Continuum Audio

Patients with severe acute brain injury often lack the capacity to make their own medical decisions, leaving surrogate decision makers responsible for life-or-death choices. Patient-centered approaches and scientific methodologies can guide clinicians’ prognostications. In this episode, Teshamae Monteith, MD, FAAN, speaks with Susanne Muehlschlegel, MD, MPH, FNCS, FCCM, FAAN, author of the article “Prognostication in Neurocritical Care,” in the Continuum® June 2024 Neurocritical Care 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. Muehlschlegel is a professor (PAR) in the departments of neurology, anesthesiology/critical care medicine and neurosurgery, division of neurosciences critical care at Johns Hopkins University School of Medicine in Baltimore, Maryland. Additional Resources Read the article: Prognostication in Neurocritical Care Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @headacheMD Guest: @SMuehlschMD Transcript Full transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic- based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the Journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you’re not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. Dr Monteith: This is Dr Tesha Monteith, Associate Editor of Continuum Audio. Today, I'm interviewing doctor Susanne Muehlschlegel about her article on prognostication in neurocritical care, which is part of the June 2024 Continuum issue on neurocritical care. Well, Susanne, thank you so much for coming on the podcast, and thank you for writing that beautiful article. Dr Muehlschlegel: Thank you so much for having me. Excited to be here. Dr Monteith: Why don't we start with you just introducing yourself? Dr Muehlschlegel: Yeah, sure. My name is Susanne Muehlschlegel. I'm a neurointensivist at Johns Hopkins in Baltimore, Maryland. I have been a neurointensivist for about eighteen years or so. I worked previously at the University of Massachusetts and recently arrived here at Hopkins. Dr Monteith: Cool. So, what were you thinking about - What information did you want to convey - when you set out to write your article? Dr Muehlschlegel: Yeah. So, the article about neuroprognostication is really near and dear to my heart and my research focus, and I'm very passionate about that part. And as neurologist and neurointensivist, prognostication, you know, might be considered the bread and butter of what we're asked to do by families and other services, but as the article states, is that we don't usually do a great job (or physicians sometimes believe they do). But when you actually do research and look at data, it’s probably not as good as we think, and there’s a lot of room for improvement. And, so, the reason for this article really was to shine the light at the fact that I think we need to really make neuroprognostication a science, just like we make prediction models a science - and, so, that is the main topic of my research, as well as the article. Dr Monteith: So, we know about your interest in research in this area, but what got you into critical care to begin with? Dr Muehlschlegel: Yeah. It's, pretty much, a story of always being drawn to what's exciting and what others may want to avoid. So, in medical school, people were afraid of neurology and learning all the anatomy, and I just loved that and loved interacting with these patients. And then, in neurology residency, I was drawn to not just treating the brain and the spinal cord, but also the entire patient (so the lung and the heart and the interaction of all the organs). And then, naturally, I'm a little bit of an impatient person, and so I like the environment of the ICU of rapid change and always having to be on my toes. And so that's what drew me into neurocritical care. It was a very new field when I was training, and so, I was probably, you know, one of the, maybe, first- or second-generation neurointensivists. Dr Monteith: And it sounds like you're maybe okay with uncertainty and a lot of variability? Dr Muehlschlegel: Well, you know, neuroprognostication - I think everyone has to acknowledge that we cannot take away uncertainty, right? So, folks who pretend that they know for sure what's going to happen - I think the only time we can say that is in a patient who's braindead. But everyone else, we really don't know for sure, and all we can do is do the best to our ability to give a rough outlook - but we need to acknowledge uncertainty, that's for sure. Dr Monteith: So, can you just give us a few of the biggest causes of variability when it comes to withdrawing life-sustaining therapies in patients with severe acute brain injuries? Dr Muehlschlegel: So, that's the focus of quite some research. And, of course, there are many epidemiological factors, patient severity of disease, and, you know, how fast someone might arrive to the hospital, ethnic, racial, social demographic factors (and there's research on that), but when you adjust and control for all of those factors, variability remains. And so, what I've observed in my practice and what I also describe in the article is that maybe it's the way physicians describe prognostication or communicate with families, meaning there is potentially the chance for physician bias - that may also drive prognostication. And I can tell you from my own experience, what really drove me into this area is anecdotal experience that probably we've all had of other physicians kind of nihilistically prognosticating, thinking, you know, "This is going to be bad no matter what”, and not even wanting to try to provide aggressive care to patients. So, I think these what we call “self-fulfilling prophecies” we need to be very aware of. So, I think some of the variability may be driven by other factors other than family, patient, or health system factors. Dr Monteith: And you outline that really nicely in the article, so thank you for that. Why don't you just give us an example of a challenging case that maybe you're still thinking about today, that maybe happened years ago, that helps us understand what you go through? Dr Muehlschlegel: Yeah, I’ll rephrase the case. I still have, you know, very vivid memories about this, but I tell my residents about this case. When I was a fellow, there was a young patient in his early forties, a father of several children, a young family man who had a big right MCA stroke and really was progressing to the point that it was clear that he needed a hemicraniectomy or he was going to die. Discussed this with my attending, who said I should consult neurosurgery. At the time, the neurosurgical service had a transition to practice service for these emergencies - and so, these were fairly young, chief residents or early-year attendings. And the person came in, went into the patient's room, and I didn't even know about it, and came out and then just said, “Family decided for CMO”. I was very surprised and shocked and was trying to understand how this happened, and this provider, all he said was, “Well, it's all how you put it to the family. I told him that he probably shouldn't be a vegetable. They didn't want him to be a vegetable, and so this was the only option.” And, so, I was very shocked, and the patient did progress to die within a few days. And, so, that was a dire example of how biased prognostication can drive families to maybe an unnecessary outcome. Dr Monteith: And what’s CMO? Dr Muehlschlegel: I’m sorry. Comfort measures only - so, essentially, a withdrawal of life-sustaining therapies. Dr Monteith: Yeah. That is a good example of that and how our bias can inform families and maybe not with the exact amount of data to support that, as you outlined so nicely in your article. Dr Muehlschlegel: And I do want to emphasize, I don’t want to generalize that all providers are like that, but it is an example that really still sticks in the back of my mind, and I think, you know, we need to shine a light at how we do this and how we do it right or wrong. Dr Monteith: And wouldn’t it be nice to just have more objective measures (right?) to guide us? So why don’t we talk about existing tools that are used to help guide neuroprognostication? Dr Muehlschlegel: Yeah, so I think, in general, we can break down prognostication to two pieces (and I outline that in the article as well). So, one is, kind of, a derivation of prognostication in the head of a physician or, you know, clinician – and what may go into that is how the patient presented, examination, radiology or other diagnostics, biomarkers, you name it. But, then the second part of it (that also is really important) is how we put it to the family, right? Because we can influence families in a way that we may not even be aware of, and I think we all have unconscious biases, and how we talk to families is really important and may drive what happens to the patient as well. So, I always say there's two pieces to that – so, first of all, how we come up with a prognosis, and then how we disclose that to the family. Dr Monteith: So how can we better handle uncertainty? Dr Muehlschlegel: So, we actually did some research on that and we asked stakeholders, "How do you want physicians to handle uncertainty?”. People are aware that no physician can be certain (again, other than in the case of brain death), and so families are very aware of that. And there's quite some data out there to suggest that if physicians have very absolute statements - you know, want to close the door by saying something very absolute - is that the optimistic bias in families goes up. So, the mistrust in what the physician is saying, coming up with their own (you know, “This is a fighter, and he or she is going to do better than what you’re saying”) - and, so, I think, you know, there's no true answer to what's the absolute right way to do it, but some have suggested to maybe fully acknowledge that there is uncertainty. That's actually what families want you to do, based on some qualitative research we've done – is to say, “I do not have a crystal ball. There will be uncertainty”, but then to potentially go into a best/ worst-case scenario. But again, there, all we can do is give a best gross estimate and guess. And so, the work is not really clear at this point. There's research ongoing as to what should be the best way of doing it, but currently, that's what is suggested. Dr Monteith: And in your article, you spoke about some pretty innovative approaches, such as modeling, to help guide shared decision-making. And, so, you know, how reliable is that? Dr Muehlschlegel: That's a good point, right? So, that is up to statisticians or those who are inventing these new models. So, you know, in the old days we used logistic regression, maybe linear regression. Now, there are fancy machine-learning modeling and other Bayesian models that people use, and they certainly have some advantages that I outlined in the article. Bayesian models, for example, may use serial data as it comes in throughout the patient's hospital course - and that's kind of how we do it in real life. But, I think what's really important before we apply models is that we know that there's always outliers, and we don't know if this one patient might be the outlier, and that we need to validate these models, and most importantly, look at calibration. So, I talk in the article about how, you know, all models always report the what's called “area under the receiver-operating curve (the AUC)”, which is discrimination. But, what's actually more important for a model to be applied to a patient at the bedside is calibration, meaning how well does it actually predict a potential outcome. And, you know, there’s a lot of research into that, that only maybe half of the papers that report on a new model actually report calibration - so, I think it's really important to pay attention to that (has the model been validated and calibrated before we actually use these models?). I think prediction models have definitely a important role. But, then again, as the article says, we also have to think about how we then apply that to the patient and how we do it in individual patients. Dr Monteith: And then, of course, there's some variability between institutions. Dr Muehlschlegel: That's for sure. You know, there's these systematic approaches or system-based cultures in certain institutions. And then, of course, you know, there's still this model of learning from a role model or a mentor or an attending - meaning you look at how this person does it and then you may adapt it to your own practice. I think we need to critically examine whether we need to continue with that kind of apprenticeship model of learning how to neuroprognosticate, or whether we need to have other educational ways of doing that. So, especially in the field of palliative care, there's a lot of education now around communication - and I think med students get that exposure, and residents may get that exposure, too - but I think we need to practice it and study it systematically, whether having a standardized approach to do this leads to more patient-congruent decisions. Dr Monteith: And, you know, we do have a lot of trainees, residents, and fellows that listen in. So, what are some key messages that you want to make sure gets conveyed? Dr Muehlschlegel: Key messages is that, I think, we need to move away from looking at a patient the first one or two weeks and then concluding that we will know what will happen to this patient in six months or a year or further down the line. I think there's not a lot of longitudinal studies out there now that show that patients actually probably do better than expected if they're allowed to live. And what I mean by that is many studies allow early withdrawal of life-sustaining therapies within the first three days or maybe two weeks - but if we actually allow these patients to live, people wake up more than we thought, people may do better than we thought. So, referring to the article, I discuss in detail some twelve-month data from the TRACK-TBI study or very interesting results from South Korea where withdrawal of life-sustaining therapies is forbidden by law. And, so, you can actually do a true natural-history study of what happens with these patients if you allow them to live. And, surprisingly, a lot of people that, you know, within the first two weeks were still comatose actually ended up waking up. And, I think it's really important to look at those studies and to continue to conduct those studies so that we know better what might happen. I always shudder a little bit when I hear, “We need an MRI in the first few days or first week for neuroprognostication”. And then I always question, “Well, what is it really going to tell you about that patient who clearly isn't brain dead and still has certain, you know, exam findings?” and “Shouldn't we just give those patients time?”. I think some of those were a bit too quick to provide poor prognostication if we really don't know. Dr Monteith: And, so, I want to know how did you get into research? You know, it can be competitive to get funding, grant funding - so, tell us about that in terms of, you know, your day-to-day, what's it like? And then, also, what makes you most excited about research happening in this area? Dr Muehlschlegel: Yeah, I mean, there's a lot of research happening in that area. I think there's a huge focus on biomarkers and models and all sorts of new diagnostic tools to predict outcome, big push over decades now to do large longitudinal epidemiological studies - and all of those are very, very important, you know. I just mentioned as an example, the TRACK-TBI study is one of many other examples. I'm also excited about doing research in the second part of neuroprognostication that I mentioned - the communication and disclosure part - and the potential of bias as we speak to families. So, I get very excited about that part. It's not easy to get funding, but I think what's important is to focus on the potential impact. And, of course, then you try to convince funders that this is important research that has to be done in addition to funding model development and large epidemiological studies. What my day-to-day looks like? Well, you know, we have several ongoing projects (I won't get into details on that), but to get involved would probably be the best time as a trainee - so, I have medical students working with us, residents and fellows (although their time can be limited). And then to continue to just be curious and ask questions. Dr Monteith: And what do you find most exciting about the work that you do? Just, kind of, overall? Dr Muehlschlegel: I mean, without a doubt, the potential impact, right? So, changing the field a little bit. I'm not claiming that my research is doing that - I hope it might. But, most importantly, it's the potential impact on families and patients. I think our goal is not to have less withdrawal of care (although, sometimes, I just think we need to give people more time), but I think it's important to focus and ask about what patients might want, and then really focus families onto that. I think that can be difficult, because patients don't always tell families what they would want or families want something different than what they know the patient might want - and so, we spend quite some time on that when we speak to families. And then, I also talk about the disability paradox. So, you know, at one point, the family might say, “Well, he would not want to live if he can’t walk”, but then, patients, as they learn to live with this new normal, may actually later say, “Well, it's not as bad as I expected it to be, and I'm actually very happy to be alive, even if I'm not able to walk”. And so, that's something that others are doing research on, and that's also important to consider. Dr Monteith: Yeah, that's cool. Thinking about outside of the ICU, right? Dr Muehlschlegel: For sure. Yes. Dr Monteith: Great. Thank you so much for being on our podcast. I know that our listeners are going to really enjoy reading your article and all the thought that you put into that. Dr Muehlschlegel: Thank you so much for having me.   Dr Monteith: Again, today, we've been interviewing Dr Susanne Muehlschlegel whose article on prognostication in neurocritical care appears in the most recent issue of Continuum on neurocritical care. 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 doctor Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, please consider subscribing to the journal. There's a link in the episode notes. We'd also appreciate you following the podcast and rating or reviewing it. AAN members, go to the link in the episode notes and complete the evaluation to get CME for this episode. Thank you for listening to Continuum Audio.

