and there's plenty of updates within the issue on that and other topics. Okay. So now back to our Continuum audio trivia question. And just to remind our listeners, there are now more than 20 drugs approved by the FDA for the treatment of MS. What was the first disease-modifying therapy approved for MS? And when was it approved? Dr Solomon, do you want to take the honors and answer the question? Dr Solomon: Sure. It was way back in 1993. You had to get on a wait list, I believe, initially to get on it. There was some sort of lottery, and it was Betaseron. Dr Jones: Betaseron in 1993, was the first disease-modifying therapy approved by the FDA for the treatment of MS. It just shows how much water under the bridge we've had since then. 1993 was also the first year of the Jurassic Park series of movies. It was the biggest movie of the year, the song of the year in 1993 was “I Will Always Love You” by Whitney Houston. It was also the year you can tell that I look back into 1993 to see what else happened. It was also the first year the World Wide Web became publicly available, which is it kind of puts brackets on the era or the epoch of MS disease modifying therapy. And finally, the Super Bowl champs that year were the Dallas Cowboys, who unfortunately, have not had much luck in Super Bowls since the 1990s. Maybe they will have more opportunities like we've seen with MS therapeutics. So, Dr Solomon, I want to thank you for joining us today. I want to thank you for such a wonderful discussion of the latest in MS. I think the updated diagnostic criteria are really going to be critical for our listeners to understand and incorporate into their practice. Really grateful for your leadership of the issue, putting together a really stellar group of experts for all of our articles and grateful for your time today. Thank you for joining us. Dr Solomon: Thanks so much for having me. Thank all the other listeners out there for joining us as well. I'm really excited about this issue of Continuum. Dr Jones: Again, we've been speaking with Dr Andrew Solomon, guest editor of Continuums most recent issue on multiple sclerosis and related disorders. Please check it out. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the Journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. Thank you for listening to Continuum Audio. /episode/index/show/continuumjournal/id/40683385

Neurologic Complications of Drug and Alcohol Use With Dr. Adeline L. Goss 03/25/2026

Neurologic Complications of Drug and Alcohol Use With Dr. Adeline L. Goss Neurologic complications of substance use may be the first symptoms that lead patients with substance use disorders to seek care. Neurologists have a key role in identifying patients with substance use disorders and connecting them to treatment. In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Adeline L. Goss, MD, author of the article “Neurologic Complications of Drug and Alcohol Use” in the Continuum® February 2026 Neurology of Systemic Disease 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. Goss is a neurohospitalist and associate chief of neurology for Highland Hospital in Oakland, California. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Jones: A big part of neurology is solving mysteries. Patients can show up with all kinds of mysterious symptoms. Sometimes the diagnosis comes from within, some internal disruption of neurophysiology. But sometimes the problem is a complication of drug or alcohol use. Today we have the pleasure of speaking with Dr Adeline Goss, who recently authored an article for Continuum on this exact problem, a topic all neurologists need to be familiar with. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today I'm interviewing Dr Adeline Goss, who recently authored an article on the neurologic complications of drug and alcohol use for our latest issue of Continuum on the neurology of systemic disease. Dr Goss is a neurohospitalist and the associate chief of neurology at Highland Hospital in Oakland, California. She's also an accomplished writer, broadcaster and podcaster. Dr Goss, welcome, and thank you for joining us today. Why don't you introduce yourself to our listeners? Dr Goss: Great to speak with you, Dr Jones. Yes, I'm Adeline. I also go by Addie Goss. Dr Jones: So, before we get into the discussion, we're going to start off today with something fairly new to the podcast, the Continuum Audio trivia question. So, we all know that alcohol and other substances have many potential complications in that use of these substances fluctuates over time. But this one stood out to me from your article, Dr Goss, just for the sheer size of the change. So, for our listeners, here's the question. Accidental exposures to what substance increased a whopping 1,375% between 2017 and 2021? I'll read that again. Accidental exposures to what substance increased 1,375% between 2017 and 2021? So, stick around to the end of our interview for the answer. And let's get right to it, Dr Goss. If you had a single most important message to our listeners from your article, what would it be? Dr Goss: Well, I mean, many of us went into neurology because of the way that neurologic illnesses can be life-changing for patients. And I work as a neurohospitalist at a public hospital in Oakland, California. Many of my patients are admitted for neurologic conditions related to substance use. And when I see my patients later in the discharge clinic, many tell me that the last day that they used meth or the last day they used cocaine, the last day they smoked, was the day they had their stroke or whatever they came into the hospital for. I think the most important message is that hospitalization for a neurologic condition related to substance use can interrupt use patterns, can motivate change. And therefore, as neurologists, we really have an opportunity to connect to our patients and connect our patients to substance use treatment and make a dramatic difference in people's lives in this regard. Dr Jones: I think that's a fantastic point. I enjoyed a point you made in your article---and I can't remember exactly how you phrased it, I won't say it as well---that you think of the syndromes through which alcohol and drug exposures can present. Those syndromes almost always could end up of other primary neurologic disorders. So, put a different way, when a patient presents with a neurologic problem, most of the time an exposure could be on the differential. And so, we really do have a responsibility as neurologists to be familiar with these. Dr Goss: To be familiar with these and to know how to connect patients to resources to try to get treatment. Dr Jones: Totally agree. And you touched on the public health aspect of this. It's really hard to talk about drug or alcohol use without acknowledging the public health impact particularly of opioids, which has been a crisis for most of this century. Right? And I think most of our listeners will be familiar with the rapid rise in opioid-related deaths. But there might be a glimmer of optimism there. Is what I've seen true, that opioid-related deaths may have plateaued? Dr Goss: So, yes, it's true that opioid-related deaths, overdose deaths in general, have begun to decline, actually, since 2023. And that's in part because overdose deaths really surged early on in the Covid-19 pandemic, in the setting of all of the social disruption, reduced access to services, and social isolation that occurred with the pandemic. But there were really multiple factors there. So, as you mentioned, there was this really rapid rise in illicitly manufactured fentanyl. Fentanyl became a major driver in overdose deaths starting in the mid-2010s. And by the late 2010s, it overtook heroin and prescription opioids as drivers of overdose deaths. And then this just collided with the pandemic in 2020, causing skyrocketing deaths. So, as we know as neurologists, fentanyl is more potent, it's shorter-acting, and it's also cheaper than heroin. It can cost as little as 50 cents or a dollar a pill. Thankfully, as services have rebooted and also as naloxone has become more widely distributed, there has begun to be a decline in opioid overdose-related deaths. So, we're relying on provisional data from the CDC for the most recent years, but that shows about a 24% decline in annual overdose deaths, comparing late 2023 to late 2024. And that's real. That comes out to 70 lives saved per day. Unfortunately, deaths still remain above prepandemic levels, and we're still talking about 87,000 drug overdoses per year. So, I would agree, a glimmer of hope. But we're still seeing overdose as the leading cause of death among young Americans aged 18 to 44. And there's a very long way to go. Dr Jones: 23% is a big number, and that is certainly exciting to think about, but we're still above that long-term secular trend. So, hopefully whatever is happening to bring that down, hopefully it continues. And we talk a lot about- appropriately, we talk a lot about opioid exposures and some of the neurologic presentations of opioid use and toxicity, but alcohol use disorder is the most common substance use disorder, correct? I learned that from your article. And it has been for some time, and it has well-known acute and chronic toxicities. But I think many of us have been taught something of a myth in the acute treatment of patients who may have thiamin deficiency or Wernicke's encephalopathy. Can you tell us a little more about that? Dr Goss: Yeah, sure. So, boy, what is my favorite vitamin? As a neurologist, I think thiamin is my favorite vitamin. Thiamin is a cofactor in- for several enzymes that are involved in glucose catabolism. And it's necessary to synthesize myelin and several neurotransmitters. And as we know, alcohol use disorder leads to reduced nutritional intake and impaired digestion and absorption of nutrients. And this can lead to deficiencies in water-soluble B vitamins, including thiamin, as well as trace elements. The thing about thiamin is that thiamin deficiency often appears first, because the body's stores of thiamin deplete in about 4 to 6 weeks. You know, we're traditionally taught if a patient presents with symptoms concerning for Wernicke's encephalopathy, that if they're also hypoglycemic or just in general, we have to get glucose into them first, because we don't want to tax these thiamin-dependent glucose catabolism pathways. But really, there's no reported case of a single glucose bolus precipitating some dramatic symptomatic thiamin deficiency. It's thought that harm would come potentially from prolonged carbohydrate administration without thiamin. And so, if a patient in front of you is both thiamin deficient and hypoglycemic, you just treat both. You treat both emergently. But it doesn't really matter in what order you do so. Dr Jones: That's good to know that doing the right thing for the patient can involve using either of those in whatever order. And I agree with you, I don't think I've ever hurt anybody by giving them thiamin. It's an easy one to miss and an important one to remember in the right context. And speaking of, and I think a lot about in your article, Dr Goss, I can see a neurologist seeing a patient in the emergency department or in the hospital or even in the clinic thinking about the wonderful points in your article. But we know that when alcohol or substance use enters our mind on the differential, the next impulse is to test for it. And we also know there are pitfalls of drug screening, doing urine drug screens, etc. How do you approach testing when you think about a potential drug-related complication in their differential? Dr Goss: So, like most people, I would start with a urine drug screen for any patient who's presenting with a possible toxidrome or some substance-related neurological presentation. These urine drug screens, they're rapid, they're inexpensive, they're immunoassays for traditional drugs and their metabolites. So, usually amphetamines, cocaine, opiates, plus/minus cannabis. But I think the first thing to note is that they miss entire categories of drugs, and not just drugs that are not in that list. They miss synthetic opioids, including fentanyl. One group is keeping track of this number. So, I have an update for mid-2025. And that's that 30% of U.S. ED overdose encounters as of mid-2025 included fentanyl testing. Only 30% for patients who are presenting with an overdose syndrome. Dr Jones: And that's for one of the most widely used synthetic opioids. So that's really a striking number. Dr Goss: Yeah, one of the most widely used and one with the greatest rate of complications. So, states can make a difference here. In 2022, California passed a law requiring fentanyl testing on hospital urine drug screens and several states have followed. And so that number is rising, the rate of testing for fentanyl. But that's just a really key thing to know, that that one is often missed. Other just important pitfalls, the timing of the urine drug screen matters because for most substances, it only picks up the drug within 24 to 72 hours after the last use. With amphetamines and cocaine going out a couple more days after that, especially in patients who use repeatedly. And then also, notably, there's a risk of false positives. This is especially true with amphetamine use, and beta blockers are one of the drugs that can lead to false positives on an amphetamine test, on a urine drug screen. So, I'll share that I've had several patients who have presented with intracerebral hemorrhage and who tested positive on the emergency department’s urine drug screen and who adamantly stated that they do not use amphetamines, they've never used amphetamines, and they didn't ingest anything that could have contained amphetamines. And when we did serum confirmatory testing, in fact, their amphetamine testing was negative, and all those patients had received esmelol or the labetalol in the ED to treat their blood pressure related to their ICH. So false positives can occur with, you know, other medications like decongestants and certain antidepressants. But beta blockers are a key one to know. And then finally, there are just a number of things outside of that short list of substances that I mentioned, including a huge range of novel psychoactive substances that would not be tested for on a standard urine drug screen. And for those, you'd require serum testing, or at some large academic centers or specialty toxicology labs, you can actually do liquid chromatography high-resolution mass spectrometry, with- which is basically unbiased testing for any substance that's present in the patient sample. So, I guess, you know, you asked about my approach. Start with the urine drug screen, but there's no substitute for good history-taking and close examination of your patient's general examination, not just their neurologic presentation. And if patients are presenting with a toxidrome that I would expect would show up on a urine drug screen but it's negative, there are other confirmatory tests that can be sent, although they're often send-out labs and come back in a very delayed fashion. Dr Jones: So, in other words, it's complicated, which usually means it's humbling. And if I'm understanding it correctly, there's the risk of the false positive on the urine drug screen. And then there's the risk of the false negative if we think we're screening for something that might not even be on that initial screen. So, that's a wonderful reminder that these are clinical diagnoses and we have to keep our clinician hats on while we're thinking about how to establish these diagnoses or exclude them. So, back to opioids, Dr Gross. There are some really peculiar neurologic syndromes associated with opioid overdose. Tell us a little about those. Dr Goss: Well, I mean, some of these were described first with heroin. So, we can start with the one that almost anybody has heard of, heroin-associated spongiform leukoencephalopathy, which we know is associated with a practice known as “chasing the dragon,” which is inhaling vapors of heroin heated on foil. But we know now that this syndrome can occur with other opioids, including fentanyl. The clinical features are, you know, apathy, cerebellar signs, quadriparesis, parkinsonism, myoclonus, and some patients progress to coma or even death. But on MRI you're seeing, you know, these confluence symmetric white matter diffusion restriction and T2 hyperintensities in the cerebellar white matter and the posterior limb of the internal capsule that spare the subcortical U-fibers. So, you know, I think this is kind of the classic example of something that's symmetric, that has a very obvious and interesting MRI pattern. But as time is passing, we're seeing more and more similar types of syndromes of leukoencephalopathies, but with different clinical presentations and MRI characteristics. So, another of these is CHANTER syndrome. This is an opioid overdose-related presentation where people have stupor and coma. And on the MRI there, you see bilateral symmetric diffusion restriction in the cerebellar cortex, in the hippocampi, in the basal ganglia. And it spares the cerebral cortex. And notably in these cases, patients can progress to cerebellar edema, to obstructive hydrocephalus. And some require suboccipital craniotomy. I had a week recently at Highland Hospital, where I work, where we had two of these cases in the same week, in just a community hospital. And there's a similar syndrome in children known as POUNCE syndrome with profound cerebellar edema, and many patients require posterior decompression. So that's another different distribution of findings with a different outcome. Fortunately, there's a milder sort of phenotype of opioid-associated amnestic syndrome, is what it's been described, where there's primarily DWI changes in the hippocampi and the globus pallidus. So, patients primarily present with an amnestic syndrome, mostly anterograde amnesia. Seeing these in practice, I'm not sure that patients always fall into one bucket or another. But in general, you'll see some degree of symmetric diffusion restriction or symmetric white matter changes that clearly point to a toxic presentation, a toxic syndrome, as opposed to pure anoxia, for example. And it's important to know that because from a prognostic standpoint, anoxic brain injury, which can occur after cardiac arrest and after opioid overdose, can look different than some of these syndromes. Finally, heroin has been associated with myelopathy, but also that's been reported on with fentanyl. So, I think some of these conditions got their reputation from heroin. But as fentanyl has proliferated---and prior to that as prescription opioid, you know, misuse had proliferated---we're seeing similar syndromes with all of the opiates. Dr Jones: And I think it's a good case in point that you can have multifocal disease and it be a manifestation of an intoxication, and I think that's a really good reminder that we have to have many of these syndromes in our differential, we have to be aware of them, otherwise we might miss them or attribute them to another mechanism. Dr Goss, our last issue of Continuum that was dedicated to the neurology of systemic disease came out in 2023, and here we are in 2026 publishing our latest issue, including your article and this podcast. Since 2023, have there been any emerging patterns or novel agents of abuse or misuse out there? Dr Goss: The short answer is yes, and I would say the reason is just the supply is moving at more and more rapid speed. The relationship between the internet and drug supply has really informed what's out there at any given moment. So, the turnover in the market can change in weeks, not in years. And there's all of this distribution through social media and encrypted apps. And then manufacturers are kind of continuously tweaking chemical structures to evade law enforcement. In the process of researching this article, I came across some, I mean, really wild examples. To be clear, these are not- not all these are common substances, but I think the general phenomenon should be known that people can walk into a vape shop or walk into a gas station or meander around online and buy some really weird stuff. So, in 2024, there was this nationwide recall of a product called Diamond Shrooms that was sold online and in smoke and vape shops, and this was billed as, like, a hemp and mushroom mixture. But it led to multiple- I mean, over 100 cases of seizures and agitation and depressed consciousness and a few possible deaths. And when the contents were analyzed, they included psilocybin analogs and pregabalin. I mean, some weird stuff. And so, those have been pulled. But people are constantly inventing and marketing these different substances. I think another example… we all know about nitrous oxide and its association with B12 myopathy. But the use of nitrous oxide has really changed. Companies are selling large canisters online and in vape shops, and they're flavored, like, in blue raspberry flavor. And unfortunately, there's been a rise of nitrous among youth. So, we're seeing not just increased cases of myelopathy, but also a 2025 study in JAMA found a spike in deaths attributed to actual nitrous oxide overdose. And so nitrous, I think, had not been that commonly used a few years ago, but has become more common in the last couple of years. A final one I'll just mention is ketamine. So, ketamine has certainly appeared in reviews of neurological syndromes related to substance use for a long time, and it's also been studied and used off-label for mood disorders in outpatient infusion clinics... /episode/index/show/continuumjournal/id/39968225

