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Dr. Casey Albin, a neurology and neurosurgery assistant professor, discusses managing neuromuscular emergencies in neurocritical care. Topics include challenges of ICU diagnosis, managing conditions like myasthenia gravis, Guillain-Barre syndrome, and ALS suspicions. They also touch on ventilatory support needs, engaging with the neuro Twitter community, and academic productivity strategies.

Dr. Alexandra Reynolds discusses neuroinfectious emergencies, highlighting atypical presentations and the importance of a high index of suspicion. The podcast explores diagnosing infections without typical signs, evaluating febrile and confused patients for meningitis and encephalitis, and managing neuroinfectious emergencies in immunocompromised patients. Additionally, it delves into disparities in healthcare access for patients with neurologic infections.

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.

Dr. Soojin Park discusses emergent management of spontaneous subarachnoid hemorrhage, focusing on detecting and treating delayed cerebral ischemia. The podcast covers updates and trials influencing management, the use of data science and AI in patient monitoring, challenges in managing aneurysmal SAH, and future advancements in treatment strategies like lumbar drainage and stellate ganglion blockade.

Dr. T. M. Leslie-Mazwi discusses neurocritical care for ischemic stroke patients, covering topics such as the management of large vessel occlusion strokes, post-thrombectomy care challenges, advancements in neurocritical care, and proactive intervention strategies for better patient outcomes.

Dr. Sarah Wahlster and Dr. Aaron Berkowitz discuss neurocritical care examination and workup, highlighting the importance of prompt evaluation. They cover conducting neurological exams in critical care, considerations for intubating patients with neurological conditions, challenges in monitoring neuro ICU patients, and navigating diagnosis and management complexities.

Dr. Ariane Lewis, a neurology and neurosurgery professor, discusses the June 2024 Neurocritical Care issue. Topics include ethical debates, disparities in care access, and the appeal of neurocritical care for trainees. Dr. Lewis shares insights on editorial responsibilities and the skill set needed in the field.

Dr. Peter Goadsby discusses indomethacin-responsive headache disorders, highlighting the absolute response to the medicine. Topics include mentorship in neurology, differentiating headache types, potential 'cure' for migraines, importance of taxonomic classification, and promoting neurology resources.

Dr. Stephanie Nahas, an expert in cranial neuralgias, discusses the challenges of diagnosing and managing these rare but debilitating disorders. Topics include patient history importance, research challenges, disparities in care, personal journey in studying headache disorders, advocacy efforts in the headache community, and managing cranial neuralgias with a witty exchange on wigs.