In this episode, Gordon Smith, MD, FAAN speaks with Casey S.W. Albin, MD, author of the article “Neuromuscular Emergencies,” in the Continuum® June 2024 Neurocritical Care issue. Dr. Smith is a Continuum® Audio interviewer and 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. Albin is an assistant professor of neurology and neurosurgery in the departments of neurology and neurosurgery, division of neurocritical care at Emory University School of Medicine in Atlanta, Georgia. Additional Resources Read the article: Neuromuscular Emergencies Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @gordonsmithMD Guest: @caseyalbin Transcript  Full transcript available here  Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening.   Dr Smith: Hi. This is Dr Gordon Smith. I'm super excited today to be able to have the opportunity to talk to Dr Casey Albin, who will introduce herself in a second. She's well known to Continuum Nation as the Associate Editor for Media Engagement for Continuum. She's also a Neurointensivist at Emory University and wrote a really outstanding article for the neurocritical care issue of Continuum on neuromuscular emergencies. Casey, thanks for joining us. Tell us about yourself. Dr Albin: Sure. Thank you so much, Dr Smith. So, yes, I'm Casey Albin. I am a Neurointensivist. I practice at Emory. We have a really busy and diverse care that we provide at the Emory neuro ICUs. Just at the Clifton campus, there’s over forty beds. So, although neuromuscular emergencies certainly do not make up the bread and butter of our practice - I mean, like many intensivists, I spend most of my time primarily caring for patients with cerebrovascular disease - this is a really interesting and just kind of a fun group of patients to take care of because of the ability we have to improve their outcomes and that some of these patients really do get better. And that's a really exciting thing to bear witness to. Dr Smith: I love finding neurointensivists that are interested in neuromuscular medicine because I share your interest in these patients and the fact that there's a lot that we can do for them. You know, how did you get interested in neurocritical care, Casey? Dr Albin: You know, I was always interested in critical care. It was really actually the neurology part that I came late to the party. I was actually, like, gearing up to apply into emergency medicine and was doing my emergency medicine sub-I (like, that was the route I was going to take), and during that sub-I, I just kept encountering patients with neurologic emergencies - so, you know, leptomeningeal carcinomatosis and obstructive hydrocephalus, and then a patient with stroke - and I realized I was just gravitating towards the neuroemergencies more so than just any general emergencies. And I had really enjoyed my neurology rotation. I did not foresee that as the path I was going to take, but after kind of spending some time and taking care of so many neurologic emergencies from the lens of an emergency department, sort of realized, like, "You know, I should go back and do a neurology sub-I.” And so, kind of, actually, late in the game is when I did that rotation and, like, dramatically changed my whole life trajectory. So, I have known since sort of that fourth year of medical school that I really wanted to focus on neurocritical care and neurologic emergencies, and I love the blend of critical care medicine and the procedural aspect of my job while doing it with the most interesting of all the organ systems. So, it's really a great blend of medicine. Dr Smith: Did you ever think about neuromuscular medicine? Dr Albin: Uh, no. Dr Smith: I had to ask. I had to ask. Dr Albin: No, I mean, I do really love neuromuscular emergencies, but I've known for forever that like, really wanted to be in an acute care setting. Dr Smith: You know, I think it's such a great story, Casey, and I know you're an educator, too, right? And, um, we hear this from learners all the time about how they come to neurology relatively late in medical school, and it's been really great to see the trajectory in terms of fellowship determination dates and giving our students opportunities to make their choice, you know, later during their medical school career. And I wonder whether your journey is an example of what we’re seeing now (which is more and more students going into neurology because we’re giving them the free space to do that), and then also in terms of fellowship decisions as well (which was what I was alluding to earlier)? Dr Albin: Yeah, absolutely. I think having more exposure to neurology and getting a chance to be in that clinical environment - you know, when you are doing the “brain and behaviors” (or whatever your medical school calls the neurology curriculum) - it is so hard and it's so dense, and I think that that's really overwhelming for students. And then you get into the clinical aspect of neurology, and sure, you have to know neurolocalization - and that is fundamentally important to everything we do - but the clinical application is just so beautiful and so much fun and it's so challenging, but in a good way. So, I totally agree. I think that more students need more exposure. Dr Smith: Well, I mean, that's a perfect segue to something I wanted to talk to you about, which is you brought up the beauty of neurology - which is, I think, you know, neurologic formulation, really – and we talk a lot about the elegance of the neurologic examination. But one of the things I really liked about your article was its old-school formulation – you talk about the importance of history, examination, localization, pattern recognition – I wonder if, maybe, you could give us some pearls from that approach and how you think about acute neuromuscular problems and the ICU? Dr Albin: Absolutely. I really do think that this is the cornerstone of making a good diagnosis, right? I will tell you what’s really challenging about some of these patients when they are admitted to the ICU is that we are often faced with sort of a confounded exam. The patient may have been rapidly deteriorating, and they may not be able to provide a good history. They may be intubated by the time that we meet them. And so not only are they not able to provide a history themselves, but their exam may be confounded by the fact that they're on a little bit of sedation, or they were aspirating and now they have a little bit of pneumonia. I mean, it can be really challenging to get a good neurologic exam in these patients. But I do think the history and the physical are really where the money is in terms of being able to send the appropriate test. And so, when I think about these patients who get admitted to the neuro ICU, the first thing that we have to have is someone who can provide a really good collateral history, because so much of what we're trying to determine is, "Is this the first presentation, and this is a de novo (new) neuromuscular problem?” or “Had the patient actually had sort of a subacute or chronic (even) decline and they’ve been undiagnosed for something that was maybe a little bit more indolent, but (you know, they had an abrupt decline because, you know, they got pneumonia, or they have bloodstream infection, or whatever it was allowing them to sort of compensate) they have no longer been able to compensate?”. And so, I really do think that that's key. And when I am hearing the story the first time, that's really one of the focuses of my history – is, "Was this truly a new problem?”. And then, when we think about, you know, "Where do we localize this within the nervous system?”, it's actually quite challenging because, you know, patients with acute spinal cord pathology may also not present with the upper motor neuron findings that are classic for spinal cord pathology. And so I think, again, it's a little bit recognizing that you can be confounded and we have to keep a broad differential, but I am sort of examining for whether or not there's proximal versus distal (like, the gradient of where they’re weakest), is there symmetry or asymmetry, and then, are there other, sort of, features that go along with helping us localize to something to the nerves (such as sensory symptoms or autonomic symptoms)? So when I think about, you know, where we're putting this, you can put anything in sort of the anterior horn cells or to the nerves themselves, to the neuromuscular junction, and then to the muscles. And teasing that out, I put in some figures and tables within the article to help kind of help the reader think about what are features of my patient's exam, my patient's history, that might help me to put it into one of those four categories. Dr Smith: Yeah, I was actually going to comment on the figures in your article, Casey. They're really fantastic, and I encourage all of our listeners to check it out. There's, you know, figures showing muscle group involvement and different diseases and different muscle disorders and different forms of Guillain-Barré syndrome - it's a really beautiful way of visualizing things. I wonder if we could go back, though, because I wanted to delve down a little bit in this concept of patients who have chronic neuromuscular diseases presenting into the ICU. I mean, this happens surprisingly frequently with ALS patients or, like, myotonic dystrophy. I've seen this a number of times where folks are, just, they're not diagnosed and they're kind of slowly progressing and they tipped over the edge. Can you tell us more about how you recognize this? You talked a little bit about collateral history - other words of wisdom there? Dr Albin: I would say this is one of the hardest things that we encounter in critical care medicine, because quite frequently - and I see this more with ALS than myotonic dystrophies - but, I would say, like, I don't know, once every six months, we have a patient who’s undiagnosed ALS present. And I think it can be extremely difficult to tease this out because there's something that's tipped them over the edge. And as an intensivist, you were always focused on resuscitating the patient and saving them from that life-threatening thing that pushed them over the edge, and then trying to tease out, “Well, were they hypercarbic and did they have respiratory failure because, you know, they've got a little bit of COPD, and is that what's going on here?” or, "Have they been declining and has there been sort of this increase in inability to ventilate actually because of diaphragmatic weakness and because of neuromuscular weakness?” Again, the collateral history is really important. One of the things that I think we are challenged by is how difficult - and I'm sure you can comment on this, as someone who is a neuromuscular guy - is how difficult it is to get a good EMG and nerve conduction study in the ICU in patients who may have been there for a little bit, you know? I think about this, sort of, the electrical interference, the fact that the patient's body temperature has fluctuated, the fact that they are, usually, by this time, like, they're a little volume overloaded – they’re puffy. You know, it can be very frustrating. I think, actually, you probably would know more about, like, what it's like to do that exam on our ICU patients. Dr Smith: Sometimes, it's really challenging, I agree. And it's the whole list of things that you raised - and I think it goes back to the first question, really. You put a premium on old-school formulation, pattern recognition, localization, and taking a good history - you know, thinking of that ALS patient, right? I mean, one of the challenges, of course, that you have to deal with in that situation is prognostication and decisions regarding intubation, right? And that’s very different from (I'll give another scenario that sometimes we run into, which is the other extreme) a patient with myasthenia gravis who, maybe we expect to be able to get off a ventilator very quickly, but sometimes they’re reluctant to be ventilated because of their age or advanced directives and whatnot. I wonder if you could talk a little bit about how you approach counseling patients regarding prognosis related to their underlying neuromuscular disease and the need for intubation in a period of mechanical ventilation? Dr Albin: Just like you said, it really ranges from what the underlying diagnosis is. So, one of the things that, you know, like you said, myasthenia - these patients, when they're coming in in crisis, we know that there is a good chance that they're going to respond pretty quickly to immunotherapy. I mean, I think we've all seen these patients get plasma exchange, and within a day or two, they are so much stronger (they're lifting their head off the bed, they're clearing their secretions), and every now and then, we're able to temporize those patients with just noninvasive ventilation. You know, when we're having a discussion about that with the patient and with the care team, we really have to look at the amount of secretions and how well they're clearing them, because, again, we certainly don't want them to aspirate - that really sets people back. But, you know, I think, often in those cases, we can kind of use shared decision-making of, you know, “Can we help you get through this with noninvasive?” or, you know, "Looking at you, would you be all right with a short term of intubation?” Knowing that, usually, these patients stabilize not all the time, but quite frequently, with plasma exchange, which we use preferentially. The middle of that is, then, Guillain-Barré - those patients, because of the neuropathy features (the fact that it's going to take their nerves quite some time to heal, you know) - when those patients need to be intubated, a good 70% or more are going to require longer-term ventilation. And, so, again, it's working with a family, it's working with a patient to let them know, "We suspect that you're going to need to be on the ventilator for a long time. And we suspect, actually, you would probably benefit from early tracheostomy”. And there was a really nice guidance that was just presented in the Journal of Neurocritical Care about prognosticating in patients with specifically Guillain-Barré (so that's helpful). And then, we get to the, really, very difficult (I would say the most difficult thing that we deal with in neuromuscular emergencies) - is the patient who we think might have ALS (we are not positive), and then we are faced with this diagnosis of, “Would you like to be intubated, knowing that we very likely will never extubate you?” - and that, I think, is a very difficult conversation, especially given that there is a lot of uncertainty often in the diagnosis. I would say, even more frequently, what happens is they have been intubated at an outside hospital and then transferred to us for failure to wean from the ventilator and, "Can you work it up and say whether or not this is ALS?” – and that, I think, is one of the most difficult conundrums that we face in the ICU. Dr Smith: Yeah. I mean, that's often very, very difficult. And even when the patient wants to be intubated and ultimately receive a tracheostomy, getting them out of the hospital can sometimes be a real challenge. There's so much I want to talk to you about, and, you know, you talked about prognostication - really great discussion about tools to prognosticate in GBS, both strengths of things like EGRIS and the modified EGOS, and so forth – but, I wonder (given that I'm told time is limited for us) if you could talk a little bit about bedside guidance in terms of assessing when patients need to be intubated? You provide really great definitions of different respiratory parameters and the 20/30/40 rule that I'll refer listeners to, but I wonder if you could share, what's your favorite, kind of, bedside test - or couple of bedside tests - that we can use to assess the need for ventilatory support? And this could be particularly helpful in patients who have, let's say, bifacial weakness and can't get a good seal. So, what do you recommend? Is it breath count? Is it cough? Something else? Dr Albin: I think for me, anecdotally (and I really looked for is there any evidence to support this), but for me, anecdotally - and knowing that there is not really good evidence to support this - whether or not the patient could lift their head off the bed, to me, is a very good marker of their diaphragmatic strength. You know, if they've got good neck flexion, I feel a lot better about it. The single breath count test is another thing that I kind of went down a rabbit hole of, like, "Where did this come from?” because I think, you know, it was one of the first things I was taught in residency - like, “Oh, patient with neuromuscular weakness, have them take a deep breath and count for as many breaths as they can.” We have probably all done that bedside test. It's really important to recognize that the initial literature about it was done in myasthenia patients who were in clinic (so, these were not patients who are, like, abruptly going to need intubation), and it does correlate fairly well with their forced vital capacity (meaning how much they're able to exhale on bedside perimetry), but it is not perfect. And I put that nice graph in the article, and you can see, there's a lot of patients who are able to count quite high but actually have a very low FVC, and patients who count only to ten but have a very good FVC. So, I do like the test and I continue to use it, but I, you know, put an asterisk by it. It's also really important - and I would encourage any sort of neurology trainees, or trainees in any specialty - if you're taking care of these patients, watch the respiratory therapist come and do these at the bedside with them. You'll get a much greater sense of (a) what they're doing, but (b) how well the patient tried. And it is really, I mean, we have to interpret this number in the context of, "Did they give a really good effort?” So, I'll often go to the bedside with the RT and be the one coaching the patient - saying, like, you know, “Try again”, “Practice taking this”, “Do the best you can”, “Go, go, go! Go, go, go!” (you know, like, really coaching the patient) - and you would be surprised at how much better that makes their number. And when you're really appropriately counseling them, that we actually get numbers that are much better predicting what they're doing. Then, you also have a gestalt just from being at the bedside of what they looked like during this. Dr Smith: Yeah. I used to work with a neuromuscular nurse who was truly outstanding who was the loudest and most successful vital capacity coach ever. But, you know, she'd be doing it in one room, and you'd be in the next room with a patient. They'd be like, “What are they doing next door?” She was shouting and exhorting the patient to go harder and breathe better. So, it was always, “Wow, that sounds exciting over there”. All right, this is all in a prelude. What I really want to ask you, Casey, is, you know, whenever we do Continuum Audio interviews, we, like, look up people, and it’s not hard to look you up because you’re everywhere on the Internet. And come to find out, you’re a fully credential neuro Twitter star - and that's the term I saw, a star. So, what's it like being a Twitter star? I guess it's an X star. I don't even know what we call it anymore. Dr Albin: I guess it's that. I don't know. I don't know, either. It's so funny, um, that that has become so much of my, like, academic work. I got on Twitter, or X (whatever it is) during the pandemic because, really, my interest is in, you know, innovatives and medical education, and I really had been trained to do simulation. So, I really wanted to develop simulation curriculum. I love doing sims with our medical students to our fellows. So, I was, like, developing this whole curriculum, and then the pandemic came along, and the sim lab at Emory was like, “Mm, yeah, we're not going to let people go in the sim lab. Like, that's not exposure that we want (people in a room together)”. So one of our fellows at the time was doing a lot on Twitter and he was like, "You would love this. You have cases that you want to teach about. You should really get on board”. And I, sort of, reluctantly agreed and have found the NeuroTwitter community to be, like, just a fantastic exchange of, you know, cases, wisdom, new studies - I mean, it's the way that I keep up with what is being published in the many fields that are adjacent to neurocritical care. So, it's very funny that that has ended up being sort of something that is a really big part of my academic time. But now that we're talking about it, I will give a plug for any of the listeners who are not on X. Dr Jones and I post cases, usually twice a week, that come directly from the Continuum articles or from our files (because, you know, sometimes we can spin them a little bit), but it's an amazing, sort of case-based, way to do some, like, microteaching from all of the beautiful Continuum articles, all the cases - and because there are free articles released from the issue, you know we'll link directly to those. So, for any of the listeners who have not, kind of, joined X for all the reasons that many people cite of not joining, I would say that there’s so much learning that happens - but Dr Jones and I are people to follow because of our involvement with Continuum and the great cases that we’re able to showcase on that platform. Dr Smith: I think that's a great point. And, you know, there are certainly organizations that are questioning their engagement with X, and I'm on a board of an organization that's talked about not actually participating, and I brought up this point that I think the NeuroTwitter (NeuroX) community is really amazing. You'll have to give me some tips, though, I'm at, like, 498 followers or something like that. Do you know how many followers you have? I looked it up yesterday. I've got it for you if you don't know. Dr Albin: I don't know recently. Dr Smith: Yeah, 18,200 as of yesterday. That's amazing! Dr Albin: Yeah, it's worldwide. We're spreading knowledge of Continuum across the globe. It's fantastic. Dr Smith: That's crazy. Yeah, that's great work. It's really great to see the academic, kind of, productivity that comes of that. And I agree with you - Continuum has a really great presence there, and it's a great example of why you're the Associate Editor for Media Engagement. I think we're going to have to, I guess, gamify would be the right thing? Maybe we should, uh, see what the Las Vegas book is on the number of followers between you and Lyell Jones, I think. Dr Albin: Totally. Dr Smith: Yeah. Hey, Casey, this has been awesome. I've been so excited to talk to you - and I could keep talking to you for hours about your NeuroTwitter stardom – but in particular, neuromuscular weakness. I really encourage all of our listeners to check out the article. It's really, really, really, great - really enjoyed it. I learned a lot, and it reminded me a lot of things that I had forgotten. So thank you for the great article, and thanks for a really fun discussion. Dr Albin: Thank you, Dr Smith. It was truly a pleasure.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, please consider subscribing to the journal. There's a link in the episode notes. We'd also appreciate you following the podcast and rating or reviewing it. AAN members, go to the link in the episode notes and complete the evaluation to get CME for this article. Thank you for listening to Continuum Audio.

Neurologic infections become emergencies when they lead to a rapid decline in a patient’s function; however, neurologic infections are often challenging to recognize. In this episode, Aaron Berkowitz, MD, PhD, FAAN, speaks with Alexandra S. Reynolds, MD, author of the article “Neuroinfectious Emergencies,” in the Continuum® June 2024 Neurocritical Care issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of neurology at the University of California San Francisco, Department of Neurology and a neurohospitalist, general neurologist, and a clinician educator at the San Francisco VA Medical Center and San Francisco General Hospital in San Francisco, California. Dr. Reynolds is an associate professor in the departments of neurosurgery and neurology at Icahn School of Medicine at Mount Sinai Health System in New York, New York. Additional Resources Read the article: Neuroinfectious Emergencies Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Transcript Full transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the Journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening.     Dr Berkowitz: This is Dr Aaron Berkowitz, and today, I'm interviewing Dr Alexandra Reynolds about her article on neuroinfectious emergencies, which is part of the June 2024 Continuum issue on neurocritical care. Welcome to the podcast, Dr Reynolds. Um, would you mind, please, introducing yourself to our audience?   Dr Reynolds: Sure. Thank you for the invitation. I’m Alex Reynolds, and I am a neurointensivist at Mount Sinai Hospital in New York City.   Dr Berkowitz: Fantastic. Thanks for joining us. Dr Reynolds has written a really comprehensive article with lots of clinical pearls for the evaluation of patients with neurologic infections. So, to start off, when should we consider a neurologic infection as the cause of a patient's neurologic symptoms?   Dr Reynolds: That is a, really, much more complicated question than I think you recognize. I feel like a lot of it has to do with the risk factors of the patient. So, certainly, you know, a lot of times, we think about a patient who comes in with fever and altered mental status, and that's sort of the patient we're thinking about as having an intracranial infection – but, I do think there are a lot of risk factors that, sort of, may push us in that direction even if the patient doesn't have a fever or even if the patient doesn't seem like meningitis (for example). So, you know, a lot of patients nowadays are immunosuppressed, either because of infections or because of the therapies that we're using as immunosuppressants (so, autoimmune diseases, transplants, bone marrow patients). And then, I think, any patient who has had an intracranial procedure or a spinal procedure, we sort of just have to have in the back of our mind that surgical procedures come, by definition, with risk of infection (and so, that’s always something to think about). And then, certainly, anything in terms of endemic risk factors (so a patient who has come from a country that has an endemic infection), we need to just be a little bit more broad about what we're thinking about in that patient population.   Dr Berkowitz: That's very helpful. You mentioned something I wanted to pick up on. We always think fever, of course we're going to be thinking about a neurologic infection, but some types of neurologic infections and in some patient populations, it's possible to have an infection of the nervous system with no fever, sometimes even no white count. What other clues should be considered, or when would you think about pursuing infection even in patients who don't have a fever or an elevated white count?   Dr Reynolds: So, certainly, in patients who have imaging that’s a little abnormal. I think, oftentimes, the patients that I’ve seen with sort of indolent infections have a subdural collection that just doesn’t look quite right or doesn’t make sense with the clinical history (you know, you can have P. acnes infections that go on for months that people really don’t necessarily notice) - so any imaging, oftentimes on MRI, you’ll see, sort of, diffusion restriction where you don’t really expect to see it. So, those sorts of patients might be ones where if the story is just not really fitting, you might want to think about infection. So, I think it's also important to remember that patients who have procedures elsewhere in the body can sort of seed themselves, and either by direct spread or by hematogenous spread, those infections can kind of seed the CNS - so, patients with valve procedures in the heart, patients who have intraabdominal procedures, there really is no reason that those infections can't travel to the CNS as well. And so, I was sort of always taught, you know, if the story doesn’t make sense, then you have to consider infection, even if the patient doesn’t have a white count or fever. So, I think just having, sort of, that suspicion in the back of your mind that if you can't really make sense of the story, then consider an infection.   Dr Berkowitz: Yeah. So, obviously, fever, white count, those would clue us in that a patient with new neurologic symptoms (signs) may have an infection as a cause. But, as you said, they may not be present in patients who have had any type of neurosurgical procedure (or you've just taught us even non-neurosurgical procedures elsewhere in the body) that could have led to bacteremia. And then, you mentioned earlier, also patients who are immunocompromised may develop a neurologic infection without fever or white count, and our threshold is certainly lower to pursue that possibility in that population as well. Other points on that before we move on?   Dr Reynolds: I had an attending that told me if you're thinking about a lumbar puncture, you better just do it – so, I think those are wise words to sort of live by. If you're thinking about an infection, you better just work it up.   Dr Berkowitz: Yeah. I think that's right. I heard something similar that if you're standing around on rounds debating whether the patient should get a lumbar puncture, probably, if you've talked about it that much, you should probably do it. I think we've heard the same things in different places. Along those lines of who needs a lumbar puncture, many patients with systemic infections can develop a headache, even if it's just from systemic infection (you don't necessarily have meningitis and cephalitis), and many patients, particularly older patients, develop confusion in the course of systemic infections, like pneumonia and urinary tract infections. And as neurologists, we are often consulted on these patients because they are confused, they are febrile, they may have an elevated white count, and people start to wonder, Could this patient have meningitis? Could this patient have encephalitis? In many cases, at least in my experience (I'm curious to hear your experience), it turns out that these patients have a systemic infection and the confusion and/or headache are related to that systemic infection, not a primary neurologic infection - but based on that topic we just discussed about, if you've talked about lumbar puncture enough, probably best to do it. How do you think about these patients who are, for example, admitted to a medical service for fever and confusion, may or may not have had a systemic source identified, but the suspicion is there? How do you think about which of those patients need a lumbar puncture, or what clues you into thinking to have a higher concern for meningitis, encephalitis, abscess, other neurologic infections in this context?   