Podcast appearances and mentions of Gordon Smith

The inflammatory and infectious optic neuropathies are a broad, heterogeneous, and common group of diseases producing visual loss. Although many now-distinct syndromes have been previously combined as “typical or atypical optic neuritis,” recent developments highlight the importance of precision terminology as well as an individualized evaluation and treatment approach. In this episode, Gordon Smith, MD, FAAN speaks with Eric Eggenberger, DO, MS, FAAN, author of the article “Optic Neuritis” in the Continuum® April 2025 Neuro-ophthalmology issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Eggenberger is a professor of ophthalmology, neurology, and neurosurgery at the Mayo Clinic in Jacksonville, Florida. Additional Resources Read the article: Optic Neuritis 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 Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: This is Dr Gordon Smith. Today I'm interviewing someone who really needs no introduction, Dr Eric Eggenberger, about his article on optic neuritis, which appears in the April 2025 Continuum issue on neuro-ophthalmology. Eric, welcome to the podcast, and maybe you can introduce yourself to our audience. Dr Eggenberger: Thank you. Thanks for having me. So, my name is Eric Eggenberger. I work at Mayo Clinic Florida, and I am involved exclusively in neuro-ophthalmology. Dr Smith: I just had the pleasure, Eric, of talking yesterday with Lindsey De Lott about non-optic neuritis causes of optic neuropathy. And so, I'm going to kind of reference a little bit what I learned yesterday. She was great. I wonder if you might begin by talking a little bit about nomenclature. You talk about the need for use of precise terminology in your article. And yesterday she taught me a lot about the risk of misdiagnosis and other causes of optic neuropathy, and the two seem related. So, I wonder if you can maybe lay the foundation for our conversation by talking about terminology? Dr Eggenberger: I think that's a great point. So, we are in an era now where, instead of lumping all these different diagnoses together, we have learned to split apart some of these clinical entities. And so, I think it's really important that we focus on precise terminology and recognize that all optic neuritis is not the same. And we have very different, distinct clinical pathways for these imaging pathways, treatment pathways, for these different types of optic neuritis, whether that's MS related, whether it's MOG related or aquaporin-4 related. Dr Smith: So, I wonder maybe we can begin by just, you know, giving our listeners wisdom, pearls, and pitfalls about, how do you recognize when someone with a suspected optic neuropathy has optic neuritis versus a noninflammatory optic neuropathy? Dr Eggenberger: So, that's a really important issue because there's a lot of clinical overlap in terms of exam findings. So, for instance, in any optic neuropathy, let's say it's unilateral, you typically are going to see decreases in acuity and field and color, and you're going to see a relative afferent pupillary defect. And then it's really the context that that occurs in that helps us distinguish different disease entities. So, with optic neuritis, typically you're going to have pain. And that's oftentimes going to be in the younger populations compared to some of the other common optic neuropathies we see, like ischemic optic neuropathy, for instance. Dr Smith: Right. So maybe we can talk a little bit about, kind of, your overall diagnostic approach, right? A lot of this is, of course, based on age and context, but young people get ischemic lesions and older people can have inflammatory lesions. So, what's your overall approach to the patient you just described? Let's say it's a forty-eight-year-old woman who comes to the emergency department with subacute unilateral vision loss and there's dyschromatopsia, APD, reduced acuity. And, you know, let's just say a fairly, you know, benign-looking fundoscopic exam. What do you do to evaluate that patient? Dr Eggenberger: In that particular context, I think we're looking at other contextual clues. Is there other vascular risk factors or other things to point you in one direction or the other? One of the important parts you mentioned was the fundus exam. So, we know with ischemic optic neuropathy, 100% of the time with AIOM, you're going to see disc edema. And so, in the context of that story, we want to confirm on our exam an optic neuropathy, and then we can kind of focus on the retrobulbar courses or different types of optic neuropathies. From an exam perspective, in that particular patient we'd be looking to measure the acuity, quantify that. And in the ER, you're not going to be able to do a perfect field, but you'll get some sense of the field and how much field loss there is. And then as you mentioned, the afferent pupillary defect is critical. And we're going to get a little bit of the historical features in terms of pain. With typical retrobulbar optic neuritis, most of those patients are going to experience some pain, and usually it's pain on eye movements. And those would be the clinical things to focus on. Other exposures the patient may or may not have had, any other concomitant conditions, would all help point you in different directions, perhaps, and then we're probably on towards imaging. Dr Smith: Yeah, maybe you can talk a little bit about that? What's the appropriate use of imaging? I mean, presumably the patients, like the one I just threw out there, are pretty much all going to get neuroimaging. What's your approach to that? How do you protocol the study? What should we be looking for? Dr Eggenberger: In our clinic, we would typically be ordering an MRI orbit and brain, and each of those has a specific purpose. The orbit is going to show us the extent of the optic neuropathy. So, we're particularly looking for a longitudinally extensive optic nerve lesion or more than half of the optic nerve involved. And most patients acutely, if it isn't an “itis" situation, we'll see enhancement. And then the MR brain is going to be useful for looking for other evidence of demyelination within the central nervous system. We may at some point get down to doing an MR cord, but I think acutely it's going to be brain and orbit that most of our patients are getting. Dr Smith: Let's say that we did the scan and, sure enough, there's sort of a shorter segment, so less than half the length of the nerve region of enhancement. What's the rest of your diagnostic evaluation look like for that patient? Dr Eggenberger: So, in that particular case, we would look at the remainder of the brain. So, we're looking for other evidence of demyelination and any other contextual clues, systemically that would point you one direction or another. But with a shorter segment involved, one of the more common things we might encounter would be multiple sclerosis-related optic neuritis. Dr Smith: Would you look for aquaporin-4 and MOG in a patient with what appears to be an isolated, uncomplicated short segment optic neuritis? Dr Eggenberger: So, I think it really depends a bit on the context. I would never fault anybody for looking at MOG or an aquaporin-4 in that context because those are really treatment-altering diagnoses, but the yield in this particular case with a short segment involved and depending on the acuity and other features is probably going to be pretty low. Dr Smith: I really liked as an aside- I wasn't going to go there next, but you kind of got me thinking about it, you have a really nice section in your article. Which, all of it's great, but talking about how to manage low titer MOG antibodies. I wonder if you could talk about that because I think that's a lesson, maybe, that is transferable to a lot of other testing that we do. in terms of pre-prior probability and titer and so forth. Dr Eggenberger: Yeah, that's really an important point. So, we've seen this come up a number of times where the MOG antibody is a very good test, but in low titer it has a relatively low positive predictive value, perhaps 50%. In those cases, particularly without a classic clinical context, you have to be extremely alert for some other diagnosis that could mimic what you think is inflammatory demyelinating optic neuritis, but in fact is infectious or some other cause. Dr Smith: Yeah, super, super important and helpful. In terms of aquaporin-4, how does that compare in terms of predictive values, lower titer positive results? Dr Eggenberger: So aquaporin-4, the test has a very high specificity. So, it's quite useful if positive. You have to keep in mind there can be some false negatives, but the test otherwise is quite specific. And that is a diagnosis, you know, we never want to miss. It's a vicious disease. It tends to be a blinding disease, particularly without treatment. Bad things happen when we miss that, and we want to get on that diagnosis early and do pretty aggressive early and prophylactic treatment. Dr Smith: Your article covers not only the common causes of optic neuritis and, you know, MS, isolated optic neuritis, MOGAD NMO, you talk about a bunch of other things. I wonder, in this patient that we've been discussing, in the absence of any other historical information that seems relevant---or maybe you can define what would seem relevant---would you do other evaluation in that individual, other serologic evaluation and so forth, just in terms of diagnosis? Dr Eggenberger: In that particular case, without other red flags, I don't think I would initially. And follow-up is going to give you a lot of this context. So, you'd be on the lookout for other systemic conditions. So, if the patient had some arthropathy, if the patient had any pulmonary disease hints, if there was anything else that could lead you on a broader expedition. But I think in the context of this case, acutely in the ER, I probably wouldn't do a big lab plug for this. I probably would kind of go down the most likely road and start our treatments, and then follow that patient up. Dr Smith: Yeah, I know your article does a really great job, I think, of outlining when do you need to think about some of these less common causes. Well, can we talk about treatment, Eric? Because I want to move on to some other things. But- so, we've got a patient with isolated optic neuritis, nothing else, you know, in terms of the other antibodies we've talked about. What state-of-the-care- or, state-of-the-art treatment for that patient? Dr Eggenberger: So, the acute treatment for these inflammatory, optic neuritis-type cases is very similar Initially. High dose steroids remains kind of the standard. And then, in MS-related optic neuritis, we may or may not see a taper. So many times it's just an acute treatment of three to five days high dose. Whether that's oral or PO, we could institute either depending on the particular case. And then the taper would depend on the potential cause. So, for instance, with these antibody-driven diseases---so with MOG- or particularly with aquaporin-4---if it's a longitudinally extensive region of optic nerve involved, we tend to use a longitudinally extensive taper. And so, we use prednisone in those cases for several months while we're getting everything else set and deciding what the overall course is going to bring. Dr Smith: What about IV versus oral? There must be something about my practice. I was telling this to Lindsey. Every time on our hospital service, we seem to have at least two patients with optic neuropathies, which I always enjoy, but I find it's a little weird to admit someone who's doing just fine otherwise to the hospital with three days of IV SOLU-MEDROL. So, I'm always trying to figure out, like, how can I get this patient home? And your article had the best term I've heard in a long time, which is “SOLU smoothies.” I mean, are there other strategies that you sometimes use, other than just high-dose IV methylprednisolone? Dr Eggenberger: So, I agree with you. It's sometimes hard to admit somebody for just an IV therapy. And we'll do this as an outpatient, high-dose IV, but we'll also use high-dose orals. And in times in the past when there's been methylprednisolone shortage, we've used high-dose oral or IV dexamethasone as well. I think the IV form, although it's the gold standard, the high-dose oral forms have pretty equivalent bioavailability and are pretty tolerable in my experience. And certainly more convenient. Dr Smith: I wonder if we should switch and maybe talk a little bit about aquaporin-4, I mean, you emphasized that this is a vicious disease---I love the way you describe that---and often blinding. What updates do you have in terms of our therapeutic approach to NMO? That's been rapidly evolving of late. Dr Eggenberger: Right, so these are cases we're always going to share with neuroimmunology. And it requires kind of a multidisciplinary approach, in my opinion, for ideal or for best outcomes. And so, all of these patients are going to get put on prophylactic medications. So, this is a disease you just can't leave untreated. Bad stuff will happen for sure. And we now, fortunately, have some approved, FDA-approved medications that can positively impact the course of this disease. So, that's been a welcome addition. Dr Smith: What are the FDA-approved medications at this point for NMO? Dr Eggenberger: So, there are several at this point, and this is an area that's in growth, fortunately. And again, these are cases we're going to be sharing with our neuroimmunology colleagues. So, these are IV medications typically aimed at complement or CD19. And they all are relatively effective at quieting the course of the disease. Dr Smith: Maybe we can talk a little bit about MOG? I think that most of our listeners are probably pretty familiar with aquaporin-4 and NMO, what- maybe you could describe MOG a little bit and the therapeutic approach for patients with MOG-associated disease? Dr Eggenberger: So, MOG has been a real interesting kind of condition to learn more about. We certainly see a lot of MOG, and I'm sure we saw MOG before it was formally described, but I think we just thought it was kind of a benign, maybe monophasic MS type of presentation. But MOG tends to come in with a loss of acuity that kind of rivals aquaporin-4. So, the acuity tends to be pretty, pretty depressed, but it's very steroid-responsive. So, a lot of times these are the patients, you'll see that their vision will start to improve even when they're on the initial few days of the high-dose steroids. And many times we can get their vision back to 20/20 or very close to that. Dr Smith: And do these patients need chronic management? Dr Eggenberger: So, that's an area of controversy to some degree. About 50% of the optic neuritis MOG-related cases are going to have a relapsing course. And because the disease is steroid-responsive, many times we'll follow these patients after a first attack to see if this is the condition that's going to declare itself to be relapsing or if this is just going to be a monophasic kind of presentation of optic neuritis. We don't have great biomarkers to separate patients who are going to be in that 50% monophasic course versus the other half. It'll be relapsing. And so, it depends on the patient. If there's somebody that's, as many of these patients are, been very steroid responsive, they get back to 20/20, we can teach them about the disease so that if they do have a relapse, we can get them high-dose steroids in a relatively rapid fashion and they're otherwise healthy, we're probably going to watch that patient. And if it's somebody that doesn't recover 100%, there's other issues with treating them with high-dose steroids potentially in the future, then we may learn more towards an earlier prophylactic approach in that patient. Dr Smith: And what would that approach look like? Is it different from NMO or using more IVIG or B cell depletion as opposed to complement inhibition, for instance? Dr Eggenberger: In MOG, we know that the B cell depletion strategies don't work as well. And so most times we're turning to IVIG, and we found that pretty effective. That's kind of our go-to at this point. Dr Smith: Eric, it's a joy talking to you and I'd love to keep going about content, but I'll refer our listeners to your outstanding article. I mean, you're such a highly regarded neuro-ophthalmologist and educator. I wonder if you could talk to us about why you've done neuro-ophthalmology, and maybe this is an opportunity for you to convince all of our great residents that are listening or students what's great about being a neuro-ophthalmologist. Dr Eggenberger: I think neuro-ophthalmology is by far the most interesting part of neurology. So, it's an area that I think a lot of general neurologists, in my view, don't get enough of in their residency. But it's kind of the essence of neurology, where in neurology you're localizing down to the millimeter and in neuro-ophthalmology,  we're localizing down to the micron level. We have several new emerging diseases like these varieties of optic neuritis we're focused on. We're learning lots about those. You get to be involved in lots of different areas of neurology. So, we'll see not just demyelinating conditions, we'll see trauma as it relates to the visual system. And we'll see tumor, and we see all different flavors, stroke, and in any piece of neurology, commonly we'll have some vision aspect that we that we get involved in. So, we see a wide variety of conditions. So, I think it's been a really exciting place to be within neurology. And it's rapidly changing at this point. We're getting new therapeutics. So, it's, I think it's a great time to be a neuro-ophthalmologist. Dr Smith: Yeah, listening to you talk and just reflecting on it, it's really true. Neuro-ophthalmology does cover the entire span of neurology, right? I'm a neuromuscular guy and we see a lot of ocular myasthenia, which is another super exciting area. But we've been talking about optic neuritis, and your article talks about infectious causes and the paraneoplastic and a whole host of things. So, you're a great advocate and salesperson for your field. You convinced me. Dr Eggenberger: Efferent neuro-ophthalmology we love, we could talk about ocular myasthenia and other aspects for another hour. And we get involved in all kinds of cases: third nerve palsies, ocular myasthenia, trauma that involves the efferent system, all different aspects. It's really a great subspecialty, and you get to see a bit of all of neurology. Dr Smith: I'm trying to remember who it was, Eric. It was an attending of mine at medical school. I went to medical school at the Mayo Clinic in Rochester, and I want to say it was Manny Gomez, who was a very famous tuberous sclerosis person, who told me that neuro-ophthalmology was the most elegant specialty within neurology. That stuck with me. Thank you so much for joining me today. I really appreciate it. Dr Eggenberger: Thank you. I appreciate it as well. Dr Smith: So again, today I've been interviewing Dr Eric Eggenberger about his really wonderful article on optic neuritis, which appears in the most recent issue of Continuum on neuro-ophthalmology. Be sure to check out Continuum audio episodes from the neuro-ophthalmology 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 practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