Neurologic Complications of Pregnancy and Menopause With Dr. Sara C. LaHue 03/18/2026

Neurologic Complications of Pregnancy and Menopause With Dr. Sara C. LaHue Neurologic care during pregnancy and menopause requires careful attention to the dynamic interplay between hormonal transitions, evolving evidence on diagnostic and treatment safety, and the lifelong risks associated with neurologic complications of pregnancy. In this episode, Katie Grouse, MD, FAAN, speaks with Sara C. LaHue, MD, author of the article “Neurologic Complications of Pregnancy and Menopause” in the Continuum® February 2026 Neurology of Systemic Disease 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. LaHue is an assistant professor of neurology for the Weill Institute for Neurosciences in the Department of Neurology at the University of California, San Francisco School of Medicine in San Francisco, California Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Dr Grouse: Despite the high prevalence of neurologic conditions in women, critical gaps remain in training, research, and clinical guidelines on sex and gender specific considerations across the lifespan. Today, I have the opportunity to speak with an expert on neurologic complications of pregnancy and menopause and coauthor of the and women's neurology curriculum core competencies, Dr Sara LaHue about the latest issue of Continuum on neurology of systemic disease. Dr Jones: This is Dr Jones, editor in chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Grouse: This is Dr Katie Grouse. Today I'm interviewing Dr Sara LaHue about her article, Neurologic Complications of Pregnancy and Menopause, which appears in the February 2026 Continuum issue on Neurology of Systemic Disease. Welcome to the podcast and please tell us more about yourself. Dr LaHue: Well, thanks so much for having me. I'm really excited to talk about this topic. So, I'm Sara LaHue. I'm a neurologist at UCSF, assistant professor of neurology, and a neurohospitalist. So much of my role is taking care of people who are coming into the hospital with urgent and emergent neurologic conditions. And so that's very much a framing that I come to this chapter with. Dr Grouse: I just want to start by congratulating you on your article, which is such a phenomenal compendium of important neurologic issues related to pregnancy and menopause, which I think I really needed and a lot of us really need and was missing, I think, in all of the literature out there. This article will be such an important clinical resource. I know for me, and I'm sure for many of our listeners, this may be a difficult question to answer because of how comprehensive the article is. But what do you hope will be the main takeaway for those who read your article? Dr LaHue: So, I really hope that listeners walk away with understanding that pregnancy and menopause are not contraindications to providing excellent neurologic care. I think too often we default to withholding treatment, pseudo-assumed risk, rather than actual evidence of harm. And so, I think that the key message here is that protecting maternal health is protecting fetal health, and that under-treating neurologic conditions during pregnancy can harm both mother and baby. Dr Grouse: You did say specifically in your article that I thought it was so important that presumption of harm from medications during pregnancy, due to lack of evidence rather than evidence of harm, was something that we really had to be aware of, of that bias. And how do you recommend neurologists listening to this podcast approach situations where diagnostic or management strategies become less certain due to safety considerations in pregnancy? Dr LaHue: Yeah, that's such an important question. I really frame it as a risk-benefit calculation with a patient, and I'm very transparent about what we know and what we don't know. And I emphasize that untreated disease may also impact fetal health. I use resources like LactMed and pregnancy registries that can help provide some of the more latest data. And then when evidence is limited, I document our discussion thoroughly, and I'll often involve maternal-fetal medicine colleagues for their multidisciplinary input. So, the goal is really to have an informed, shared decision-making process rather than a reflexive avoidance of all treatments. Dr Grouse: I think that's really important to reiterate, and I think something that we're all I think working on as we try to manage these difficult situations and conditions. Now, I want to switch gears a little bit and ask. Your article was so comprehensive and so helpful, but what isn't in the article that you wanted to put in? Dr LaHue: There was a fair amount that I ended up having to take out. So, this is a question that's near and dear to my heart. So, I would have liked to include more on the neurodevelopmental outcomes for children who are exposed to various neurologic medications in utero. And I also wanted to discuss more about transgender and non-binary individuals who are experiencing pregnancy and menopause, as they're often underrepresented in research. They've faced unique challenges accessing care. Dr Grouse: Now, I was really struck by one statistic in your article, specifically that intimate partner violence is a leading cause of head injury during pregnancy, and that actually homicide is a leading cause of death during pregnancy in the postpartum period in the US, which was absolutely a surprising statistic to me. What does this mean for our listeners caring for pregnant patients with concussions and head injuries? What should we be doing differently? Dr LaHue: This is also something that really struck me when I first encountered it. I think that the statistics should really fundamentally change how we approach head injuries in pregnant patients. I think we need to screen everyone routinely and privately for violence in the home and in the relationships, and to document injuries very carefully. But we also need to be prepared if someone does screen positive. And so, it's important to be familiar with what's available in terms of resources within your community, where you work, and also to remember that that strangulation in particular is something that can cause dissection and stroke. And so, to maintain a high index of suspicion for any kind of vascular injury in these cases. So not just thinking about head injury itself, but also thinking about complications of strangulation as well. Dr Grouse: Really a great reminder of the role that we can play in our own careers and our own clinical settings when we see cases like this. So, I really appreciate that this point was made, and I hope this will change people's practice. Now switching gears to stroke in pregnancy. Could you walk us through your evaluation and management of a patient who comes in with acute stroke in the peripartum period? Dr LaHue: This is such an important topic, and I think the first thing I'd like to emphasize is that time is brain. Whether or not you're pregnant. It's important to get whatever imaging modality is going to be fastest. Get the CT or get the MRI as soon as you can. Don't delay for fetal concerns. The radiation risk is minimal compared to missing a treatable, disabling stroke. In terms of treatment, thrombolysis and mechanical thrombectomy should be considered just as in a non-pregnant person, when the benefits outweigh the risks. And so, I think the key is involving obstetrics early for shared decision making, and being very transparent with what treatment options are available for the individual, and to not let pregnancy alone stop you from offering standard stroke therapies. Dr Grouse: Definitely a helpful resource, and I think the resources that you put in specifically around the considerations and differentials in these various populations. Postpartum, while still pregnant during the period of period, I think is all just so helpful and a great review. So, I encourage our listeners to check that out. Now switching over to the topic of menopause. I have to say, I really appreciated your coverage of neurologic issues related to the perimenopause period. What do you think is the biggest debate or controversy in this area? Dr LaHue: I think this has to be our understanding of the use of menopausal hormone therapy. The pendulum, when using menopausal hormone therapy, has really swung dramatically. So, we went from routine use to predominantly avoidance. After the Women's Health Initiative was published in 2002, and now we're finding that we're starting to come more to a middle ground. I think there's still great debate when it comes around timing of initiation, formulation of the different therapies, a route of administration and also the dosing, as well as just including how to individualize therapy for individuals with neurologic conditions. Dr Grouse: Well, going into that a little further, I know I get a lot of questions about the use of hormone therapy as it relates to stroke risk and particularly in higher risk patients such as patients who've had prior strokes, dissections, a history of migraine with aura. And I find it hard to get the answers in the literature that's out there. How are you counseling these patients? Dr LaHue: So, I think this is where discussions around the route of administration and dosing become especially important. And this is where there's emerging literature that I think is helping to guide some of these discussions. So, for higher risk patients, I discuss how low dose transdermal formulations which can bypass hepatic metabolism and reduce clotting risk. These are medications that can appear safer in those higher risk individuals. I think the key is really individualizing the risk-benefit discussion with the patient. For a woman with severe vasomotor symptoms that are affecting sleep and cognition, who had a remote stroke. I think this is a person for whom low dose transdermal patch might be a reasonable option. All of these factors end up being considerations for that shared decision-making. Dr Grouse: Now your article covers another topic that I often get questions about, and that's specifically regarding safety of vaginal delivery for patients with neurologic conditions that are sensitive to increased intracranial pressure. Could you summarize your advice for these types of questions when they come up? Dr LaHue: So broadly speaking, most neurologic conditions don't require C-section delivery. And this is a procedure that, just globally speaking, as has been increasing dramatically. And so, I think that's the key message that really, most neurologic conditions don't require a C-section as a main indication. And really, the indication should be based on obstetric considerations. For most conditions, like controlled idiopathic intracranial hypertension, a vaginal delivery is fine. But for patients with mass effect or obstruction at the foramen magnum, a C-section with general anesthesia, it's probably going to be safer. The transient increase in intracerebral pressure that can come with pushing. It hasn't really been shown to harm patients who have stable, treated neurologic conditions. Dr Grouse: I really appreciated the advice that you given in the article, which was that if generally you feel like this would be a patient who would be safe to get a lumbar puncture, you have a little less concern about vaginal delivery versus those that you feel would not be safe to get a lumbar puncture, that you'd be more leaning towards a C-section. Dr LaHue: Yeah, that's exactly right. Dr Grouse: Now, why do you think we have so many gaps in our understanding of how pregnancy and menopause affect neurologic conditions? Dr LaHue: So, I think it really comes down to a perfect storm of factors. So, in 1977, the USFDA came down with the recommendation, stating that it was best to exclude all women of reproductive potential from both phase one and phase two studies. And this recommendation wasn't reversed until 1993. And there are also concerns around liability and also the fact that pregnancy is a temporary state is something that may falsely minimize the potential for delays. The potential for harms that come with delays in treatment. And I think that the fact of menopause is also historically been dismissed, despite this is something that is affecting half of the population. I think we need systemic change. We need to mandate inclusion in research. We need funding for dedicated studies. We also need to recognize women's health as a core competency and not just a special interest. Dr Grouse: That all sounds like a great roadmap for improving our knowledge. And I really hope we get there. But hearing you talk about it really does give me hope that we can improve how we are understanding and treating these conditions. Now, your article included a really helpful overview of headaches in pregnancy, and that's certainly something I think many of our listeners are very familiar with. We do have a lot of questions around that, and I think there's a lot of areas where we don't really always know what the best thing to do is. I think that your article really gave a lot of great information and a really great framework to think about. It would be wonderful to hear you walk through your approach to evaluation of a patient who was pregnant with a new onset headache. Dr LaHue: You'll see in this chapter that I introduce a mnemonic that's spelled out pericardium as a framework for thinking about headache and pregnancy. And here are the you specifically points to an unusual headache, referring to a new or atypical presentation of headache for the patient. I think this is an important place to start, because one of the initial considerations should be this is a new headache, or is this an old headache? If this is a patient who already has a preexisting diagnosis of migraine or some other primary headache disorder, then it's certainly possible that the headache that they're experiencing during pregnancy is also a continuation of their primary headache disorder. But certainly, our role is to make sure that we're not missing a scary complication, a secondary headache that could be dangerous to the patient. And so, then this is where I also think about, well, where are they in the course of their pregnancy. Is this person currently pregnant or are we in the postpartum period? When someone is after 20 weeks gestation, one of the first things to consider is going to be preeclampsia. And so, it's important in those individuals to check blood pressure, check urine to rule out preeclampsia, as this is always going to be top of mind after 20 weeks. I think it's also important to emphasize that preeclampsia is not just a condition that can occur when someone is pregnant. This is also something that can occur postpartum. One needs to be vigilant for looking out for this complication during both time periods. And then I think for new headaches, I really want to focus on what the timing is and any other red flags. For example, if it's a thunderclap headache and onset, then I might be worried about something like RCBS or cerebral venous sinus thrombosis. If the headache itself is orthostatic and patient may have had an epidural, then I might think about a post-dural puncture headache, which is a, unfortunately very common complication and reason for headache in the postpartum period. I think the key is that most dangerous headaches often will occur late in the third trimester or early postpartum. And I think it's also important to remember that if you need imaging to make the diagnosis, and you should get it. The risks of missing something serious far outweigh concerns that one might have around imaging. And when possible, it's certainly preferred to get an MRI if that's available. Dr Grouse: I really did appreciate articles, overview of the various imaging modalities out there and the overview of risk versus benefits and times where they may or may not be needed. So, yet another very useful piece of information that I think that our listeners will appreciate in your article. Now, I'm curious how did you get interested in this area of neurology? Dr LaHue: So, it really was my interest in both reproductive health and neurology that led me to go to medical school in the first place. I knew early on at the beginning of medical school that I was interested in neurology, but I also was very drawn to obstetrics, and I recognized in medical school and then further on as, as a resident, just how vast the knowledge gaps were. When I was counseling my own patients and I found this to be just a very frequent source of frustration as both a clinician and a researcher, I very much feel an obligation to try to help fill these gaps. And I've also just been very encouraged by an outstanding community of other neurologists that I've been able to meet in this space. It's been a just a wonderful collaborative network that we've been able to grow, both within United States and even more globally, when it comes to other neurologists who are interested in this topic. And I'm just very excited to see the direction that this field is going in. Dr Grouse: Well, we can't wait to learn more as this field develops and more is understood about the right way to approach these types of diagnostics and treatments. So, thank you for all your work in this space. And it's been absolutely fascinating reading your article and talking with you today. Dr LaHue: Well, thank you so much for having me, and I'm just so thrilled that these important topics are going to be part of this issue of Continuum. Dr Grouse: Again, today, I've been interviewing Dr Sara LaHue about her article and Neurologic Complications of Pregnancy and Menopause, which appears in the February 2026 Continuum issue on Neurology of systemic disease. 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 the link in the episode notes to learn more and subscribe AA and members. You can get to me for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio. /episode/index/show/continuumjournal/id/39968180