The majority of children and adolescents experience headache, with pooled estimates suggesting that approximately 60% of youth are affected. Migraine and tension-type headache are the leading cause of neurologic disability among children and adolescents 10 years and older. In this episode, Allison Weathers, MD, FAAN speaks with Serena Orr, MD, MSc, FRCPC, author of the article "Headache in Children and Adolescents," in the Continuum® April 2024 Headache issue. Dr. Weathers is a Continuum® Audio interviewer and an associate chief medical information officer at Cleveland Clinic in Cleveland, Ohio. Dr. Orr is an assistant professor in the departments of Pediatrics, Community Health Sciences, and Clinical Neurosciences at Cumming School of Medicine, University of Calgary and a pediatric neurologist at Alberta Children's Hospital in Calgary, Alberta, Canada. Additional Resources Read the article: Headache in Children and Adolescents 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 Guest: @SerenaLOrr 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 Weathers: This is Dr. Allison Weathers. Today, I'm interviewing Dr. Serena Orr on pediatric headache, which is part of the April 2024 Continuum issue on headache. Dr. Orr is an Assistant Professor at the University of Calgary, and a Pediatric Neurologist at Alberta Children's Hospital in Calgary, Alberta, Canada. Welcome to the podcast. So, thank you, Dr. Orr, for taking the time to speak with me about this fantastic article that covers such an important topic – headache in the pediatric population, in children and adolescents. First, I'd love to start by learning a little bit about you. Where do you practice, and how did you get interested in this topic? I love learning more about the authors of these incredible articles and how they became interested in their fields. So, you know, pediatric neurology is already a pretty subspecialized area of medicine – how did you become interested even further subspecializing in headache? Dr Orr: Well, thank you for the invitation. Nice to meet you, Dr. Weathers. I'm Serena Orr. I'm a clinician-scientist, pediatric neurologist, and headache specialist based in Canada at the Alberta Children's Hospital in Calgary, Alberta, just outside of the Rockies. I'm really passionate about headache medicine. I think I came to it because it allowed me to marry my interests in neurology and psychology together. I did my undergraduate studies at McGill in psychology and really wanted to take a biopsychosocial approach to my practice. The first child neurology patient I ever saw was a child who was experiencing migraine and having a lot of disability from it, with lots of impacts on her life - and I really saw an opportunity to take a holistic approach to the patient and marry my interests in neuroscience, neurology, and psychology together. So, I'm very excited to talk to you today about this topic that I'm really passionate about and that I think is underserved – um, hopefully get more people excited about it. Dr Weathers: But so great, and I'm sure we will do that just based on how excited I was just reading your article. So, I always like to start, actually, with what you feel is the most important clinical message of your article. What is your biggest takeaway you want to leave our listeners with? Dr Orr: Yeah, well I think this is a really big topic in neurology. So, if you look at the reasons for consulting a child neurologist, headache falls into the top three. 60% of youth experience headache in youth. If we look at what presents to neurology in terms of headache, the majority is migraine – and so that's a big focus of this article, because anywhere between a half to 88% of headache consultations in neurology are for migraine. And as I kind of alluded to in discussing my interests in this area, you know, it's really important to take a biopsychosocial approach to managing any chronic pain disorder, including migraine and headache disorders. Another big takeaway point from the article is that - specific to pediatric headache - there's really high placebo response rates that we're still trying to understand and grapple with in the field, and I think this underscores the importance in really doing patient-centered care and ensuring that you're educating patients and families about the level of evidence that we have about the placebo response rates and engaging in shared decision-making when you're choosing treatments together. So, I think those would be the main take-home points. Dr Weathers: I think both really critical. And I think even without – I'll put my plug in – even without the placebo effect, I think that shared decision-making is such an important concept for all of us in neurology to think about - but I think you make such the important point that with it, it becomes absolutely critical. I want to expand on a concept that you were just talking about. Pediatric headaches are so incredibly common, and you make the point in the article so well that they're one of the leading causes of neurological disability in pediatric patients. They have such a significant impact that really touches all aspects of these children's lives - both at school, how they impact their hobbies - pretty much everything that they do, and these long-reaching impacts. But then you go on to say that pediatric headache remains the most underfunded pediatric disease category when you take into account allocated public research dollars, which was just staggering to me. Why do you think this is? Dr Orr: I think there's a few reasons. So, one of the main reasons, I think, is that headache medicine has been underserved - there haven't been enough people who have gravitated to this field. I think this is rapidly