Optic neuropathies encompass all congenital or acquired conditions affecting the optic nerve and are often a harbinger of systemic and central nervous system disorders. A systematic approach to identifying the clinical manifestations of specific optic neuropathies is imperative for directing diagnostic assessments, formulating tailored treatment regimens, and identifying broader central nervous system and systemic disorders. In this episode, Gordon Smith, MD, FAAN speaks with Lindsey De Lott, MD, MS, author of the article “Optic Neuropathies” in the Continuum® April 2025 Neuro-ophthalmology issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. De Lott is an assistant professor of neurology and ophthalmology at the University of Michigan in Ann Arbor, Michigan. Additional Resources Read the article: Optic Neuropathies 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: @lindseydelott Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: Hello, this is Dr Gordon Smith. Today I'm interviewing Dr Lindsey De Lott about her article on optic neuropathies, which appears in the April 2025 Continuum issue on neuro-ophthalmology. Lindsey, welcome to the podcast, and perhaps you can introduce yourself to our audience. Dr De Lott: Thank you, Dr Smith. My name is Lindsey De Lott and I am a neurologist and a neuro-ophthalmologist at the University of Michigan. I also serve as the section lead for the Division of Neuro-Ophthalmology, which is actually part of the ophthalmology department rather than the neurology department. And I spend a good portion of my time as a researcher in health services research, and that's now about 60% of my practice or so. Dr Smith: I'm super excited to spend some time talking with you. One, I'm a Michigan person. As we were chatting before this, I trained with Wayne Cornblath and John Trobe, and it's great to have you. I wonder if we maybe can begin- and by the way, your article is outstanding. It is such a huge topic and it was actually really fun to read, so I encourage our listeners to check it out. But you begin by talking about misdiagnosis as being a common problem in this patient population. I wonder if you can talk through why that is and if you have any pearls or pitfalls in avoiding it? Dr De Lott: Yeah, I think there's been a lot of great research looking at misdiagnosis in specific types of optic neuropathies; in particular, compressive optic neuropathies and optic neuritis. A lot of that work has come out of the group at Emory and the group at Washington University. But a lot of neuro-ophthalmologists across the country really contributed to those data. And one of the statistics that always strikes me is that, you know, for example, in patients with optic nerve sheath meningiomas, something like 70% of them are actually misdiagnosed. And a lot of those errors in diagnosis, whether it's for compressive optic neuropathy or some other type of optic neuropathy, really comes down to the way that physicians are really incorporating elements of the history in the physical. For example, in optic neuritis, we know that physicians tend to anchor pretty heavily on pain in general. And that often tends to lead them astray when optic neuritis was never the diagnosis to begin with. So, it's really overindexing on certain things and not paying attention to other features of the physical exam; for example, say presence of an afferent pupillary defect. So, I think it just really highlights the need to have a really relatively structured approach to patients that you think have an optic neuropathy when you're trying to sort of plan your diagnostic testing and your treatment. Dr Smith: I do maybe five or six weeks on our hospital service each year, and I don't know if it's just a Richmond thing, but there's always at least two people in my week who come in with an optic neuropathy or acute vision loss. How common is this in medical practice? Or neurologic practice, I should say? Dr De Lott: Optic neuropathies themselves… if you look across, unfortunately we don't have any great data that puts together all optic neuropathies and gives us an actual sort of prevalence estimate or an incidence estimate from year to year. We do have some of those data for specific types of optic neuropathies like optic neuritis and NAION, and you're probably looking around five-ish per one hundred thousand. So, these aren't that common, but at the same time they do get funneled to- often to emergency rooms and to neurologists from our ophthalmology colleagues and optometry colleagues in particular. Dr Smith: So, one other question I had before kind of diving into the topic at hand is how facile neurologists need to be in recognizing other causes of acute visual loss. I mean, we see acute visual loss as neurologists, we think optic neuropathy, right? Optic neuritis is sort of the go-to in a younger patient, and NAION in someone older. But what do neurologists need to know about other ophthalmologic causes? So, glaucoma or acute retinal disorders, for instance? Dr De Lott: Yeah, I think it's really important that neurologists are able to distinguish optic neuropathies from other causes of vision loss. And so, I would really encourage the listeners to take a look at the excellent article by Nancy Newman about vision loss in this issue where she really kind of breaks it down into vision loss that is acute and chronic and how you really think through distinguishing optic neuropathies from other causes of vision loss. But it is really important. For example, a patient with a central retinal artery occlusion may potentially be eligible for treatments. And that's very different from a patient with optic neuritis and acute vision loss. So, we want to be able to distinguish these things.  Dr Smith: So maybe we can pivot to that a little bit. Just for our listeners, our focus today is going to be on- not so much on optic neuritis, although obviously we need to talk a little bit about how we differentiate optic neuritis from non-neuritis optic neuropathies. It seems like the two most common situations we encounter are ischemic optic neuropathies and optic neuritis. Maybe you can talk a little bit about how you distinguish these two? I mean, some of it's age, some of it's risk factors, some of it's exam. What's the framework, of let's say, a fifty-year-old person comes into the emergency room with acute vision loss and you're worried about an optic neuropathy? Dr De Lott: The first step whenever you are considering an optic neuropathy is just making sure that the features are present. I think, really going back to your earlier question, making sure that the patient has the features of an optic neuropathy that we expect. So, it's not only vision loss, but it's also the presence of an apparent pupillary defect in a patient with a unilateral optic neuropathy. In a person who has a bilateral optic neuropathy, that apparent pupillary defect may not be present because it is relative. So, you really would have to have asymmetric vision loss between the two eyes. They should also have impairment of their color vision, and they're probably going to have some kind of visual field defect, whether that's central scotoma or an arcuate scotoma or an altitudinal defect that really respects the horizontal meridian. So, you want to make sure that, first and foremost, you've got a patient that really meets most of those- most of those features. And then from there, we're looking at the other features on their history. How acute is the onset of the vision loss? What is the progression over time? Is there pain associated or not associated with the vision loss? What other medical issues does the patient have? And you know, one of the things you already brought up, for example, is, what's the age of the patient? So, I'm going to be much more hesitant to make a diagnosis of optic neuritis in a much older patient or a diagnosis on the other side, of ischemic optic neuropathy, in a much younger patient, unless they have really clear features that push me in that direction. Dr Smith: I wonder if maybe you could talk a little bit about features that would push you away from optic neuritis, because, I mean, people who are over fifty do get optic neuritis- Dr De Lott: They do. Dr Smith: -and people who get ischemic optic neuropathies who are younger. So, what features would push you away from optic neuritis and towards… let's be broad, just a different type of optic neuropathy? Dr De Lott: Sure. We know that most patients with optic neuritis do have pain, but that pain is accompanied---within a few days, typically---with vision loss. So, pain alone going on for a number of days without any visual symptoms or any of those other things I listed, like the afferent papillary defect, the visual field defect, would push me away from optic neuritis. But in general, yes, most optic neuritis is indeed painful. So, the presence of optic disc edema is unfortunately one of those things that an optic neuritis may be present, may not be present, but in somebody with ischemia that is anterior---and that's the most common type of ischemic optic neuropathy, would be anterior ischemic optic neuropathy---they have to have optic disc edema for us to be able to make that diagnosis, and that is a diagnosis of NAION, or nonarteritic ischemic optic neuropathy. An APD in this case, again, that's just a feature of an optic neuropathy. It doesn't really help you to distinguish, individual field defects are going to be relatively similar between them. So then in patients, I'm also looking, like I said, at their history. So, in a patient where I'm entertaining a diagnosis of ischemic optic neuropathy, I want to make sure that they have vascular risk factors or that I'm actually doing things like measuring their blood pressure in the office if they haven't seen a physician recently or checking a lipid panel, hemoglobin A1c, those kinds of things, to look for vascular risk factors. One of the other features on exam that might push me more- again, in a patient with ischemic optic neuropathy, where it might suggest ischemia over optic neuritis, would be some other features on exam like a crowded optic disc that we sometimes will see in patients with ischemic optic neuropathy. I feel like that was a bit of a convoluted answer. Dr Smith: I thought that was a great answer. And when you say crowded optic disc, that's the- is that the “disc at risk”? Dr De Lott: That is the “disk at risk,” yes. So, crowded optic disk is really a disk that is smaller than what we see in the average population, and the average cup to disk ratio is 0.3. So, I think that's where 30% of the disk should be. So, this extra wiggle room, as I sometimes will explain to my patients. Dr Smith: And then, I wonder if you could talk a little bit about more- just more about exam, right? You raised the importance of recognizing optic disc edema. Are there aspects of that disc edema that really steer you away from optic neuritis and towards ischemia-like hemorrhages or whatnot? And then a similar question about the importance of careful visual field testing? Dr De Lott: So, on the whole, optic disc edema is optic disc edema. And you can have very severe optic neuritis with hemorrhages, cotton wool spots, which is essentially just an infarction of the retinal nerve fiber layer either overlying the disc or other parts of the retina. And ischemia, you can have some of the same features. In patients who have giant cell arteritis, which is just one form of anterior ischemic optic neuropathy, patients can have a pallid