Neurologic Complications of Cancer and Its Treatment With Dr. Amy A. Pruitt 03/11/2026

Neurologic Complications of Cancer and Its Treatment With Dr. Amy A. Pruitt Prompt recognition of direct and indirect neurologic complications of systemic cancers and their evolving treatments is essential. Neurologists should be familiar with common and rare neurologic toxicities of conventional chemotherapy, immune checkpoint inhibitors, and CAR T-cell therapy. In this episode, Teshamae Monteith, MD, FAAN, speaks with Amy A. Pruitt, MD, FAAN, author of the article “Neurologic Complications of Cancer and Its Treatment” in the Continuum® February 2026 Neurology of Systemic Disease 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. Pruitt is the William N. Kelley Professor of Neurology, Vice Chair for Education, and Division Chief in the Department of General Neurology for the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, Pennsylvania. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Monteith: As neurologists, we have a critical role in diagnosing neurologic complications of cancer from metastatic disease, seizures to neuropathies. Increasingly, the rapid development of novel treatments themselves, like immunotherapies, Car-T cells, and targeted drugs are causing new neurologic side effects, which we need to recognize, manage and anticipate as therapeutic developments evolve. Dr Jones: This is Dr Jones, editor in chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Monteith: Hi, this is Dr Teshamae Monteith. Today I'm interviewing Dr Amy Pruitt about her article on neurologic complications of cancer and its treatment, which appears in the February 2026 issue on neurology of systemic disease. Welcome to our podcast. How are you? Dr Pruitt: Thanks for having me. Dr Monteith: Absolutely. Why don't you introduce yourself? Dr Pruitt: As you said, my name is Dr Amy Pruitt. I'm a professor of neurology at the University of Pennsylvania, where I am also the clerkship director and have been for a long time. I'm the division chief of general neurology and the vice chair for education in my department. Dr Monteith: You have a lot of hats. Dr Pruitt: I do. Dr Monteith: Okay. So, before we dive into all this great work that you did in the article, why don't you just let us know just a little bit about what led you to this career path? Dr Pruitt: Sure. So, I've always been interested in the intersection between internal medicine and neurology; in fact had I've not been a neurologist. I probably would have been either an oncologist or infectious disease specialist. And that leads to doing neuro oncology and seeing a fair amount of CNS infections. I see both inpatients and outpatients and really enjoy my neuro hospitalist time because, honestly, as all of you who do consults on inpatient services know, there is an incredibly changing landscape of consequences of cancer therapies. And if you haven't been on service for a while, you probably don't even know the name, is much less the adverse effects of these medicines. Dr Monteith: Okay, so you were just like me to write this article. Dr Pruitt: Well, I think where it is directed, I think, as I said, that people who are seeing a lot of inpatients and who may not know it's a new consequences of cytotoxic or immunotherapies or T cell therapies and the different appearances and really prognoses, which have changed dramatically in the last few years in the field of systemic cancer. Dr Monteith: Any other essential points of your article? Dr Pruitt: So, I think there are certain areas where neurologists are going to intersect with oncologic patients even before oncologists do so, what tumors might present synchronously in the brain and the rest of the body. And those would include things like small cell and non-small cell lung cancer and melanoma, to a lesser extent, women who are surviving much longer now with good therapies for various versions of breast cancers, have one of the solid tumors most likely to present at first relapse in the brain, either in the brain metastases category or in the leptomeninges. So, these are the areas where I think it most likely that our neurologists are going to intersect with oncology. And then there is the burgeoning, thankfully, realm of long-term survivors who have had cancer therapies in young adult lives, sometimes in childhood. And we need to be abreast of the ever-changing spectrum of complications that will plague these people all their lives. And we can do a great deal to improve the quality of survival in these patients. Dr Monteith: And of course, there has been a lot of great development in cancer research, which has led to novel therapeutics. So, can you tell us about a few of these therapeutics and their complications that neurologists need to know about? Dr Pruitt: Sure. Well, as I said, some of the cancers you're most likely to encounter are lung cancer and melanoma. And here the prognosis has changed dramatically. A few years ago, someone with metastatic melanoma might have had a couple months prognosis. And now we're talking honestly about long term survivors, complete responses in lung cancer and melanoma, and really good responses in the breast cancer realm as well. So, these are dramatic changes. And these are ways neurologists need to know what the actual nuanced and much more variable prognosis is among patients with brain metastases. In order to give the patients good advice and also to give the radiation oncologist and the oncologist, the medical oncologist, good advice. So, for example, just in the realm of brain metastases, a stage change has been that people with asymptomatic metastases for, let's say, non-small cell lung cancer or melanoma might have systemic therapy rather than local therapy, local therapy being gamma knife radiation or less likely, whole brain radiation therapy, but really systemic therapy with responses and the brands that are nearly as good as those in the rest of the body. And sustained, durable responses. The article goes into great detail about what's available in the way of therapies for these cancers, like breast, HER2-positive breast cancer, like EGFR‑positive lung cancer and melanoma of various types. It's really quite amazing actually, to have anybody quote a seven-year survival of little over 40% in people who presented with non-symptomatic melanoma metastases. Unheard of, really. So, I think if you're still practicing, quote unquote old school neuro-oncology, you need to get up to date because you're giving patients and their caregivers good advice that will lead them to the very important therapies. You mentioned some of the immunotherapies. If we have time, I'm happy to go into those because those are really important for neurologic consultants in the hospital. Dr Monteith: Yeah. Let's talk about immune checkpoint inhibitors. What do we need to know about them and their complications? Dr Pruitt: So, they have a novel set of central nervous system and peripheral nervous system complications. These include both acute and subacute presentations. They can arise after the very first dose and usually do so within the first several doses. Importantly, even though the patient may be quite sick, about three quarters will recover entirely. However, the most common ones are actually the peripheral nervous system, and they have the highest morbidity and mortality rate. So, a very unfortunate combination of myasthenia, myocarditis and skeletal myositis has a high mortality rate and is very hard to treat in a group of people who have received these immune checkpoint inhibitors in the central nervous system, there can be cerebellitis, encephalitis. These again can be acute or subacute presentations. And the big discussion with the attending oncologist is, can we continue these therapies after we've withdrawn them, and for instance, treated them with steroids? Because you can imagine that if you knock down the immune system with steroids, you might make the patient temporarily better. But in so doing, you're negating the important consequences of the mechanisms of immune checkpoint inhibitors. So, I would say probably in a given week on the inpatient service, I'll see five or so. So nearly a daily event when I see some major complication of immune checkpoint inhibitors. And again, I've already mentioned the histology in which those have been useful, but they're not indicated for a variety of other malignancies as well. And the Car-T cell therapies are a whole different set of side effects. And some of your listeners may know about cytokine release syndrome, which is nearly universal right after the infusion of the car T cells. But a few days later is where we come into action with the immune effector cell-associated neurotoxicity syndrome. Or ICANS can say that I'll refer to it as ICANS since then. These include focal neurologic symptoms and the form of what's often a conduction sort of aphasia, a predictable deterioration, and handwriting along with confusion. As far as the radiology of that syndrome, that's really pretty odd. It can range from a dramatic cerebellitis, just a dramatic basal ganglia syndrome, a dramatic and enhancing leptomeningeal syndrome to an absolutely normal MRI scan. And the important thing for our consultant consultants to remember is that the patient can look really, really ill, and you can turn to the team and say, you know what, there's a very good chance that it's going to get all better. So, supporting people through what are very good diagnostic and therapeutic algorithms that exist in the literature and are quoted in the Continuum chapter to help know when you should be giving steroids, when you should be giving tocilizumab, etc. these are tried and true therapies now, and the Car-T world has improved not only the prognosis of patients. And I remember seeing some of the very first Car-T patients, and we really didn't know what to do to help them, how to turn off the cascade of this immunologic reaction. Now we know how to do that. And it's important to stay up to date on those algorithms because you can make a big difference for these patients. Dr Monteith: Yeah. So, this is great. We're going to dive back into the diagnostics, which is really related to my follow up question. I think you gave a really great pearl. And it's always can we keep going? Do we stop? So, I want to like dive into that question. And I assume that there are categories. Yes. You can, somewhere in between, and absolutely not. And so, tell me a little bit more about that thinking. Dr Pruitt: Well that's a very nuanced question. And so, the answer that some oncologists will give you as well, they've had such a dramatic response. So maybe we don't need it anymore. It's never the neurologist’s decision. It's always the joint decision with the oncologist. So, for instance, with a Merkel cell cancer patient develops a severe anti‑AChR syndrome on an immune checkpoint inhibitor. And we tell the oncologist maybe you shouldn't go back and do that again. And the person says, never mind, he'll be fine. He's already had the response that we want, but that's a difficult question to answer because, for instance, in a slightly different subset, let's look at multiple myeloma patients. And I spent a fair amount of time on multiple myeloma in the article because it affects the nervous system in so many ways. And we have so many different therapies for these patients, one of which is a Car T-cell. And this is a B-cell maturation antigen, Car-T. It's different from the ones that we know for lymphoma and leukemia. And it has a different set of neurologic problems, which unfortunately do preclude going back to taking a Car-T cell therapy again. And just to make a long story short, this particular complication makes the patient look Parkinsonian. The consult you're probably going to get from the medical services is patients weak. Well, the patient is not exactly weak. He is Parkinsonian. He has a extrapyramidal rigidity, sometimes a tremor a negative cat scan and a B-cell maturation antigen syndrome occurs not at the sort of 5 to 7 day mark about ICANS that we just discussed, but rather a month or so out and a month or so out. It's not when you're expecting to see Car-T cell therapies. So, patients end up getting worked up extensively for, let's say, some sort of infection, when in fact, what we should be looking at is a newly described complication of Car-T cell therapy. So, the part of my article on multiple myeloma is one that's really important because as you know, it's such a common hematologic problem among older people. And many of these people may have direct complications of multiple myeloma, such as direct tumor infiltration of nerves. POEMS syndrome. So, it's really a wealth of neurological issues for us to contend with for these people. Dr Monteith: Yeah. And I know you've really done a great job of adding lots of wonderful charts, including understanding the time course of some of these complications, when to anticipate, because I think some of it is about when to anticipate some of these complications. Dr Pruitt: Well, exactly. Yes. Given the time constraints, I've made a lot of tables because there was a lot of information. And those, I think, are the kinds of things that a consultant should know: what should I be thinking about at this point in time? And that sort of leads us to what are the later complications of these things. And those include many medical things, from failure due to neoplasia, morbidity, radiation, chemotherapy agents, the long-term and medium-term consequences of these things for people. Are going to come back to our office as well. Immunocompromised patients, such as the ones and heavily treated patients that I just mentioned, may lack a robust inflammatory response. And they can have infections really at any time out. Some are predictable, as in our leukemia patients who have had hematopoietic cell transplant. So, we kind of know when to expect viral infections, nosocomial infections, progressive multifocal leukoencephalopathy, many other things down the road. But in this era of COVID, we know that these patients are more susceptible to the dire effects of COVID, and they may not mount a good vaccination response. We have seen types of neurologic complications of all sorts of infections, including babesiosis this year, and persistent enteric viral meningitis. So, the patient can present a very atypical fashion. And the neurologic consultant has to keep a really open mind about the broad differential of what might be happening. Dr Monteith: And you do have a section under imaging and metastatic disease. Are there any like new sequences or a way to kind of tease out complexities? Dr Pruitt: So, there is marked variability in the radiographic appearance of brain metastases. And I must confess that I made a very large collage of all the different representative types of things. And I think that's important for neurologic consultants to recognize that some metastases don't enhance. They don't all look like ring-enhancing lesions. Some can be much more diffuse, particularly if the patient has received something like a VEGF inhibitor like bevacizumab therapy can look exceedingly different. They can involve the dura, which should be treated differently. There can be simultaneous leptomeningeal and disease. So as far as I know, sequences perhaps not so much. Although if one is thinking about the differential between radiation-related injury and someone who's already been treated versus tumor recurrence, then we have some pretty good microscopic data, some susceptibility weighted images, other ways of getting whether this is really radiation related change or tumor recurrence, a major problem obviously. What we also know about radiation is kind of a theme of the article is use it as infrequently as possible, because we just talked about some of the other therapies that we have. We may need to give local therapy for symptomatic patients, but we give as little as possible, and we try never to give whole brain radiation therapy. I'll go on record as saying that it's certainly necessary. Sometimes people have diffuse lymphoma, this disease that's recurred, they have multiple metastases in a sort of miliary fashion may be necessary, but if you can use gamma knife radiation, if you cause any use form of focal radiation, new in the leptomeningeal world is proton therapy for spinal metastases. So quick sparing techniques. And this is something that should always be considered when you're consulting on someone in a place in which you have the option of proton therapy. So, I would say that distinguishing between radiation necrosis and recurrent tumor and the use of protons are the big news in the radiation therapy world. And don't give whole brain radiation therapy if you can avoid it. Dr Monteith: Yeah. I'm getting a flashback from residency because, you know, that always happens. And the radiologist saying, you know, we need more information when you put in those orders. And so, I think with this whole era of new chemotherapeutic agents and how they could present on imaging and give the radiologists as much information, including the type of chemotherapeutic agent used. Dr Pruitt: Yeah, I think particularly in the transplant world. So, the leukemia lymphoma patients who have received one of the calcineurin inhibitors, like tacrolimus or cyclosporine, that induces a whole set of complications, some of which are visible radiographically. There's a delayed leukoencephalopathy. There can be stroke. There can be SMART syndrome, stroke like migraine after radiation therapy. And perhaps many of our listeners have been confronted with someone who has a prolonged focal deficit, say, a hemianopia and maybe a hemisensory deficit with or without a subsequent headache. It goes on for days to hours. It looks peculiar on the MRI scan because it's not then a vascular distribution. There's sort of diffuse gyral swelling, flattening of the EEG on that side, the patients getting steroids and valproate and anticoagulation and angiography and all. It doesn't need any of that. The syndrome of stroke, like migraine after radiation therapy, needs to be recognized. And best thing to do is don't just do something. Stand there. You should wait until it goes away. And so, I think that's we are seeing this increasingly, that we first reported this in young adults who had been treated years ago for medulloblastoma. So, it was posterior fossa tumors primarily. But this has now been broadened, as you know, to include supratentorial tumors of many types and adults at various times out from their radiation therapy from a few months to many years. Dr Monteith: I should ask you in writing this article, clearly you have a wealth of knowledge, but in kind of just putting this together, what surprised you? Dr Pruitt: I think what surprised me is the increasing range of complications and that virtually anything needs to be thought of central nervous system or peripheral nervous system. With some of these newer therapies. There is a chart in there about the conventional cytotoxic therapies, and we're all familiar with things like methotrexate and that sort of thing. But what surprised me really is the increasing diversity of complications of these newer drugs, and also the fact that I didn't know some of the third and... /episode/index/show/continuumjournal/id/39968120