changing as we train more people and show the world how important this topic is and how much exciting translational research is going on. But, historically, this has been a very small subspecialty that's been underserved relative to disease burden (so not enough scientists equals less research funding) - but there's another aspect to this as well. There was a paper published in 2020 by Mirin – who actually looked at research dollars in NIH based on disease burden and whether the diseases were male or female dominant - and found that there's a significant gender bias in research funding. Male-dominant diseases tend to be significantly overfunded relative to female-dominant diseases when you look at disease burden - and if you look at the female-dominant disease table, headache disorders and migraine are in the top three most underfunded disease categories amongst the underfunded female-dominant diseases. That data has been replicated looking at NIH dollars on the pediatric side as well. They didn't look at gender breakdown in the pediatric paper that was published a couple of years ago, but found, actually, that pediatric headache disorders are the most underfunded in terms of NIH research dollars to pediatric diseases – so, top underfunded relative to disease burden. So, yeah, being underserved as a field - and then, I think, gender bias has also played a significant role in what gets funded over time. Dr Weathers: Wow, that is hard to think about. And I think those are really insightful points and ones we really need to think about as we think about the bias in our research and our funding. Why is access to care and treatment for these children and adolescents so important? I know this seems like a super obvious one, but it feels like the answer is actually really much more complex. Dr Orr: Well, there's data to show that earlier diagnosis can lead to better long-term outcomes for youth with migraine - and this is really important, because if you look at the incidence curves for migraine, you see that at least a third, if not more, of incident cases occur before adulthood. We also know there's some GWAS data to show that youth-onset migraine has a higher genetic loading when looking at polygenic risk scores than adult-onset migraine, so people who have migraine onset in youth may be more genetically loaded (that may be important). And we also know that early access to diagnosis and treatment gives them a better long-term prognosis. We know that headache disorders and migraine are associated not only with long-term potential for disability on the physical side, but also increase the risk of psychiatric comorbidities developing over time, so there's really a huge opportunity in accessing a diagnosis and treatment early to improve long-term function - both on the medical side, but also potentially avert poor mental health outcomes - and also diagnose and treat a subset of people with the disease that may be more genetically loaded. We don't know if that impacts outcomes, but potentially, it does. So there's lots of reasons, I think, that we can get in there early and make a big impact – and even for those who it takes a while to find effective treatment for, really having access to education early so that they understand their disease and also ways that they can engage in self-management strategies, I think, is really empowering to the patient and really important (even if we're struggling to find the best medical therapy). Dr Weathers: You laid out a lot of really important reasons, and again, it goes back to the arguments made at the beginning about why it's so important to increase the funding so that this is no longer an area that's underserved, so that we are able to increase the access, and that everybody who needs this kind of care is able to get it. I want to shift a little bit and think about how we diagnose and work up patients who present with a headache. So as a neurologist - and also as a parent - one of the scariest considerations for me is figuring out if a headache is just a headache or if it's a sign of something else (you know, what we think of as a secondary headache disorder). What is your approach to distinguishing between the two? Dr Orr: We take a very clinical approach to diagnosis. We don't have specific biomarkers for different headache disorders, so we're still, you know, relying on a really detailed history and physical exam in order to sort out the diagnosis. As I discussed in the article, really the key first branch point (like you say) is, is this a primary headache disorder or a secondary headache disorder? There's some tools that we can use in practice to try to get at that, I think the most useful of which is the SNOOP tool - it's an acronym that goes over headache, red and orange flags. Every time I write an article where I discuss this, it's expanded to include more red or orange flags (it's in its probably third or fourth iteration now), but there's a nice table in the article that goes over some of these red and orange flags. It includes things like systemic feature (like headache, nuchal rigidity), if there's a history of cancer, if there's associated, you know, headache waking child up in the morning with vomiting - and a variety of features. I have to say the level of evidence for some of the features is relatively low, and our understanding of some of the red flags has changed over time. As one example, we used to think occipital headaches in youth were almost always associated with a secondary headache disorder, but now there's more emerging data to show that it's actually relatively common for youth with migraine to have an occipital location. So, really, using the tool is about kind of putting the whole picture