Dr Reynolds: It's such a good question, because I think, especially as we get older, you know, even things like nuchal rigidity might be hard to assess in a patient who’s sort of started to fuse their spine - so, I think it can be really challenging. I think, you know, always go back to basics. Is there any new laterality that doesn't really make sense? Is there a sort of disconnect between imaging and how the patient looks? And it can be so confounded, because these are patients who are also on antibiotics (which themselves can be neurotoxic), and so, it can be really hard to sort of parse that out. But, I do think that there are some less invasive things you can try to do first to sort of help risk stratify your patient. So, you know, certainly, getting a CAT scan and just making sure that everything looks as you would expect it to look - there's no, sort of, hydro out of proportion to what you might expect. I’ve definitely seen patients who have meningitis that we caught because they have just a little bit of pus in the ventricles that was interpreted as intraventricular hemorrhage. And you sort of just have to sit there and think, like, Does that make sense, or is it an infection? EEG can be helpful, too, if it’s lateralizing. You know, I think we don’t think as much about HSV in the hospital. But, certainly, if you have something lateralizing on your EEG that just doesn't make sense, I think that could sort of push you in that direction as well. But, again, I think in most cases, unless the patient's very thrombocytopenic or coagulopathic, the risk of an LP sort of doesn't really outweigh the benefit of feeling confident that you haven't missed something, because I think, you know, one of the big points of this article is that if you catch these CNS infections early, people can actually do really well, and, really, most of the morbidity and mortality is from missing the infection - so we've been trying to move away from LP-ing everybody on admission, but I do think that you should be tapping some people that are not infected, because then you're probably catching everyone who is.   Dr Berkowitz: It's great to hear your approach, and I think that aligns with my thinking as well. I do want to ask as a follow-up to that question (I've asked this of internists I work with and other neurologists) - I totally agree with everything you said in the sense that, you know, we are consulted by our internists, we presume that they haven't found a reason that the patient is febrile and confused from a systemic standpoint, and that's why we're being consulted. There are, obviously, many patients who are febrile and confused in the hospital where neurology has not been called because there's other obvious reasons, as you have mentioned. However, as you said, if the patient has some immunocompromise, maybe there’s some features that are suggestive in the history or nuchal rigidity - as you said, harder in older patients - but there’s something there that you sort of think, maybe we should just do a lumbar puncture just to make sure we sort of settle this because we keep thinking about it. The question is, in your experience, when you've gotten a lumbar puncture more as a rule-out, or you think, I think this is the patient's pneumonia and they're confused because they're delirious in the hospital (sort of toxic metabolic encephalopathy), have you ever been surprised? Talking to an internist colleague, I've said, I feel like I haven't actually seen that much bacterial meningitis in the U.S., fortunately, thanks to vaccination. And, usually, the patient is coming in with a pretty profound syndrome of meningitis or encephalitis. But, as far as patients in the hospital with a fever, where you’re thinking, "This is kind of a rule-out, so just make sure, even though I don’t think I’m going to find meningitis in a patient who is immunocompetent”, have you ever been surprised and found meningitis encephalitis when you didn't expect to find it? Or, what's been your experience when you, as you said, tap these patients because you'd rather get a few normal ones in there to make sure you never missed the abnormal?   Dr Reynolds: I would say the few times that I've been surprised were not with fully immunocompetent patients. You know, someone with a splenectomy who otherwise looks immunocompetent, someone with pretty advanced cancer - those are examples where you wouldn't necessarily have thought about it as being immunocompromised, but they are. Certainly, I think patients with advanced cancer can, really - they're much higher risk than I used to think about. The more I've taken care of them, the more I've realized how sensitive they are to infections and how quickly that can spread, even if they're not actively getting chemotherapy. But, I would say in general, for the truly immunocompetent patient, I would say I haven't really diagnosed anything super exciting.   Dr Berkowitz: Yeah, that's good to hear. I love to, on these Continuum Audio interviews, poll experts in other institutions who trained other places and, you know, learn from different patient populations if your experience resonates with mine and others I've spoken to. Yeah, that sounds similar to my experience as well, yeah, if the patient is immunocompromised - and as you said, we maybe need to broaden that from being truly profoundly immunocompromised by congenital immunodeficiency or HIV or immunomodulatory therapy to have a slightly broader perspective on what could constitute immunocompromise - and, of course, we'd have an extremely low threshold to perform a lumbar puncture in such patients, as you said. You reminded me of a case I was trying to remember the details (which I don't) – it was a patient, actually, with a temporal lobe glioblastoma that had been resected and had some recurrence and was worsening, and it looked like it was tumor recurrence/progression. And I don't - wasn't my patient, I just sort of heard about it - but I don't know which attending or resident or fellow decided that the patient should get a lumbar puncture, and the patient actually developed HSV encephalitis of the temporal lobe, where the glioblastoma was.   Dr Reynolds: Wow.   Dr Berkowitz: Patients with cancer, especially with all the new immunotherapies - and even without them, as you said - this is a state in which people may be vulnerable to infections and ones you might not immediately think of. So, those are some great pearls. Speaking of pearls, you have a really fantastic section in your article on neurologic complications of CNS infections. In other words, you've already diagnosed the meningitis, encephalitis, abscess, or otherwise, and all the other neurologic complications that can occur in the course of this illness. So, it'd be great to talk with you a little bit about that here. So, if a patient is diagnosed with infectious meningitis or encephalitis (we've made that diagnosis by the clinical picture, the lumbar puncture findings, and/or the neuroimaging), we're following them along, we think we have them on appropriate therapy, (antimicrobial therapy), and their neurologic status worsens - what's the differential diagnosis for this worsening? What are some things we can think about? How do we look for them on exam? How do we work them up?   Dr Reynolds: Yeah. It's funny, because, you know, the topic of this is neuroinfectious emergencies, and when I first heard about it, I was like, “Every neuroinfection is an emergency”, and I think part of the reason I felt that way is because as a neuro ICU physician, I see the complications a lot more. You know, I think, from a meningitis and encephalitis standpoint, certainly cerebral edema (whether it be focal or global) is sort of your biggest concern. If you've used your adjunctive steroid therapy at the beginning before you've started antibiotics, you know the idea is that might help – and, certainly, it should help with potential hearing loss as a result of meningitis - but I would say cerebral edema or development of abscesses because of delayed antibiotic initiation is certainly a concern. If a patient’s getting lethargic, hydrocephalus can often be a concern - and that may be obstructive hydrocephalus or communicating hydrocephalus – either way, that is a situation where, really, the patient may need, depending on the etiology of the hydrocephalus, either another lumbar puncture (for example, in the case of cryptococcal meningitis) or an external ventricular drain placement (which would bring them to the ICU in cases where there is an obstructive component). So, I do think hydrocephalus is hard to diagnose. My go-to is to sort of check tone in the legs every day, because a lot of times, patients with developing hydro will start to have really high tone in their legs - so, that's sort of my go-to physical exam finding, although, obviously, hydrocephalus can present as just sort of generalized lethargy or even, you know, worsening nausea and vomiting, for example. And then, I think, you know, if someone starts to be localizing on exam, I think that can be concerning not only for abscess, but potentially for ischemic stroke related to a vasculopathy, for example, or hemorrhage in the context of mycotic aneurysm formation, for example - and, so, I do think there is a role, if a patient starts to become lateralizing, for emergent imaging. And generally, we should be able to see most of the stuff on just a plain CAT scan to start. You know, certainly, localizing stuff can also be as a result of seizures, but I think that that's sort of a diagnosis of exclusion, and rapidly imaging a patient with new focal signs is probably the way to go before putting them on EEG.   Dr Berkowitz: Very helpful pearls. So, um, shifting gears a little bit, right before we began our conversation, you were telling me you had done some work in Malawi, and you were reflecting on some of the differences in epidemiology of neuroinfectious disease and resources available to diagnose neuroinfectious disease. So, I'm sure it would be very interesting for our listeners to hear a little bit about the perspective you bring to the diagnosis and treatment of patients with neurologic infections from your experience in Malawi.   Dr Reynolds: Yeah. So, I was lucky enough as a trainee to be able to go to Malawi for a few weeks with my neuroinfectious disease attending, and I think that it’s pretty striking (the difference that we see in lower income countries, compared to the U.S.). I think a lot of the disease processes that we sort of take for granted as being easily treatable are not necessarily easily treatable, not only because of lack of access to medications and antibiotics, but also because of sort of a stigma that might be associated with the workup. So, for example, a lot of people were very hesitant to consent to lumbar puncture, because they had seen that their friends and family members who had gotten lumbar punctures ultimately died, and it didn't seem necessarily clear that the reason that they had died was from the primary infection itself. So, I think that really being attuned to disparities not only abroad, but even - you know, working in New York City, I can say that there are definitely disparities in terms of access to care and health equity, and, certainly, the timing of your presentation almost necessarily will change the outcome, and people who are presenting to the hospital later because of infections that were sort of ignored or because of lack of access to healthcare, those patients, really, by definition, end up doing worse - and so, I think that that is really a big thing to think about in our resource-rich areas, think about these infections.   Dr Berkowitz: Well, thank you for sharing those valuable and important perspectives both from Malawi and from your work in New York City.   Dr Reynolds: Thank you.   Dr Berkowitz: Well, thank you so much, Dr Reynolds, for joining me today on Continuum Audio. I've enjoyed our discussion and learned a lot from it. Again, today, we've been interviewing Dr Alexandra Reynolds, whose article on neuroinfectious emergencies appears in the most recent issue of Continuum on neurocritical care. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to all of our listeners for joining today.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, please consider subscribing to the journal. There's a link in the episode notes. We'd also appreciate you following the podcast and rating or reviewing it. AAN members, go to the link in the episode notes and complete the evaluation to get CME for this episode. Thank you for listening to Continuum Audio.

Despite validated models, predicting outcomes after traumatic brain injury remains challenging, requiring prognostic humility and a model of shared decision making with surrogate decision makers to establish care goals. In this episode, Lyell Jones, MD, FAAN, speaks with Jamie E. Podell, MD, an author of the article “Traumatic Brain Injury and Traumatic Spinal Cord Injury,” in the Continuum June 2024 Neurocritical Care 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. Podell is an assistant professor in the department of neurology, program in trauma at the University of Maryland School of Medicine in Baltimore, Maryland. Additional Resources Read the article: Traumatic Brain Injury and Traumatic Spinal Cord Injury Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @LyellJ Guest: @jepodell Transcript Full transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier, topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening.   Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr Jamie Podell, who has recently authored an article on traumatic brain injury and traumatic spinal cord injury in the latest issue of Continuum on neurocritical care. Dr Podell, welcome. Thank you for joining us today. Why don't you introduce yourself to our audience and tell us a little bit about yourself?   Dr Podell: Thanks, Dr Jones. It's great to be here. As you mentioned, I'm Dr Podell. I'm neurocritical care faculty at University of Maryland Shock Trauma. I have a primary interest in traumatic brain injury, both from a research and clinical perspective. I previously have more of a cognitive neuroscience background, but I think it kind of ties into how I think about TBI and outcomes from traumatic brain injury. But what I really like doing is managing acutely ill patients in the ICU, and I think TBI really affords those kinds of interventions, and it's a really rewarding kind of setting to take care of patients. Dr Jones: Yeah, and I really can't wait to talk to you about your article here, which is fantastic. For our listeners who might be new to Continuum, Continuum is a journal dedicated to helping clinicians deliver the best possible neurologic care to their patients, just like Dr Podell was talking about. We do that with high quality and current clinical reviews, and Dr Podell's article - it's a massive topic - traumatic brain injury and traumatic spinal cord injury. And, you know, as we start off here, Dr Podell, we have the attention now of a massive audience of neurologists. If you had one most important practice change that you would like to see in the care of these patients who have trauma, what would that practice change be? And, I think, maybe, we'll give you two answers, because you cover TBI and you cover spinal cord injury. What would be the most important practice changes you'd like to see?   Dr Podell: So, this isn't that specific, but I think it's really important. I think we need more neurologists, and specifically neurointensivists, managing these patients. I think there's a lot of variability across institutions and how acute severe TBI and spinal cord injury patients are managed. They're often in surgical ICUs, and neurology may be involved in consultation but not in the day-to-day management. But I think what we're seeing is that, you know, there's a lot of multisystem organ dysfunction that happens in these patients, and that has a really strong interplay with neurologic recovery and brain function. And I think, you know, neurointensivists are very well equipped to think about the whole body and how we can kind of manipulate and really aggressively support the body to help heal the brain with special attention to, kind of, the nuance of any individual patient's brain injury. Because TBI is extremely heterogeneous and there's not just a cookie-cutter script for how these patients can be managed, I think, you know, people like neurologists, neurointensivists who have a lot of attention to the nuance - that's really helpful in their management.   Dr Jones: I'm so glad you said that, and not just because I'm a neurologist who's a fan of neurologists, but I do think there are some corners of neuroscience care where neurologists could be a little more present - and trauma definitely seems like one of those, doesn't it?   Dr Podell: Yeah, I think it's tough, because some patients with severe TBI and spinal cord injury can have a lot of multisystemic trauma with, you know, pulmonary contusions, intraabdominal pathology - you need to go to the OR for their other injuries, and so I think it really makes sense to have kind of a collaborative multidisciplinary approach to these patients, but I think neurologists should play a very big role in that approach, however that's done (there are lots of different ways that it's done). But I think having a primary neurology-trained neurointensivist – I know I’m biased, but I think that’s where I’d like to see the field moving.   Dr Jones: And, obviously, neurocritical care is an intuitive place for neurological trauma care to start, and even with the sequelae of downstream things, I think neurologists could be more engaged. I wonder if neurology hasn't historically been as involved because it's sort of gravitated to surgical specialists. And I think part of it is, you know, trauma is not usually a diagnostic mystery, right? The neurologist can't pretend to be Sherlock Holmes and try to figure out what's going on when it was pretty clear what the event was, right?   Dr Podell: Right. Yeah, I agree with both of those points. I think, for one, I think postacute care is also a big area where neurologists can be involved more - and patients kind of fall through the cracks. A lot of times, these patients will just follow up with a neurosurgeon and get a repeat head CT and it’ll look stable. We started implementing post-TBI neural recovery clinics, which I think other places are starting to do as well, and I think that's kind of a good model for getting neurologists involved - but also, rehab specialists are involved in that. But in terms of, yeah, the diagnostic mysteries and stuff, I think there still can be some, though, with TBI. Yes, obviously, the initial primary insult is obvious, but the secondary pathology that can happen in patients is really nuanced, and it is so variable, and, sometimes, it does take that detective eye to see, “Oh, this patient has one cerebrovascular injury, their risk of stroke to this territory? How are we going to manage it? and thinking about all the kind of sources of secondary decline that are possible. I think it takes that neurology detective sometimes to think about, too.   Dr Jones: Yeah. We never stop pretending to be detectives, right?   Dr Podell: Yeah.   Dr Jones: And on a related note, you know, in your article, you mentioned some of the novel serum and electrophysiologic and imaging biomarkers that are being used to care for these patients. How are you using those in your practice, Dr Podell?   Dr Podell: That's a good question. I think, unfortunately, as with a lot of clinical care, the clinical care does kind of lag behind the research and what we know what we can learn about these patients and their outcomes through retrospective studies. So, to be completely honest, you know, even the serum studies that I mentioned in the article (like GFAP, UCH-L1) - those kind of things, that's not clinically available at our institution. We don't use those. I think a lot of the imaging biomarkers that we see, some of them are coming from more advanced imaging – like, we're talking about FMRI - that requires a lot of post processing (so, again, we're not necessarily using that clinically). But what I would say is that we use imaging to kind of try to predict what complications patients might be at risk of and to try to predict their clinical course. And I think it comes down to trying to break down the heterogeneity of these patients and to try to kind of lump them into different bins of, “What's this patient at risk for?”, “What's their trajectory going to be like?”, “When can I start peeling back how aggressive I am with this patient?”. And, so far, I don't think any of the markers that we have are really clear black-white prescriptive indicators of what to do (I don't think we're quite there yet). So, again, I think we just kind of use all of the data in combination to come up with a management plan for these patients. I think some of the markers, (like some of the electrophysiologic markers), looking at EEG for things like background can provide prognostic information, especially in patients who are comatose that you're wondering about if they're going to wake up (so a lot of this can inform family discussions). But, you know, we used to think that grade three diffuse axonal injury on MRI portended a very poor prognosis (and in the past, some surgeons and ICUs might use that to limit care in patients), but more and more, we're finding that even that is quite nuanced and we're detecting more and more diffuse axonal injury on images in patients who then wake up, or have already woken up and they have the MRI later, and you're like, “Hmm, they had DAI. It's a good thing you didn't get the MRI early and decide not to move forward with aggressive care”. But, I think, in a patient who's comatose and you don't have a good explanation, sometimes, looking for those additional biomarkers to explain what kind of injury pathology you have can just provide more information for families.   Dr Jones: Yeah, and that's a great point that comes up in a lot of our articles and interviews (that the biomarkers really do have to be in a clinical context). So, if I understand you correctly, really, no individual biomarker that has emerged as a precise predictor or prognosticator for outcomes - but you do talk a lot about recent advances in the care of these patients. What would you want to point out to our listeners that's come up recently in the care of trauma?   Dr Podell: Yeah. I think the evidence basis for severe TBI is limited because, again, there's so much heterogeneity and different things going on with different patients, but some of the evidence that has come out more recently involves, kind of, indications for surgical procedures and the timing of those procedures. Some of that is still kind of expert consensus-based. But, for example, doing a secondary decompression for elevated ICP with the DECRA and RESCUEicp trials. We do have better high-quality evidence that doing a secondary decompression for more refractory, elevated ICP can improve both mortality and functional outcomes in patients, so that has kind of become more standard of care. Additionally, I think timing for spinal cord injury, neurosurgical procedures - that's been a topic that's been studied in more evidence-based to perform earlier decompressive surgeries. And then, I think, you know, more and more is emerging just about the pathophysiology of secondary injury - and some of those things haven't necessarily translated to what to do about it - but we've learned about things like cortical spreading depolarizations being associated with worse outcomes in traumatic brain injury, and we've also identified that ketamine or memantine can both actually stop those cortical spreading depolarizations. But the overall impact of managing them is still unknown, and the way that we detect those, it requires an invasive electrocorticography monitor which not all centers have. So, I think, one of the important things as we move forward in TBI care is, as we get this better mechanistic understanding of some of the pathophysiology that's happening in these TBI patients, figuring out a way to be able to translate that across all clinical settings where you can actually do the monitoring invasively - that's also an issue we see. Even intracranial pressure monitoring is pretty standard of care, but not all centers do that, and we have to be able to apply practice recommendations to centers where there isn't necessarily access to the same things that we have at large academic trauma centers.    Dr Jones: Got it. Obviously, there's a lot of research in this area, a lot of clinical research, and I'm glad you mentioned the secondary injury - things that are happening at the tissue level are important for us to think about. As the care of patients with trauma has evolved (and I'm thinking now of patients with spinal cord injury), we still see patients who receive high-dose corticosteroids in the setting of acute spinal cord injury - and obviously, that's something that's evolved. Can you tell our listeners a little bit more about what they should be doing when they're seeing a patient with a traumatic spinal cord injury?   Dr Podell: Yes. So, the steroids story for spinal cord injury is kind of interesting. There were a series of trials called the NASCIS trials that looked at corticosteroids and spinal cord injury, and they were initially interpreted that high-dose steroids had a beneficial effect on spinal cord injury recovery - but then, kind of in relooking at the data and recognizing that these were kind of unplanned subgroup analyses that showed benefit, and then looking at kind of pooled reanalysis and meta-analysis of all the data out there, it was determined that there actually was no clear benefit from steroids and that there was a clear incidence of more complications from high-dose steroids. So, in general, corticosteroids are not recommended for spinal cord injury. Same for traumatic brain injury, too (even though some people will still give steroids for that) - there was a CRASH study that looked at corticosteroids in TBI and found worse outcomes in TBI (so there actually is high-level evidence not to use steroids in that case). That's not to say that there's not an inflammatory process that's going on that could be causing secondary injury - I think that's still, really, you know, an area of active research is to try to figure out what is the balance between potential adaptive mechanisms of inflammation that are happening versus more maladaptive sources of secondary injury from inflammation and how and when do we target that inflammation to improve outcomes. So, there's still, I think, more to come on that.   Dr Jones: And, you know, we are guided by evidence, obviously, but also, we learn from our experience as clinicians. You work in the neurocritical care unit. You take care of all patients with critical neurologic problems. When it comes to TBI and spinal cord injury, what kind of management tips or tricks have you learned that would be good for our audience to hear?   Dr Podell: I think the way that I would sum it up is that you should be very aggressive - supportive care early on, and then thoughtfully pull back and let the brain and spinal cord heal itself. And, you know, the patients come in with TBI (for example) very sympathetically aroused. They do need sedation, they need blood pressure support, they need mechanical ventilation - they need help kind of maintaining homeostasis. And other autonomic effects with spinal cord injury happen, too - you get neurogenic shock (you need very aggressive management of blood pressure, volume assessments), you know, in both cases in trauma patients, managing things like coagulopathy - but, you know, over time, usually, these things start to, kind of, heal themselves to some degree. And then, kind of thoughtfully figuring out when you can peel back on the different measures that you're doing to support them through their acute injuries. Different protocols have been developed, and the Brain Trauma Foundation has developed evidence-based guidelines that have improved (just having a protocol, we know, improves) trauma outcomes overall at centers - but I think those protocols are just guidelines, and you really have to pay attention to the individual patient in front of you. For TBI, for example, our guideline will say to aggressively manage fever within the first seven days with surface cooling. But in a patient that, for example, developed kind of a stroke or progressive cerebral edema even on day five (or something) you're looking at them, and on day seven, they're still having a lot of swelling in their brain, I'm not going to peel off the temperature management. So, there is nuance - you can't just kind follow a rule book in these patients.   Dr Jones: Got it. And I think that point about aggressive support early is a good takeaway for any listeners who might be engaged in the care of these patients. You know, I imagine working in that setting and taking care of patients who are in the midst of a devastating injury - I imagine that can be pretty challenging, but I imagine it could be pretty rewarding as well. What drew you to this particular area of interest, Dr Podell, and what do you find most exciting about it?   Dr Podell: A lot kind of converged for me in this area. I went into neurology thinking I would be a cognitive neurologist. I had more of a neuroimaging background and an interest in neural network pathology that certainly happens to patients with TBI (and patients with TBI often will have neuropsychiatric and neurocognitive problems after injury). But then, during residency, I found myself. My personality clicked in the ICU, and I just liked managing sick patients - I liked the pace of it, I also really liked it. It's kind of a team sport in the ICU with multiple people involved - the bedside nurses, respiratory therapists, neurosurgeons, trauma surgeons - all working together to figure out the best management plan for these patients, so you don't feel alone in managing them. And not all outcomes are good, obviously, but you can see people get better even during their course of their ICU stay - and that's really, really rewarding. And I think what we're seeing even in the literature following patients out longer and longer, the recovery trajectory for TBI is different than what we see in other neurologic injuries (like stroke, where the longer you go - up to ten, twenty years, even - people are still improving). I think the idea that you can keep hope alive for a lot of these patients and try to combat any kind of nihilism - obviously, there's a time and place for that after a really devastating injury, but I've seen a lot of patients who are really, really sick, needing therapeutic hypothermia, barbiturate coma, decompression, still then recovering and being able to come back into the ICU and talk to us.   Dr Jones: We might have some junior listeners who are thinking about behavioral neurology or neurocritical care, and it's probably - I don't know if it's reassuring, or maybe concerning, to them to know that they might swing completely to the other end of the spectrum of acuity, which is kind of what you did.   Dr Podell: Yeah, and what I'm trying to do now is, I'm very interested in autonomic dysfunction that happens in these patients. It's related a lot to multisystem organ dysfunction and, I think, may contribute to secondary injury, too, with changes in cerebral perfusion, especially in patients who have storming or even just the early autonomic dysregulation that happens early on. I think it's induced by neural network dysfunction from the brain injury, kind of similar to the way that there are other phenotypes that would be induced by neural network dysfunction (like coma).  So, we're trying to look at MRIs of acute TBI patients and trying to identify what structural imaging pathology then gives rise to these different kinds of clinical phenotypes - trying to bring it back to this neuroscience focus.   Dr Jones: Well, that gives us and our listeners something to look forward to, Dr Podell. And again, I just want to thank you for joining us, and thank you for such a great discussion on the care of patients with TBI, and spinal cord disorders and thank you for such a wonderful article.   Dr Podell: Thank you very much. It is my pleasure.   Dr Jones: Again, we've been speaking with Dr Jamie Podell, author of an article on traumatic brain injury and traumatic spinal cord injury in Continuum’s latest issue on neurocritical care. 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, please consider subscribing to the journal. There's a link in the episode notes. We'd also appreciate you following the podcast and rating or reviewing it. AAN members, go to the link in the episode notes and complete the evaluation to get CME for this article. Thank you for listening to Continuum Audio.  