Neurologic Complications of Critical Illness With Dr. Shivani Ghoshal 03/04/2026

Neurologic Complications of Critical Illness With Dr. Shivani Ghoshal Nearly one in five patients in intensive care units (ICUs) requires neurologic consultation. The neurologic complications of critical illness can be unique to its underlying processes and can persist as independent disease states even after resolution of the inciting critical illness. In this episode, Casey Albin, MD, speaks with Shivani Ghoshal, MD, author of the article “Neurologic Complications of Critical Illness” in the Continuum® February 2026 Neurology of Systemic Disease issue. Dr. Albin is a Continuum® Audio interviewer, associate editor of media engagement, and an assistant professor of neurology and neurosurgery at Emory University School of Medicine in Atlanta, Georgia. Dr. Ghoshal is an assistant professor of neurology for the Columbia University Vagelos College of Physicians and Surgeons in New York, New York. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Albin: The ICU can be such an intimidating place. There's unresponsive patients, there's beeping equipment and a seemingly endless way in which the nervous system can be compromised. But fortunately, today I have the opportunity to speak with Dr Shivani Ghoshal about her paper, Neurologic Complications of Critical Illness, which is going to help us demystify the approach to these patients and provide some clinical pearls that you can take to your next consult in the ICU. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Albin: Hello, this is Dr Kasey Albin. Today I'm interviewing Dr Shivani Ghoshal about her article on neurologic complications of critical illness, which appears in the February 2026 Continuum issue on neurology of systemic disease. Welcome to the podcast, Dr Ghoshal. It's really such a treat for me to get to interview you, someone who I know and have worked with in the past. But for those who do not know you, please give us a little background about what brought you to this topic and what you do in your clinical life. Dr Ghoshal: Thank you so much. It's a thrill to be interviewed by someone that I know well and get to work with. Outside of writing this article for Continuum, I am a neurointensivist. I'm an assistant professor of neurology at Columbia University and the program director for the Neurocritical Care Fellowship between Columbia Cornell and New York Presbyterian. So, a lot of what I do in my day-to-day is thinking about acute brain injury along with the neurology of systemic disease and how, really, the two interplay with each other, of how neurologic complications can arise from systemic illness and the other way around. Dr Albin: Yeah, you are the absolute perfect person to kind of walk us through the complexity of the brain and body connection. Dr Ghoshal: I don't know if I can deal with that kind of praise, but thank you. Dr Albin: And you’ve really written a powerhouse article on just the myriad of complications that really arise in the ICU, and you've broken it down into what I think is a very thoughtful way of sort of bucketing these complications. So, tell us a little bit about the approach you took here. Dr Ghoshal: I love this article because neurologic complications are just so common in so many types of acute critical illness. And I think we have to think for each organ system, how does this affect the brain, and then how does the brain then interplay, let's say, in kidney failure, in hepatic failure, in sepsis, right? Which is so common that I think we don't even think a lot about, like, what are types of septic encephalopathy for all the antibiotics we give; like, what are the implications of this? I really enjoy taking each system and thinking about, how does it specifically affect neurologic complications? Dr Albin: Yeah. And then there was a really nice breakdown in terms of some of the procedures that will happen within the ICU in general. You know, the things that are happening to the patients at the bedside also put them at risk for neurologic complications. Then there are those neurologic changes that are happening because of some of the underlying problem that brought those patients to the ICU. And then the unfortunate number of problems that arise because the patient has been in the ICU for such a long period of time. Dr Ghoshal: You know- and I think that that first part you mentioned, just about procedures in the neuro-ICU, right? Or in the ICU in general. I think that we don't think about that on a day-to-day level, right? Just like arterial lines are one of the most associated with any kind of peripheral nerve injury, especially axillary arterial lines. I learned quite a bit, even going through this article and then looking at other sources. So, thank you also for pointing that part out. Dr Albin: Yeah. When I was thinking about how do we distill all of what was covered through this article, I actually really thought it would be sort of most interesting to have you model sort of your approach to these patient complications and how you approach the complexity of an ICU patient. And so, if it's okay with you, we'll just walk through a couple cases. Dr Ghoshal: Oh my gosh, let's do it. Dr Albin: All right. So, these are all, of course, composite cases. You know, there is no patient violation here. Let's say that this is a 64-year-old patient and they're admitted with influenza, and they develop ARDS. And they're in the MICU. And this patient, they were pretty sick on arrival and they were intubated for three days. But now the patient's been extubated, and the MICU team calls you because today she's having trouble swallowing and her voice, you know, the family says that this is not what she normally sounds like. And the team is really quite worried that she's had a stroke. And so they are calling for a neurology consult because they want to know what they should do. So, walk us through your approach to that patient. Dr Ghoshal: Well, I think the primary team being concerned for a stroke is definitely reasonable, but I think, taking a bigger step back, what I would first want to think about, is this neurologic or non-neurologic? Neurology, you know, there's a parcel of things we can go through, but even just a non-neurologic, like, is this just primary injury to the vocal cords, right? I think about the cough were there, the ET tube, it wasn’t overinflated which caused direct damage, right? And then after that, then I would think a little bit more about my approach for what is going on neurologically. Thinking about either, is this a brain process or is this a- more of like a spinal cord cervical cord injury process or more cranial nerve issue? Dr Albin: Yeah. How would you approach the exam in that patient? Dr Ghoshal: Yeah. You know, I- and just to, again, take a step back, right? To remember that when we do intubate someone, the physical maneuvers that we have are a chin lift and regular endoscopy, right? They have, like, significant movement for the cervical spine. So, I might want to know even before I examine the patient, right, or their history, right, do they have anything like, do they have known cervical stenosis? Do they have any, like, cervical spine pathology? Was it a difficult intubation? Right? So, these are the kind of the things I'd want to know even from the history, along with whatever vascular risk factors they may have. And then, to your question about the actual exam. Yes, you know, I may look for, like, crossed findings, right? If we're thinking about, let's say, a medullary lesion, etc. I think all listening to this podcast know about MRI testing there. But beyond what I would be looking for, let's say, in a medullary stroke, I'd also want to be looking at just, like, water paresis, right? I might want to be interested in, let's say, signs of neurogenic shock. You know, you mentioned they're in septic shock, ARDS. I might want to actually take a look to see, like, was this all septic, right? Or what are their other shock types present. Dr Albin: So, what I hear you're saying is you're evaluating A, first of all, answering the consulting question, you know, is there a real risk for some sort of cerebrovascular phenomenon, but then actually going to the bedside to examine the patient, to say, does that make sense? Do we see hemibody involvement here? And it's a good thing that you're approaching it that way. Because actually, when you go to the bedside, she does have some difficulty speaking. And reading the notes, this was actually quite a difficult intubation. From just the cranial nerve, you know, where she has maybe some dysphonia and dysphagia. But you also, on exam, then find that she's got some pretty symmetric distal weakness in her arms bilaterally. And so, when you find that, what are some of the imaging that you're going to think through to try to pin down exactly what's going on here? Dr Ghoshal: I love these cases because it's not so straightforward. Now, let's say if she has, like, an upper extremity weakness and lower cranial nerve deficits, you know, things I'd be looking for, like any injury to, like, hypoglossal nerve, vagus nerve. The vagus nerve is going to be hard to tell, right? Recurrent laryngeal nerve, you know, the lingual nerve. I might be thinking more about stretch injury, which we think of as tapia syndrome, right? So, just a textbook answer. The hypoglossal recurrent laryngeal nerve injury. And what we're going to be looking for is dysphonia, dysphagia, and unilateral tongue paralysis. Could be a bilateral as well. But I guess, then, the next question after I'm going through my physical exam findings is thinking about my imaging choice. Dr Albin: So, for this patient, given that she's got this bilateral upper extremity, maybe some tepia syndrome where there may have been some stretch injury to some of those hypoglossal nerves. She may have also just had some trauma to the vocal cords. Like, as you said, these procedures can really put patients at risk for just mechanical injury to some of those structures. But knowing that upper extremity weakness, what kind of imaging, then, do you look at for the court? Dr Ghoshal: I think it's not unreasonable to do an MRI brain, right; with that, it then cuts through the brain stem. And then doing an MRI of the cervical spine. I guess the point that you mentioned at the very beginning, that this is three days after she was intubated… you do run the risk beyond 72 hours of, let's say, a primary injury. Let's say if she had, you know, God forbid, an injury to the cervical spine, those hyperintensities, especially when associated with ligamentous injury, they can pseudonormalize beyond that time. I would say yes, absolutely. MRI of the brain, cervical spine, then cuts through the brain stem. But I would worry that if too much time elapses, you may miss some of those injuries that you would otherwise find. Dr Albin: Yeah. I think those are some really important take-home pearls, and when we're thinking about the cord injury that could occur through the intubation process, that we really do need to be aware of student normalization of the T2 hyperintensities after that 72 hours. And so, I think that's a really important pearl for us to take home. So, kind of summarizing this case here, there was probably a multitude of things going on, which highlights to me the complexity of ICU patients. Less likely in this case, and they did not find a stroke. But that is, of course, something that we must keep on the differential for any critical care, critically injured, critically ill patient. But tapia syndrome where you have some stretch injury to the hypoglossal nerve and the recurrent laryngeal nerve, which can put people at risk for dysphasia or dystonia after intubation. And then that hyperextension injury that can happen for patients who are intubated, because people, especially for difficult intubations, are really having to manipulate the neck. And for an elderly patient who may have some cervical stenosis, that hyperextension can actually result in a central cord syndrome, which is what they discovered with the C-spine MRI in this case. So, cognizant of all of the cervical injuries that might accompany the procedure of intubation. Dr Ghoshal: And you know what I would say, right. Because I think that our population is overall aging. I think with that, we're going to end up with, like, more cervical spine pathology for these patients that are ongoing intubation, just as you, you know, very astutely pointed out. Right? Trying to have at least, like, manual inline stabilization, right, or even like, considering fiber optic intubation in some of these patients is probably going to be a safer way to go to avoid these kind of injuries. Dr Albin: Yeah, I think that that's so true and really emphasizes the importance of communication between the neurology team and the critical care team. Dr Ghoshal: Totally. Dr Albin: Neurology is probably not the person intubating the patient. Right? But it's really important for any of these consults to have a good appreciation and that robust communication with the critical care team about what has been going on systemically for this patient, even opening that intubation note and saying, was this an easy intubation? Was it a difficult intubation? I think sometimes we forget that key skill of just communicating across the teams to have a holistic picture of what's been happening in MICU. Dr Ghoshal: Yeah, I totally agree. It's kind of why my first part of this case you mentioned is just like asking the team, like, what happened during the intubation, right? Dr Albin: It's a really important takeaway. All right. We're going to shift gears from procedural complications, reminding our listeners there is a fantastic summary of all of the things that can happen to ICU patients, just because we're doing things to them, putting needles in places where needles aren't usually, such as for arterial lines, for central lines, intubating patients; all of these have complications that can affect neurologic function downstream. But let's shift gears and let's talk now about a 72-year-old man. And he's admitted to the ICU with pyelonephritis and bacteremia. He's got nephrolithiasis. And the team calls you because he, like many patients in the ICU, has some, quote, “shaking events.” And he's altered, and they want to know what to do. Dr Ghoshal: So, there's a lot to unpack there. Sepsis is so common, right? When you're saying this patient is altered, sepsis-associated encephalopathy occurs in 70% of patients. So, like, in sepsis or septic shock. And we know that, you know, they say it affects mortality, long-term cognitive outcomes. But because, I think, it's so common, we don't really take the time to think about what is going on in sepsis in the brain. Dr Albin: The brain is an end organ perfusion. And the end organs are what we're sort of monitoring in sepsis, and the brain is such a key marker of that. Dr Ghoshal: Absolutely. I think there are a lot of things that happen with sepsis in the brain. But if I were going to pick like 1 or 2 points that I really wanted to hone in on, it’s thinking about that blood brain barrier disruption that happens in sepsis. And so, what that does when you disrupt the blood brain barrier is that you end up with this inflammatory milieu, for lack of a better term, that, like, comes into the brain. You have, like, a disordered sort of microglial activation, cytokine release. You know, all of these things are creating more oxidative stress, neuronal damage. And the other hand of this, right, along with that blood brain barrier disruption, is disordered cerebral auto regulation. Dr Albin: And I think that those two things are probably underappreciated. The complications and why, maybe, they lead to this downstream difficulty in recovering and then probably are also setting the patient up to be at risk of downstream delirium that is so frequent in the ICU. Dr Ghoshal: I couldn't agree more. And, you know, for this patient's case, right, where you're saying, like, they're altered, they're shaking, I bring up this idea of cerebral autoregulation. Right? Just because for normal patients---or normal people, rather, right?---normal cerebral autoregulation allows us to have, like, stable brain perfusion through whatever range of pressures we have. A lot of these patients are septic; whether they are hypertensive or not, they have significant changes in cerebral vasoconstriction, vasodilation, right? And this can create anything from, let's say, like, neuronal excitotoxicity, metabolic alterations. Right? Just in that setting of cerebral inflammation. So, these patients, yes, are at a very high risk of encephalopathy. And then from these changes, right, from blood brain barrier disruption, whether that's from a cerebral autoregulation or just from that inflammatory milieu, they're at a super high risk of stroke and seizure. Dr Albin: Yeah. So, they… in calling you to the bedside, someone comes to meet you and they say, we sent a bunch of labs off and we just got one back, and it's his ammonia, and his ammonia is 92. So, do you think that's what's going on here? This is so common. Right? Hyperammonemia. Give us sort of your approach to kind of triaging, is the hyperammonemia really a problem or is it just some sort of bystander? Dr Ghoshal: Oh, you know, ammonia is such a slippery lab, right? That… well, it's very hard not to have a strong opinion on it one way or the other. And so, I think what I would say is that ammonia can be elevated for, like, a parcel of reasons. Right? Like if someone has tonic colonic movements, you can have ammonia. That's just, like, part of like enteral metabolism, muscle breakdown, whatever it may be. And ammonia can go up for a lot of reasons. And it's true also that ammonia can contribute encephalopathy. And there are a few mechanisms that can go through in a little bit. I would first want to know… a part of understanding, I guess, any lab is understanding in this context of, like, what was the ammonia before? Right? What is their baseline ammonia? Is this a significant rise? Like, how much of a rise should you care about? Dr Albin: Yeah, absolutely. So, you look back and they live sort of at the upper range of normal with 60 being their sort of baseline. Dr Ghoshal: Yeah. You know, I don't know that I would be so concerned about this particular ammonia level. I may trend it. But, you know, just to talk a little bit about ammonia and why we care about encephalopathy, right? So, the reason why it's so concerning, I guess I should say, in any kind of acute illness is that ammonia will cross the blood brain barrier. And then it's converted into ammonium ions, and it will go into astrocytes and, like, they can increase interstellar osmolarity. Right? So, these cells swell. Right? And because water is drawn into the astrocytes, they cannot interfere with actual functioning of the astrocytes. Also worsen cerebral auto regulation and cause, I guess, sort of an excitotoxic environment. Right? So, ammonia can be concerning, I think when you send in a lab, right? I think it's important to remember that there's no direct relationship between ammonia level and encephalopathy severity. Dr Albin: Right. I think that's a really key point to drive home that it's usually not until we're in the hyperammonemic ranges above the 120s-150s up into the high two, three, four hundreds that we really need to be concerned about that cerebral... /episode/index/show/continuumjournal/id/39968055