optic disc edema where the optic disc is swollen and white-looking. But on the whole, swelling is swelling. So, I would caution anyone against using the features of the optic nerve swelling to make any type of, sort of, definitive kind of diagnosis. It's worth keeping in mind, but I just- I would caution against using specific features, optic nerve swelling. And then for visual field testing, there are certain patterns that sometimes can be helpful. I think as I mentioned earlier, in patients with ischemic optic neuropathy, we'll often see an altitudinal defect where either the top half or, more commonly, the bottom half of the vision is lost. And that vision loss in the field corresponds to the area of swelling on the disk, which is really rewarding when you're actually able to see sectoral swelling of the disk. So, say the top half of the disk is swollen and you see a really dense inferior defect. And other types of optic neuropathy such as hereditary optic neuropathies, toxic and nutritional optic neuropathies, they often cause more central field loss. And in patients who have optic neuropathies from elevated intracranial pressure, so papilladema, those folks often have more subtle visual field loss in an arcuate pattern. And it's only once the optic nerves have sustained a pretty significant injury that you start to see other patterns of field loss and actual decline in visual acuity in those patients. I do think a detailed visual field assessment can often be pretty helpful as an adjunct to the rest of the exam. Dr Smith: So, we haven't talked a lot about neuroimaging, and obviously, neuroimaging is really important in patients who have optic neuritis. But how about an older patient in whom you suspect ischemic optic neuropathy? Do those patients all need a MRI scan? And if so, is it orbits and brain? How do you- how do you protocol it? Dr De Lott: You're asking such a good question, totally controversial in in some ways. And so, in patients with ischemic optic neuropathy, if you are confident in your diagnosis: the patient is over the age of fifty, they have all the vascular, you know, they have vascular risk factors. And those vascular risk factors are things like diabetes, hypertension, high blood pressure, hyperlipidemia, obstructive sleep apnea. They have a “disc at risk” in the fellow eye. They don't have pain, they don't have a cancer history. Then doing an MRI of the orbits is probably not necessary to rule out another cause. But if you aren't confident that you have all of those features, then you should absolutely do an MRI of the orbit. The MRI of the brain probably doesn't provide you with much additional information. However, if you are trying to distinguish between an ischemic optic neuropathy and, say, maybe an optic neuritis, in those patients we do recommend MRI orbits and brain imaging because the brain does provide additional information about other CNS demyelinating disorders that might be actually the cause of a patient's optic neuritis. Dr Smith: I wonder if you could talk a little bit about posterior ischemic optic neuropathy. That's much less common, and you mentioned earlier that those patients don't have optic disk edema. So, if there's a patient who has vision loss that- in a similar sort of clinical scenario that you talked about, how do you approach that and under what circumstances do we see patients who have posterior ischemic optic neuropathy? Dr De Lott: So, you're going to most often see patients with posterior ischemic optic neuropathy who, for example, have undergone a recent surgery. These are often associated with things like spinal surgeries, cardiac surgeries. And there are a number of risk factors that are associated with it. Things like blood pressure, drain surgery, the amount of blood loss, positioning of patient. And this is something that the surgeons and anesthesiologists are very sensitive to at this point in time, and many patients are often- this can be part of the normal informed consent process at this point in time since this is something that is well-recognized for specific surgeries. In those patients, though… again, unless you're really certain, for example, maybe the inpatient neurology attending and you've been asked to consult on a patient and it's very clear that they went into surgery normal, they came out of surgery with vision loss, and all the rest of the features really seem to be present. I would recommend that in those cases you think about orbital imaging, making sure you're not missing anything else. Again, unless all of the features really are present- and I think that's one of the themes, definitely, throughout this article, is really the importance of neuroimaging in helping us to distinguish between different types of optic neuropathy. Dr Smith: Yeah, I think one of the things that Eric Eggenberger talks about in his article is the need to use precise nomenclature too, which I plan on talking to him about. But I think having this very structured approach- and your article does it very well, I'll tell our listeners who haven't seen it there's a series of really great tables in the article that outline a lot of these. I wonder, Lindsey, if we can switch to talk about arteritic optic neuropathy. Is that okay? Dr De Lott: Sure. Yeah, absolutely. Dr Smith: How do you sort that out in an older patient who comes in with an ischemic optic neuropathy? Dr De Lott: Yeah. In patients who are over the age of fifty with an ischemic optic neuropathy, we always need to be thinking about giant cell arteritis. It is really a diagnosis we cannot afford to miss. If we do miss it, unfortunately, patients are likely to lose vision in their fellow eye about 1/3 to 1/2 the time. So, it is really one of those emergencies in neuro-ophthalmology and neurology. And so you want to do a thorough review systems for giant cell arteritis symptoms, things like headache, jaw claudication, myalgias, unintentional weight loss, fevers, things of that nature. You also want to check their inflammatory markers to look for evidence of an elevated ESR, elevated C-reactive protein. And then on exam, what you're going to find is that it can cause an anterior ischemic optic neuropathy, as I mentioned earlier. It can cause palette optic disc swelling. But giant cell arteritis can also cause posterior ischemic optic neuropathy. And so, it can be present without any swelling of the optic disc. And in fact, you know, you mentioned one of my mentors, John Trobe, who used to say that in a patient where you're entertaining the idea of posterior ischemic optic neuropathy, who is over the age of fifty with no optic disc swelling, you should be thinking about number one, giant cell arteritis; number two, giant cell arteritis; number three, giant cell arteritis. And so, I think that is a real take-home point is making sure that you're thinking of this diagnosis often in our patients who are over the age of fifty, have to rule it out. Dr Smith: I'll ask maybe a simple question. And presumably just about everyone who you see with a presumed ischemic optic neuropathy, even if they don't have clinical features, you at least check a sed rate. Is that true? Dr De Lott: I do. So, I do routinely check sedimentation rate and C-reactive protein. So, you need to check both. And the reason is that there are some patients who have a positive C-reactive protein but a normal sedimentation rate, so. And vice versa, although that is less common. And so both need to be checked. One other lab that sometimes can be helpful is looking at their CBC. You'll often find these patients with giant cell arteritis have elevated platelet counts. And if you can trend them over time, if you happen to have a patient that's had multiple, you'll see it sort of increasing over time. Dr Smith: I'm just thinking about how you sort things out in the middle, right? I mean, so that not all patients with GCF, sky-high sed rate and CRP…. And I'm just thinking of Dr Trobe's wisdom. So, when you're in an uncertain situation, presumably you go ahead and treat with steroids and move to biopsy. Maybe you can talk a bit about that pathway? Dr De Lott: Yeah, sure. Dr Smith: What's the definitive diagnostic process? Do you- for instance, the sed rate is sky-high, do you still get a biopsy? Dr De Lott: Yes. So, biopsy is still our gold-standard diagnosis here in the United States. I will say that is not the case in all parts of the world. In fact, many parts of Europe are moving toward using other ancillary tests in combination with labs and exam, the history, to make a definitive diagnosis of giant cell arteritis. And those tests are things like temporal artery ultrasound. We also, even though we call it temporal artery ultrasound, we actually need to image not only the temporal arteries but also the axillary arteries. The sensitivity and specificity is actually greater in those cases. And then there's high-resolution imaging of the vessels and the- both the intracranial and extracranial distributions. And both of those have shown some promise in their predictive values of patients actually having giant cell arteritis. One caution I would give to our listeners, though, is that, you know, currently in the US, temporal artery biopsy is still the gold standard. And reading the ultrasounds and the MRIs takes a really experienced radiologist. So, unless you really know the diagnostic accuracy at your institution, again, temporal artery biopsy remains the gold standard here. So, when you are considering giant cell arteritis, start the patient on steroids and- that's high dose, high dose steroids. In patients with vision loss, we use high dose intravenous methylprednisolone and then go ahead and get the biopsy. Dr Smith: Super helpful. And are there other treatments, other than steroids? Maybe how long do you keep people on steroids? And let's say you've got a patient who's, you know, diabetic or has other factors that make you want to avoid the course of steroids. Are there other options available? Dr De Lott: So, in the acute phase steroids are the only option. There is no other option. However, long term, yes, we do pretty quickly put patients on tocilizumab, which is really our first-line treatment. And I do that in conjunction with our rheumatology colleagues, who are incredibly helpful in managing and monitoring the tocilizumab for our patients. But when you're seeing the patients, you know, whether it's in the emergency room or in the hospital, those patients need steroids immediately. There are other steroid-sparing agents that have been tried, but the efficacy is not as good as tocilizumab. So, the American College of Rheumatology is really recommending tocilizumab as our first line steroid-sparing agent at this point. Dr Smith: Outstanding. So again, I will refer our listeners to your article. It's just chock-full of great stuff. This has been a great conversation. Thank you so much for joining me today. Dr De Lott: Thank you, Dr Smith. I really appreciate it.  Dr Smith: The pleasure has been all mine, and I know our listeners will be enjoying this as well. Again, today I've been interviewing Dr Lindsey De Lott about her article on optic neuropathies, which appears in the most recent issue of Continuum on neuro-ophthalmology. Be sure to check out Continuum Audio episodes from this and other issues. I already mentioned Dr Eggenberger and I will be talking about optic neuritis, which will be a great companion to this discussion. Listeners, thank you for joining us today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