The critical care management of spontaneous subarachnoid hemorrhage (SAH) is similar to that of other acute brain injuries, with the addition of detecting and treating delayed cerebral ischemia. Recent trials are influencing practice and providing guidance for standardizing management. In this episode, Kait Nevel, MD speaks with Soojin Park, MD, FAHA, FNCS, author of the article “Emergent Management of Spontaneous Subarachnoid Hemorrhage,” in the Continuum June 2024 Neurocritical Care issue. Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana. Dr. Park is an associate professor of neurology (in biomedical informatics) at Vagelos College of Physicians and Surgeons, Columbia University in New York, New York and medical director of critical care data science and artificial intelligence at NewYork-Presbyterian Hospital in New York, New York. Additional Resources Read the article: Emergent Management of Spontaneous Subarachnoid Hemorrhage Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @IUneurodocmom Guest: @soojin_soojin Full episode transcript   Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening.   Dr Nevel: This is Dr Kait Nevel. Today, I'm interviewing Dr Soojin Park about her article on emergent management of spontaneous subarachnoid hemorrhage, which is part of the June 2024 Continuum issue on neurocritical care. Welcome to the podcast. It's so great to be talking to you today.   Dr Park: Thank you so much, Kait. Nice to be here.   Dr Nevel: Before we get started, could you introduce yourself for the audience?   Dr Park: Sure. So, I am an Associate Professor of Neurology - also in Biomedical Informatics - at Columbia University here in New York City. I trained in vascular neurology and neurocritical care.   Dr Nevel: Great. And so, I always like to ask at the beginning of these interviews, you know, if we could take away one thing from your article — and this is specifically (I'll direct this) towards the neurologists out there that are covering inpatient consults and ER consults — and so, for our clinical neurologists listening out there, what is the most important thing that you think that they should take away from your article?   Dr Park: So, I guess the most important thing for the general neurologists out there is that it may have been a while since they were aware of some updates that have occurred. There are some recent trials that are influencing practice and will potentially influence practice in the next few years that readers should really know about, and it provides a little bit stronger guidance to drive more standardized management. There have been two recent guidelines published this year. But there remain several gray areas for management where you need to be a bit more nuanced, and so I'm hoping the article gives the readers a framework to deliver more expert care.   Dr Nevel: Yeah, and I really, of course, always urge the listeners to go back and read the article and reference the article, because I do think that you do that really nicely and are clear when there are things where there's more higher-level, evidence-based reasons for things and where there's, kind of, just more expertise and guidelines on certain things. So, could you tell the listeners a little bit more about yourself, what interests you about subarachnoid hemorrhage specifically, and how you approach that interest and clinical background in writing this article?   Dr Park: So, I mentioned that I trained in both vascular neurology and neurocritical care back when many people used to do that. As a result, I’ve trained or practiced in four different academic medical centers who have specialized neurointensive care units. And the patients with subarachnoid hemorrhage tend to have a substantial ICU length of stay, and the neurointensive care that we provide can have a very large impact on patient outcome. And what I saw, though (practicing across four different centers), was that the management of patients with subarach can be quite variable across institutions and across patients within institutions, and it's reflective of a couple of things. One, there's, like, complexity in detecting ischemia, even when your patient is a captive audience in their ICU room. Second, there's many clinical mimics that occur (the patients with subarachnoid hemorrhage, they have a risk for), such as hydrocephalus, seizure, and things like delirium. And then, finally, there's limitations in the technology that we even have available in terms of monitoring these patients. But, for me, it was this complexity and the variability of management that kind of posed an opportunity, and it really sparked my curiosity early on and has sustained me. So, I'm particularly interested in the role that, kind of, the complex analysis of existing monitoring technologies can play to improve outcome for patients with subarachnoid hemorrhage, and that's where the marriage of both being a neurointensive care physician and a biomedical informatics person comes in.   Dr Nevel: Yeah. That's really interesting, and I could see that, because I always felt, even during my training, that some of the management and, you know, what diagnostics were even ordered to follow patients throughout the ICU was expertise based and seemed to vary without a lot of really solid, again, high-level studies, guiding what was done. So how do you marry the bioinformatics with your interest in SAH?   Dr Park: Right. So, I have two grants on - basically, I guess you would say AI, but really data science - on how we can manage patients with bleeds, specifically ICH and subarachnoid hemorrhage and hydrocephalus. So, we use data that comes from the monitors and we process that in a multimodal fashion and apply signal processing and machine learning and we build predictive analytic tools. So, I'm very interested in this pipeline of developing clinical decision support (information that we don't really have), and we're trying to glean from all the data and turn it into information that clinicians might use. The problem in subarachnoid hemorrhage patients is that a lot of what we're looking for is subclinical - so, it's not quite obvious, either because you can't possibly be in the room to be constantly monitoring for it (and, currently, the best monitor is the human, is examination), but, specifically in patients who have disordered consciousness, even the examination can be somewhat limited, and that’s where we rely upon some of our neuromonitors. So, my interest has come in taking those multimodal monitors - but even nonneurologic monitors (stuff about your physiology, like your heart rate and blood pressure, et cetera) - and able to find signals that might tell us that a patient is getting into a dangerous zone. So, that’s what my research portfolio has been 100% about - it’s about subarachnoid hemorrhage patients and trying to optimize management, both for prevention and intervening in a timely fashion.   Dr Nevel: Wow. That’s really interesting and would be so wonderful, it sounds like, for this patient population, if, you know, something was able to be identified that you could easily monitor to kind of predict or catch things early. So, kind of segueing from that, what do you think are the most — and you outline these nicely in your article, and I’m going to reference the listeners to, I believe it’s the first table (table 5-1) - but what are, just like in general, the most important initial steps a clinician should take when managing somebody with an aneurysmal subarachnoid hemorrhage?   Dr Park: So, I think it’s sort of along the timeline. So, at the time of presentation of a patient with subarachnoid hemorrhage, the focus you should have should be really on differentiating the etiology of the subarachnoid hemorrhage. At the same time, if the patient has any coagulopathies, you should manage that coagulopathy reversal, blood pressure management, and then detection and management and treatment of hydrocephalus. That’s first and foremost. But then there is a longer timeline of neurocritical care management, and that’s really centered on prevention, detection, and treatment of delayed cerebral ischemia, and that can occur anytime from onset of subarachnoid hemorrhage to two to three weeks out. And then that period of neurocritical care is made challenging because you have early brain injury (which is the period of seventy-two hours after onset), cerebral edema, and then, like we talked about, disordered consciousness. This kind of knowing how to augment your management strategies with monitoring or imaging is really key.   Dr Nevel: Yeah. And you, you know, spend some time in your article really going through delayed cerebral ischemia really nicely. And I would love to hear your take on what is the most challenging aspects of delayed cerebral ischemia in both, you know, diagnosis and management - and you alluded to it a little bit earlier, I think, with some of your research, but I would love to hear you talk about that.   Dr Park: Yeah. And actually, this is probably one of - if there was a controversial area in this topic, it would be about this - because there does not seem to be one best way to operationalize how you either survey for, or monitor for, delayed cerebral ischemia. There has been, historically, a merging of these definitions of vasospasm and delayed cerebral ischemia, which are not the same thing.  And so, if you were to draw a Venn diagram, not all patients who have cerebral vasospasm end up having symptomatic or delayed cerebral ischemia, and not all patients who have delayed cerebral ischemia have any discernable vasospasm - and, so, to use the terms interchangeably leads to a little bit of confusion. I mentioned the clinical mimics - you know, the causes of which are myriad (could be delirium, or hydrocephalus, or early brain injury) - and so that also poses another challenge. And, so, what I always say is that delayed cerebral ischemia, sometimes - when you're thinking about it in the context of subarachnoid hemorrhage - is sometimes a retrospective diagnosis. And it really kind of came from a really earnest attempt to standardize what the community is talking about, so that we can better understand how to define (if you understand how to define it better, then you can tailor treatments, study treatments, you're talking about the same disease) - but we're still not there, and I think that's where a lot of the controversy or confusion comes from. My personal approach is really to focus on the symptomatology, so, if a patient has vasospasm - whether that is, you know, screened for with a transcranial Doppler (if your institution does use transcranial Dopplers, it might be a nice screening tool) - but the fact of the matter is that not all patients can get a transcranial Doppler every single day. You know, most of the institutions that I have worked in offer that technology Monday through Friday and not on holidays, not on weekends, and so you can't fully rely upon something like that. The advantage of it is that it has pretty high sensitivity but it does have a lower specificity (so it overcalls vasospasms), so to treat just based on a TCD would probably be erroneous. Not all people agree, but I think that's the majority of the sentiment - is that you should then be triggered to go look for confirmation with some neuroimaging and really potentially wait for symptoms so that it might be a trigger to optimize the patient in terms of volume and blood pressure, but not necessarily to treat. So, yeah, operationalizing that workflow of how do you trigger, you know, confirmatory neuroimaging, what type of neuroimaging you should then choose? This is where the variability exists. But, in general, I focus on symptomatology. The extra challenge comes in the patients who have disordered consciousness. And so, at an institution like mine, we do rely upon invasive neuromonitoring, and that's now called for in the guidelines as well.   Dr Nevel: And I imagine these are high-intensity situations where also I would suspect decisions, you know, need to be made quickly on some of these things that you're talking about, too.   Dr Park: That's right.   Dr Nevel: What do you think is a misconception - or maybe (I hate to call it a mistake, but for lack of a better term) like an easy mistake that one can make - when treating patients with aneurysmal subarachnoid hemorrhage?   Dr Park: Hmm, an easy mistake. I guess, you know, time is brain, so it's an opportunity to miss ischemia - or actually attribute everything to ischemia and ignore the possibility for things like seizure (so nonconvulsive seizures), a resurgence of more of a delayed hydrocephalus - and so, I think it’s important as you’re managing a patient not to get kind of pigeonholed into looking for one particular thing (only looking for delayed cerebral ischemia), but being really vigilant that there could be lots of different reasons for a neurological change of a patient. And so, timely monitoring - kind of figuring out the etiology of a change in neurological status - is really important. And then, also, on the flip side of that, is we're really good at being aggressive in both inducing hypertension or managing a patient (trying to prevent ischemia), we're not that great about starting to pull back - and so I think being vigilant about opportunities to reassess your patient's risk for ongoing ischemia and deciding when that period of risk is over and starting to peel back on therapies, because these patients are also at risk for the down sides of inducing hypertension, which is PRES - and we have seen that in patients, and, you know, the phenotype of that will look very much like ischemia.   Dr Nevel: Yeah, it's complicated because you're taking care of patients with often impaired consciousness who have a lot of symptoms that could represent many different diagnoses that you would treat very differently, so I could see that that might be easy to do to kind of fall into the mindset of thinking that it's definitely one thing without fully evaluating for everything. So, caring for patients with aneurysmal subarachnoid hemorrhage obviously can be really, you know, challenging from the medical perspective, but also from the perspective of, you know, communication with families, and families asking questions about prognosis and things like that (and you mentioned this in your article about prognostication a little bit) - and can you talk a little bit about our ability to prognosticate long-term outcomes for patients who are in that acute phase (maybe even early first, you know, couple of days or a week) with a subarachnoid hemorrhage?   Dr Park: I think one of the most rewarding aspects of caring for patients with subarachnoid hemorrhage is that these patients can look, really, very sick in the beginning, and they're quite complex to manage, but you can see some very impressive recovery. And from a neurointensivist perspective, seeing that recovery in kind of a rapid timeline is rare - and we get to see that in subarach patients. We see patients who just have refractory recurrent vasospasm and delayed cerebral ischemia getting all of the tools thrown at them and you're really kind of, you know, concerned that there seems to be no end - but there is this peak of that injury, and then after that window of secondary brain injury risk kind of resolves, the patient can very much recover (so seeing patients who look the sickest be able to leave and go home). I think there is a hidden cost to subarachnoid hemorrhage where, maybe on our gross measures of outcome, patients look great, but there are this hidden cost of social psychological outcome that is unmeasured the way that we are currently measuring it. And I think our field is getting better at adopting some of the ability to measure those kind of hidden costs, and we're able to see that, even a year out, patients are really not back to where they were before (even though on the scales we currently have, they do look great, right, in terms of motor function, and things like that) - so, I think as clinicians, we have to be sensitive to that. So, when we talk to families, we have to remain hopeful that they are going to have a remarkable potential recovery but prepare families that they really should be on the lookout for any opportunity to rehabilitate in all aspects of function.   Dr Nevel: Yeah. And you mentioned in your article that as we're moving into the future  - and even currently - that there is some focus on gathering more patient-reported outcomes for people who are, you know, out of the ICU back in their normal lives after subarachnoid hemorrhage (which speaks to this that you're talking about, that even if their motor function is normal, they may not be back to their normal lives). So, what is something you think that's really important that we've learned in the past ten years - I'll give it ten years, you can go back further, make that time frame shorter if you want, but about the past ten years - about subarachnoid hemorrhage’s impact on patient care, and then what do you think we're going to learn in the next ten years that will impact the way we care for these patients?   Dr Park: So, you know, subarach - in terms of the literature that is forming, that has formed - like I said, the guidelines had not been updated for over a decade, and we're fortunate to have not just one, but two sets of guidelines from two professional societies that were published right next to each other this past year in 2023 - but the field is fast moving, so even after the publication of those guidelines, there was one of the first randomized controlled trials in the field to be published maybe a month or two after that (that was the early lumbar drain trial). So, the key areas that I think where the literature has really helped strengthen our practice in terms of bringing standardization is in the antifibrinolytics. And so, in that space, recently, there was a very nicely performed randomized controlled trial for early administration of antifibrinolytics. It's a practice that, even when I was training, was sort of based on old literature back when we used to treat subarachnoid patients very differently - so we were really kind of extrapolating from that literature into our practice, and we were all sort of just giving it uniformly to patients early on with the good intention to try to prevent rebleeding, (which we understood, prior to aneurysm securement, was a high source of morbidity/mortality). So, in trying to reduce that risk of rebleeding (which happens very early) as much as we could, we were giving it. But the length of treatment (you know, who should we give that medication to) was really kind of uncertain - and this recent randomized controlled trial really gave a definitive answer to this, which is that it probably makes no difference. It should be seen with a caveat, though, that the trial (like any trial) was a very specific population. So, it could probably be said that for patients who are secured very early, there’s no role for antifibrinolytic therapy, but, potentially, for patients who may be in a lower-middle-income environment or lower-income environment or for whatever reason can't reach aneurysm securement within that seventy two-hour period - you could consider, you know, greater than twenty-four hours you should consider the use of antifibrinolytics - but largely has brought an end to uniform administration of antifibrinolytics. This is where that expert nuanced care comes to, right?   Dr Nevel: Mm-hmm.   Dr Park: Another area is, really, kind of something as basic as blood pressure management. I think we were taught very early on that we should be very rigorous, bring that blood pressure down - and so, I think, across all types of stroke now, we're realizing there is a little bit of nuance, right? You have to think about your patient, about prior existing renal failure, about prior existing chronic hypertension that's poorly controlled - and in subarachnoid hemorrhage, the additional impact of that early brain injury. If you have cerebral edema, you should be considering, do we really want to control our blood pressure that low? Because we might be inducing secondary brain injury from our presumed protective intervention. So, these types of things are being revisited - so, the language around that in the new guidelines is a little bit softer, and it does sort of refer more to, “let's consider the whole patient”.   Dr Nevel: Yeah, rather than making a blanket statement that doesn't apply to maybe everybody.   Dr Park: Yeah. And you also asked about future.   Dr Nevel: Yeah. Where do you think things are heading in the future? What's exciting in research, and if you had a crystal ball, what do you think we're going to figure out in the next ten years that's going to impact care?   Dr Park: Well, fortunately, for patients with subarachnoid hemorrhage and for people like me who are treating patients with subarachnoid hemorrhage, there's a lot going on. So, I mentioned lumbar drainage because there was a very nice trial that was published - I think we'll see in the next few years how much of that diffusion of innovation travels across the country in the world about the usage of this. There are some who point to prior studies that may have conflicting results and so want to wait and see it be validated. Others are pretty convinced, you know, by the quality of the study that was done and are trying to incorporate it into their protocols now. I think we're going to see more usage and more study of things like intravenous milrinone, early stellate ganglion blockade, intraventricular nicardipine, and even maybe optimized goals for cerebral perfusion or blood pressure - and this is for looking at a myriad of outcomes, including the prevention and treatment of vasospasm and ischemia, improving outcomes, and preventing infarction. There's also a lot to come about early brain injury (and I kind of talked about that). It’s like a seventy-two-hour period window after subarachnoid hemorrhage, and it comprises processes like microcirculatory dysfunction, blood-brain barrier breakdown, and things like oxidative cascades, et cetera. While currently, there doesn't exist any practice besides, like, the nuance and expert determination of blood pressure goals prior to aneurysm securement, I think this will be an area that hopefully will become a target for intervention, because it has an independent and influential impact on poor outcomes for subarachnoid hemorrhage patients. So, watch the space.   Dr Nevel: Yes, absolutely. Looking forward to seeing what comes. Well, thank you so much for talking to me, Dr Park, and joining me on Continuum Audio.   Dr Park: It was my pleasure.   Dr Nevel: Again, today, I've been interviewing Dr Soojin Park, whose article on emergent management of spontaneous subarachnoid hemorrhage appears in the most recent issue of Continuum in neurocritical care. 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 practice - and right now, during our spring special, all subscriptions are 15% off. Go to Continpub.com/Spring2024 or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members, go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.