Neurologic Complications of Hematologic Disorders With Drs. Lauren Patrick and Mark Terrelonge 02/25/2026

Neurologic Complications of Hematologic Disorders With Drs. Lauren Patrick and Mark Terrelonge Neurologic complications of hematologic disorders are frequently encountered in clinical practice and can involve both the central and peripheral nervous systems. Early recognition and appropriate management in collaboration with a hematologist are essential to reduce morbidity and mortality. In this episode, Kait Nevel, MD, speaks with Lauren Patrick, MD, and Mark Terrelonge, MD, MPH, authors of the article “Neurologic Complications of Hematologic Disorders” in the Continuum® February 2026 Neurology of Systemic Disease issue. Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana. Dr. Patrick is an assistant professor of neurology at the University of California, San Francisco, in San Francisco, California. Dr. Terrelonge is an associate professor of neurology at the University of California, San Francisco, in San Francisco, California. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Nevel: Thick blood, thin blood. These are terms often used by patients and caregivers to describe some of the hematologic disorders that can lead to neurological diseases such as stroke. So, when should we consider a hematologic disorder as a potential cause for neurological conditions, such as stroke or neuropathy. Today I have the opportunity to interview Drs Lauren Patrick and Mark Terrelonge to learn more about neurologic complications of hematologic disorders in their recent article in Continuum. Dr Jones: This is Dr Lyell Jones, editor-in-chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Nevel: Hello, this is Dr Kate Nevel. Today I'm interviewing Drs Lauren Patrick and Mark Terrelonge about their article on neurologic complications of hematologic disorders. This article appears in the February 2026 Continuum issue on neurology of systemic disease. Welcome to the podcast, and please introduce yourself to the audience. Dr Patrick: Thank you for having us. We're both thrilled to be here. I'm Lauren Patrick, a vascular neurologist and assistant professor at the University of California, San Francisco, and program director for the Vascular Neurology Fellowship here. Dr Terrelonge: And I'm Mark Terrelonge, I'm an associate professor of neurology and neuromuscular medicine here at UCSF and one of the associate program directors for the adult neurology residency. Nice to meet you. Dr Nevel: Nice to meet you both. Really looking forward to getting into your article and learning more. So, to kind of kick us off, I always like to ask what do you think is the most important takeaway from your article for the practicing neurologist? And maybe since there are two of you and I suspect you covered slightly different aspects of this article, maybe you could give us two most important takeaways. Dr Patrick: Sure. I think the biggest takeaway is to keep hematologic disorders on the differential when evaluating patients with neurologic symptoms. Conditions like sickle cell disease, myeloproliferative neoplasms, or plasma cell dyscrasias and paraproteinemia can cause strokes or peripheral neuropathies, and many have specific and targetable treatments. The early recognition and collaboration with our hematology colleagues can truly change patient outcomes, whether that's by initiating cytoreductive therapy, managing thrombocytopenia, or optimizing antithrombotic therapy. Dr Nevel: Great. So, this is a really big and diverse topic. As always, I'm going to urge our listeners to read the article because there is a lot of really good stuff in your article that we just don't have time to get into during this interview today. But you cover a lot of different hematological disorders and how they can cause neurological complications. One of the major neurological complications of hematological disorders is cerebral vascular events. So, I'm hoping, Warren, that you can walk us through a little bit. When should we consider workup of potential hematologic disorder as a cause when we see a patient with ischemic stroke, because certainly not all patients with ischemic stroke should be getting a broad hematological disorder work up. So how can we kind of identify early on that there might be something else at play? Dr Patrick: Absolutely, great question. So, in many cases, the underlying hematologic disorder is already known, such as sickle cell disease or polycythemia vera. But sometimes stroke is the initial presentation or manifestation of the disease. So red flags can include young age, recurrent cryptogenic strokes or thrombosis, and unusual locations like the cerebral venous system. Laboratory clues such as unexplained erythrocytosis, thrombocytosis, thrombocytopenia, or hemolytic anemia should raise suspicion for an occult hematologic disorder. In the setting of acute illness, immune-mediated or heparin-induced thrombocytopenia or thrombotic microangiopathies should be suspected in patients that have hemorrhagic and or thrombotic complications, particularly when relevant lab disturbances are present. Acquired thrombophilia such as anti-phospholipid antibody syndrome should be considered in young patients with autoimmune disease, prior venous or arterial thrombotic complications, or pregnancy morbidity. Now, these are rare causes overall, but they're important to catch because the management can differ dramatically from our typical stroke care. Dr Nevel: Great. And what are some of the most common inherited or acquired thrombophilias and when should we be sending these labs? Dr Patrick: The hematologic causes really account for small minority of arterial strokes approximately one to two percent, but among those, sickle cell disease, anti-phospholipid antibody syndrome and the myeloproliferative neoplasms are the most common. Timing of testing is key. So, the genetic thrombophilia panels can be drawn at presentation, but lab values such as protein C, protein S, and antithrombin levels may be falsely low during acute thrombosis, so they're often repeated weeks later. Similarly, for anti-phospholipid antibody testing that should be done at presentation and when positive, confirmed at twelve weeks, since transient positivity can occur with affections or acute events. So, in patients that are already anticoagulated for anti-phospholipid antibody syndrome, testing becomes particularly tricky, especially with lupus anticoagulant assays. Some results need to be interpreted carefully or repeated when feasible. The main message is to collaborate early with our hematology colleagues to guide the timing and interpretation of these studies. Dr Nevel: Yeah, wonderful. Thank you. I'll ask some similar questions about neuropathy. So when should we consider an underlying hematologic disorder as being the cause for someone's neuropathy? Dr Terrelonge: So, luckily for a neurologist, then serum protein electrophoresis or an SPEP is already a part of the first pass evaluation for even the most common neuropathies we see, technically already considered every time we do an evaluation. However, we do know that most neuropathies progress very slowly and don't really lead to significant limitations in patient activities of daily living. And for those, the initial workup step, you may not need to do any additional search for any hematologic diseases after that first step. Within patients who start to have more unusual features with their neuropathy, including a rapid progression, early proximal weakness, significant and extremely painful neuropathies, significant ataxia, or new tremor or anything that's kind of outside of the garden variety neuropathy, then you should start to think about a hematologic cause. Additionally, if a patient already has a known hematologic malignancy or process before their neuropathy, there should be some form of assessment to see through exam or electrodiagnostically if the two are correlated. I do have to add one caveat, though, and that's just because someone has a hematologic malignancy or a paraprotein seen in their blood, their neuropathy and the neurologic syndrome don't necessarily have to be causally related. So, we have to do some additional testing to determine if the patient's presentation of the paraprotein are actually linked. Dr Nevel: Can you walk us through a little bit how we determine if they're associated or just coincidental? Dr Terrelonge: Yeah. So, for some of the proteins, there's a specific phenotype that will come with the specific protein. For example, an anti MAG proteinopathies or MAG standing for a myelin associated glycoprotein, it usually leads to a distal sensor and motor polyneuropathy where the most distal portions of nerves are affected. So, in that case, people might notice that they have numbness and weakness in their toes and their fingers, and it doesn't follow that typical length dependent pattern. So, in that case, if you have the anti mag neuropathy and the electrodiagnostic signature of an anti mag neuropathy along with the symptoms, you're more likely to think that the two are related then if not. Dr Nevel: Great. Thank you. And I was hoping you could speak a little bit more about amyloidosis just because I think that that's one that can be really tricky to diagnose. And I see patients, you know, have sometimes more drawn out evaluations or see multiple providers before a diagnosis is reached. So, can you speak a little bit more to how we diagnose amyloidosis in relationship to neuropathy or other neurological conditions and when we should push for more invasive testing like a nerve biopsy? Dr Terrelonge: So, amyloidosis certainly is a tricky diagnosis. I've been tricked by it and I think most of my neuromuscular colleagues have probably been tricked by it at least once. It's a hard diagnosis to make is it usually requires a pretty high index of suspicion, and also requires a tissue diagnosis to cinch. There're some patients who will come in with a prior history of amyloidosis and they're a little bit easier to figure out if the neuropathy is related. Maybe it's started in their heart or their kidney first and then you can just see if the type of amyloid they have usually deposits in nerve, and that may be enough. But if there's any diagnostic uncertainty, you could go forward with tissue biopsy. But it's patients in which the neuropathy is the first symptom that amyloidosis can be especially tricky to diagnose. It's a primarily light chain disease. So, if you do only an SPEP as a part of your initial neuropathy evaluation, you could miss it. But usually, the patients will have either a severely painful neuropathy, early autonomic dysfunction, or really prominent bilateral carpal tunnel syndrome. So, if they have any of those, usually we'll add in an amyloid workup as a part of that of the rest of the workup, which would include both light chain evaluations to see if there's any increase in Lambda or Kappa light chains and then also biopsy. Biopsy can be of the skin or fat pad first, which have reasonable sensitivity for picking up disease, but they're not necessarily a hundred percent. So if the suspicion remains high in those cases, a nerve biopsy should be considered. And the reason why this is important is that the chemotherapeutic agents that we have now can actually help arrest a lot of these diseases and stop further organ involvement. So, if you think about it, it is important to keep pushing and looking until you find it. Dr Nevel: Thank you so much for that. And a follow up question to that, once patients are started on appropriate therapy, the diagnosis is made, chemotherapy is started, what's the typical clinical course that you see in terms of their neuropathy? Do you ever see improvement or is it arrest of worsening? Dr Terrelonge: Usually for amyloid, there is an arrest of disease, but in some patients, they could have some improvement, not necessarily a dramatic improvement, but some patients could see some reversal of symptoms. That may not necessarily be because nerves injured nerves are regrowing, but because of reorganization of nerves to muscle, they could have some strength increases or at least less pain. Dr Nevel: Yeah, thank you. So, when should we involve a hematologist in aiding in the evaluation of patients we suspect may have an underlying hematological disorder? You guys really outlined very nicely in your article some of the laboratory workup or other workup like you just talked about with amyloidosis. But at what point in that workup should we reach out to our hematology colleagues? Dr Patrick: I would say almost always. So, these disorders are inherently multi-system and benefit from early co-management. In acute sickle cell stroke, for example, hematology helps direct emergent exchange transfusion. For myeloproliferative disorders they guide cyto reduction and long term antithrombotic strategy. And for antibody mediated or plasma cell disorders, hematology determines disease specific therapies. So, neurology may help with identifying the presentation, but the definitive management is almost always shared with our hematology colleagues. Dr Nevel: And as you both have mentioned that a lot of times in these cases, their hematologic disorder may be already known before they present with their neurological symptoms. So, I imagine obviously in those cases that a hematologist hopefully is already heavily involved in their care. What do you think is the most difficult aspect of identifying and diagnosing patients with neurologic illness as having an underlying hematological disorder? Dr Patrick: The hardest part is maintaining a high index of suspicion, especially since hematologic causes account for a very small minority of arterial strokes. Most strokes are from traditional vascular risk factors like you mentioned, or cardio embolism, so it's easy to stop diagnostic evaluation after standard studies have been performed. An example of a challenging case is a patient that's young, they've had recurrent cryptogenic stroke, and they could have antiphospholipid antibody syndrome, but it can be easy to miss if their antibody titers are borderline or if they're already anticoagulated, which would complicate retesting. So, it's about balancing the urge to over-test with recognizing the few cases where identifying A hematologic cause truly changes that management. Dr Terrelonge: And then on the neuropathy side, probably the hardest part is deciding what's causal and what's coincidence. Monoclonal gammopathy of unknown significance, or MGUS, is really common in older adults, so not every M-spike on an SPEP explains a neuropathy. And even sometimes there's times when the neurologic picture will develop a little bit faster than the hematologic one. So, it's hard to put the two together. Dr Nevel: Yeah. What's the most rewarding aspect of taking care of patients with complications from their hematologic disorders? Dr Patrick: It's deeply rewarding when a targeted diagnosis leads to a tangible improvement in that patient's care. For example, identifying A cryptogenic stroke is being due to myeloproliferative neoplasm or an inherited thrombophilia allows us to move from empiric treatment to possible disease specific strategy. It’s really gratifying to give patients that clarity, to give them a diagnosis and in some cases prevent future events. Dr Terrelonge: Agreed. And even on the neuropathy side, almost all of the neuropathies that are hematologically related are treatable. So, it's so satisfying whenever you have a patient with say an anti-MAG neuropathy or Waldenström can start the patient on therapy, and you can see someone who's been having a progressive decline to stability and in those cases sometimes even significant recovery. Dr Nevel: Yeah, absolutely. Very rewarding when you can identify the problem and make it better. That's what it's all about. So, what are the future areas of research in this area? What do we still need to learn? Dr Patrick: There's still a lot to learn. I think we need better data on the safety of acute reperfusion therapy and antithrombotic agents, particularly in patients that are at dual risk for bleeding and thrombosis. Other examples, secondary prevention strategies and anti-phospholipid antibody syndrome. What's the best target INR? Do you add aspirin to warfarin or not? All of that is often left up to expert opinion. What's the best management for adults with sickle cell stroke? There are many open questions there. A lot of the protocols that we have in place for sickle cell patients that are adults as derived from pediatric literature and there's vast potential in terms of disease modifying therapies, especially in the fields of sickle cell disease and amyloidosis. And we'll need to reassess how those treatments may change neurologic outcomes. Dr Terrelonge: I think on the neuropathy side that having some form of new biomarkers to help us clearly know of the neuropathy and that hematologic illness are associated would be very helpful. On the treatment side, a lot of this is really being driven by the hematology space, but new therapies that treat hematologic plasma cell disorders, including some of the new BTK inhibitor, may be incorporated relatively soon into the algorithm for how we treat many of our patients. I'm excited to see what's to come from this. Dr Nevel: Wonderful. Thank you so much for sharing your knowledge with us today. I know I've certainly learned a lot by reading your article and through our discussion today. Highly encourage our listeners to read your wonderful article, which is a very thorough review of hematologic disorders and neurological complications. Again, today I've been interviewing Dr Lauren Patrick and Dr Mark Terrelonge on their article Neurologic Complications of Hematologic Disorders, which appears in the February 2026 Continuum issue on Neurology of Systemic Disease. Please be sure to check out Continuum Audio episodes from this and other issues. And as always, thank you so much to our listeners for joining today, and thank you so much to Lauren and Mark. Dr Terrelonge: Yeah, thank you so much for having us. Dr Patrick: Thank you so much for having us and for highlighting this topic. We hope the issue encourages clinicians to think broadly about hematologic causes of neurologic disease and to continue collaborating closely with our hematology colleagues. It's a complex but very fascinating intersection for both of our fields. 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. /episode/index/show/continuumjournal/id/39967950