Dr. Gordon Smith and Dr. Jennifer Morganroth discuss the trends in thymectomy utilization for myasthenia gravis. References:  https://www.neurology.org/doi/10.1212/CPJ.0000000000200335  

Dr. Gordon Smith talks with Dr. Jennifer Morganroth about the increase in thymectomy procedures following the MGTX trial, the differences in access to these surgeries among various demographic groups, and the growing role of minimally invasive surgical techniques. Read the related article in Neurology® Clinical Practice. Disclosures can be found at Neurology.org.

Dr. Gordon Smith and Dr. Timothy Miller discuss compelling clinical data suggesting that ALS may be a treatable disease for a subset of patients.

Dr. Gordon Smith talks with Dr. Timothy Miller about compelling patient stories and clinical data that highlight the potential for recovery in ALS patients, emphasizing the importance of early intervention and understanding the disease mechanisms. Disclosures can be found at Neurology.org.

Genetic testing plays a key role in the evaluation of epilepsy patients. With the expanding number of choices for genetic tests and the complexity of interpretation of results, genetic literacy and knowledge of the most common genetic epilepsies are important for high-quality clinical practice. In this episode, Gordon Smith, MD, FAAN speaks Sudha Kilaru Kessler, MD, MSCE, author of the article “Epilepsy Genetics,” in the Continuum February 2025 Epilepsy issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Kessler is an associate professor of neurology and pediatrics at Perelman School of Medicine at the University of Pennsylvania and Children's Hospital of Philadelphia in Philadelphia, Pennsylvania. ADDITIONAL RESOURCES Read the article: Epilepsy Genetics 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: @gordonsmithMD Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Smith: Hello, this is Dr Gordon Smith. Today I've got the great pleasure of interviewing Dr Sudha Kessler about her article on epilepsy genetics, which appears in the February 2025 Continuum issue on epilepsy. Sudha, welcome to the podcast and please introduce yourself to our audience. Dr Kessler: Oh, thank you so much. I'm Sudha Kessler. I am a pediatric epileptologist here at the Children's Hospital of Philadelphia and the University of Pennsylvania. Dr Smith: Tell us a little bit about yourself. Are you a geneticist too, or how did you get into this particular topic? Dr Kessler: Yes, I want to emphatically say that I am not a geneticist. I'm not an expert in epilepsy genetics at all. I take care of all sorts of patients with epilepsy. I actually do mostly epilepsy surgery-related care. But this part of epilepsy is, every year, increasingly important to our everyday practice. And I think it's fascinating, often a little daunting. I think I was asked to get involved with this article as a non-expert to help translate from the experts to the rest of us. Dr Smith: We're going to get there, because one of the things you do a really good job of in the article is talking about genetic concepts that are germane to everything we do. And I think you're an expert. You do it in a way that I understood. So, I'd like to get there, but- and this is a really hot area. For instance, I really loved your figure that shows the arc of discovery of genetic causes for epilepsy. It's really breathtaking, something we wouldn't have thought possible that long ago. And it's also a lot to digest. And so, I wonder if maybe we can begin by thinking about a framework and, for instance, you talk about these different groups of disorders. And one that seems to be particularly impacted by this unbelievable A-rated discovery. Our developmental and epileptic encephalopathies, or DEEs. What can you tell our listeners about that group of disorders? Dr Kessler: Sure. I think that, you know, most of what we think about in epilepsy genetics now has to do with disorders that are attributable to changes in a single gene. Genetics is obviously much more complicated than that, but that's still where we are in the stage of discovery. And the graph in the article is definitely one to take a look at because it represents the explosion that we've had in our understanding of single gene disorders leading to epilepsy and related manifestations. The DEEs are a group of disorders where any individual disorder is fairly rare, but as a group they are not that rare, and very impactful because they often cause epilepsy at a very young age. And either as a consequence of seizures or as a consequence of the underlying pathophysiology of that gene change, they are typically associated with really significant developmental impairments for a child 's entire life. Dr Smith: My understanding is that there's therapeutic development going on in this space. So, the early recognition of these genetic testing offers the promise of very impactful treatment---like we now do for SMA, for instance---early in the disease course. Dr Kessler: I think that's right. That's one of the most exciting parts of this field is that so much, just around the corner, for drug development, therapy development in this area. And as you can imagine, with a lot of these disorders, earlier intervention is likely to be much more impactful than later intervention when a lot of the developmental consequences are sort of… you know, when the cat 's already out of the bag, so to speak. Dr Smith: Yeah. So, this is really transformational and something that everyone who takes care of kids with epilepsy needs to know about, it seems. So on the other extreme, I guess, there are the self-limited epilepsies. I didn't really know about this in terms of genetic discovery, but can you talk about those disorders? Dr Kessler: Yeah, sure. I mean, I think some of these are the classic childhood epilepsy syndromes that we think about like childhood absence epilepsy or what we used to call benign romantic epilepsy and now call self-limited epilepsy of childhood with centrotemporal spikes. It's a mouthful, shortened to SeLECTS. Those are the epilepsies that occur typically in previously healthy children, that affects them for a few years and often remits so that epilepsy is just age-limited and doesn't continue for life. They clearly have genetic influences because they tend to run in families, but the genetics of them is not generally single gene associated. And so, we haven't actually explained why most of those kids actually get epilepsy. I think that'll be sort of another interesting area of discovery that will help us even understand some really fundamental things about epilepsy, like, why does this syndrome start at this age and tend to resolve by adolescence? Dr Smith: And the other thing I found interesting is disorders that I might have thought going into it would have a defined genetic cause or some of the disorders that there are not. So JME, for instance, or childhood absence, which is a little counterintuitive. Dr Kessler: It's completely counterintuitive. We call them genetic generalized epilepsies, and we know that they run in families, but we still know so little. I would say of all of the disorders that are mentioned in this article, that is the group where I think we have explained the genetic underpinnings the least well. Dr Smith: Yeah. Isn't that interesting? It's… wasn't it Yogi Berra who said, it's hard to predict things, particularly the future? So… Dr Kessler: Yes. Dr Smith: Who would have thought? So, we've talked a lot about kids. What about adults? You know, what role does genetic testing play in adults who have unexplained epilepsy? Dr Kessler: Yeah, I think that that is also a really important emerging area of knowledge. I think many epileptologists may think of genetic epilepsy as being solely pediatric. There are definitely not how many of these disorders can manifest for the first time in adulthood. Not only that, many of our children with childhood onset epilepsy that is due to a genetic problem grow up to become adults and will then need adult epilepsy care. In order to take care of both of those groups, it's really important for all epileptologists, including those that take care of adults, to have some knowledge of the potential impact of genetic testing. And how do you even approach thinking about it? Dr Smith: The message I guess I'm getting is if our listeners take care of patients with epilepsy, no matter how old those patients are, they need to be familiar with this. And the other message I'm getting is, it sounds like there are a lot of patients who really need genetic testing. And this came through in one aspect of your article that I found really interesting, right? So, what are the recommendations on genetic testing? So, the National Society of Genetic Counselors, as I understand it, said everyone needs genetic testing, right? Which I mean, they're genetic counselors, so. Which is great. In the International League Against Epilepsy, they recommended a more targeted approach. So, what's your recommendation? Should we be testing anyone with unexplained epilepsy, or should we be focusing on particular populations? Dr Kessler: Well, I guess I think about it as a gradation. There are certain populations that really deserve genetic testing, where it is going to be absolutely critical. You know, it's very likely that it will be critical knowledge to their care. If you diagnose somebody with epilepsy and you do imaging and that imaging does not reveal an answer, meaning you don't see a tumor or you don't see an old stroke or some other sort of acquired lesion, the next pillar of testing for understanding underlying etiology is genetic testing. That is the point at which I typically send my patients, and that's whether they're refractory or not. I think in the past some people felt that only patients with refractory epilepsy deserve or require testing. I think the reason why not to limit it to that population is that what's on a person's mind with epilepsy, or a family's mind with epilepsy, is what's going to happen to my child or to me in the future? And if genetic testing can shed some light on that, that will have a huge impact on that person's life. Dr Smith: You've got great cases in your article, which, I just want to give you a compliment. The information and entertainment, frankly, for per page: off the charts. It's not a long article, packed with useful information. And, I mean, some of your cases are great examples of patients who are heading down the surgical epilepsy path and you discovered, nope, there's a genetic cause that really impacted their care. What's the yield, right? The number of patients that you send genetic testing on for epilepsy, what percentage come back positive for a relevant sequence variant that you think is either causing or contributing to their epilepsy? Dr Kessler: That's a great question. I think that is actually still in flux because it depends on the population of patients that are being sent for testing, obviously, and then also on what testing is being done. So, I know in at least one large recent meta-analysis, the overall yield was 17%. And somebody hearing that number might think, oh, that's not very high, but it's actually very comparable to the yield for imaging. And we all do MRIs and patients that have new-onset epilepsy where the yield of MRI testing is about 20%  or so. So, quite comparable. And then with children with DEEs, the yield is much, much higher than that. Dr Smith: So, 17% is actually a really great diagnostic yield. When I think of my yield and doing genetic testing on patients who have an axonal CMT phenotype, right? I mean that's better than what I get. So, good for you. That's exciting. Dr Kessler: It's interesting. I think that maybe an assumption might be that you're working somebody up. You do a genetic test, it reveals a difference, and thus surgery is off the table. It's