Management of stroke due to large vessel occlusion (LVO) has undergone unprecedented change in the past decade. Early identification and aggressive treatment are important in mitigating negative effects on patients’ prognoses. In this episode, Allison Weathers, MD, FAAN, speaks with T. M. Leslie-Mazwi, MD, author of the article “Neurocritical Care for Patients With Ischemic Stroke,” in the Continuum June 2024 Neurocritical Care issue. Dr. Weathers is a Continuum® Audio interviewer and an associate chief medical information officer at Cleveland Clinic in Cleveland, Ohio. Dr. Leslie-Mazwi is a professor and chair in the department of neurology at the University of Washington in Seattle, Washington. Additional Resources Read the article: Neurocritical Care for Patients With Ischemic Stroke Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Transcript Full transcript available

In neurocritical care, the initial evaluation is often fast paced, and assessment and management go hand in hand. History, clinical examination, and workup should be obtained while considering therapeutic implications and the need for lifesaving interventions. In this episode, Aaron Berkowitz, MD, PhD FAAN, speaks with Sarah Wahlster, MD, an author of the article “The Neurocritical Care Examination and Workup,” in the Continuum June 2024 Neurocritical Care issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of neurology at the University of California San Francisco, Department of Neurology and a neurohospitalist, general neurologist, and a clinician educator at the San Francisco VA Medical Center and San Francisco General Hospital in San Francisco, California. Dr. Wahlster is an associate professor of neurology in the departments of neurology, neurological surgery, and anesthesiology and pain medicine at Harborview Medical Center, University of Washington in Seattle, Washington. Additional Resources Read the article: The Neurocritical Care Examination and Workup Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Guest: @SWahlster Full Episode Transcript Sarah Wahlster, MD   Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by clicking on the link in the Show Notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the Show Notes. AAN members: stay tuned after the episode to hear how you can get CME for listening.  Dr Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Sarah Wahlster about her article on examination and workup of the neurocritical care patient, which is part of the June 2024 Continuum issue on neurocritical care. Welcome to the podcast, Dr Wahlster. Can you please introduce yourself to the audience? Dr Wahlster: Thank you very much, Aaron. I'm Sarah Wahlster. I'm a neurologist and neurontensivist at Harborview Medical Center at the University of Washington. Dr Berkowitz: Well, Sarah and I know each other for many, many years. Sarah was my senior resident at Mass General and Brigham and Women's Hospital. Actually, Sarah was at my interview dinner for that program, and I remember meeting her and thinking, “If such brilliant, kind, talented people are in this program, I should try to see if I can find my way here so I can learn from them.” So, I learned a lot from Sarah as a resident, I learned a lot from this article, and excited for all of us to learn from Sarah, today, talking about this important topic. So, to start off, let's take a common scenario that we see often. We're called to the emergency room because a patient is found down, unresponsive, and neurology is called to see the patient. So, what's running through your mind? And then, walk us through your approach as you're getting to the bedside and as you're at the bedside. Dr Wahlster: Yeah, absolutely. This was a fun topic to write about because I think this initial kind of mystery of a patient and the initial approach is something that is one of the puzzles in neurology. And I think, especially if you're thinking about an emergency, the tricky part is that the evaluation and management go hand in hand. The thinking I've adapted as a neurointensivist is really thinking about “column A” (what is likely?) and “column B” (what are must-not-miss things?). It's actually something I learned from Steve Greenberg, who was a mutual mentor of us - but he always talked me through that. There's always things at the back of your head that you just want to rule out. I do think you evaluate the patient having in mind, “What are time-sensitive, critical interventions that this patient might need?” And so, I think that is usually my approach. Those things are usually anything with elevated intracranial pressure: Is the patient at risk of herniating imminently and would need a neurosurgical intervention, such as an EVD or decompression? Is there a neurovascular emergency, such as an acute ischemic stroke, a large-vessel occlusion, a subarachnoid hemorrhage that needs emergent intervention? And then other things you think about are seizures, convulsive/nonconvulsive status, CNS infection, spinal cord compression. But I think, just thinking about these pathologies somewhere and then really approaching the patient by just, very quickly, trying to gather as much possible information through a combination of exam and history. Dr Berkowitz: Great. So, you're thinking about all these not-to-miss diagnoses that would be life-threatening for the patient and you're getting to the bedside. So, how do you approach the exam? Often, this is a different scenario than usual, where the patient's not going to be able to give us a history or maybe necessarily even participate in the exam, and yet, as you said, the stakes are high to determine if there are neurologic conditions playing into this patient's status. So, how do you approach a patient at the bedside? Dr Wahlster: So, I think first step in an ICU setting (especially if the patient has a breathing tube) is you think about any confounders (especially sedation or metabolic confounders) - you want to remove as soon as possible, if able. I think as you do the exam, you try to kind of incorporate snippets of the history and really try to see - you know, localize the problem. And also kind of see, you know, what is the time course of the deterioration, what is the time course of the presentation. And that is something I actually learned from you. I know you've always had this framework of “what is it, where is it?” But I think in terms of just a clinical exam, I would look at localizing signs. I think, in the absence of being able to do the full head-to-toe neuro exam and interact with the patient, you really try to look at the brainstem findings. I always look at the eyes right away and look at, I think, just things like, you know, the gaze (how is it aligned? is there deviation? is there a skew? what do the pupils look like? [pupillary reactivity]). I think that's usually often a first step - that I just look at the patient's eyes. I think other objective findings, such as brainstem reflexes and motor responses, are also helpful. And then you just look whether there's any kind of focality in terms of - you know, is there any difference in size? But I think those are kind of the imminent things I look at quickly. Dr Berkowitz: Fantastic. Most of the time, this evaluation is happening kind of en route to the CT scanner or maybe a CT has already happened. So, let's say you're seeing a patient who's found down, the CT has either happened or you asked for it to happen somewhat quickly after you've done your exam, and let's say it's not particularly revealing early on. What are the sort things on your exam that would then push you to think about an MRI, a lumbar puncture, an EEG? You and I both spend time in large community hospitals, right, where “found down” is one of the most common chief concerns. In many cases, there isn't something to see on the CT or something obvious in the initial labs, and the question always comes up, “Who gets an MRI? Who gets an LP? Who gets an EEG?” - and I'm not sure I have a great framework for this. Obviously, you see focality on your exam, you know you need to look further. But, any factors in the history or exam that, even with a normal CT, raise your suspicion that you need to go further? Dr Wahlster: It's always a challenge, especially at a community hospital, because some of these patients come in at 1 AM where the EEG is not imminently available. But I think - let's say the CT scan is absolutely normal and doesn't give me a cause, but as an acute concerning deterioration, I think both EEG and LP would cross my mind. MRI I kind of see a little bit as a second-day test. I think there's very rare situation where an acute MRI would inform my imminent management. It's very informative, right, because you can see very small-vessel strokes. We had this patient that actually had this really bad vasculitis and we were able to see the small strokes everywhere on the MRI the day later, or sometimes helps you visualize acute brainstem pathology. But I think, even that - if you rule out a large-vessel occlusion on your CTA, there's brainstem pathology that is not imminently visible on the CT - it's nothing you need to go after. So, I do think the CT is a critical part of that initial eval, and whereas I always admire the neurological subspecialties, such as movements, where you just – like, your exam is everything. I think, to determine these acute time-sensitive interventions, the CT is key. And also, seeing a normal CT makes me a little less worried. You always look at these “four H” (they're big hypodensity, hyperdensity, any shift; is there hydrocephalus or herniation). I think if I don't have an explanation, my mind would imminently jump to seizure or CNS infection, or sometimes both. And I think then I would really kind of - to guide those decisions and whether I want to call in the EEG tech at 2 AM - I would, you know, again, look at the history and exam, see if there's any gaze deviation, tongue biting, incontinence - anything leading up towards seizure. I think, though, even if I didn't have any of those, those would strengthen my suspicion. If I really, absolutely don't have an explanation and the patient off sedation is just absolutely altered, I would still advocate for an EEG and maybe, in the meantime, do a small treatment trial. And I think with CNS infection - obviously, there are patients that are high risk for it - I would try to go back and get history about prodromes and, you know, look at things like the white count, fevers, and all of that. But again, I think if there's such a profound alteration in neurologic exam, there's nothing in the CT, and there's no other explanation, I would tend to do these things up front because, again, you don't want to miss them. Dr Berkowitz: Yeah, perfect. So many pearls in there, but one I just want to highlight because I'm not sure I've heard the mnemonic - can you tell us the four Hs again of sort of neurologic emergencies on CT? Dr Wahlster: Yeah. So, it's funny; for ages - I'm actually not sure where that's coming from, and I learned it from one of my fellows, one of our neurocritical care fellows - he's a fantastic teacher and he would teach our EM and anesthesia residents about it and his approach to CT. But yeah, the four H - he was always kind of like, “Look at the CT. Do you see any acute hypodensities, any hyperdensities?” And hypodensities would be involving infarct or edema; hyperdensities would be, most likely, hemorrhage (sometimes calcification or other things). Then, “Do you see hydrocephalus?” (because that needs an intervention). And, “Look at the midline structures and the ventricles.” And then, “Do you see any signs of herniation?” And he would go through the different types of herniation. But I thought that's a very good framework for looking at the “noncon” and just identifying critical pathology that needs some intervention. Dr Berkowitz: Yeah – so, hypodensity, hyperdensity, herniation, hydrocephalus. That's a good one – the four Hs; fantastic. Okay. So, a point that comes up a few times in your article - which I thought was very helpful to walk through and I'd love to pick your brain about a little bit – is, which patients need to be intubated for a neurologic indication? So, often we do consultations in medical, surgical ICUs; patients are intubated for medical respiratory reasons, but sometimes patients are intubated for neurologic reasons. So, can you walk us through your thinking on how to decide who needs to be intubated for the concern of depressed level of consciousness? Dr. Wahlster: It's an excellent question, and I think I would bet there's a lot of variation in practice and difference in opinion. There was actually the 2020 ESICM guidelines kind of commented on it, and those are great guidelines in terms of just intubation, mechanical ventilation of patients, and just acknowledging how there is a lack of really strong evidence. I would say the typical mantra (“GCS 8, intubate”) has been proposed in the trauma literature. And at some point, I actually dug into this to look behind the evidence, and there's actually not as much evidence as it's been put forth in guidelines and that kind of surprised me - that was just recently. I was like, “Actually, let me look this up.” I would say I didn't find a ton of strong evidence for it. I would say, as neurologist – you know, I'm amazed because GCS, I think is a - in some ways, a good tool to track things because it's so widely used across the board. But I would say, as neurologists, we all know that it sometimes doesn't account for some sort of nuances; you know, if a patient is aphasic, if a patient has an eyelid-opening apraxia - it can always be a little confounded. I'm amazed that GCS is still so widely used, to be frank. But I would say there is some literature - some school of thought - that maybe just blindly going by that mantra could be harmful or could not be ideal. I would say – I mean, I look at the two kind of functional things: oxygenation and ventilation. I think, in a neuro patient, you always think about airway protection or the decreased level of consciousness being a major issue (What is truly airway protection? Probably a mix of things). Then there's the issue of respiratory centers and respiratory drive - I think those are two issues you think about. But ultimately, if it leads to insufficient oxygenation - hypoxia early on is bad and that's been shown in several neurologic acute brain injuries. I think you also want to think about ventilation, especially if the mental status is poor to the point that the PCO2 elevates, that could also augment an ICP or exacerbate an ICP crisis. Or sometimes, I think there's just dysregulation of ventilation and there's hyperventilation to the point that the PCO2 is so low that I worry about cerebral vasoconstriction. So, I worry about these markers. I think, the oxygenation, I usually just kind of initially track on the sats. Sometimes, if the patient is profoundly altered, I do look at an arterial blood gas. And then there are things like breathing sounds (stridor, stertor [the work of breathing]). And I think something that also makes me have a lower threshold to intubate is if I'm worried and I want to scan, and I'm worried that the patient can't tolerate it - I want an imminent scan to just see why the patient is altered, or seizing, or presenting a certain way. Dr Berkowitz: All great pearls for how to think through this. Yeah - it's hard to think of hard and fast rules, and you can get to eight on the GCS in many different ways, as you said, some of which may not involve the respiratory mechanics at all. So, that's a helpful way of thinking about it that involves both the mental state, kind of the tracheal apparatus and how it's being managed by the neurologic system, and also the oxygen and carbon dioxide (sort of, respiratory parameters) – so, linking all those together; that's very helpful. And, related question – so, that’s sort of for that patient with central nervous system pathology, who we're thinking about whether they need to be intubated for a primary neurologic indication. What about from the acute neuromuscular perspective (so, patients with Guillain-Barré syndrome or myasthenic crisis); how do you think about when to intubate those patients? Dr Wahlster: Yeah, absolutely - I think that's a really important one. And I think especially in a patient that is rapidly progressing, you always kind of think about that, and you want them in a supervised setting, either the ER or the ICU. I mean, there's some scores - I think there's the EGRIS score; there's some kind of models that predict it. I would say, the factors within that model, and based on my experience, often the pace of progression of reflex motor syndrome. I often see things like, kind of, changes in voice. You know, myasthenia, you look at things like head extension, flexion - those are the kind of factors. I would say there's this “20/30/40 rule” about various measures of, like, NIF and vital capacities, which is great. I would say in practice, I sometimes see that sometimes the participation in how the NIF is obtained is a little bit funky, so I wouldn't always blindly go by these numbers but sometimes it's helpful to track them. If you get a reliable kind of sixty and suddenly it drops to twenty, that makes me very concerned. But I would say, in general, it's really a little bit the work of breathing - looking at how the patient looks like. There's also (at some point) ABG abnormalities, but we always say, once those happen, you’re kind of later in the game, so you should really - I think anyone that is in respiratory distress, you should think about it and have a low threshold to do it, and, at a minimum, monitor very closely. Dr Berkowitz: Yeah, we have those numbers, but so often, our patients who are weak, from a neuromuscular perspective, often have facial and other bulbar weakness and can't make a seal on the device that is used to check these numbers, and it can look very concerning when the patient may not, or can be a little bit difficult to interpret. So, I appreciate you giving us sort of the protocol and then the pearls of the caveats of how to interpret them and going sort of back to basics. So, just looking at the patient at the bedside and how hard they are working to breathe, or how difficult it is for them to clear their secretions from bulbar weakness. Moving on to another topic, you have a really wonderful section in your article on detecting clinical deterioration in patients in the neuro ICU. Many patients in the neuro ICU - for example, due to head trauma or large ischemic stroke or intracerebral hemorrhage, subarachnoid hemorrhage, or status epilepticus - they can't communicate with us to tell us something is getting worse, and they can't (in many cases) participate in the examination. They may be intubated, as you said, sedated or maybe even not sedated, and there's not necessarily much to follow on the exam to begin with if the GCS is very low. So, I'd love to hear your thoughts and your pearls, as someone who rounds in the neuro-ICU almost every day. What are you looking for at the bedside to try to detect sort of covert deterioration, if you will, in patients who already have major neurologic deficits, major neurologic injury or disease that we're aware of? I’m trying to see if there is some type of difference at the bedside that would lead you to be concerned for some underlying change and go back to the scanner or repeat EEG, LP, et cetera. Dr Wahlster: Yeah. I think that's an excellent question because that's a lot of what we do in the neuro ICU, right? And when you read your Clans, your residency, like, “Ah, QNR neuro checks, [IG1]  ” right? We often do that in many patients. But I think in the right patient, it can really be life or death a matter, and it is the exam that really then drives a whole cascade of changes in management and detects the need for lifesaving procedure. I would say it depends very much on the process and what you anticipate, right? If you have, for example, someone with a large ischemic stroke, large MCA stroke, especially, right, then there's sometimes conversations about doing a surgical procedure before they herniate. But let's say, kind of watch them and are worried that they will, you do worry about uncal herniation, and you pay attention to the pupil, because often, if the inferior division is infarcted, you know, you can see that kind of temporal tickling the uncus already. And so, I think those are patients that I torture with those NPi checks and checking the pupil very vigilantly. I would say, if it's a cerebellar stroke, for example, right, then you think about, you know, hydrocephalus. And often patients with cerebellar stroke - you know, the beauty of it is that if you detect it early, those patients can do so well, but they can die, and will die if they develop hydrocephalus start swelling. But I think, often something I always like to teach trainees is looking at the eye movements in upgaze and downgaze because, often, as the aqueduct, the third ventricle gets compressed and there's pressure on the colliculi – you kind of see vertical gaze get worse. But I would say I think it's always good to know what the process is and then what deterioration would look like. For example, in subarachnoid hemorrhage, where you talk about vasospasm - it's funny - I think a really good, experienced nurse is actually the best tool in this, but they will sometimes come to you and say, “I see this flavor,” and it's actually a constellation of symptoms, especially in the anterior ACA (ACom) aneurysms. You sometimes see patients suddenly, like, making funky jokes or saying really weird things. And then you see that in combination with, sometimes, a sodium drop, a little bit of subfebrile temperature; blood pressure shoot up sometimes, and that is a way the brain is sometimes regulating. But it's often a constellation of things, and I think it depends a little on the process that you're worried about. Dr Berkowitz: Yeah, that's very helpful. You just gave us some pearls for detecting deterioration related to vasospasm and subarachnoid hemorrhage; some pearls for detecting malignant edema in an MCA stroke or fourth ventricular compression in a large cerebellar stroke. Patients I find often very challenging to get a sense of what's going on and often get scanned over and over and back on EEG, not necessarily find something: patients with large intracerebral hemorrhage (particularly, in my experience, if the thalamus is involved) just can fluctuate a lot, and it's not clear to me actually what the fluctuation is. But you're looking for whether they're developing hydrocephalus from third ventricular compression with a thalamic hemorrhage (probably shouldn't be seizing from the thalamus, but if it's a large hemorrhage and cortical networks are disrupted and it's beyond sort of the subcortical gray matter, or has the hemorrhage expanded or ruptured it into the ventricular system?) And yet, you scan these patients over and over, sometimes, and just see it's the same thalamic hemorrhage and there's some, probably, just fluctuation level of arousal from the thalamic lesion. How do you, as someone who sees a lot of these patients, decide which patients with intracerebral hemorrhage - what are you looking for as far as deterioration? How do you decide who to keep scanning when you’re seeing the same fluctuations? I find it so challenging - I'm curious to hear your perspective. Dr Wahlster: Yeah, no - that is a very tricky one. I mean, unfortunately, in patients with deeper hemorrhages or deeper lesions - you know, thalamic or then affecting brainstem - I think those are the ones that ultimately don't have good, consistent airway protection and do end up needing a trach, just because there's so much fluctuation. But I agree - it's so tricky, and I don't think I can give a perfect answer. I would say, a little bit I lean on the imaging. And for example - let's say there's a thalamic hemorrhage. We recently actually had a patient - I was on service last week - we had a thalamic hemorrhage with a fair amount of edema on it that was also kind of pressing on the aqueduct and didn't have a lot of IVH, right? But it was, like, from the outside pushing on it and where we ended up getting more scans. And I have to say, that patient actually just did fine and actually got the drain out and didn't need a shunt or anything, and actually never drained. We put an EVD and actually drained very little. So, I think we're still bad at gauging those. But I think, in general, my index of suspicion or threshold to scan would be lower if there was something, like, you know, a lot of IVH associated, if, you know, just kind of push on the aqueduct. It's very hard to say, I think. Sometimes, as you get to know your patients, you can get a little bit of a flavor of what is within normal fluctuation. I think it's probably true for every patient, right? - that there's always some fluctuation within the realm of like, “that's what he does,” and then there's something more profound. Yeah, sorry - I wish I could give a better answer, but I would say it's very tricky and requires experience and, ideally, you really taking the time to examine the patient yourself (ideally, several times). Sometimes, we see the patient - we get really worried. Or the typical thing we see the ICU is that the neurosurgeons walk around at 5 AM and say, like, “She's altered, she's different, she's changed.” And then the nurse will tell you at 8 AM, like, “No, they woke up and they ate their breakfast.” So, I think really working with your nurse and examining the patient yourself and just getting a flavor for what the realm of fluctuation is. Dr Berkowitz: Yeah - that's helpful to hear how challenging it is, even for a neurocritical care expert. I'm often taking care of these patients when they come out of the ICU and I'm thinking, “Am I scanning these patients too much?” Because I just don't sort of see the initial stage, and then, you know, you realize, “If I'm concerned and this is not fitting, then I should get a CT scan,” and sometimes you can't sort it out of the bedside. So, far from apologizing for your answer, it's reassuring, right, that sometimes you really can't tell at the bedside, as much as we value our exam. And the stakes are quite high if this patient’s developed intraventricular hemorrhage or hydrocephalus, and these would change the management. Sometimes you have these patients the first few days in the ICU (for us, when they come out of the ICU) are getting scanned more often than you would like to. But then you get a sense of, “Oh, yeah - these times of day, they're hard to arouse,” or, “They're hard to arouse, but they are arousable this way,” and then, “When they are aroused, this is what they can do, and that's kind of what we saw yesterday.” And yet, as you said, if anyone on the team (the resident, the nurse, the student, our neurosurgery colleague) says, “I don't think this is how they were yesterday,” then, very low threshold to just go back and get a CT and make sure we're not missing something. Dr. Wahlster: Exactly. Yeah. I would say the other thing is also certain time intervals, right? If I'm seeing a patient that may be in vasospasm kind of around the days seven to ten, for the first fourteen day, I would be a little bit more nervous. Or with swelling - acute ischemic stroke says that could peak swelling, when knowing which [IG2]  , I would just be more anxious or have a lower threshold to scan. Yeah. Dr Berkowitz: Yeah - very helpful. Well, thank you so much for joining me today on Continuum Audio. Dr Wahlster: Thank you very much, Aaron. Dr Berkowitz: Again, today we've been interviewing Dr Sarah Wahlster, whose article, “Examination and Workup of the Neurocritical Care Patient” appears in the most recent issue of Continuum, on neurocritical care. Be sure to check out Continuum Audio episodes from this and other issues. And thank you so much to our listeners for joining us today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practice. And right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024 or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members: go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.