Neurologic Complications of Endocrine Disorders With Dr. Rafid Mustafa 02/18/2026

Neurologic Complications of Endocrine Disorders With Dr. Rafid Mustafa Neurologic complications of endocrine disorders are diverse and may arise before systemic manifestations. Early recognition is essential because neurologic symptoms may represent the presentation of an undiagnosed underlying endocrine disorder, and because many neurologic complications of endocrine disorders are reversible with timely treatment. In this episode, Gordon Smith, MD, FAAN, speaks with Rafid Mustafa, MD, author of the article “Neurologic Complications of Endocrine Disorders” in the Continuum® February 2026 Neurology of Systemic Disease issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Mustafa is an assistant professor of neurology for the Department of Neurology at Mayo Clinic in Rochester, Minnesota. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Smith: So what group of disorders causes cognitive changes, weakness, fatigue, neuropathy, and seizures? Kind of sounds like all of neurology in one, doesn't it? It turns out that disorders of the endocrine system can cause all of these neurological problems and others. And kind of reminds me of William Osler, who famously said at the end of the 19th century that “he or she who knows syphilis knows medicine.” Syphilis was the great imitator of his time. I wonder if in our time, the great imitator is actually endocrine disorders because it can cause all of these different problems. Today I have the great opportunity to talk with Dr Rafid Mustafa from Mayo Clinic about the neurological complications of endocrine disorders, which is a really terrific article in the February 2026 issue of Continuum. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: This is Dr Gordon Smith. Today I'm interviewing Dr Rafid Mustafa about his article on neurological complications of endocrine disorders, which appears in the February 2026 Continuum issue on neurology of systemic disease. Rafid, welcome to the podcast, and please introduce yourself to our listeners. Dr Mustafa: Well, thank you for having me, Dr Smith. Like you had mentioned, I'm Dr Rafid Mustafa. I'm a neurohospitalist at the Mayo Clinic and I had the pleasure of writing this issue with Dr Aaron Berkowitz, and it's been such a fun ride to be a part of Continuum for this issue. Dr Smith: Yeah, it's a really exciting issue. And I have to say, I was really excited to have the opportunity to talk to you. Even though my research is in diabetes and I'm looking forward to talking about that---not my research, but about diabetes---I think the area of endocrine and neurological complications of endocrine disorders is confusing to us. And I guess maybe you could begin by just this concept that most of us check a few endocrine labs on just about everything. But how do you bring order to this when there's a group of disorders that all cause just about every domain of neurological problem, be it weakness, neuropathy, cognitive changes, and so forth? Dr Mustafa: Yeah, I think it's super interesting. I think that's why, you know, this issue on systemic diseases is fun. I had a mentor one time telling me that your interim year in residency is important so you can learn about all these organ systems that are there to keep the brain alive. And so, I think neurologic complications of systemic disease are fun. You know, like you said, the endocrine system, whenever it goes awry, you can get all sorts of neurologic complications. Putting order to it can be challenging. I think it's important to know what the different parts of the endocrine system do, the different glands and how they're connected, and what to look out for when you encounter neurologic problems, because sometimes those neurologic manifestations can be the very earliest sign of something wrong with different parts of the endocrine system. Dr Smith: You knew exactly where I was heading without having to tip my cards. I mean, that's exactly where I wanted to begin, because I think of this as an intimidating topic, but in reading your article, you outlined kind of the glandular structure or anatomy of the endocrine system and sort of the logic of its function. And actually, it's not as complicated as I was thinking going in. You did a good job of framing. And I wonder if maybe you can begin by just reminding our listeners the basic anatomy and functional logic that they'll need to keep in mind. Dr Mustafa: Yeah, absolutely. The system itself is this network of different glands and hormones that work to influence each other, just like our, you know, our nervous system is all interconnected as well, too. But this is more ensuring homeostasis in various ways. So, you have the hypothalamus all the way at top that secretes things, usually just to stimulate the pituitary, which often ends up being the controller of the endocrine system. And then there are these various other organs that have different jobs or things to do. So, there's, you know, the thyroid, parathyroid, adrenal glands; you have your pancreas, there's gonads. And all of these different things have different roles to keep us healthy and regulated. to function appropriately, you know, whether that's just generalized metabolic things from the thyroid gland or more flight or fight responses from the adrenal gland, even, you know, renin, aldosterone, etc, etc, from the adrenal. And then you know, the pancreas, diabetes, all sorts of things there. Gonads are important for sexual health. It's kind of cool how it's all regulated together and there's these feedback loops and- ah, we'll have fun talking about it. Dr Smith: Just listening to you, it kind of feels almost like the endocrine system is part of the nervous system, isn't it? I mean- and there are these sort of relationships between the two that I know we'll get into. We think of insulin sensitivity, for instance, and, you know, patients with diabetes. I mean, there's neuronal insulin resistance as well. So, they're very, very interconnected systems. Dr Mustafa: Absolutely. You're absolutely right. Dr Smith: I wonder if you can talk about this idea of feedback loops. This is something that we all learned in medical school, but probably worth reminding ourselves of as we begin the conversation. Dr Mustafa: Yeah, one part of the endocrine system is important for secreting a hormone that will influence another part of the endocrine system. And that new end target will have some kind of function, and then it all loops together. So, for example, the hypothalamus, it secrets out thyrotropin-releasing hormone and that stimulates the anterior pituitary gland to secrete thyroid-stimulating hormone, and then that hormone acts on the thyroid gland itself to produce the final-acting thyroid hormones themselves, like T3 and T4. Now, if any of these are thrown off, then it throws off other parts of the system. So, for example, maybe you’re hyperthyroid and you have too much T3 and T4 coming from the thyroid gland. That may signal the hypothalamus and pituitary to reduce levels of thyrotropin-releasing hormone and thyroid-stimulating hormone to in turn affect the thyroid gland and help reduce production of those end-target thyroid hormone. Or vice versa, it just depends on the condition. You can see this at all aspects of the system at various accesses. So, it's kind of this complicated neural network in a way, but just from endocrine purposes, glands and hormones. Dr Smith: I wonder if we can start talking about the pituitary gland. Your article has all kinds of really cool information. One pearl that I wasn't really aware of is that 10% of adults have a pituitary microadenoma. It's pretty amazing. You point out that most of these aren't clinically significant, but they clearly come up on, kind of, an evaluation now and again. I mean, how should our listeners sort through how to approach these situations, right? Most of them aren't clinically significant, but some of them are. What does a neurologist need to know about this? Dr Mustafa: Yeah, To me, it's like anything else in our field. You scan enough people, you're going to find incidental things. You scan a spine, you're probably going to find a disc herniation. The question is, how clinically relevant is that and how is that affecting your patient? What are the things you need to be worried about and how do you work through it? As you mentioned, yeah, 10% of the population has a pituitary microadenoma. Those are the small ones. Most of them are clinically insignificant. So, if you find it, you know, usually it's not something to worry about too much. You might repeat serial imaging just to make sure it's not growing. But if they're not having neurologic symptoms because of mass effect or physiologic symptoms because of hormonal effect, then most of the time it's just an incidental finding and you just have to work really hard to reassure your patient. Now sometimes, there can be mass effect as the tumor itself grows, as benign tumor, or there can be hormonal effects. And then you might start thinking about how you're going to intervene. Dr Smith: Let's talk about macroadenomas and mass effect. You spend some time, and I actually have a really good example of pituitary apoplexy as well as the relationship between macroadenomas and other headache syndromes. So maybe you can talk about the relationship between macroadenomas and headache? Dr Mustafa: Yeah. So, you know, when pituitary adenomas become large, usually over 10 millimeters or so, we call it a macroadenoma. And the neurologic symptoms that come to play are usually because of mass effect. I think many of us are trained to recognize visual defects like a, you know, bitemporal hemianopia from compression of the optic chiasm. That's one of the classic things. But even just the mass effect alone in that area can cause symptoms like headache. Many of this will be, you know, migrainous in nature. Sometimes you can get a typical trigeminal-type phenomenon, just given everything that's in the region. And with something like pituitary apoplexy that you alluded to, I mean, that usually comes on very quickly. It can be a thunderclap headache. So, not all thunderclap headaches are subarachnoid hemorrhage from aneurysms. You have to think about other things on the differential, and that includes pituitary apoplexy. Dr Smith: Yeah, I mean, I think one of the things I found interesting was the fact that headaches can be associated with pituitary macronoma that are migranous or even look like a trigeminal autonomic cephalgia. I mean, is that something that commonly influences your management of either the headache or the macroadenoma? I mean, if you have a patient with a macroadenoma, do you treat the headache syndrome any differently, or are you particularly attentive for pituitary findings in someone that you're scanning because of headache? Dr Mustafa: Yeah. From my perspective, if I know there's a pituitary macroadenoma and they have these associated headaches, my practice is in general to treat the headache symptomatically, focusing on the phenotype, whether it's migrainous or more, you know, like an attack, a trigeminal autonomic cephalalgia. Now if it starts with they had an atypical headache like a trigeminal autonomic cephalgia, maybe I'm doing the imaging as a result of that to explore why they may be having this from a structural perspective. And if indeed it is because of a pituitary macroadenoma, we'll probably be monitoring the characteristics of the adenoma on a serial basis to see how it transforms over time. And if it's enlarging, you know, those symptoms might be a reason to consider intervention from a surgical resection standpoint. Dr Smith: So, I wonder if we should pivot and talk a little bit about how neurologists encounter patients who have symptoms related to endocrine disorders. And presumably the clues come with the impact of the distal endocrine gland, for instance, either over- or underproduction of the thyroid hormone. Is that the right way of thinking of it? And then, you know, having identified that, you'll start to look whether it's a primary glandular problem or upstream in the pituitary. Dr Mustafa: Absolutely. That's in general my approach. You know, often these patients are coming to the neurologist with specific symptomatology, and being familiar with how that's related to the endocrine system is what's important. So, I try to organize this article kind of by parts of the endocrine system and how that's related to neurologic manifestations. But really, it's about being familiar. So, if the patient presents in a comatose status and it's not a clear-cut structural reason, neurologically, as to why they're comatose, you might be exploring metabolic reasons for their coma. You may find disturbances in thyroid hormone levels, and that can influence you to work your way back up the axis---just like you mentioned, Gordon---to see where the problem is coming from that influences the thyroid problem. Dr Smith: So, you know, maybe we can use that as a good hook to hang our coat on, right? So we have a patient in the unit, comatose, not clear why. Are there specific pearls or indicators that would trigger you to really think about, is this a thyroid problem? Is it adrenal or whatnot? I mean, you give some great examples of, like, myxedema coma, which is very interesting. But what's the clue that we should be going down this pathway? Or, you know, on the other extreme, do you just look for thyroid abnormalities in everyone with a coma that you're having a hard time figuring out? Dr Mustafa: Great question. I am slightly more of a traditionalist in my approach to neurologic disease that, instead of shotgunning every single possible test, I try to localize in any way I can. And what's cool about these disorders of the endocrine system is that there's so much on your examination that can help clue you in. And it's not just the neurologic exam, it's the systemic exam as well, too. So, important to keep an eye out for those things. Since we're on the topic of thyroid, patients with mixed edema coma, you know, they may have neurologic signs like myoedema, etc, but they may also have systemic signs like hair loss, changes in weight, changes in temperature regulation, that you can pick up on history as well, too. And it's putting all that together to localize to not just part of the nervous system now, but part of the body that helps you with your testing. And that's how I tend to approach things. Dr Smith: So, so many questions I have for you. I wonder, can we talk a little bit about Hashimoto's encephalopathy? Dr Mustafa: Oh, yes, absolutely. Dr Smith: What's the deal there? That's something I've always found a little bit challenging. So, when should we think about it? There are lots of people out there with elevated thyroperoxase antibodies. How do you make the connection between serology and clinical phenotype and management? Dr Mustafa: Yeah, it's a great point of contention among groups, this diagnosis of Hashimoto encephalopathy. There are those that believe in this is a distinct autoimmune, essentially encephalitis entity associated with abnormal thyroid antibodies. And then there are those that believe that patients have this encephalopathy, but it's just incidental that we find these abnormalities in thyroid testing. What I'll tell you is there's been some really nice studies looking at Hashimoto's or what's to be Hashimoto's encephalopathy, and most patients that present with what is thought to be that actually have normal thyroid function studies. The other thing is finding abnormal antithyroid antibodies is also pretty prevalent in the general population. So, I think in my approach to thinking about Hashimoto's encephalopathy, you’ve just got to take everything with a grain of salt. You got to recognize that some things are just very prevalent, and you have to keep your clinical suspicion high for what you normally would see and consider other things on the differential. My personal thought is that there probably is some unique antibody-driven disease process that represents what we think of as Hashimoto's encephalopathy, but we just haven't fully classified what that antibody may be quite yet. And then there's probably some overlap, because in general a lot of these thyroid diseases themselves are reflective of underlying autoimmunity. So, there's probably something going on, but I don't think it's a direct effect of something like, you know, thyroid peroxidase antibodies. Dr Smith: Maybe we should pivot and spend a little time talking about the most common endocrine disorder that we encounter in neurologic practice, which is diabetes. And as I mentioned earlier, it's a topic near and dear to my heart. What's the latest that our listeners should know about regarding peripheral nervous system complications of diabetes? We're all familiar with distal symmetric polyneuropathy. Or are there other new updates or pearls that we should be thinking about? Dr Mustafa: Absolutely. So, the complications on the nervous system extend far beyond just your distal symmetric polyneuropathy is probably the most common thing we see, but you can get all sorts of unique manifestations. In fact, I recently just took care of a patient that had many of these. You can get a single thoracic radiculopathy. You can have what we see often at Mayo Clinic here, a diabetic lamosacral radicule plexus neuropathy where patients have profound, initially, usually pain in their lower limbs, and then this spreading of profound weakness in their lower limbs. That can be a huge complication of association with rapid control of glycemic status. And especially this day and age where we have newer medications that are very effective at controlling diabetes, we're seeing this more and more. I wrote this article before some recent publications that come out highlighting the association with GLP-1 agonists. But with these types of medication, rapid glycemic control can result in, you know, associated DLRPN quite frequently. Dr Smith: Yeah, it's interesting. I think we think of the, kind of the neuro-ophthalmological manifestations or risks of GLP-1 agonists, but the relationship too, of treatment-induced neuropathy and diabetes. And I'm curious of your experience. My sense is that if you aren't attuned to these sort of problems, you often miss them. And you certainly see people that come close to having surgical interventions or, you know, end up going off in the wrong direction with these acute neuropathies that I think are probably a little more common than we often give them credit for. Dr Mustafa: Absolutely. Yeah. I think, you know, learning about these things and being familiar is very important. It's important to keep a good broad differential because there can be mimickers, whether it's infectious things or malignant things like lymphoma, but I wanted to highlight in this article how common something like diabetic radiculoplexus, Lumbosacral radiculoplexus neuropathy can be. I mean, in fact, we see this more than things like Guillain-Barré syndrome, CIDP, etc. And so, I think practicing neurologists everywhere should at least be familiar and know what to look for so that they can make the diagnosis... /episode/index/show/continuumjournal/id/39967895