together to try to risk stratify. In the majority of youth who present with recurrent headaches, who don't have any red or orange flags, and who have an unremarkable neurological examination without focal deficits, it typically is such that we don't have to do further investigation - but any red or orange flags (or a combination of them), any focal deficits on exam, would typically be where we would be considering neuroimaging. It's very unusual that we have an indication to do an EEG or large amounts of blood work in youth with headache, but it is context specific - for example, a case presenting with recurrent hemiplegia (you may have Todd's paralysis on the differential and you may want to do an EEG), or in a youth who also has GI symptoms (I picked up some youth with celiac disorder who have chronic headaches as well). So there are specific circumstances where blood work, EEG may be indicated (or obviously lumbar puncture in the case of suspected infection, et cetera), but for the most part, we're really relying on a very thorough history and physical exam to sort out our pretest probability of a secondary headache disorder and whether we need to do neuroimaging and further investigations. Dr Weathers: I think keeping in mind that systematic approach and really working through the algorithm is really reassuring and makes sense that, one, you won't miss something kind of worrisome, but on the other hand, that you're also not doing unnecessary testing, either. Along those lines, what do you think is the easiest mistake to make when treating children and adolescents with headache, and how do you avoid it? Dr Orr: I think the easiest mistake to make is undertreatment. Both for acute and preventive therapies, I often see undertreatment. I think families are often hesitant to give medication to their children, and so I have a lot of families say, "Oh, well, you know we typically wait the attacks out until they get more severe, we try to avoid medication, we use cold compresses, et cetera." So, explaining to families that acute treatment (of course, we don't want to overuse it) and overusing simple analgesics (NSAIDS) more than three days a week can increase the risk of higher frequency of attacks and medication overuse headache - but undertreatment is a risk, too. And the way I like to explain it to families is in the scientific basis of pain chronification - so I'll say to families, "You know, we have these pain pathways in our brain. If we let them go off for long periods of time, they get stronger (and so that's where we want to get medication in quickly to try to shorten the exposure of the attacks). When you don't do that, those pain pathways may start out like a dirt road - and maybe then you have lots of long attacks, and then it gets paved, and then it becomes a highway." I find it's a useful way to help families understand the concept of pain chronification and why we want them to treat attacks. The same thing goes for undertreatment on the preventive side. If you know a youth is having frequent attacks that are impacting their life and their ability to function, we really should be thinking about a daily preventive treatment, because we know that pill-based interventions will result in a significant reduction in headache frequency in at least two-thirds of youth - and again, allowing the youth to have frequent attacks contributes to that pain chronification (and explain it to families in a similar way to what I just explained for acute treatment) - but there can be a lot of hesitancy to engage with pill-based treatments, even though we know that they can be helpful. Dr Weathers: I think that's a really powerful point - and I think something we also, frankly, probably tend to do on the adult side as well – but, especially, I could see where there's even probably more hesitancy in children and adolescents (this concern that we're going to overtreat them and then end up inadequately treating, which leads to increased problems). And also goes back to the concept you were talking about earlier about the importance of shared decision-making and really engaging with the patient and their families in the discussion early on to help avoid that, as well to have everybody aware of the benefits and the side effects of all of the different options, I think is so critical. I was also really excited to see you (in the article) write about the importance of a trauma-informed care approach. This is an area I'm really passionate about in my work as a clinical informaticist and how we can leverage the electronic health record to support trauma-informed care and raising awareness of what a patient's triggers may be. Can you explain to our listeners who may not be knowledgeable about this approach what it means, and why you think that this might be applicable to children adolescents with headache? Dr Orr: Thanks for bringing that up. I think it's really important as well. We've done some work in my lab (and many others have as well) to show that there's a relationship between adverse childhood experiences and the development of headache disorders in youth and adults. By adverse childhood experiences, I mean exposure to highly stressful (like toxic stress) environments in early childhood, such as experiencing death of a parent, divorce, abuse, neglect. So, we know that adverse childhood experiences are associated with higher risk of developing migraine and headache disorders, and knowing that and how common these are amongst our patients - really think it's important to advocate for screening all children, adolescents coming in with recurrent headaches for adverse childhood experiences and exposure to trauma, because it really will impact not only how you interact with the