In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Ariane Lewis, MD, who served as the guest editor of the Continuum® June 2024 Neurocritical Care issue. They provide a preview of the issue, which published on June 3, 2024. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Lewis is a professor of neurology and neurosurgery and director of the Division of Neurocritical Care at NYU Langone Medical Center in New York, New York. Additional Resources Continuum website: ContinuumJournal.com Subscribe to Continuum: shop.lww.com/Continuum More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @LyellJ Full episode transcript  Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the Show Notes. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr Ariane Lewis, who recently served as Continuum's guest editor for our latest issue on neurocritical care. Dr Lewis is a Professor of Neurology and Neurosurgery at NYU, where she serves as the Director of the Division of Neurocritical Care. Dr Lewis, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners? Tell us a little bit about yourself. Dr Lewis: Thank you so much for having me, Dr Jones. It was a pleasure to be an editor of this issue, and I'm really excited for it to come out. As you mentioned, I'm a Professor of Neurology and Neurosurgery at NYU. I'm also a fellow of the American Academy of Neurology and a fellow of the Neurocritical Care Society. I serve on the Ethics Law and Humanities Committee for the AAN. I was a past chair of the Ethics Committee for the Neurocritical Care Society and also the past chair of the Ethics Committee at NYU. Dr Jones: So, pretty diverse professional interests. And I was going to ask you about the ethics - that feels like something that ties in pretty well to neurocritical care. I imagine that expertise comes in handy, right? Dr Lewis: Yes, absolutely. My area of expertise is related to brain death and ethical, social, and legal complications related to brain death determination. Dr Jones: Got it. And when we were talking before we started recording here, you're from the New York area and a lifelong Yankees fan, is that right? Dr Lewis: Yes, that's correct. Dr Jones: How are they going to do this year? Dr Lewis: We're hoping we're going all the way. Dr Jones: Okay. Dr Lewis: In a while. Dr Jones: Our listeners heard it here first. So, the issue – let’s get into the neurocritical care topics – phenomenal issue, full of detailed diagnosis and management strategies for patients with, you know, all manners of severe neurologic disorders requiring critical level of care. With your perspective (which is a unique perspective) - you've just edited a full issue on neurocritical care, you got to delve into all the topics - what were you most surprised to learn, Dr Lewis? Dr Lewis: Well, you know, I think that one of the most exciting things about this issue is the fact that, in addition to dealing with the typical topics related to neurocritical care - like hypoxic ischemic brain injury and stroke and intracerebral hemorrhage and subarachnoid hemorrhage, of course - the issue delves into some very unique topics related to neurocritical care. There's an article written by Dr Barry Czeisler that focuses on emergent management of tumefactive and aggressive demyelinating disorders, Dr Casey Albin wrote about neuromuscular emergencies, and doctors Maciel and Busl wrote about neuroonc emergencies – and I think that these areas are really important areas for neurologists and trainees to know about, and they’re not talked about all that often. And these topics are often focused on, of course, by other subspecialties, but the perspective of a neurointensivist related to these topics is infrequently addressed. So I think that these are really the most exciting aspects of this issue, because it’s something so unique in terms of the spin on these topics. Dr Jones: Fantastic. And what else can we look for in this issue? What other topics can our listeners and readers expect to find there?  Dr Lewis: So, the issue starts off with the examination and workup of the neurocritical care patient. Dr Sarah Wahlster and Nick Johnson from the University of Washington did an awesome job really bringing the reader into the topic of neurocritical care as they address an overview of neuroemergencies, red flags related to life-threatening conditions, herniation syndromes, vascular territories, and mechanisms and management of acute neurodeterioration, and they summarize monitoring modalities in neurocritical care and clinical and radiographic scales and scores that are commonly used in neurocritical care – and that’s a really nice overview to introduce the reader to this issue. The rest of the issue focuses on a wide range of topics pertaining to the emergent management of neurocritical care issues, including hypoxic ischemic brain injury (which was addressed by Dr Steinberg from the University of Pittsburgh),  management of stroke due to large vessel occlusion (which was addressed by Dr Leslie-Mazwi from the University of Washington), management of ICH (addressed by Dr Murthy from Weill Cornell), and then also management of spontaneous subarachnoid hemorrhage (addressed by Dr Soojin Park). Dr Clio Rubinos addressed emergent management of status epilepticus. Emergent management of TBI and spinal cord injury was addressed by Dr Podell and Dr Morris from the University of Maryland. And then neuroinfectious emergencies – which, again, is another unique topic in this issue – was  addressed by Dr Reynolds from Mount Sinai. And then the issue concludes with a paper that focuses on prognostication and neurocritical care by Dr Susanne Muehlschlegel from Johns Hopkins University.  Dr Jones: Yeah. And what a great list of authors and expertise. And really, you know,  having seen these articles, really just phenomenal guidance on a lot of different subtopics. And I imagine – you know, this is a dynamic area, there’s a lot of evidence – but, you know, sometimes, there are controversies or debates or unresolved questions in the field. Having just reviewed and edited the issue, what do you think the biggest debate or controversy is in neurocritical care right now?  Dr Lewis: So there’s definitely a lot of controversies that are addressed in each of these individual articles. For example, in the paper on subarachnoid hemorrhage, Dr Soojin Park provides a summary that compares the guidelines on management of subarachnoid hemorrhage that were written by the Neurocritical Care Society and the American Health Association / American Stroke Association in 2023 and really walks through what’s similar and what’s different between these guidelines. For the most part, they are very similar, but there are areas of differences. Additionally, in terms of management of acute neuroemergencies related to neuromuscular issues (in some cases, it’s not clear whether to treat patients with IVIG or with plasmapheresis), Dr Casey Albin creates a nice summary addressing these issues in terms of what are the pluses and minuses associated with each of these medications. Additionally, there are a number of novel therapies that are not traditionally considered for various neuroemergencies that are walked through in each of the individual articles. For example, in the paper that focuses on management of status epilepticus, Dr Rubinos addresses alternative therapies, like immunomodulatory agents or neuromodulation, for management of super-refractory status epilepticus. So, I think, in addition to addressing the more traditional therapies for various neuroemergencies, the issue really goes above and beyond to address novel interventions.  Dr Jones: That’s fantastic. And obviously, it continues to be a rapidly evolving area.  When you look out to the horizon – and the next generation of care for patients with critical neurologic illness – what do you see on the horizon? What should our listeners and readers be aware of to watch out for?  Dr Lewis: I think one thing that is really important to be aware of related to patients with neuroemergencies is the Curing Coma Campaign (which is organized by the Neurocritical Care Society), which focuses on research in terms of improving the clinical management, the prognostication, and the care of patients and addresses the goals for  improving recovery for patients who are comatose. And obviously, coma can be due to a wide range of different etiologies (many of which are described in this issue), and so I think that their work as we move ahead will be incredibly important and interesting to see how things evolve in that domain. Dr Jones: We will be on the lookout for the Curing Coma Campaign – sounds like a great initiative. And, I think, medicine is a team endeavor, right? We were talking about the Yankees earlier (baseball) as a team sport – so is medicine. When you think about the importance of teams, it’s hard to imagine a setting where it’s more critical to have, you know, well-functioning teams than in the neuro ICU. But there’s also parts of the team (people on the team) who are outside the neuro ICU – and I’m thinking of other neurologists, our listeners and readers who might work in the inpatient setting, but not in this really specialized environment. When you think about those neurologists, is there a key message for those hospitalist neurologists or inpatient neurologists that you would want to share from your perspective as a neurocritical care specialist?  Dr Lewis: So, I think it’s imperative for all neurologists to have an understanding of the existence of various neuroemergencies and the identification of when a patient is  having a neuroemergency so that they can escalate the management if it’s something beyond their skills or expertise to somebody who is capable of appropriately managing the patient. Each of these articles walks through the differential diagnosis, the identification of the neuroemergency, the first steps in terms of management, the laboratory workup, and then the subsequent steps as well. And I think that, you know, for all neurologists, really, the key things to know about (even if you’re not specializing in  neurocritical care) is how to identify a neuroemergency and what needs to be done as the first steps in terms of intervening and diagnosing these emergencies. Dr Jones: Great message, and that’s one of the key things we learn in training, right,  is when to recognize that someone’s sick and you need to escalate their level of care. What about – you know, I imagine the neurocritical care field is a relatively small community, and you know a lot of these folks – any key message that you would want to share with that audience? Dr Lewis: So, I think that this issue is still really important for all neurointensivists (in addition to for general neurologists and trainees), because of the fact that every article  really addresses in depth each of these aspects of neurocritical care and provides tidbits of information that not every neurointensivist would know. So, I think that the issue is beneficial both for trainees, general neurologists, and people who have expertise in the field of neurocritical care. Dr Jones: That’s a great point. I think the fact that it is such a rapidly changing and broad field (you mentioned all the different article topics that are in the issue), it’s a challenge to stay up to date on everything. And I think that’s what this issue really brings  to the neurointensivist – is, you know, this is all (as of what’s the latest in 2024) for the care of patients with critical illness. It’s all there, right?  Dr Lewis: Absolutely. I think, you know, the issue is unique because neurocritical care is unique in that our role involves taking care of patients with a wide range of different neurologic disorders. So, the issue touches upon stroke (both ischemic and hemorrhagic). It touches upon seizure management. It touches upon management of traumatic brain injury. It addresses demyelination (so types of aggressive MS and other demyelinating disorders), neuromuscular issues, neuroonc issues – so I think that, really, there are so many subspecialties within neurology that it’s important for them to have awareness of the emergencies that can emerge within their individual field. Dr Jones: So, we know that neurocritical care is pretty specialized work, and I imagine the expertise and the resources are not necessarily going to be available in every community. Are you aware, Dr Lewis, of any disparities in access or outcomes to neurointensivist expertise?  Dr Lewis: Yeah, absolutely. Unfortunately, as you look internationally, first, there are many places that don’t have neurointensivists, so patients with neuroemergencies are being taken care of, in some cases, not even by general neurologists, but by specialists just in medicine. Additionally, the resources are often not available in terms of having an intensive care unit, having nurses with a good ratio to care for neurocritical care patients, having access to therapists who can participate in rehab and promote rehab, for patients having access to medications that are necessary, having access to various interventions (such as access to neurosurgeons who can do neurosurgical procedures or placement of an external ventricular drain), or other monitoring modalities are not available and accessible. So, all of these issues – in terms of resources, in terms of funding, in terms of other issues related to the existence of protocols as to how to  manage patients in the neuro ICU – all impact the outcome for patients in neurocritical care. Additionally, social issues and cultural issues can impact the outcome for patients in the neuro ICU. So, there’s a lot of issues pertaining to equity in terms of the management of neurocritical care patients around the world.  Dr Jones: Those are great points. I know you and I both work with trainees in our field,  and when I talk to residents who are interested in neurocritical care, I think part of what draws them in is when they are exposed to it and they see how much, you know, the value of what their expertise brings to the outcome for that patient. I mean, it really does make a difference to understand the brain when you’re caring for people with these critical neurologic disorders – and I think that’s part of the appeal, right?  Dr Lewis: Yeah, absolutely. I think that people who are interested in going into the field of neurocritical care are interested in the more fast-paced aspect of neurology, rapid decision making, dealing with emergencies, also dealing with prognostication,  discussions (unfortunately, at end of life) – so that’s really the kind of individual who turns to the field to specialize in. Dr Jones: And what about you, Dr Lewis? What drew you to this, you know, pretty high-pressure, intense, dynamic environment?  Dr Lewis: So I think, actually, you know, all the buzzwords you just used are really the things that made me want to go into neurocritical care. I am interested in much more  fast-paced management of patients, and, you know, unfortunately, obviously emergencies happen, and I find them to be exciting to be able to manage patients in that setting. And, you know, as you mentioned earlier, in the neuro ICU, it’s a very multidisciplinary team, and I really enjoy being able to work with nursing, social work, care management, therapists, a variety of consultants – and addressing very acute issues with these individuals as a team in the ICU setting is really very rewarding.  Dr Jones: Yeah, and I hear that from others who are drawn to the field, and I think you really have to have kind of a broad skill set to manage actively, you know, critically ill patients, but also do the communication competencies and other things that are necessary. So, anecdotally, I would say I see more interest among trainees in this field. I don’t know if you’ve seen the same thing in your world. Dr Lewis: Yeah. I think that, you know, as you mentioned, it’s really important to emphasize that being a neurointensivist does not  just require expertise in the medical aspects of care for these patients, but really, also it’s very important to ensure that we  promote education related to communication and neuroprognostication. So, our last article on this issue (by Dr Susanne Muehlschlegel) addresses prognostication and includes a variety of different details about how to address uncertainty, how to implement family and patient-centered prognostication and promote shared decision-making – and these topics are so important for everyone to know about when they’re communicating with patients and families to address goals of care and to prognosticate. Dr Jones: Yeah. Thank you. And before we wrap up our discussion here, Dr Lewis, in addition to being a neurointensivist and being an expert on ethics and all of your clinical and research work, you do editorial work. You have editorial responsibilities not only for this issue of Continuum, but also at Seminars in Neurology and at “The Green Journal”.  For our listeners who might be interested in that career pathway, how did you get into that?  Dr Lewis: I very much enjoyed writing, and so I published a lot. And then I think that, you know, making connections is incredibly important and really looking out for those types of opportunities. Once you build a semblance of expertise in an area, then that often tends to lead to opportunities. So, I’m a Deputy Editor for the Disputes and Debate section of the Neurology journal. I’m also a Deputy Editor of Seminars in Neurology. I edited a book with Dr Jim Burnett on advances in neuroethics related to death determination by neurologic criteria, areas of controversy and consensus. And then I’ve also been a Guest Editor for a number of other journals, like the AMA Journal of Ethics that focused on socially situated brain death, a neurosurgical focus issue on primary and secondary infections of the brain, and a issue of Seminars in Neurology focused on ethics in neurology. Dr Jones: You must have like a twenty-eight or twenty-nine-hour day, Dr Lewis. I don’t know how you do all that. I wasn’t even aware of all those things that you do, but I can tell you, having looked at this issue, your editorial skills are off the charts. I really want to thank you not just for a wonderful issue, but for joining us today and for such a thoughtful, fascinating, and thorough discussion on the field of neurocritical care.   Dr Lewis: Thank you so much. I'm so excited for all the readers to look at our issue and learn about all of these different topics.  Dr Jones: Again, we've been speaking with Dr Ariane Lewis, Guest Editor for Continuum’s most recent issue on neurocritical care. 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 practice - and right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024, or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. Thank you for listening to Continuum Audio.