Neurologic Manifestations of Renal and Electrolyte Disorders With Dr. Eelco Wijdicks 02/11/2026

February 2026 Neurology of Systemic Disease Issue With Dr. Aaron Berkowitz 02/04/2026

February 2026 Neurology of Systemic Disease Issue With Dr. Aaron Berkowitz In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Aaron L. Berkowitz, MD, PhD, FAAN, who served as the guest editor of the February 2026 Neurology of Systemic Disease issue. They provide a preview of the issue, which publishes on February 2, 2026. 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. Berkowitz is a Continuum® Audio interviewer and a professor of neurology in the Department of Neurology at the University of California, San Francisco, in San Francisco, California. Additional Resources Read the issue: Subscribe to Continuum®: Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Jones: The human nervous system is so complex. You can spend your whole career studying it and still have plenty to learn. But the human brain does not exist in isolation. It's intricately connected with and reliant on other bodily systems. When those systems go awry, sometimes the first sign is in the nervous system. Today we will speak with Dr Aaron Berkowitz, an expert on the neurology of systemic disease, and learn a little about how these disorders can present and what we can do about it. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about subscribing to the journal, listening to verbatim recordings of the articles, and exclusive access to interviews not featured on the podcast. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr Aaron Berkowitz, who is Continuum's guest editor for our latest issue of Continuum on the neurology of systemic disease. Dr Berkowitz is a professor of clinical neurology at the University of California, San Francisco, and he has an active practice as a neurohospitalist and in outpatient general neurology---and, importantly, as a clinician educator. In addition to numerous teaching awards, Dr Berkowitz has published several books and also serves on our editorial board for Continuum. Dr Berkowitz, welcome. Thank you for joining us. Why don't you introduce yourself to our listeners? Dr Berkowitz: Thanks, Lyell. As you mentioned, I'm a general neurologist and neurohospitalist here in San Francisco, California at UCSF and very involved in resident education as well. And I was honored, flattered and a little bit frightened when I received the invitation to guest edit this massive issue on the neurology of systemic disease. But I've learned a ton, and it's been great to work with you and the incredible authors we recruited to write for us. And I'm excited to have the issue out in the world. Dr Jones: Yeah, me too. And you and I have talked about it before: you're one of a very small group of people who have guest edited multiple issues on different topics, right? Dr Berkowitz: That's right. I did the neuroinfectious disease issue in… was it 2020? 2021? Something like that. Dr Jones: Yeah. So, congratulations, more people have walked on the moon than done what you've done. And I'm looking forward to chatting, Aaron, and really grateful for your work putting together a fantastic issue. I think our listeners will appreciate that the nervous system does not function in isolation. It's important to understand the neurologic manifestations of diseases that originate within the brain, spinal cord, nerves, muscles, etc., but also the manifestations of diseases that begin in other systems and, you know, may masquerade as a primary neurologic disorder. So, it's obviously an important topic for neurologists, since many of these patients are receiving care in another setting, perhaps from another specialist. I almost think of this issue of Continuum as a handbook for the consultant neurologist, inpatient or outpatient. I don't know. Do you think that's a fair characterization of the topic? Dr Berkowitz: Absolutely. I completely agree with you. I think, yeah, many of us go into neurology interested in our primary diseases, whether it's stroke or Parkinson's or neuropathy or particular interest in neurologic symptoms, whether they're cognitive, motor, sensory, visual. And we quickly learn in residency, right? As you said, a lot of what we see is neurologic manifestations of primary diseases. So, I don't know how similar this is to other training programs. But it seemed like, if I'm remembering correctly, my first year of residency was mostly on primary neurology services, general stroke, ICU. And we moved into the consultant role more in the PGY-3 year the next year. And I remember explaining to students rotating with us on the consult services, this is actually much more complex in a way, because the patient has some type of symptom in a much broader and much more complicated context of multiple things going on. And I call it “neurology in the wild.” There's, like, neurology of, this patient’s had a stroke and we know they have a stroke and we're trying to figure out why and treat it. That's all interesting. But our question here, is there a stroke needle buried in this haystack of all of these medical or surgical complications? And learning what I call neurology of X, which is really what this issue is; as you said, that there's a neurology of everything. There's a neurology of cardiac disease. There's a neurology of the peripartum. There's a neurology of rheumatologic disease. There's every new treatment that comes out in oncology has a neurology we learn, right? There's a neurology of everything. Dr Jones: There's a lot of axes, right? There's the heart-brain axis and the kidney-brain axis. And… I think we cover everything except the spleen-brain axis, which maybe that's a thing, maybe not. I'll probably hear from all the spleen fans out there. So, I want to do a little bit of an experiment. We're going to do something new today on the podcast. Before we get into the questions, we're going to start with a Continuum Audio trivia question. So, this will be a first time ever. Dr Berkowitz, we all know that chronic hyperglycemia, or diabetes, can lead to many neurologic and systemic complications and that optimal glucose control is our goal. For our listeners, here's the question: what neurologic complication can occur from correcting hyperglycemia too quickly? What neurologic complication can occur from correcting hyperglycemia too quickly? Stick around to the end of our interview for the answer. So, Aaron, let's get right to it. You had a chance to review all the articles in this issue on the neurology of systemic disease. What do you think in all of those is the most exciting recent development for patients who fit into this category? Dr Berkowitz: Yeah, that's a great question. I think we talked about when we were putting this issue together, right, a lot of the Continuum subspecialty topics; there should have been updates on particular disease diagnostics, treatments, new phenotypes. Whereas here probably a lot less has changed in primary heart disease, primary cancer. As I'd like to say to our students trying to excite them about neurology, most specialties have new treatments, but I can name a large number of new diseases, right, that have been discovered since we've been out of training. So, a lot of the primary medicine stays the same, and the neurologic complications stay the same. But probably the thing that many readers will want to keep handy and will probably be much in need of update again in three years are the neurologic complications of all the new cancer treatments. So, if we think back to I finished training just over ten years ago when a lot of the fill-in-the-blank-umabs were coming out, CAR T therapy, and we were starting to see a lot of neurology, I remember, related to these and telling the oncologists and they said, oh, you just wait. We are seeing at the conferences that there's a lot of neurology to these. And I feel like that is always a moving target. And I think we are seeing a lot of those and it's hard to keep up with which treatments can cause which complications, which syndromes and which severities require holding the treatment when you can rechallenge longer-term complications of CAR T cell therapies now that we've learned more about the acute complications. So, Amy Pruitt from Penn has written us a fantastic article for this issue that covers a lot of the updates there. And I learned a lot from that. I feel like that's the one that just like every time the carnioplastic diseases are reviewed in Continuum, it seems like the table is another page longer from your colleagues there in Rochester teaching us about new antibodies. And I feel like, for this issue, that's one of the areas that felt like there was a lot of very new content to keep up with since last time. Dr Jones: That's good news, right? It's good that we have new immunotherapies for cancer, but it does lead to neurologic catastrophes sometimes, and it is a moving target, really rapid. So, you mentioned that just over ten years ago you finished your training and now we see a lot more of these complex immunotherapy-related neurologic complications. What about in the other direction? Are there any things that you see less commonly now in your practice than you might have seen ten years ago right when you were finishing training? Dr Berkowitz: I would say no, I think. I think we're seeing a lot of new stuff, and we're still seeing a high volume of the classic consults we tend to get, whether that's altered mental status in a patient who's systemically ill; weakness or difficulty reading from the ventilator in a patient who's critically ill; patient has endocarditis and has a stroke hemorrhage or mycotic aneurysm, what do we do? Yeah, one of the parts that was really fun and educational editing this issue is, I really wanted to ask the experts the questions I find that are really troubling and challenging and make sure we could understand their perspective on things like the endocarditis consult, which I always feel like each time there's some twist that even though the question is what do we do about this stroke and/or hemorrhage and/or aneurysm and is surgery safe? It seems like each time I always feel like I'm reinventing the wheel, trying to really sort out how to think about this. And we have a great article from Alvin Doss at Beth Israel and Steve Feskey from Boston Medical Center. It covers a lot of cardiology, as you know, in that article about a great section on endocarditis where every time it came back for review, I would say, but what about this? This comes up. What about this? Can you explain how you think about this for our readers? I don't know. I'd be curious to hear your perspective. It sounds like we agree on what has become more common. I don't think anything in neurology seems to become less… Dr Jones: Well, no, I guess we haven't really solved anything, I guess we haven't cured any problem. But that's okay, right? I mean, it's building on an established foundation of experience and history in our field. And you know, we mentioned earlier that in many ways this issue is kind of like a neurology consultant's handbook. We did something a little different with it in that sense. In addition to you serving as the guest editor, you have authored an article in the issue. It touches on something that we've talked about a couple of times, and I'd be interested to hear you talk through it with our listeners a little bit on how to approach the neurologic consultation. Tell us a little more about that and your article and how you approached it. Dr Berkowitz: Oh, yeah, thanks. Well, thanks first of all for inviting me to think about a sort of introductory article to this issue. And I was trying to think about what to write about because, as you've said and we've been talking about, no one could know every neurologic complication of every medical disease, treatment, surgery, hospital context. Probably many of us don't even know all the muscle diseases, right, within neurology. So how could we know all this stuff? And we need some type of manual from our colleagues that can explain, okay, I know this patient has inflammatory bowel disease and they've had a stroke. Is that- are these related? Are these unrelated? And I thought the articles kind of answer all of these questions. What would I say beyond this patient has disease X and is on drug Y? Well, look up in this issue disease X and see what the neurology can be, common and rare and how often it's associated, how often it's the presenting feature, how often it means the treatment is failing, etc. I thought, I'm not sure there's much to say there. That's about a paragraph. And I thought, well, let's think even more broadly about neurologic consultation. And as you know, I like to think about diagnostic reasoning and clinical reasoning. And we talk a lot about framing bias right? And I think that is very common in consultative neurology because we'll be told in the consult or in the page or E-consult or whatever it is, this is a blank-year-old blank with a history of blank on treatment blank. And right away your mind is starting to say, oh, well, the patient just had heart disease, or, the patient is nine months pregnant, or, the patient is on an immune checkpoint inhibitor. And whether you want to do it or not, your mind is associating the patient's neurology with that. And it's- even if we know we're framing or anchoring, it's hard to kind of pull away from that. And most of the time, common things being common, a patient with cancer develops new neurology, It's probably the cancer, the treatment, or sometimes a paraneoplastic syndrome. But I've definitely found if you do a lot of inpatient neurology and a lot of consults that you're seeing so much and you have no choice but to apply these heuristics, because you're seeing a lot of volume quickly and the patients are in the hospital or they're being closely followed and outpatient setting by another specialist. You presume if you didn't get it quite right the first time, it's going to come back to you. And there's a little bit of difficulty figuring out, this is a case, actually, of all the altered mental status in acutely ill patients I got today, this is the one I should dig deeper in that I think this could turn out to be a stroke or encephalitis as opposed to delirium. I felt like that I really haven't approached that except knowing that it's easy to fall into traps. And so, I started to think about framing bias. You know, we talked about if we become aware of our biases, right, we're better at not falling prey to them. But it's subconscious. So, we might be applying it without even realizing, or even saying, I might be framing this case the wrong way, you can go right on framing it the wrong way. So, I want to kind of get a little more granular on what types of framing biases actually are relevant, specifically, to the console setting. And so, I tried to come up with a few more specific examples and try to think about ways that we could at least have a quick, if our knee-jerk is to associate primary disease X that the patient has or primary treatment X with neurologic symptom Y, what's at least a quick counter-knee jerk to say, what if it could be something else? So, for example, one of them I call “low signal-to-noise ratio bias.” Altered mental status in the acutely ill hospitalized patient. What would you say, Lyell? 99 out of 100- 99.9 out of 100, it's not a primary neurologic disease. Is that fair to say? Dr Jones: Very high, yep. I agree. Dr Berkowitz: Yeah. But could it be a stroke? Could it be non-convulsive status epilepticus, meningitis encephalitis? So, how do we sort of counteract low signal-to-noise ratio bias, acknowledging it exists, acknowledging most of the time there is a low signal-to-noise, that it's not going to be neurology---to just for example, use the time course. This is pretty acute. Have I convinced myself this is not a stroke or a seizure or an acute neurologic infection? And if I'm not sure at the bedside, should I err on the side of more testing? Or the “curbside bias,” as I call when your colleague just sends you a text message on your phone, No need to even open the chart, Dr Jones. Patient had a cerebellar stroke. Incidental. They're here for something else. Aspirin, right? Just like a super tentorial stroke. And you might reply thumbs up. And then imagine you open the CT scan and it's a huge cerebellar stroke with fourth ventricular compression- and patient can hide a lot of stroke back there, might just have a little ataxia. You were curbsided and that framed you to think, oh, they asked me, is aspirin okay for a cerebellar stroke and I said yes, without realizing actually the question should have been posed is, how do you manage a huge stroke with mass effect in the posterior fossa? So, these types of biases, I come up with five of them, I won't go through all of them. I'm in the article to sort of acknowledge for the reader, most of the time it's going to be what you look up in this issue, but how to think about the times where it might not be and how to be more precise about what framing is and different types of framing that occur specifically in the consultant arena. Dr Jones: And I think the longer we practice, the more of those low-frequency exceptions that you see. And, you know, and then it sticks in our mind and sometimes the bias swings the other way; people, you know, think primarily about the low frequency. And so, it's tricky. And what I really enjoyed about that article, we started talking about this probably more than a year ago, and more than a year ago, I would say relatively few clinicians were using a now widely popular large language model for clinical decision-making; we won't name the model. And now I think most clinicians are using it almost every day, right? And I think it puts a premium on how to think and how to engage with the patient, and less about the facts and the lists that a lot of conventional medical education really is derived from. So, I really appreciate that article. We can pat ourselves in the back. We had some foresight to put it in the issue, and I think it's a great addition to it. Dr Berkowitz: Thank you. Dr Jones: So, the list of potential topics when we think about the neurologic manifestations of systemic disease, we tend to break it down by organ systems, right? But the amount of things that could end up in the issue is almost infinite. Is there anything that, when you were putting this issue together---either in terms of the topics or editing the articles---is there anything that you wanted to include, but we just didn't have room? Dr Berkowitz: I certainly won't say we covered everything, but I will say we were able to recruit a fantastic team of authors. And as you and I also talked about at the beginning, although you could say, we're doing the movement disorders issue, let's find all the top movement disorders folks who are expert specialists in this field, there's not really a neurohematologist or a neurogastroenterologist out here. So, you and I put our heads together to think of phenomenal general neurologists in most cases, some subspecialists who know a lot about this but were also excited to read a lot more about it and assemble the existing knowledge by the practicing neurologist for the practicing neurologist. And I think with that approach and letting folks have kind of, you know, I asked some specific questions. These are topics I hope you'll cover. These are vexing questions in this area. I hope you'll find some... /episode/index/show/continuumjournal/id/39850600