actually quite different than the head, which is that some results may make surgery be even more “on the table” because you might find a gene that is known to be associated with a propensity to vocal cortical dysplasia, for example. And you may take a good second look at that person's MRI imaging or do other imaging to reveal the MRI invisible vocal cortical dysplasia. Dr Smith: Outstanding point. Let's talk a little more about the genetic testing itself. So, we've got all these genes. We understand when to test. What do you do? For instance, last night I just looked at the company that we use for most of our neuromuscular testing and they have a genetic epilepsy next gen panel with, I don't know, three hundred and twenty genes, right? Do you use that kind of panel? Do you go directly to a whole EXO? What's the right approach? Dr Kessler: Yeah, I think that that is quite dynamic right now, meaning that recommendations seem to change often enough that I rely on help. I have the enormous good luck of working here at CHOP where there is a fantastic epilepsy genetics group that I can easily refer to, and I know not everyone has that resource. The current recommendation is to start with an exome if that is available and is covered by that patient's insurance. When exome is not available, then the next best thing is a gene panel. You know, in recent years there have been a lot of sponsored gene panels, meaning free to the patient, administered by a company that then, you know, has other uses for compiled or grouped genetic data. And I think that as long as all of that can be clearly explained to a patient, and- along with all of the other things so you have to explain to a patient before doing genetic testing, about the pluses and minuses of doing it, I think that you sort of go for the best test you can that's available to that patient. Dr Smith: The sponsored programs can be very, very helpful, particularly from a payer or a patient payment perspective. And so, I guess the lesson there is it's great if you got the resources and CHOP to help you decide, but better to get whatever panel you can get than to do nothing; or, of course, refer to a center if you're not comfortable. Dr Kessler: And also, just know that these things change often enough that if it's been a couple of years and you might want to recheck whether the EXO is available to that patient or whether a gene panel can be sent that includes more than they had eight years ago. Dr Smith: So, are there situations to go to the other extreme where you just do targeted sanger sequencing? Like, just sequence the specific gene of interest?  Dr Kessler: Yeah, absolutely. I'm still a big proponent of thinking clinically about a patient. If there are clues in that patient's history, exam, imaging, anything that gives you some sense of the disorder that this patient might have. And I think a classic example would be tuberous sclerosis. If you see an infant who has new onset spasms, you see hypopigmented macules on their skin and their MRI shows a tuber, you know, also known as a focal cortical dysplasia, then sure, send the targeted sequencing for the TSC1 and TSC2 genes. Dr Smith: And Rett syndrome?  Dr Kessler: And Rett syndrome would be another example. And there are many examples where, if you feel like you have a good sense of what the disorder is, I think it's completely acceptable to send the targeted testing.  Dr Smith: So, I'm going to get further down the rabbit hole and get to from easier to harder. I always get confused about things like chromosomal microarrays or, like, karyotypes and rings and stuff like that. What role do these tests play and what do our listeners need to know about them? Dr Kessler: Yeah, I think that it is really important to have at least some knowledge of what each test can't tell you. I tell my medical students at my residence that all the time. With anything in medicine, you should know what you're asking of a test and what answers a test can tell you and can't tell you. It is baseline knowledge before requesting anything. And if you don't know, then it's best to ask. So, chromosomal microarray is used when you think that there is a large-scale derangement in a bunch of genes, meaning there is a whole section of a chromosome missing---that would be deletion, or that that information is duplicated or is turned around in a, you know, in a translocation. That is what- the kinds of things that that test can tell you. I think of doing a microarray when a child has not just epilepsy and intellectual disability, but also has, for example, other organ systems involved, because sections of chromosome can include many, many, many different genes and it can affect the body in larger ways. That's often when I think about that. So, a child with multiple congenital anomalies. Karyotype, which we think of as the most old-fashioned way of looking at our genes, still has some utility because it is useful for looking at a specific situation where the ends of arm of a chromosome get cut off and get sticky and then stick to each other and make a ring. For example, ring chromosome 20 is a disorder which can cause epilepsy, particularly hard-to-treat frontal lobe epilepsy, and that sometimes doesn't show up until adolescence or even early adulthood. That's just one example of something that karyotype can tell you.  Dr Smith: And it goes without saying, but just to emphasize, these are things that you would miss completely on a next generation panel or a next genome? Dr Kessler: That's correct. Because this isn't about sequencing. This is about large structures. You know, with my patients, it's sometimes, I think, very hard to explain. It's hard enough to explain it to other physicians who aren't in genetics, but it's a whole other undertaking to explain it to families who may not have a lot of literacy about cell biology or genetics or, you know, anything related to that. So, I often rely on analogies. And one analogy I use is that if you're- all of your genetic information is like a book, that book is split into chapters and those are the chromosomes. And you can be missing entire paragraphs or have paragraphs duplicated. And that would be the kind of thing that we would be looking for with the chromosomal microarray with sequencing or, you know, with sequencing, we're looking for spelling of words, and we can look at one word at a time. That would be targeted sequencing. Or we can look at many, many words at a time. And that would be next gen sequencing.  Dr Smith: I just want to say that you are the genetic whisperer. You know, translator. I love it.  Dr Kessler: You can continue using it down to the level of explaining the possibility of a variant of unknown significance, which I think is sometimes difficult to explain. So, I often will say, I know how the word color is spelled: C O L O R. But sometimes in other places it will be spelled C O L O U R and that's still the same word, that's still color. That's just what we would call a population variant. If it is spelled C O M O R, that changes meaning; that is not a word, and that is probably a pathogenic variant. But if it gets misspelled and it's K O L O R, then I'm not sure. Could that be a variant that means something different or not. And so that I would call that a variant of unknown significance, meaning its impact is to be determined. Dr Smith: So, I was going to ask you about variant calling, but you'd beat me to the punch. And that's a great metaphor that I will definitely remember. All right, here's another concept that I think people often find challenging, which is read depth. Can you tell us about reading depth or sequence depth?  Dr Kessler: Yes, hopefully I can. Again, not an expert here, but as I understand it, the way next gen sequencing works is that pieces of DNA are getting read. And the number of times any given nucleotide is read in this process is the read depth. It basically just translates to the number of times the processor, the machinery of doing this, pays attention to anyone site. The reason it's important is that the process by which this reading is done can sometimes result in errors. The greater your depth, the more times something is read, the less likely you are to have a mistake.  Dr Smith: In either direction. So, you're presumably less likely to have a false positive or false negative. Yep, again, very well explained. You know, I've got a lot of other questions I want to ask you, but I do want to be respectful of our listeners' time. I wonder if we could pivot a little bit and just let's go back to where we began. Really exciting time, right? Amazing. And you've been doing this long enough. I'm sure you didn't think when you started that it was going to look like this. What does the future look like? I mean, we talked a little bit about therapeutics, but the world's changing fast. Five, ten years from now, what's your hope for that?  Dr Kessler: Oh, that's such a great question. You know, we are at the point with genetic epilepsies that gene-based therapies, either antisense oligonucleotide-based therapies or viral vector-based gene therapies, are actually now being developed and administered in trial situations to actual patients. And so, it always feels like we're on the cusp, but I think actually now we really are on the cusp of having gene-based therapies for genetic epilepsies. I think that there is still so much to sort out, both from basic scientific point and from a practical administering these things to patients and what are the potential long term consequences.For example, unlike medications, which are therapies that you can stop if there are adverse effects, often administering a gene therapy is a one-and-done thing that can't be retracted. Thinking even about the ethical framework of that and the framework of explaining to patients that we don't know the ten, twenty-year consequences of that, is part of the informed consent process, for example. So, there's still so much work that is going to be transformational, not just from the, you know, the big picture, but from developing all, you know, from going through all of these steps to really make these kinds of therapies a reality. Dr Smith: Well, it's really amazing. And, you know, we're seeing this in multiple different areas in neurology. So, well done. You run the child neurology residency program there, I understand. I try to snoop on people before I talk to them because we haven't met before this. And you're obviously a very a very good educator. Thank you so much for talking with me today. I don't spend a lot of time in epilepsy, but every time I do one of these, I kind of want to go back and do something different because it's such a neat field. Thank you.  Dr Kessler: You're welcome. It was my pleasure.  Dr Smith: Again, today I've been interviewing Dr Sudha Kessler about her article on epilepsy genetics, which is truly outstanding. This article appears in the most recent issue of Continuum on epilepsy. Be sure to check out Continuum audio episodes from this and other issues. And thank you, listeners, for joining us today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

AJ's joined by Gordon Smith to take a spin around the world of soccer. New Atletico Ottawa left-back Brett Levis also joins the program to talk about coming to the CPL

Gordon Smith joins us this week to kick off our run through the season of 1982/83. He talks honestly about his experience at Brighton as a whole, the deal that inspired him to get into football agency, his guitar session with Paul McCartney and of course, the famous FA Cup run, his goal and his miss. If you want to support the podcast or want your episodes without ads and a couple of days earlier then head over to patreon.com/NessunDormaPodcast where you can subscribe for only $3.99 a month. Learn more about your ad choices. Visit podcastchoices.com/adchoices