Indomethacin-responsive headache disorders are rare conditions whose hallmark is an absolute response to the medicine and include paroxysmal hemicrania and hemicrania continua. In this episode, Gordon Smith, MD, FAAN, speaks with Peter Goadsby, MD, PhD, FRS, author of the article “Indomethacin-Responsive Headache Disorders,” in the Continuum® April 2024 Headache issue. Dr. Smith is a Continuum® Audio interviewer and 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. Goadsby is a professor of neurology at King’s College London in London, United Kingdom and professor emeritus of neurology at the University of California, Los Angeles in Los Angeles, California. Additional Resources Read the article: Indomethacin-Responsive Headache Disorders Subscribe to Continuum: continpub.com/Spring2024 Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @gordonsmithMD Guest: @petergoadsby Transcript Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the Show Notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the Show Notes. AAN members: Stay tuned after the episode to hear how you can get CME for listening. Dr Smith: This is Dr Gordon Smith. Today, I've got the great pleasure of interviewing Dr Peter Goadsby on indomethacin-responsive headache disorders, which is part of the April 2024 Continuum issue on headache. Dr. Goadsby is a Professor of Neurology at King's College London, in London, United Kingdom and a Professor Emeritus of Neurology at the University of California, Los Angeles, which is located in Los Angeles, California. Dr Goadsby, welcome to the podcast. Well Peter, I'm super excited to have the opportunity to talk to you. And I think, before we begin, we probably ought to expand on your introduction. I think there may be three or four neurologists who don't know who you are, and I think they should know who you are because you've got a really amazing story. These are exciting times in headache, right? And a lot of that's because of your work and you've been widely acknowledged for that; you received the appropriately named “Brain Prize,” which (if I'm correct) is the largest neuroscience award in the world; got to meet Danish royalty; you’re - more recently, the ABF Scientific Breakthrough Award, which is super excited. So, particularly interested in hearing about your Continuum article. But before we get there, I think it would be really great to hear your story. How did you get into this in the beginning, and what's inspired you along the way to the many achievements you've had? Dr Goadsby: Why, it's a very kind introduction. People have been nice to me. It has to be said, Danish royalty were very nice, I have to say, and the very jolly chap, the Prince of Denmark. I got into neurology - I guess it's all about mentoring for me. I got into neurology because I got into medical school pretty much by accident. I really wasn't that interested and heard a lecture by James Lance, who was Professor of Neurology, University of New South Wales, at the time. He was talking about a nondominant parietal lobe. I'd seen the case as a medical student; it sort of just seemed weird to me and I wasn't that interested. But he set out this way of thinking about things to try and understand why a clinical presentation is what it is - what he described as a physiological approach to clinical neurology. He described a number of things, but he described that in this lecture and then gave a reference to some work that Mountcastle did on nondominant parietal recordings from awake behaving monkeys in the Journal of Neurophysiology. And I thought to myself, “Wow, this is really interesting - you could really get to the bottom of something,” and had that sort of “puzzle-y” thing going on. And I thought Lance was just wonderful, so I became interested in that. And then eventually I asked him about research - actually, I asked him about research after a lecture he gave on migraine, and the explanation of the time was some circulating substance - probably just as silly now. I went up to him afterwards and said to him, I thought the explanation he was giving was wrong. Like, here was a global person - he described Lance-Adams syndrome; this was someone who trained at Mass General, trained at Queen Square; was the first professor of neurology in Australia. I was just – like, it was a stupid thing to do. But I couldn't resist myself - I told him I thought it was wrong. And he's very polite, and he said, “Well, perhaps you could come and help us by doing some research.” And I thought, “Okay, that's a very nice response.” Interestingly, his daughter described him as unfailingly polite at his funeral. Of the many things you'd say about him, he was a kind person. Whether it's science or just the way you practice - that word (kind) - you can know as much about a subject as you like, but if you're not kind to patients, you're probably in the wrong game. He taught me to be curious about a problem and got me interested in headache, and to be kind in clinical practice - just kind – and I think they were very important lessons. So, I got into it because of excellent mentoring, and I’d like to think I've helped some others along the way. Dr Smith: Well, you certainly have helped a lot of people, Peter, and what a great story. I'm reflecting - I think the first vignette in The Man Who Mistook His Wife for a Hat was a right parietal syndrome - wasn't it? You've read that book? Dr Goadsby: Yes, I have. And I've met Sacks. When Sacks came to Australia, he wanted to see Lance, and Lance said, “Fine, but you have to meet me between the morning round and the afternoon clinical meeting.” And he got him to come and have lunch with him in the hospital cafeteria at the Prince Henry Hospital and invited me to this lunch. And I sat there and watched them chat. But it was a measure of Lance and how people were interested in him that Oliver Sacks had to get in a taxi and come out to a hospital cafeteria to have lunch if you wanted to have a chat. Because it was - it was a privilege to train with the person. You know, I've done okay, but I only do okay if you've got – you know, you can work with patients, you've got great collaborators, and you've got someone you can get advice from (a great mentor). Dr Smith: Yeah, that's actually really great words of wisdom for the residents and fellows and junior faculty listening to this. Maybe we should actually talk about your article, which was really great. Your article was on indomethacin-responsive headaches - and we can maybe talk about some specific questions - but what's the main take-home point? If our listeners needed to take or were to take home one point from your article, what would it be, other than it's indomethacin-responsive (that's in the title)? Dr Goadsby: Yeah, it's what it says on the jar. Well, I think the one thing to take home is that there are forms of headache that seem relatively pedestrian, like one-sided headache that feels like it ought to be migraine that's strictly one-sided, and a small percentage of them respond almost like switching a light off to indomethacin. So, I think you have to have a high index of suspicion. And I’m sure I give indomethacin to ten, twenty times as many people - or thirty - who end up (or even more, probably) who end up having a response. But we do it for a short period of time. For those who get the response - I can tell you, when they come back, they're crying, their partners crying, or the other day I saw one, their child's crying, because all of a sudden, you've basically fixed the problem up. So, the message would be, if you've heard about something and it feels a bit “maybe, could be” - you've heard this indomethacin thing - just do it for a couple of weeks. The worst thing that can happen is nothing (nothing happens). For a couple of weeks, they're not going to have a problem with the tummy (and I'm not advocating taking people with a active gastric ulcer, trying to bump them off). But you cover them properly, you give them a short trial, and occasionally in your practice, you will be so rewarded by that - you will dance home. Dr Smith: Well, this is going to be my next question. There are very specific criteria, right, for defining cluster, SUNCT, SUNA (and there was a really great Continuum Audio conversation I had with Mark Burish I'll refer our listeners to about cluster, SUNCT, and SUNA), but the indomethacin-responsive headaches - and even migraine - that sounds to me, as someone who's not a headache person, like, that could be challenging to sort out. If you see someone who has consistent, unilateral headache, do you just do an indomethacin trial, or do you select based on other criteria from the classification system? Dr Goadsby: I'd like to think I was aware of the criteria, and I am. But the longer I practice, the more I'm inclined simply to give the indomethacin and get the question off the table because I don't think there's a sine qua non; there's nothing that will - apart from the indomethacin effect - there's nothing that will convince me 100% to be able to not do it. I've seen enough people who haven't clearly read the classification in detail (patients, I mean) and took indomethacin, and got a response where you wouldn't have predicted it, and they're very happy and the story ends well. So, I would advise people not to worry too much about whether it ought to or not respond, but find out if it does. Dr Smith: So, the obvious next question is, how does this work? It's pretty unusual in medicine, certainly in neurology, to have something that's so dramatically effective. What's the mechanism? Dr Goadsby: Well, that's the easiest question - we don't understand it. It is particular to indomethacin - it's weird. Some patients will say, “We'll give you a little bit of a hint by telling you (maybe) that ibuprofen was useful,” but most don't give you that much of a hint (some will even say aspirin is useful). But we haven't really gotten to the bottom of it. What are the current thoughts? It must be something that's not simply cyclo-oxygenase because other cyclo-oxygenase inhibitors don't do that – so, that's helpful. The other broad things people think about are whether there's a nitrergic aspect to it. We've got some basic science work that can show that nitrergically induced changes in experimental animal model of these trigeminal autonomic cephalalgias can be modified by indomethacin in one part of the model, where naproxen (for example) can't. So, we think there may be a nitrergic component to it. The other thing is the structure of the molecule makes you think about melatonin, if you put the two up – it's a work in progress. Of the things I would like to do in my life, I'd really like to get to the bottom of it, I have to tell you, because if we could work out what it is that's great about indomethacin and then get rid of the GI thing . . . Then, if you talk about cure - because when people get a response to this (you know, the oldest reported case with a response took it for thirty-seven years; they died of something else) - and continue to respond. It's one of the sort of upsides and downsides when you diagnose it - you can tell a person that they're going to continue to respond (take a breath) until they die basically, because unfortunately, the problem doesn't tend to settle down - at least the treatment stays consistent. If we could get rid of the tummy problem, that would be real progress. Dr Smith: So, what do you do with the patient who has the tummy problem? Is there another approach? Dr Goadsby: Well, there's a range of things you try and do; you use PPIs (proton pump inhibitors) and H2 blockers pretty liberally; you try to get the lowest dose, and that's usually best done by the patient. I give them the ordinary-release indomethacin; it's an impression that I have, over the years, that the slow-release indomethacin is not as efficient (just as a recommendation). I let patients - they take it three times a day, or twice - I let them work out what the littlest amount is that they need, having given them a regime to iron it out, because they can work it out for themselves. It's a partnership. It'll be very individual. If someone wants to take two in the morning and one at night and feels happy, have at it. If they want to take one three times a day, if they want to take one at lunchtime - whatever they - let them work out the minimal amount. And the other thing that we found useful - small percentage (maybe one in five) will find the coxibs useful (like celecoxib), but that's not universal at all; it generally takes the edge off. A palpable percentage will find adding melatonin in can be indomethacin sparing. Then the other (probably most important) thing is that the noninvasive vagal nerve stimulator can be very useful in reducing indomethacin dosing or even getting patients entirely off indomethacin dosing. How that works, of course, is as mysterious in the sense of these problems as is indomethacin. But that's something really worth thinking about - can be very, very useful in getting the doses down. Dr Smith: You've been doing this for a while, right? And you've seen a lot of – Dr Goadsby: Let's not emphasize that “for a while” side, right, okay? Dr Smith: For a while – just a little while, Peter. Dr Goadsby: A little while. Dr Smith: I’m just thinking - and I'm a neuromuscular guy, so give me a little latitude - but when I was a resident, our concept of headache was pretty simple; it was migraine, classic or common, and we knew a little bit about cluster. And no one talked about SUNCT or SUNA or all these other things, and wow, what an amazing several decades it's been. What's the future look like? And - maybe think big – so, is a cure for migraine in the foreseeable future? What's coming next? Dr Goadsby: If you think really big (and I'll think really big), if “cure” means that we could control it sufficiently that you wouldn't notice it, I think that's very much - it's almost here, for some. Now, I think of it like cholesterol - someone's got high cholesterol; they take a statin, and if they don't get any problems, the cholesterol normalizes. I'm simplifying things (I'm not a cardiologist), but you take your cholesterol tablet - you take it once a day; everything's fine and dandy. You never get “cured,” as such, but the effect is an effective cure from manifestations of the problem - and I am simplifying things a little bit. If I look at it like that, then I think we're getting to a place where some patients, we can treat them so well, and the problem is so suppressed, and they have so few problems with side effects (and some have none), that we're really getting there. We saw a study of the promontory phase of migraine using a gepant (ubrogepant), and we saw the ability (if you recognize the attack early enough) to treat and never have pain. Never have pain. Well, that's pretty close. It might sound crazy to think about it as a cure because someone will say, “Well, they've still got their genes,” and so on. Fine. But migraine is about disability, and if you can stop the disability and give a person full function in their life, well, you're pretty much there. And we're getting there, as we understand the disease. Dr Smith: Really amazing. I have another question that I've actually been really dying to ask you. I'm a peripheral nerve guy, and you may not be aware of this, but those of us who are interested in therapeutic development in peripheral neuropathy, or advocacy, or recognition of neuropathy as a substantive, meaningful entity, are inspired by the work of you and your colleagues in headache. Examples might be advocacy for federal funding or having CDMRP funding - things like this. But an area where - I'm just curious - we spent a lot of effort (and it seems like it's been really transformational for you guys) is having taxonomy, which isn't a particularly sexy topic. But maybe you can talk about the power of having a taxonomic classification and getting towards a cure. Because looking through this Continuum issue - it's really remarkable – it’s just all sorts of things that I never would have thought of twenty years ago, and each of them is treated a bit differently. Dr Goadsby: Yes. As with all things in medicine, if you don't get the diagnosis, you can't get to the base - you've got to be able to get a diagnosis. And our taxonomy, the International Classification of Headache Disorders, has gone through three editions. We're working on the fourth. I have the privilege of being the chairman for the fourth edition (the first three were chaired by Jes Olesen). I do think it's one of the absolute achievements of our field (and Olesen needs to be really feted for doing this) that we have a definition system - it's operational; it's reasonably straightforward; it's been translated into, like, forty languages; that every government on the planet that I know of - and I'm talking about (I think I'd better mention no governments) but every big government you can think of, without exception, has adopted (‘cause I'll just get in trouble with the ones I’ve mentioned) have all adopted this classification; all the health technology assessments (the FDA, for example; the European Medicine, for another example), the Chinese government (People's Republic), Taiwan. Just, all over the world, people use one thing. So, if we do a randomized control trial - there's one recently came out; it doesn't really matter which gepant it is - but you look at the results in North America, and then you look at the results that were done by the Chinese and the South Koreans in a study, and the placebo rates and the active rates are more or less identical. Because what we've been able to do is homogenize who gets into clinical trials and understand what's happening. So, if I get up and talk about whatever we're going to talk about now, like, in rural India, people will know what we're talking about; all the neurologists will be on the same page and so we can make progress. And when we make progress, it's global progress because we sing from the same hymn sheets. I think the taxonomy has been really important for this. And, of course, if you get the diagnosis right, then you can start to begin to get the treatments right and you can bring all the knowledge from randomized controlled trials. There's no point having a whole lot of data if you can't apply it, and what's great about our taxonomy is we can apply it everywhere in the world. Dr Smith: Wow, what a cool answer. So, I have a follow up question for you, Peter, which has to do with reproducibility. This is a huge issue, right? In reproducibility and clinical trial evidence and in many fields, this has been a big issue - in psychiatry and other areas of neurology, where trials are nonreproducible. To what extent do you think this problem in other fields is a taxonomic problem, or a internal validity problem, in terms of the populations being recruited? I'm really impressed to hear that you don't have that problem in headache. Dr Goadsby: I do think one of the advantages that the International Classification of Headache Disorders has given us (International Headache Society being the proponent of that) is that there's clinical homogeneity, relatively speaking, in our clinical trial populations. This comes back to the clinic; good clinical trials are as much about the clinicians who are involved and the care they take in recruiting patients, and so on. Which is not to say that psychiatrists are not careful - not at all. But I do think that if you want to just test a question, everyone in the laboratory will tell you that you need to have - say you're doing work with rodents, for example; you want about the same weight, you want the same strain, they're eating about the same, they're up and down at night - everything is about the same. If you want to do good clinical trial work, you have to tidy up as much as you can so the only thing that's really impacting upon the question is the medicine, or the placebo, or whatever that you're testing. So, I think you're right. I think sometimes the pain people struggle with this because, as you say, a painful neuropathy can come from a lot of places. Well, if you just take all of those etiologies, you throw them into one study, and you test it against something, it doesn't surprise me that that's not so useful, compared to taking an individual thing that's really well defined - where you've understood the clinical side, you've understood the pathophysiology as much as you could - and just test that, one at a time. I think that's been a good lesson for us. And that's why there's nothing that's ever failed in a migraine clinical trial (a properly designed one) that ever was useful, and nothing that was ever successful that didn't continue to be successful. Now, some things were successful, and they produced, like, liver enzyme problems - so, that's “no win-no foul” situation. But the homogeneity's been quite important, I think. And it comes back to good clinical practice. Dr Smith: Well, thank you for the roadmap - that's really, really interesting. I'd like to finish up with another shift in gears, and to talk about workforce. Obviously, we have a national shortage of neurologists in the United States. We're never going to be able to train enough headache neurologists to take care of all headache patients, and we need to think about systems of care, which I guess we could talk about. But my question for you is, what would you say - a lot of residents listen to Continuum Audio, and hopefully, more medical students in the future and now - what do you say to them about a career in headache? Listening to this, I kind of feel like I want to go do a headache fellowship - it's pretty exciting. What's your pitch to them? Dr Goadsby: I’ll tell you one small thing first before I say that; I did do twelve months in clinical neurophysiology, doing nerve conduction, muscle biopsies, evoked potentials. I actually did over ninety muscle biopsies (needle muscle biopsies) when I was training, so I understand your feeling. But I just got the feeling many years earlier than you've had it. What do I say to residents? Well, headache is an area where you can make a diagnosis, you can manage the patient, and you can make them better. I'd say to the resident, “Ask - just look in the mirror and ask yourself, why did you get into medicine?” You got into medicine to help people, and headache is an area where you can really help them. Plus, there's tens of millions of people with the problem, so you will always be in demand. And one of the great things about headache (I think it's probably true of neuromuscular) is it's also a very good lifestyle choice because our problems are generally with primary headache disorders - are not emergent (people don't tend to ring you up at night), and it's not really an on-call issue. You can have a proper balanced existence (work-life balance), and you can do it in a way that's really enjoyable. And then there's an extra bonus: there's all the wonderful neuroscience and neuropharmacology that's going on in headache. I just think if a resident looks in the mirror and says, “Why am I doing this?” most of them are going to look back at themselves and say, “Because I want to do good.” And they also want to do good in a way that they can have a proper life themselves. And if they're the two answers you got back when you look in the mirror (“I want to do good” and “I want to have some life myself”) - headache - that's the place to go, because there's plenty of room and you can do both. Dr Smith: Well Peter, that's great - sign me up. And I think people know where to find you to call for a recommendation. What a great conversation and a really great article. And again, I'll refer our listeners to Mark Burish’s article on cluster, which is a really great companion to your article ‘cause it gives you the full spectrum of trigeminal autonomic cephalgias (which is pretty cool), and the rest of the issue is equally amazing. Peter, you don't disappoint. The next time you see the Danish Crown Prince, say “Hi” from me (I love Denmark - it's a lovely place to be). And thanks again for doing this. Dr Goadsby: Well, thank you, and thanks for the Academy for organizing. And the other thing about residents - if you want to stay in touch with neurology, stay in touch with the Academy; they're a pretty good bunch. Dr Smith: Couldn't agree more, couldn't agree more. Again, today we've been interviewing Dr. Peter Goadsby. His article on indomethacin-responsive headache disorders appears in the most recent issue of Continuum, on headache. Be sure to check out our Continuum Audio podcasts from this and other issues. And listeners, thank you very much for joining us today.   Dr. Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practice. Right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024, or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members: go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.