Managing Prognostic Uncertainty in Neurologic Disease With Dr. Robert G. Holloway 01/28/2026

Managing Prognostic Uncertainty in Neurologic Disease With Dr. Robert G. Holloway Clinicians and patients are in a state of prognostic uncertainty when they are unsure about the future course of an illness. By embracing uncertainty while cultivating prognostic awareness, neurologists can serve the critical role of supporting patients and families through the living and dying process. In this episode, Casey Albin, MD, speaks with Robert G. Holloway, MD, MPH, FAAN, author of the article “Managing Prognostic Uncertainty in Neurologic Disease” in the Continuum® December 2025 Neuropalliative Care issue. Dr. Albin is a Continuum® Audio interviewer, associate editor of media engagement, and an assistant professor of neurology and neurosurgery at Emory University School of Medicine in Atlanta, Georgia. Dr. Holloway is the Edward and Alma Vollertsen Rykenboer Chair and a professor of neurology in the department of neurology at the University of Rochester School of Medicine and Dentistry in Rochester, New York. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Albin: Hello, this is Dr Casey Albin. Today I'm interviewing Dr Bob Holloway about his article on managing prognostic uncertainty in neurologic disease, which appears in the December 2025 Continuum issue on neuropalliative care. Welcome to the podcast, and please introduce yourself to our audience. Dr Holloway: Hi, Casey, and thank you. Again, my name is Bob Holloway. I'm a clinician and neurologist up in Rochester, New York, and I've been doing both neurology and palliative care for many years. Dr Albin: Well, that's fantastic. And I really wanted to emphasize how much I really enjoyed reading this article. I know that we're going to get into some of the pearls that you offer, but I really want to tell the listeners, like, this is a great one to read because not only does it have sort of a philosophical take, but you also really provide some pragmatic tips of how we can help our patients manage this prognostic uncertainty. But maybe just tell us a little bit, what is prognostic uncertainty? Dr Holloway: Yes, thank you. Well, I think everyone has a sense of what prognostic uncertainty is. And it's just the uncertain futures that we as clinicians and our patients face. And I would just say that a way to summarize it is just, how do we manage the “not yet” of neurologic illness? Dr Albin: I love that. In neurologic illness, there is so much “not yet” and there are so many unknowns. And what I thought was really helpful about your article is you kind of give us three buckets in which we can think about the different types of uncertainty our patients are facing. What are those? Dr Holloway: This is, I think, an area that really is of interest to me, thinking about how to organize the prognostic “not yet” or that landscape. And one way I've tried to simplify it is to think about it as data-centered. And that's the world that we mostly live in as neurologists. That's the probability distributions. We also have kind of system-level uncertainties, and that's the uncertainties that our health system affords for our patients. And then we have, also, the patient-centered uncertainties and the uncertainties that those two prior categories cause for our patients. And that's a big uncertainty that we often don't address. Dr Albin: In reading the article, I was really struck by, we spend a lot of time thinking about data uncertainty. Can we get population-based research? Can we sort of look at prognostication scoring? I live in the ICU, and so we think a lot about these, like, scoring metrics and putting patients into buckets and helping us derive their care based on where their severity index is. And I'm sure that is true in many of the divisions of neurology. But what I did not really appreciate---and I thought you did a really fantastic job of kind of drawing our attention to---is there's a lot of system-centered uncertainty. Can you give us a little bit of examples, like, what is system-based uncertainty? Dr Holloway: I think system-level uncertainties just encompass the practical information gaps that may arise during our healthcare encounter. And a lot of, I think, the uncertainty that our patients face and families, they actually describe it as they feel captive by the uncertainty. And it's just the unknowns, not just what affords from the actual information about the disease and its prognosis in the future, but actually the level of the system, like, who's going to take care of them? How do you manage arranging for nurses to come into the home or all those practical-level uncertainties that the system provides that sometimes we don't do a good job of road-mapping for patients. Dr Albin: Absolutely. Because I feel like we have a little bit of a gap in that often as physicians. Like, the family asks, what will hospice at home look like? Well, you know, that's a question for case management. I think they'll come in and they'll tell you. But it strikes me that that's a real gap of my being able to walk patients through. Will they get home health care? Will they have transportation set up? Will there be a nurse who comes in to check? How often are they available? What's the cost going to be? All of these practical aspects of dealing with an illness that are beyond sort of our scope of knowledge, but probably have a huge practical impact to the patient. Dr Holloway: Without question, every encounter patients wonder about, that kind of future wish landscape that we- all our future-oriented desires and hopes. And so much of that is the practical aspects of our health system, which is often fragmented, kind of unknown, uncertain. And that's a huge source of uncertainty for our patients and families. And then that leads to many other uncertainties that we need to address. Dr Albin: Absolutely. I think another one that we, again, maybe don't spend quite as much time thinking about is this patient-level uncertainty. What's going on there? Dr Holloway: Yeah. So, I think patient-level uncertainty is that uncertainty that they experience when confronted with the two other types of uncertainty: the actual data-centered uncertainty and the system-level uncertainty. And that's that, kind of, very huge kind of uncertainty about what it means for them and their family and their future futures. And that's a source of huge stress and anxiety, and often frankly bordering on dread and fear for our patients and families. That actually gets into very levels of uncertainty that I would call maybe over even in the existential realm. Patient-level uncertainty in the actual existential questions or the fear and the dread or the kind of just unnerving aspect of it is actually even more important to patients than the scientific or data-centered uncertainty that we focus most of our attention on. Dr Albin: Yeah, I think this is, to me, was getting towards that, like, what does the patient care about and how are they coping with what is in many times a really dramatic shift in their life expectancy or morbidity expectations and this sort of radical renegotiation about what it means to have a neurologic illness? And how does that shift their thinking about who they are and their priorities in the world? Is that right? Dr Holloway: One thousand percent, and in fact, I will say---and I think is one of the main take home messages is that, you know, managing prognostic certainty is not an end in itself. It really is to help patients and families adaptively cope to their new and often harsh new reality, that we could help them adapt to their new normal. I think that is one of our main tasks as neurologists in our care teams is to help patients find and ultimately maybe achieve existential or spiritual or well-being even in their new health states. You know, that you certainly often see in the intensive care unit, but we often always see in the outpatient realm as well, and all our other diseases. Dr Albin: I think that's really hard to do. I think those conversations are incredibly difficult and trying to navigate where patients want to be, what would bring meaning, what would bring value. I think many of us struggle to have these pretty real and intense conversations with families about what really is important. And one of the things I really liked about this article is you kind of walk us through some steps that we as clinicians can take to get a little bit more comfortable. Maybe just walk us through, what are some of the things that you have found most helpful in trying to get families and patients to open up about what brings them meaning? How are they navigating this new, really uncertain time in their life? Dr Holloway: Yeah, so I do kind of have a ten-point recommendations of how to help cultivate a more integrated awareness of an uncertain future. I mean, I think the most important thing is actually just recognizing that embracing uncertainty as an amazingly remarkable cognitive tool. I mean, let's face it, uncertainty, when it happens with neurologic illness and disease, is often fearful. It's scary. It kind of changes our world. But on the flip side of it, it's a remarkable cognitive tool that actually can help us find new ways and new paths and new creativity. And I think we can use that kind of opposites to help our patients find new meaning in very difficult situations. So, thinking about uncertainty, kind of being courageous, leaning into it and recognizing that it does create anxieties and fear, but it also can kind of help create new solutions and new ideas to help people navigate. Dr Albin: I was hoping that maybe you could give us an example of, like, how would you do that? If a patient comes in and they're dealing with, you know, a new diagnosis and they're navigating this new uncertainty, what are some of the things that you ask to help them reframe that, to kind of take some of the good about that uncertainty? How do you navigate that? Dr Holloway: One of the other recommendations is actually just resetting the timeline and expectations for these conversations. That it shouldn't be expected that patients should accept their harsh new reality immediately, that it takes time in a trusted environment. And that there's this, like, oscillating nature of hopes and fears and dread, and you’ve just got to work with them over time. And with time, and once you understand who the patient and family are and understand where they find meaning and where they find, actually, joy in their life, or what actually brings them meaning, you can start recasting their futures into credible narratives in their kind of future landscape in ways that I think can help them enter into their new realities within the, you know, framework of disease management that you can offer them within your healthcare team or your healthcare system or wherever you are in the world and the available resources that you have to offer patients and families. Dr Albin: So, this sounds like a lot to me like active listening and really trying to get to know what is important to the family, what is important to the patient. And I guess probably just creating that space even in that busy clinical environment. Do I have that right? Dr Holloway: You can absolutely do that, right. You know, and honestly, active listening, we are challenged in our busy healthcare system to do this, but I think with the right listening skills and the appropriate ways of paying attention, you can definitely illuminate these possible, kind of future-oriented worlds for patients and help them navigate those new terrains with them. Frankly, I think that's a real new space for us in neurology. We don't think about and train how to create credible narratives for patients and families. We do it on the fly, but I think there's so much more work to do. How do you actually keep, you know, that best-case, worst-case, most likely credible narratives for patients that can help them adapt to their new realities and support them on their new journeys? Dr Albin: I love that best-case, worst-case, most likely case. I find that framework really helpful. But you talk in your article, it's not just about using that best case or worst case or most likely, but it's actually building some forecasting into that and having some real data to kind of support what you're saying. And there's a lot of growth towards actually becoming good as a medical forecaster. Can you describe a little bit, what did you mean by that? Dr Holloway: You're absolutely right. I think, actually, one of the skillsets of becoming and managing prognostic uncertainty is actually becoming a skilled medical forecaster. And it's a really tall order. So, we’ve got to be both good medical forecasters as well as helping patients adaptively cope to their new reality. But the good medical forecasting is actually now going more quantitative in thinking about the data that's available to help think about the important outcomes for patients and families and then predicting what their probabilities are so you can shape those futures around. So, yes, we do have to have an open mindset. We do have to actually look at the data that's available and actually think about, what are those long-term probabilities and outcomes? And we can be honest about those and even communicate them with families. But it's a really good skill set to have. Dr Albin: Yeah. This to me was a little bit about, how do you bring in the data knowledge that we try to get over time as we develop our expertise? You're developing not just a reliance on population-based data, but in my experience, I have seen this. And that sort of ability to kind of look at the patient in front of you, think about the big picture, but also a little bit about their unique medical comorbidities or prior life experiences. So, some of that database knowledge, and then bringing in and getting to know what is important to the patient. And so, sort of marrying that data-centric/patient-centric mindset. Dr Holloway: I love it. I guess the other way of saying that, too, is we need to think with precision, but communicate in narratives. And it's okay to gently put more precise estimates on our probability predictions with patients and families, what we think is the most likely case, best and worst case. Because patients and families want us to be more precise. We often shy away from it, but- so, it's okay to think in precisions, but we’ve got to put those in narratives in the most likely, best-, and worst-case scenarios. And don't be afraid if you think in terms of ninety percents, ten percents, fifty percents; most patients and families don't mind that. And what they're telling us is they actually want to hear that, if you are comfortable talking in those terms. Dr Albin: Yeah, absolutely. And giving a sense of the humility to say, like, this is my best guess based on medical data and my experience, I would say, but again, none of us have a crystal ball. And I do think families, as long as you're sort of couching your expectations into the sort of imperfect, but I'm doing my best, really appreciate that. Dr Holloway: They totally do all the time. Just say, I simply don't know for certain, but these are my best estimates. That's a good way of just phrasing that. Dr Albin: Yeah. So powerful. I don't know for certain. And then I wanted to just kind of close out, because there's this one term that you use that I thought was so interesting. And I wanted you to kind of tell our listeners a little bit about what you mean here, which is that, when you're actively open-minded, you're using this, quote, “dragonfly eyes.” What do you mean by that? Dr Holloway: So, the dragonfly eyes, as you know, they can look at three sixty around them and they just, they move in all directions. Being actively open minded, I guess the biggest example I would say is, I don't like the term prognostic discordance, which means that there's a difference of subjective estimates of prognosis between patients and families. Being openly minded is actually embracing the potential information that the family has about prognosis and incorporating that into your estimates. So, I wouldn't say it’s discordances, per se; I think being really actively open-minded is taking that all in and utilizing that as, you know what, they know more than you do about the patient and their loved ones, and they may have insights that can inform your best estimates of prognosis. So, the true dragonfly prognosticator actually is one who embraces and doesn't consider it discord, but considers it kind of new, useful information that I just need to weigh in so I can help the family in my best professional way in terms of developing a prognosis, whatever the condition may be. Dr Albin: I can imagine this is just so challenging and something that takes a long time to sort of perfect all of this. I think you say right below that, you need a growth mindset to do this because it is hard, and it's going to take an active participation and an active desire to get better at these conversations with our families. Dr Holloway: One thousand percent. You are so right that it takes time, effort, and not feeling like you're being challenged, but that actually you are including them in your entire body of knowledge, that you're just- it's part of all you're collecting. And even, I was on service last week, and I talked to residents and students about that very issue. It’s like take their prognosis. And someone who came in, we thought CJB, very sad, tragic case, but we were thinking about what the future may look like and how do we actually work with the family who had very what we thought was unrealistic expectations. I said, well, no, this is not discordance. This is just useful information that we can take understand where they're coming from and incorporate that into the ways we want to build relationships, build trust, and over time we'll get to a point where we hopefully can work with them and have them have that fully integrated awareness of their future. Dr Albin: Yeah, that's beautiful. It really is this ongoing negotiation that really requires so much listening, understanding, and then obviously information and expertise about the data that we're presenting and the likelihood outcome, recognizing that there's a lot of uncertainty in all of this. Which, you know, again, this is kind of a 360 talk. At every level there is uncertainty, and that's what makes it so hard. Dr Holloway: Yeah, you're absolutely right. And actually, even in the article I kind of used the term radical uncertainty as that, no matter how resolvable all this uncertainty is, there will always still remain that radical element of our existence which we have to actually incorporate and be prepared for. And actually, not only of ourselves, but actually for patients and families and helping manage that. Using narratives and credible narratives and kind of ranges of possibilities is the best way to do that in a personalized way. Dr Albin: Well, this has been a fantastic conversation, and I know that we are running a bit short on time. So, as we wrap up and you think about this topic, are there any key take-home messages that you hope our listeners will walk away with? Dr Holloway: I think one main emphasis is that despite all the successes we feel we have in neurology, is that we all have to recognize that prognostic uncertainty is just going to increase in the future. But this is going to be for several... /episode/index/show/continuumjournal/id/39184770

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