Informal care partners are essential to the care of people living with dementia, but they often experience significant burden and receive minimal training, support, and resources. Multicomponent interventions can mitigate burden and other negative consequences of caregiving. In this episode, Gordon Smith, MD, FAAN speaks with Angelina J. Polsinelli, PhD, ABPP-CN, author of the article “Care Partner Burden and Support Services in Dementia” in the Continuum® December 2024 Dementia 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. Polsinelli is an assistant professor of clinical neurology at the Indiana University School of Medicine in Indianapolis, Indiana. Additional Resources Read the article: Care Partner Burden and Support Services in Dementia Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @gordonsmithMD Full interview transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Smith: This is Dr Gordon Smith. Today, I've got the great pleasure of interviewing Dr Angelina Polsinelli about her article on care partner burden and support services in dementia. This article appears in the December 2024 Continuum issue, which is on dementia. Ange, welcome to the podcast. And maybe you can begin by just introducing yourself to our audience?  Dr Polsinelli: Yeah. Well, thank you for having me. I'm very excited to be here. I'm Ange Polsinelli. I'm a neuropsychologist at Indiana University School of Medicine, where I work in the Department of Neurology. I also work with the Longitudinal Early Onset Alzheimer's Disease study that's led by Liana Apostolova. And I also do some work with the Outreach, Recruitment and Engagement Core of the Indiana Alzheimer's Disease Research Center. This topic that we're going to talk about today is extremely near and dear to my heart. Dr Smith: Well, thanks for joining me. And of course, IU is a powerhouse for Alzheimer's and basketball, in that order. So, we're really excited to have you. I'd like to get right into it. I'll emphasize, we were chatting a little bit about this, Ange, before we started recording, that your topic today is so important for all of us. And I think, you know, this is a podcast that not only neurologists listen to, but students and, and I think increasingly members of the lay public. And this conversation is going to be very important for neurologists and our neurology learners. But I lost my grandmother to Alzheimer's disease. I lost my uncle just in the last week. So, this touches all of us. So, I'm really excited. And then with that in mind, I wanted to begin with a statistic that- you can correct me if I misunderstood it, but it really blew my mind. And that is across the world, as I understand it, care partners provide one hundred and thirty three billion hours of care for people living with dementia yearly, which is pretty staggering. But what's really amazing is that by 2030 that number is expected to go to one point four trillion hours, which I couldn't grab my mind around it. So, I figured I'd try and determine how many years of person work is that and if my math is right, that's almost a hundred and sixty million person years of worth caring for people with dementia yearly across the world. One, are those numbers right? Did I get it right? And then, assuming so, can you put a human face or experience to these numbers?  Dr Polsinelli: Yeah, unfortunately those numbers are correct. And with our increasing aging population across the world, that's why you're getting that, you know, exponential increase in care per hours, compounded by the fact that the majority of the caregiving that happens is not done by doctors, physicians, but it's done by these informal care partners, these family members, these friends, these siblings, children, who are providing these really important services and unfortunately not being trained to do this, doing it largely on their own in a lot of respect. But again, these are people who are loved ones of the person living with dementia. There are a variety of kinships, as I mentioned, siblings, children, spouses, friends; and all sorts of age ranges as well. A large majority of them being spouses, and then the second largest majority being children. So, kind of a sandwich generation of people who are caring for parents with Alzheimer's or dementia and then caring for children as well. Dr Smith: Yeah, I was actually struck by the statistic that a quarter of caregivers or so called sandwich caregivers; in other words, they're taking care of a parent and a child. But listen to what you said. But just to call it out, two-thirds of care partners are women, which is a striking statistic.  Dr Polsinelli: Absolutely. Women are not only more likely to have dementia, but they are also more likely to be the care partners of somebody who has dementia. And so, the research shows, too, that if you're a care partner, you're at higher risk of developing dementia yourself. So, there's a lot of risk for women when it comes to dementia, development of dementia, but also that the burden and the majority of care needs that are that are supported by women as well. Dr Smith: Right. And there's a lot to unpack in that observation, and maybe we can come back to that. But I wonder if you might talk to us a little bit about the risk of dementia in women caregivers. That's really striking. Is there any thought regarding mechanism for that? Why is that the case? Is it a shared risk factor? Is it cause and effect? What's the story?  Dr Polsinelli: So, there are - this is kind of a dissociable or different - kind of two aspects to this, this question. There's the fact that women are at higher risk for developing dementia in general. I think the researchers feel sort of out about why exactly that is. It's not just that women are at higher risk or more likely to develop dementia because they're living longer than men, but there's probably some hormonal aspects of their higher risk factor for dementia. But then there's the other aspect of it too, is that as caregivers, caregivers are at higher risk of developing dementia. And because caregivers tend to be women, that increases or compounds the risk for women as well. We know with caregiving, particularly with someone who's living with dementia, there's more risk of developing things like depression, high stress, health problems, psychological distress, and all of these things increase somebody 's risk for developing dementia as well. Dr Smith: So, I wonder if you might talk a little more, Ange, about what you mean by burden? I think we have in our mind what that is. But in reading your article, there's a lot of- a lot more to it than may meet the eye. Dr Polsinelli: Yeah, it is a more complicated, I guess, topic or terminology that's gone through several iterations over the course of doing research into burden. But when we think about burden, it's really a kind of a combination of both objective experiences and subjective experiences. And these objective, subjective experiences fall into the categories of physical burden, emotional burden, psychological burden. So, there's a lot of different areas of life in which someone can experience burden. But really, it's a combination of factors of both the objective experience, lived experience, and the person 's perception of that experience or what they're dealing with. I should also mention that it appears to be more of that subjective experience or that perception that people have of their objective experience of stressors or burden. That really does determine the person's response to that, if whether they actually perceive their lived experience as being burdensome.  Dr Smith: One of the things I found really interesting was the societal and cultural context surrounding this, that there are different cultural expectations and societal dynamics, both in the nature of the burden care partners may feel and how they're viewed. I wonder if you could talk about that? I think it's something that it would seem all of us need to be attuned to as we're working with our patients and their families.  Dr Polsinelli: Yeah, this is a topic we could talk for a very long time on. I will try and- I will try not to kind of provide too much of a, or too lengthy of a response. But what we know now is basically that our models of stress and burden that we have typically used or historically used do not incorporate a lot of factors of cultural identity of social and structural determinants of health factors. And so, what we understand now is that stress and the way that people perceive burden is influenced by so many other factors than just kind of an experience and a perception. Because that perception is influenced by so many factors, including, as you mentioned, cultural factors that include how society's familial expectations for us, cultural expectations for us, as well as what our resources are that are determined by, again, structural and social determinants of health, what our community resources are. They're just a lot of different factors that go into how somebody perceives their ability to cope with, again, this kind of life-altering diagnosis that their loved one has received and them being the person who is caring for them through that. Dr Smith: Your article actually goes through in some detail the types of burdens and what drives the burden. And that changes over time. And so I wonder if maybe you can talk a little bit about what the specific natures of the burden are from the caregiver perspective. I mean, what  sort of tasks there are, you know, from the many of us who take care of patients, we still don't know unless we've been in the room or in the home watching this happen. So maybe you can describe that for those of our listeners who maybe haven't lived through this?  Dr Polsinelli: Yeah, absolutely. I will say upfront that the caregiving experience is going to be different for every single person. And again, kind of dependent on some of those factors that I mentioned before. So, it's going to look different for most people. It's also going to look different through the dementia journeys. The experiences and the requirements earlier on in dementia are going to be a vastly different than what occurs later on when dementia is in the more late stage, moderate or severe stages of the disease. Those care responsibilities absolutely change over the spectrum of that time as well. We know that early on the stage of disease, primary care partner might be spending forty plus hours a day. So, a full-time- or not a day. I'm sorry, a week. So, a full time job carrying it. But that number increases up to a hundred and fifty or so hours per week once the person is more advanced in their disease. So, I say that because the number of hours, I think, make all, like- putting that into perspective of somebody having a full time, multiple full time jobs, basically providing care, I think is really important. But the responsibilities of the care partner are going to range from everything from just helping the person early on in terms of managing finances or managing them, making sure they're reminding them to take their medications, scheduling their medical appointments for them, maybe taking over all of the driving to get them to their appointments or to get them to family outings and things like that. They're going to be the ones that's going to be the most responsible for reminding people to do something: to eat, to maybe stay on track for a recipe or something that they are making. So, kind of being the eyes and ears for this person right away, basically right at the beginning, even early stages. And then that progresses over time to the person who is caregiving, who is doing potentially everything for this person. So that means helping them use the restroom when they need to, helping them shower. So, there's a physical component to the caregiving as well as that- sort of what we call instrumental support in terms of organizing medical appointments and things like that. They're just basically doing it all for that person.  Dr Smith: So, what about a busy clinician who has half an hour to see a dementia patient follow up? Kind of hard to- in these days, you know, we've got, you know, these new therapies to think about as well. What advice do you have to neurologists and other professionals caring for patients? Dr Polsinelli: Yeah. And I think neurologists, I mean, we all have limited time. And I know neurology in particular is like primary care, has even more constrained time. I think one of the biggest things that neurologists can do is really check in with the care partner. So, take a moment to check in with the care partner who's there with the person with dementia to see how are they doing. You're looking for signs of burden or stress, so things like physical complaints like headaches or stomach ache, mentioning feeling burnt out or overwhelmed, maybe feeling depressed or something like that. There's also some short kind of questionnaires that you could give care partners prior to an appointment that they could fill out. You could kind of get a sense of where is this person at this point and then help connect them potentially to some resources that might be available. And I would refer people to that article that has a list of resources in there that you could just basically print out and give to somebody.  Dr Smith: Yeah, I was going to make the same point, Ange. Your article is a treasure trove of information. And you know, I'm certainly, I keep all of these on file, as you might imagine, but I'm keeping it in hand for future use. One of the things you talk about that really hit home for me among many is the idea of self-care, and I think sometimes the best care partners are susceptible to burnout because they they're so dedicated. You made the airplane oxygen mask metaphor, which I love. So maybe you can talk about what airplane oxygen masks have to do with dementia care and what advice you have for us and helping our patient's care partners take care of themselves? Dr Polsinelli: Yeah, absolutely. Self-care is the number one thing I tell care partners to do. It's also one of the hardest things for care partners to do. Like you mentioned, there is a deep, generally speaking, a deep love and caring for the person with who is living with dementia. And the focus becomes on them. And understandably so, the care partners sort of loses focus on themselves and making sure that they're doing okay. So I oftentimes use this oxygen airplane metaphor for people, which is basically, you know, when you're in an airplane and if there's some kind of pressure change in an airplane, they always tell you, put your oxygen mask on first before you help somebody else because you're not going to be any good to anybody if you're passed out. In the airplanes, the pressure changes, you know. You need to be available. you need to be getting what you need in order to help somebody else. So, I think that metaphor, that analogy really works well in dementia care is you need to be- the care partner needs to be caring for themselves and replenishing themselves in order to be the best care partner they can be for their loved one.  Dr Smith: Another challenge that, it strikes me as shared between people living with dementia and their care partner is that of social isolation and loneliness, right? If you're working a hundred and fifty hours a week doing anything, you don't have time to care for yourself or very hard to engage in social connections. And one of the loud messages I think I heard from your article is the power of social connectedness, both in terms of resilience and in many different ways. I wonder if you can talk a little bit about loneliness? And I just reflect that in a postpandemic world, this is probably a bigger issue than it was four years ago or four years and three months ago. Dr Polsinelli: Yeah, absolutely. Loneliness and social isolation was a big problem before, and it's even worse now is when I'm hearing from my patients. What I'm seeing in the literature is this postpandemic time is even more has been even more isolating and more problematic for people, but this social network cannot be, as you said, it cannot be overstated in terms of the importance for people. So that social network is important for not only providing potential instrumental care - so that practically care that care partners can use can lean on other people to come into the home to do things for the person living with dementia so the care partner can go practice self-care or go do those errands that need to be done - but also the emotional support as well that social networks can provide for people. And also, you know, social networks for not just the person, the care partner, but for the person living with dementia as well. We know that social engagement in particular is really good for brain health. I mean, we don't think about it, but social engagement is a very cognitive activity. And so, it helps give the brain a bit of a workout. So that social network is important for a lot of different reasons, and understandably a lot harder to maintain in this sort of postpandemic world as well. Dr Smith: As our time starts to come to- close to a close, we're not done yet, but I think we're probably going to have to start winding up. I wonder if we could pivot to something positive and then talk about the joy in this. And by that, I mean you describe and I think we've witnessed relationships and caring, caregiving situations that, as challenging as they are, provides fulfillment and the connection one has with a loved one or sort of that social aspect. Are there things that- predictive of that kind of positivity, and are there ways that we as professional caregivers for patients and their families can facilitate that? Dr Polsinelli: Yeah, there are. There are a couple of things. So, one of which is basically the quality of relationship between the care partner and the person living with dementia already. So that's the quality of that relationship. The better the quality of that relationship, the more likely it is that the care partner will experience more meaning and fulfillment and joy associated with caregiving, kind of outweighing that burden. But the additional piece of that is the more resources, the more mastery they feel about their caregiving or care partnering abilities, the more competent they feel and their ability to do good by the person, their loved one, the person living with dementia, the more likely they are to find that role fulfilling and meaningful. And I think that's where neurologists and other providers can kind of come in as helping people make sure that they have those resources that they are connecting to places where they can learn skills for giving appropriate care so that they can feel confident in what they're doing. There's the preexisting relationship piece that matters a lot. But I think that there's a lot of modifiability that neurologists have, too, in making a positive impact on the care partner and the person living with dementia. Dr Smith: That's really great advice, Ange. And I definitely will refer our listeners yet again to your article, which is a compendium of useful advice about this, both in terms of the text itself and in tables that provide lists of resources, websites, books, organizations, good case examples. It's a home run and I hope all of our listeners check it out. I'd like to wind up by talking a little bit about your work. And as I understand it, you obviously are very passionate about this topic, but you have specific interests in caregiver burden and underserved and marginalized communities. And then, we've touched on this, but this is a huge percentage of our population. And when you look out globally, it's even bigger than that. Tell us about what you're working on. And then maybe following that, what's the future look like? Where are we going to see advances in this in the coming years?   Dr Polsinelli: So just a really quick kind of brief history is that I've worked in dementia for almost twenty years or so now. And what I've consistently seen is when you give care partners good supports and education and resources, there are better outcomes for them and their families. The unfortunate thing is, a lot of these really great interventions and things that we have are not necessarily really accessible by a lot of people, but particularly not accessible by those living in underserved communities. The last few years in particular, I've really shifted into wanting to better understand that and better understand how do we provide culturally and socially appropriate interventions and education for these care partners and their families. With the current research project that I'm working on, we're looking at better understanding the needs of care partners of people who have early onset Alzheimer's disease, specifically from Black and African American individuals and other underrepresented groups. Again, the idea of this is to understand the needs before building an intervention for these groups, and I'm very excited about it. I know that there are lots of really great people who are working in this area, including Dr Dilworth Anderson and Kalisha Bonds Johnson, doing really fabulous work in this area. So, and building on what they're doing as well. In terms of what the future holds, one, I think we absolutely need to, we have lots of really great care partner interventions out there that have been lots of research going on, but it's not really transitioning into the clinical sphere. It's really kind of staying in that research sphere. So, I think it's really important that we get some implementation scientists who are taking those interventions and moving them into the clinical sphere, into the sort of like everyday, how do these actually work for people sphere. And then similar to some of this conversation we're having in terms of serving, making sure our interventions and making sure that our resources are appropriate and accessible for underserved communities, we really need to be taking a look at what these communities need rather than kind of saying, this is what's available. Kind of, hopefully this works for you. Speaking with these communities, engaging stakeholders and understanding what are the needs in these groups so that we can provide the appropriate resources, the appropriate interventions, the appropriate supports for care partners and people living with dementia. Dr Smith: And I'm just thinking, imagine what this looks like with effective treatments for Alzheimer's disease, that slow progression. And you know, that's going to make the caregiving even more important, it seems to me. But there's an opportunity to make it a better rewarding and a better-supported system as we develop these new therapies. So, this is a, like a Clarion call for learners listening that they should all become dementia neurologists and neuropsychologists like here. Thank you. That was outstanding. Say, Ange, I want to thank you a lot for a really engaging conversation. This fulfilled every hope I had coming into it. I was really excited to talk to you. I always love talking to neuropsychologists, but I think again, this is really useful for neurologists, learners, people who are nonneurologists everyone. And so, thank you very much. I've learned a lot and I really would encourage everyone to check out the article.  Dr Polsinelli: Well, thank you so much for having me on and giving me the opportunity to talk about the stuff that is really important to me and, I think, to most of us out there. So, hopefully people find the article and the resources in there useful and, and thanks again for having me.  Dr Smith: I'm sure they will. Again, today I've been interviewing Dr Angelina Polsinelli, whose article on care partner burden and support service in dementia appears in the most recent issue of Continuum, which is on dementia. Be sure to check out Continuum audio episodes from this and other issues. And thanks to you, our listeners, for joining us today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Greetings, my spectral spectators!