Cranial neuralgias comprise a distinct set of disorders typified by short-lasting attacks of intense pain in the distribution of a particular nerve in the cranium. Cranial neuralgia syndromes are rare but can be debilitating and go undiagnosed or misdiagnosed for years. In this episode, Lyell Jones, MD, FAAN, speaks with Stephanie J. Nahas, MD, MSEd, FAAN, MD, an author of the article “Cranial Neuralgias,” in the Continuum® April 2024 Headache 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. Nahas is an associate professor of neurology at Thomas Jefferson University and assistant director of the Headache Medicine Fellowship Program at Jefferson Headache Center in Philadelphia, Pennsylvania.   Additional Resources Read the article: Cranial Neuralgias Subscribe to Continuum: continpub.com/Spring2024 Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @ LyellJ Guest: @stephanieJnahas Full transcript available here  Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening.    Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr. Stephanie Nahas, who has recently authored an article on cranial neuralgias in the latest issue of Continuum on headache. Dr. Nahas is a neurologist at Thomas Jefferson University where she is an Associate Professor of Neurology and serves as Assistant Program Director of the Headache Fellowship program there. Dr. Nahas, welcome, and thank you for joining us today. Dr Nahas: Thanks for having me. Glad to be here. Dr Jones: So, for our listeners who are new to Continuum, Continuum is a journal dedicated to helping clinicians deliver the highest possible quality neurologic care to their patients, and we do so with high quality and current clinical reviews. Dr. Nahas, your article is a perfect example of that - it's full of really helpful (and I think clinically relevant) recommendations for neurologists who take care of patients with cranial neuralgias. And now that at this moment (during this podcast interview), you have the attention of a huge audience of neurologists - what's the one most important practice change that you would like to see in the care of these patients?  Dr Nahas: I would like to see the recognition of these cranial neuralgias and related syndromes as distinct and overlapping with other primary headaches much more often. I think far too often, clinicians will try to pigeonhole these headache and facial pain diagnoses and try to make just one diagnosis the main one, and any other symptomatology that comes along with it – “Oh, that's just a weird part of your primary syndrome, right?” I know I've fallen into this trap a number of times, because mostly what we see in a headache clinic is going to be migraine, so we kind of have a laser focus towards migraine-type symptoms (and we know migraine can do just about anything). So then when we hear a little bit about a facial pain, a little bit about some sort of neuralgia, we just try to wrap it up into migraine - but that's not always necessarily the case. You know, we know that any person on the planet can have as many diseases as they darn well please, so why not ascribe two diagnoses when it's appropriate? That can lead to better treatment outcomes, in fact. If you are focusing your treatment on two distinct, but overlapping, entities, you tend to get better results, because the treatments may not be identical (and they rarely are). Dr Jones: And that's a great example of it's Occam's razor on one side (there's one problem) versus - what is it, Hickam’s Dictum? Dr Nahas: Something like that. Dr Jones:  - where you can have as many problems as the patient wants to have, so I think that's a great example of that. And, earlier, in the same issue on headache, we do have a wonderful article by Dr. Deb Friedman, who walks through that really important history component of trying to, you know, determine which headache syndrome the patient is dealing with (which is obviously a prerequisite for the diagnosis and management) - so that's a great point. So that's the one takeaway - recognition of cranial neuralgias as a distinct entity. Keep it in mind – otherwise, we'll miss it. Is that right? Dr Nahas: You got it. Dr Jones: Okay, good. If we learn nothing else, we'll take that away. So, speaking of the history, Dr. Nahas, for many pain syndromes (including these), the history is really paramount in establishing the diagnosis for patients, specifically with trigeminal neuralgia. How do they usually describe that pain to you?  Dr Nahas: The whole spectrum of descriptors for trigeminal neuralgia-form pain is, actually, maybe broader than you would think, and I actually find that, sometimes, patients have a real hard time verbalizing and describing the way it feels, because it's so unusual - it doesn't remind them of anything they've necessarily felt before.  Sometimes, it can. For example, a patient who's no stranger to having lots of dental work - that pain that when they drill in or if they hit an irritated part of the tooth or the gums, that's usually kind of neuralgia form-like. But at the same time, patients will say, “It's still not quite like that. You know, it's really hard for me to explain. It's sharp and it's terrible like that, but it has a different quality.” And I think they just don't necessarily have the terminology, but I encourage them to try to be creative. You know, some of my patients will personify the pain - they'll describe as if there's some little creature in there that's clawing, or scraping, or pulling, or stabbing. Or they might use other descriptors, such as burning like a fire (like a blow torch is there). Or they may even use colors. You know, some of my patients are really creative, and I don't know if they actually have synesthesia or they're just bordering on that, but they'll describe different colors for the qualities of pain. (“Is it more red? Is it more like icy blue? Is it black or white?”) I don't hear that too often, but I do like to just open the door and let my patients describe for themselves in their own words - and if they can't have any words, I give them some examples and that usually gets the ball rolling. Dr Jones: So, a combination (like we usually do) with some open-ended questions, and then some directed ones to kind of clarify. That's really interesting, and it gives you some immediate empathy and sympathy for the discomfort these patients have to deal with, right (as when they describe it in those burning, clawing kind of terms)? Dr Nahas: Exactly, and they'll also put it into context for you - so not just describing what the quality of the pain is like, but they'll give you good examples of when they feel these symptoms, what brings them on, what alleviates them, how the symptoms may change from day to day depending on the situation or circumstance. And again, it just gives them an open door to express themselves, and it really does help to strengthen that alliance you're trying to create and maintain with your patient. You do get useful and valuable information when you just let them go on and describe things. Dr Jones: So, there are, I think, misconceptions in the popular world and also in the clinical side of care that, you know, folks will have a perception of a disorder that maybe doesn't really match reality. What do you think is a common misconception you've encountered in taking care of patients with cranial neuralgias?  Dr Nahas: The patients that I see tend not to have the clear-cut textbook descriptions  (like it's almost as if they're reading the criteria when they tell you your symptomatology) - because those cases are a little bit easier, they get identified more readily, they get appropriate treatment sooner, their disease doesn't necessarily progress and become complicated by, you know, any number of things that can happen with unmanaged neuralgia-form craniofacial pain. The ones that I see - they've been around the block several times, because maybe their syndrome isn't quite so typical. Maybe they didn't really have the terminology to be able to describe their symptoms. Maybe nobody really opened that door for them and invited them to just talk about what it is. Perhaps they, or whoever they were seeing, were more focused on diagnostic testing, and so their focus is more on, “Why is my MRI not showing anything? Why is my x-ray completely normal? You know, I have these symptoms. There must be an explanation.” Because that's what patients want - they want solutions. They have a problem, they want to know why they have it, and they want a solution to it. And they can get too focused on the hard data and ignore that it's a subjective experience that really guides us to help treat their symptoms, especially when we don't have necessarily an anatomic target to go after. (When we do, that's great.) But again, these straightforward cases tend not to come to me, because they’re easier to take care of. Dr Jones: Still, just as legitimate a diagnosis, even with a normal MRI, right? I do find it's sometimes hard to kind of get around that with a patient, isn't it? Dr Nahas: Absolutely, it is. You know, they're both relieved and disappointed. I often find if we order imaging for an unusual syndrome (or even a typical syndrome) and they see that, “Well, there's nothing on this report to go for. What does that mean? Does that mean that I'm crazy? Does it mean that this is all in my head, that I'm imagining it, that I'm amplifying my symptoms somehow? Is this my fault?” You know, all this self-doubt comes in, and you have to reassure these patients that, “Yes, your symptoms are real. They are in your head, because your brain is in your head, and your brain is the source of your perception and your experience. So, let's take your symptoms at face value and let's give you treatments that are directed at those symptoms.” Dr Jones: Well said, and that's where we like to keep it, the brain inside the head. I think that was day one of neuroanatomy. I know that the treatment for many of these cranial neuralgias overlaps, right? There's some common approaches to several of these. There are some things that we put in our academic writing, but there are some things that we just kind of learn from experience. Do you have any tips or tricks that you would like to share with our listeners about the management of the cranial neuralgias?  Dr Nahas: First and foremost (and I think this kind of goes for any of the disorders in the spectrum of headache and facial pain) is you need to be patient, and you need to set up appropriate expectations that, by and large, this is a trial-and-error process where we need to introduce a therapeutic intervention gradually and titrate the dose gently to effect while following for clinical response, but also keeping an eye on what our guardrails are. What do I mean by that? Let’s say, for example, we’re using oxcarbazepine for some sort of neuralgia-form disorder (I mean, take your pick for any of them – it’s fair game for most of these as a good initial trial). Dr Jones: Sure. Yeah. Dr Nahas: So, you want to start it at a low dose, start building it up slowly, and in addition to following for their clinical response - which I counsel them it may take a while  (even once we hit a target dose, it may take several more weeks, we've got to give it time) - you can monitor a serum level of oxcarbazepine and certain other antiseizure medicines for that matter. So, that can help guide you to know how high you can go. This is a little bit different from the situation with epilepsy, where you're checking levels to ensure that it's in a therapeutic range to make sure that it's not toxic - maybe to assess for adherence - but here, we're using it as a guide to know how much farther can we push the dose on this drug. And, of course, also, you want to be monitoring for any adverse events that can occur with that drug (such as hyponatremia, or changes in the CBC, et cetera) - so I do monitor these folks a little bit more closely than I otherwise ordinarily would, especially when I have a therapeutic intervention where I can actually monitor the drug level of it and be very, very precise in trying to maximize and optimize their treatment. Dr Jones: Got it. So, patience with each trial, and then patience that there might be (and I mean patience with a ‘c’ that there might be) multiple trials – I think that's a good takeaway for all of these cranial neuralgias with pretty much all of the medication treatments, right? Dr Nahas: Yes, and I do find that in some cases, one treatment is not quite enough. Because most of the treatments we draw from our antiseizure medication category, it can get complex trying to balance two, or even three, antiseizure medicines and finding the optimal dose for each. Do we push all of them to the max? Do we say this one is the undercurrent (we just want to keep it at a low level) and these other two are going to be doing the lion's share of the work? It becomes kind of fun if you like uncertainty and if you like to be creative. If you're the type of person who likes checkboxes and checklists and cut and dried results, you know this is not the game that you want to play - but that's one of the reasons that I enjoy doing this, because I have so much freedom to be creative and really finely tailor and tune the treatment specifically to the individual patient’s needs. Dr Jones: That's fantastic, and in a minute, I think we can come back to maybe what drew you to this - I'm curious to hear that. But before we get to that, you know, when we think about the medications that are available (and again, your article does a phenomenal job summarizing the therapeutic approaches to the cranial neuralgias) - what do you see on the horizon, Dr. Nahas, for the care of these patients?  Dr Nahas: I want to see a lot more research being done in this population of patients and across this spectrum of disorders. What makes it so hard is because they are somewhat rare, and because they very often co-occur with another primary headache disorder - so that makes it extraordinarily difficult to create a research study on a population that's so heterogeneous, right? That's, I think, the biggest challenge - is that we have so little to guide us other than our own clinical experience. There are not a ton of clinical trials for any of these disorders. I think one in particular that can be both underdiagnosed and overdiagnosed is occipital neuralgia - and I mentioned before that I, myself, have found myself falling into this trap of once I see a signal for migraine, I just call everything migraine, right? And, sure, with migraine, there can be allodynia in the scalp, and oh, sure, we all hear that if you push on something sore, you can have some lancinating pain. Oh, that occipital neuralgia that somebody told you about? No, no, that's just part of your migraine. You don't actually have occipital neuralgia. Well, you know, if you look at clinic-based studies (there's one in particular that I cited), most of the presentations of occipital neuralgia actually co-occurred with another headache diagnosis (either primary or secondary), and very commonly, it was migraine or probable migraine or chronic migraine. And why this is important is because you need to validate for these patients that they do have more than just migraine. They have a separate problem that, yes, it's interrelated, it's interconnected, they can influence each other - but we might have to treat them both differently. So, you have your suite of migraine treatments which might not include an antiseizure medication. Then, for the occipital neuralgia, maybe you are pulling in an antiseizure medication, or maybe you're focusing more on peripheral nerve blockade or physical therapy - or even considering a surgical referral, because as surgical treatments for nerve decompression or ablation or other interventional procedures also continue to evolve, that helps to give us some more hope in giving  these patients more relief with fewer complications. I'd also like to see some more creative solutions, not just more antiseizure medicines, not just more targeted anatomic interventions. But, hey, is there a role for some other peptides or neurotransmitters that we just haven't identified yet? Might some novel treatment approaches actually be useful for some of these patients? And, you know, again, how do we get at those answers? It's going to be challenging, because the patients - while they're out there, they're not really a homogeneous group, and the results from a particular study might not be so generalizable. Dr Jones: And we've seen such great success in the world of migraine, right (looking for novel targets) And so it would be nice to transport that over to the cranial neuralgias, right? Dr Nahas: Yes, absolutely. Dr Jones: Yeah. We should always be mindful of disparities in care of patients who have neurological problems. Are you aware of any literature around the care of these patients related to health care disparities that our listeners should be aware of? Dr Nahas: Nothing focused specifically on disparities in this population or subpopulations within this population (based, for example, on ethnicity, or race, or socioeconomic status). You're looking for subpopulations within a huge population, almost like a needle in a haystack - not quite that difficult, but again, it takes a lot of effort and diligence to try to find these individuals and then to get them to agree to enroll in some sort of research study, even if it's just a survey study or doing interviews with them trying to understand their symptomatology better. It can be quite challenging. And then again, let alone designing a rigorous clinical trial for these folks - who, again, such a heterogeneous presentation - and the willingness to participate in a placebo-controlled trial for pain that can be so heinous can be very, very challenging. You know, we've seen this as a challenge with cluster headache, too - not just because of the nature of the disease (when the cycles come and go somewhat unpredictably). But these folks aren't necessarily willing to forgo treatment for the purposes of a clinical trial - I mean, many are, and I thank them - this is another one of the reasons that research is really lacking in some of these rarer syndromes. Dr Jones: So, another part of the rationale for more investigation for these uncommon and probably underserved disorders. So, Dr Nahas, I know caring  for patients with craniofacial pain, I imagine it can be challenging. I can imagine it's also pretty rewarding as well. What drew you to this work, and what do you find most exciting about it?  Dr Nahas: Well, what brought me to headache to begin with was kind of random chance, and really, it revolves around mentorship. When I very first started as a neurology resident, Dr. Silberstein took me under his wing and wanted to turn me into a headache specialist (that was one of his goals). And, thankfully, he was successful, although he didn't really have an easy job of it, because back then, I didn't really see or understand how studying headache and facial pain could really satisfy that hunger that I have to understand the brain and the nervous system. I mean, that's why I became a neurologist in the first place, right? (I think that's why most of us did.) You know, not only are we drawn to medicine to help people and be altruistic and to study a fascinating topic, but particularly with the brain and the nervous system - I mean, this is what makes us human. This is what's so fascinating to me. And until I started to learn more about headache, I thought the best way to really learn about brain function is through disease (such as stroke or epilepsy, or movement disorders, cognitive disorders, degenerative disorders). This is how we learn, right? This is what I was taught, at least in college and med school. And then you get to the real world of actually practicing medicine or being in training. You start talking with these folks, and you hear their stories and how distinct they are from the textbooks. And again, when you invite them to really describe their experience, you see the human side of it, and you listen to them describe their symptoms - and you start to imagine yourself, what's really going on in their brain and their nervous system for them to experience that? So you start reading a lot of the literature about cortical spreading depolarization and how that can activate the trigeminal system and sensitize it - how that might be linked to the expression of aura (for example) - then, you can actually really parse out the anatomy and understand why somebody experiences those symptoms when you understand the anatomy. And there are just countless examples of this - about how studying the symptoms and what brings them about, what the pathophysiology is, and then what the treatment is, how that really informs our understanding of how the brain functions - that's really what's kept me excited about this. That, and again, forming relationships with patients and sometimes being the first person who ever just sat down and listened to them and let them talk, and they really feel like they're cared about and like they're important - because they are. I think far too often, patients with headache and facial pain disorders are stigmatized, and they're left feeling like it's not worth it trying to get better, that there is no solution. Society has beat them down, the medical system has let them down, and they just want to give up. Then, when we can finally sit and listen and give them some hope, and they see some improvement - the transformation that occurs right before your eyes is extraordinarily gratifying. Dr Jones: So, it's fascinating, and you can help people - and I can't think of a better advertisement for headache fellowship for all those neurology trainees out there.  Well said, Dr Nahas. So I've got one more question for you before we close. And I know that the headache community, including yourself, are very strong advocates for your patients and for more research (as we've talked about today) into headache disorders, understanding the pathophysiology, developing better treatments. What is it about purple hair? I've seen several headache specialists (and maybe someone on this call) post online some purple hair. What's the story behind that? Dr Nahas: A number of years ago, as part of advocacy efforts, we recognized there's got to be a way to really improve the awareness of such a common condition, of headache in general. It affects so many people, it almost becomes, again, brushed off. We say headache, it's just a nuisance. Well, no it's not. It's actually fascinating as part of the human condition. One of the things we needed was a color - our signature color - and we chose purple. We know that we share this color with other advocacy groups, but it's a great color, it's eye-catching, and you can utilize it in a number of different ways. One of the early ways was people dressing up in all kinds of purple garb - putting purple makeup on, purple sunglasses, purple tutus, purple T-shirts, and even purple wigs. A lot of us have been donning purple wigs for advocacy and for awareness efforts, particularly for events (such as Miles for Migraine, for example) - but some of us have been so bold as to not just put on a purple wig, but to actually go to a salon, bleach the hair, and dye it bright purple. I have at least one male colleague who also did this to his beard. Last year, we did it together at the same salon, took a bunch of pictures to post about. It really created a big splash online and for our social media efforts and outreach, and it caught on. Lots more people now are thinking about dying their hair purple. One of our current fellows actually did it this year. At our center, we have about 30 different purple wigs that we bought with some funds that we procured, and on the Shades for Migraine Day (June 21), we all went out parading around Center City, Philadelphia wearing our purple T-shirts and our purple wigs, and handing out flyers trying to raise awareness. We got a lot of strange looks, but we also got a lot of good feedback. And I think we actually reached some people who didn't realize that there's such a thing as a headache center that they could actually come and see us and get relief for this problem they thought was just a part of everyday life. That was kind of a long-winded answer, but - Dr Jones: No, that's great, and it worked. It got me to ask you about it, right? And I will say I admire your commitment and dedication. The best I could do today, Dr Nahas, was wear a purple tie, but I'm sure your patients appreciate that level of investment, too. It’s really, really cool. Really impressive. Dr Nahas: Yeah. A lot of them this past year have asked me, “Where's the purple hair? I thought you were going to do it every year around this time.” And, you know, it is a bit of a commitment. Dr Jones: It's a commitment, yeah. Dr Nahas: And there's some upkeep that is required and you're kind of stuck with it for a while (unless you want to go to the trouble of reversing the process, but that's really just covering it up). I said, "We've moved beyond dying the hair. We're doing wigs, and we're thinking of the next thing.”  Dr Jones: Good for you. Dr Nahas, thank you so much for joining us, and thank you for such a thorough and fascinating discussion on symptomatic management of cranial neuralgias and such a wonderful article in the latest issue of Continuum.  Really appreciate you being here today. Dr Nahas: I can't thank you enough. It's been my pleasure.   Dr Jones: Again, we've been speaking with Dr Stephanie Nahas, author of an article on cranial neuralgias in Continuum's most recent issue on headache. 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 practice - and right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024, or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members, go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.