patient, but also potentially what you will screen them for on the mental health side. And so providing trauma-informed care, I think - of course we want it to be targeted - but really taking this approach with all patients is actually a good way to think about it, because trauma is very common in our society, and some of the ways that we've measured trauma in the past (like some of the examples that I gave, divorce, death of a parent) are really narrow and don't encompass broader aspects of trauma (like systemic racism and other things that people are experiencing that haven't been adequately measured). So what trauma-informed care is - you know, there's a few core aspects, and one is screening all patients for trauma. The way I do that in clinic is just asking them if they've had any major stressful life events (and then I give a few examples), but there are standardized questionnaires that can be used for this as well. And then really trying to develop a nurturing rapport with the patient - an open listening strategy, asking open-ended questions, being empathic with patients and families - I know we all try to do this, anyway, but really focusing on that, especially in the context of trauma. And then thinking carefully about not only how you're talking to the patient, but how you're approaching them during the physical exam (so, for example, asking permission before touching the patient rather than just diving into the exam to be sensitive to that). And then also recognizing, like I said, that some of the ways that we've conceptualized trauma have been a little bit narrow, and that trauma may occur in context outside of what we traditionally think of. Dr Weathers: Again, I think that's so important and could be certainly much more broadly applied than even just to this one field, but thrilled to see that you're incorporating it into your work and your research (and again, it was discussed in the article) - and, absolutely, I think that the more that we incorporate it as well here, I think, that the better off for all of our patients and the improved care we provide. Moving on from that, I always like to end my interviews on a positive and hopeful note, and so I'd love to hear from you what you're most excited about in the field of pediatric headache. What breakthroughs do you think are coming, or what's giving you the most hope? Dr Orr: There's so much, there's so much exciting stuff going on in our field (and so, you know, I'll have to rein in myself in here), but one thing is there's been an explosion of novel treatment options on the adult migraine side in the last five to ten years, including agents targeted at the CGRP pathway, calcitonin gene-related peptide, some monoclonal antibodies, and receptor antagonists. There's been an explosion of neuromodulation options with now five devices that have various levels of FDA clearance for use in adults and/or youth with migraine. And there are, for most of these devices and novel drugs, either published studies or ongoing research into how they may be used in youth, so I'm hopeful that we will have more treatment options that are evidence based for youth going forward. This is in part due to the Pediatric Research Equity Act that came out a couple of decades ago now that has put requirements for pediatric studies when new drugs are approved by the FDA for adults - so I think that has had an impact, and I'm hopeful that we'll have an expanded treatment landscape in the years to come. There's also a lot of really exciting, more kind of fundamental research going on that I think will help us move the pediatric field forward more rapidly. In the past, we have really often borrowed from what the adult neurologists are doing for adults with headache disorders without really understanding some of the fundamental biological and psychosocial differences between headache disorders onset in youth versus adulthood, and so there is more and more research going on to understand the biology of migraine in youth and some of the risk factors at this age and some of the features that may make youth a little bit different, because it's very rare that youth are just little versions of adults for any disease or problem. And then, you know, I've seen a really large expansion in the number of trainees who are interested in headache medicine since I've entered this field (I've even got one of our residents who's going to do a headache fellowship, which is exciting), and seeing the growth and interest in headache medicine and the number of people being trained really gives me a lot of hope for the future, because there's so much work to be done in this area, and, really, that's where we're going to have the largest impact - is in mentoring and fostering the next generation of headache neurologists. So, there's lots of reasons to be excited, and I would say to the trainees listening that if you want an exciting career where there's lots of opportunity to make impact both clinically on your patients and in terms of educating the next generation and spearheading research initiatives, headache medicine is for you. Dr Weathers: I think that is incredibly inspiring and will hopefully get a lot of our listeners excited about joining this incredible field. Well, thank you for, again, this great article and for all of your time this evening, I've learned so much and really enjoyed speaking with you. Dr Orr: Thank you. Likewise, it was great to have this opportunity. I really enjoyed it. Dr Weathers: Again, today, we've been interviewing Dr. Serena Orr whose article on pediatric headache appears in the most recent issue of Continuum on headache. Be sure to check out Continuum Audio podcasts 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.