Greetings, my spectral spectators!

Atletico analyst Gordon Smith on Atletico's big win last weekend, three best teams are left in the CPL, Calvary upsetting Forge FC in the 1 v. 2 game and Atleti supports making the trip to Hamilton.

Atletico analyst Gordon Smith on Atleti's semifinal match against Forge FC, FanDuel, Giroux igniting Josh Norris and Drake Batherson and Sens and Sensibility.

Dr. Gordon Smith and Dr. Whitley Aamodt discuss end-of-life care for patients with neurodegenerative diseases, focusing on healthcare utilization, hospice enrollment, and the importance of early conversations about care preferences. Show reference: https://www.neurology.org/doi/10.1212/WNL.0000000000209925    

Atletico Ottawa analyst Gordon Smith on Atleti's blossoming rivalry with York United, and what to expect in their playoff showdown

Dr. Gordon Smith talks with Dr. Whitley Aamodt about the comparison of resource utilization between US Medicare decedents with neurodegenerative diseases and those with cancer. Read the related article in Neurology. Disclosures can be found at Neurology.org.

The controversial state Amendment 3 on this November's ballot has many conservatives split on support. Sheriff Gordon Smith gives reasons why he is a rare law enforcement leader that is in favor of the initiative, on the Friday Bob Rose Show 10-11-24

Rivers and lakes will rise in the coming days, but limited damage in Bradford County. Traffic will become a problem shortly as evacuees look to return to assess damage in their towns that were devastated by the storm.

Schools closed, shelters operating, and fuel is being restored after some stations ran out with increased evacuation traffic. Safety update ahead of Hurricane Milton with Bradford County Sheriff Gordon Smith on the Wednesday Bob Rose Show 10-9-24

Drs. Gordon Smith, Shahar Shelly, and Teerin Liewluck discuss the correlation between CMAP duration and myosin loss and their effect on mortality by comparing between patients with CIM with and without myosin loss.  Show references: https://www.neurology.org/doi/10.1212/WNL.0000000000209496 

Dr. Gordon Smith talks with Drs. Shahar Shelly and Teerin Liewluck about the correlation between CMAP duration and myosin loss and their effect on mortality by comparing between patients with CIM with and without myosin loss. Read the related article in Neurology.  Disclosures can be found at Neurology.org.

Autoimmune cerebellar ataxia and other autoimmune movement disorders encompass a broad spectrum of different clinical syndromes, antibodies, and immunopathophysiologic mechanisms. Given the overlap between phenotypes and antibodies, panel testing in serum and CSF is recommended. In this episode, Gordon Smith, MD, FAAN, speaks with Bettina Balint, MD, author of the article “Autoimmune Movement Disorders,” in the Continuum August 2024 Autoimmune Neurology 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. Balint is an assistant professor for clinical research on complex movement disorders and Parkinson's diseases, a consultant neurologist, the head of the Department of Movement Disorders, and co-lead for the Centre for Movement Disorders and Functional Neurosurgery in the Department of Neurology at the University Hospital Zurich in Zurich, Switzerland. Additional Resources Read the article: Autoimmune Movement Disorders 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: @gordonsmithMD Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME.   Dr Smith: This is Dr Gordon Smith. Today, I'm interviewing Dr Bettina Balint about her article on ataxia and other autoimmune movement disorders, which appears in the August 2024 Continuum issue on autoimmune neurology, which is a highly anticipated and exciting issue. Dr Balint, welcome to the podcast, and, perhaps, you can just introduce yourself to our audience and tell us a little bit about your practice and how you became interested in this topic.   Dr Balint: Thank you, Gordon, for having me. I am an assistant professor for clinical research in complex movement disorders and Parkinson's disease at the University of Zurich and the Head of the Movement Disorders Department at the University Hospital in Zurich. So while I'm originally German (from Heidelberg), I have now been to Switzerland since end of 2021.   Dr Smith: So, you know, how many movement disorder chiefs have a focus on autoimmune movement disorders? I found that really interesting. Most of the movement disorder folks I interact with, their primary interest is in neurodegeneration.   Dr Balint: Very good question. Even so, I never asked myself that question, really, but I think I'm the only one with this designated focus as such. Many people come from the neurology angle - most of them. Even so, movement-disorder people really welcome this field and are interested, but I think somebody who has dedicated their interest and time to it? I think I can't actually think of many other people.   Dr Smith: Yeah, I think it's really cool, and, of course, autoimmune neurology is the flavor of the day these days, right? I mean, I remember when I was at the University of Utah, we were recruiting Stacy Clardy (who I think many of our listeners will know). I remember thinking, you know, she's never going to be busy. How many of these autoimmune problems are there, really? And she was, like, deluged when she came. These are really common problems. I guess that was one question I had for you. You know, we think of these as rare disorders, and when we look at the article, you have these tables of these antibodies, and a lot of them are pretty uncommon – but, cumulatively, how common are autoimmune movement disorders?   Dr Balint: It's a very difficult question, because we don't have good epidemiological data. And if you look at series, I mean, most papers addressing this issue come actually from the ataxia field. And then, depending on where you look at, you might find varying numbers, and they might be also influenced by the fact that they come from ataxia centers with own certain biases. Even so, it's very close to my heart, but, I also still think it's overall very rare. So, in my practice, I see all sorts of movement disorders, and overall, they're still quite rare, but the point is that they are treatable and have important management implications, so you want to be sure not to miss any of them.   Dr Smith: Well, maybe we can go to that next. Part of the challenge here, of course, is there's just so many of these different syndromes and antibodies. Are there pearls that you can provide our listeners that would help them guide when they should be thinking about these disorders when they confront a patient with a particular phenotype? Like ataxia, for instance - you know, there are certain aspects of the clinical scenario that should trigger, “Wow, this might be an autoimmune problem”.   Dr Balint: So, in general, I would say there are certain scenarios where you would want to think of an autoimmune etiology in your differential. One is a very characteristic phenotype. So, speaking broadly in terms of movement disorders, stiff-person spectrum disorders have a very characteristic phenotype which you need to recognize, and then you will be able to see it when a patient enters. Important phenotypes to know which are very characteristic are faciobrachial dystonic seizures, for example, with anti-GA1 antibodies, or pseudofinalistic movements in non-REM sleep is IgLON5 antibodies, leg myoclonus is CASPR2 antibodies. I don't want to necessarily enumerate all the scenarios. The point here is there are some characteristic phenotypes where you would think of autoimmune neurology. Another scenario where you would think of autoimmune, for example, the context of late-onset paroxysmal movement disorders. So, classically, when we think of paroxysmal dyskinesia, we think of a group of genetic disorders, but if somebody develops a paroxysmal movement disorder later in life in adulthood, then you would think of autoimmune neurology, and this applies also in the context of episodic ataxias. Another red flag might be a propensity to autoimmunity. For example, somebody with type one diabetes and vitiligo coming in for cerebellar ataxia, of course, you would think of anti-GAD ataxia. And, similarly, if somebody has recently been diagnosed with a cancer and develops a rapidly disabling syndrome, of course, then you would think of a paraneoplastic autoimmune disorder. And with autoimmune syndrome, there are some symptoms which are also like tell-tale signs. So, for example, somebody with a stiff-person spectrum disorder, an ataxia with long-lasting diarrhea over months, losing weight - investigations haven't found anything, then you would think of DPPX antibodies or celiac disease. Or, if you have, like, a neuropathic pain which is otherwise not explained, then you might think of CASPR2 antibodies in somebody with a cerebellar ataxia. So, there are some features of some antibodies. (Again, I will not now list all of them which might point you to a diagnosis.) Then, of course, another scenario which is important, I think, is if you have a hemisyndrome without a structural lesion on imaging. Classically, neurologists are trained to think of a hemisyndrome - we look for a lesion on the contralateral side. But if you have, like, for example, a hemichorea without a lesion or a hemiataxia without a lesion, one should also think of an autoimmune disorder with antibodies. And then, more generally, of course, if you have changes on brain MRI or information on CSF, of course, if the clinical cause is more rapidly progressive - and last, but not least, if somebody does not really fit into our categories of the degenerative symptoms or metabolic syndromes or functionality disorders, then, of course, one should just take a step back and think, could it be something autoimmune? Having said that, if I may, I just want to say that, I mentioned that rapid disease course, and on the other hand, it's important to stress that a slowly progressive disease cause does not exclude an autoimmune etiology.   Dr Smith: So, that was a great summary. Thank you. I don't know if you're familiar with the term “Aunt Minnie” (something I learned in medical school and radiology). There are certain findings that are “Aunt Minnie”, you know what “Aunt Minnie” looks like, and if you see these particular findings, you should really think about a specific disease - and I think you gave a lot of pearls in that answer, so I appreciate that. This may seem like a bit of a random question, but it's interesting that there are some of these phenotypes that do replicate genetic phenotypes, and you used episodic ataxia, which, in a younger individual, we think of a spectrum of various genetic disorders. Is that random, or are there instances where the underlying mutation in a genetic disorder actually serves as a target for autoimmunity in a later-onset autoimmune problem? Not that the mutation causes autoimmunity, but are there shared targets - in one disease it's the mutation, and another, there's an antibody that binds to the protein, for instance?   Dr Balint: That's an excellent topic, and even though it's not addressed in the Continuum article, I actually covered this in an article in Brain from 2018, where we also discuss parallels (immunogenetic parallels) with targets seen in genetic disease or in autoimmune disease, and there are actually some examples for cerebellar ataxia, and some of the targets are, indeed, the same for the antibodies and mutation. And some targets are a little bit more difficult, because for those, the antibodies would probably not be pathogenic, but it's more like an autoimmune overall target but it's T-cell mediated. But, for example, water-gated, um, calcium channels - we have antibodies and we have mutations. Or, another example would be glycine receptor antibodies give you acquired hyperekplexia, whereas the mutations give you hereditary hyperekplexia. So, there is, indeed, a bit of an overlap between autoimmune and genetic disorders, but often, also, like, the age at onset (because that might be the next question, the age at onset), and maybe family history and associated features, should help to distinguish the two. I think more from the pathophysiological point interesting, rather than clinically too confusing.   Dr Smith: Wow, that's really cool. So, another question I have is regarding antibody panels, right? And so, I think, oftentimes (at least around here), folks confronting an unusual phenotype will send the Mayo panel - they'll send autoimmune encephalitis or a paraneoplastic panel – and, you know, I think one of the challenges I have thinking about the spectrum of phenotypes that you described, I mean, if you recognize “Aunt Minnie”, then you know where to go, but it seems to me that there's a lot of these that maybe folks don't recognize “Aunt Minnie”. What is the diagnostic utility and pearls and pitfalls of ordering these panels when you're not really certain? In other words, is there a risk of a false positive if the pretest probability is low? So, I guess that's a long question, but do you have guidance about when we should and maybe when we should not be ordering these panels? So, you know, undifferentiated ataxia that's chronically progressive - should we be sending a panel or not? Patients who are later-onset acute, maybe so. So, what's the guidance on when to order the panel?   Dr Balint: It's a tricky topic also for many people in our practice, because, of course, as you said, we don't want to miss something, but, indeed, with any test which you order with a low pretest probability and which is not quite appropriate, you might have false positives, and that might cause much additional trouble in security, or maybe unnecessary and invasive immunotherapy with adverse effects – so, it's really important to think well about antibody testing. And, generally speaking, like always in medicine, we shouldn't order random tests, and antibody panels and neuronal antibodies are not designed as a screening test, so you need to have a phenotype and a reasonable suspicion - and clinical acumen is really key, and that's why also the article is so much focused on the phenotype. It's clearly not that any movement disorder patient who enters the outpatient clinic should get a blood test for antibodies that will likely cause harm, and it has been shown that these antibodies can be falsely positive, both in other diseases but also in healthy controls, and much depends also on which tests you use (but, let's not go into too much detail over here) - so, generally speaking, I would say if you have a suspicion of an autoimmune disease clinically (I mentioned some scenarios where you would think of an autoimmune disorder). And then, ataxias are, of course, a bit tricky, because often, we don't have too many other handles there, and there's still also a significant number of acquired late-onset ataxia where we don't know what the cause is. I think in the ataxia scenario, if I don't have a good answer or explanation, I would order antibody tests a bit more freely - I mean, if you do it properly, you do the serum and the CSF, and that also increases your sensitivity but also the specificities, so I wouldn't then just do the serum, but then go for serum and CSF. In other movement disorders, it depends also a little bit on the phenotype. So, somebody with a phenotype fitting well with Parkinson's disease, I wouldn't do any testing. Somebody with clear PSP phenotype without any red flags or not-fitting features, it is very unlikely to have an antibody finding, and this has been shown also in cohorts. But, if you have something which is not fitting in the phenotypes - for example, you have somebody where you think it might be a PSP phenotype with predominantly axial Parkinsonism falls, but you notice that the oculomotor disturbance is not a vertical gaze palsy, but a horizontal gaze palsy – so, it's not really fitting phenotype as you know it. That's a scenario where would probably think of antibody testing. Then, if you do the testing theorem - and CSF, in general, is gold standard - there are some antibodies where theorem is good enough (like, for example, with aquaporin-4 antibodies), but the reason why we do serum and CSF, as I mentioned, is the increased sensitivity and specificity. And nowadays, in the antibody world, we have something similar to the genetics - we have the variant of unknown significance and in the neurology world, we coin the term “antibody of unknown significance” to also give a name to the problem that, sometimes, we get a test result and it is difficult to interpret. Another handle over there would be to try to confirm the test result in another test method. So for example, if you have a cell-based assay with an antibody finding, you would like to confirm that on immunohistochemistry - the staining pattern is in keeping with that.   Dr Smith: So, Bettina, that was a really great and comprehensive answer to the question with a lot of pearls packed into it, and I think the idea that, you know, oftentimes, it's helpful to do both serum and CSF testing is important - also looking for staining to further confirm the diagnosis. And, I think one of the things that I was struck by in your response was the example of a PSP patient who instead of vertical gaze palsy had horizontal gaze palsy as a red flag, and I think a lot of our listeners are probably familiar with the idea that maybe hyperkinetic movement disorders might be autoimmune, or certainly rapidly progressive ataxia, but at least I don't think of Parkinsonian syndromes as often. I know there are some that we need to consider. Maybe you can give us some pearls about when we should consider antibody testing in a patient who has a Parkinson syndrome?   Dr Balint: So, I will not cover now the paraneoplastic Parkinsonian syndromes (because they typically develop as rapidly that you would anyway think about it, hopefully), but go more into those conditions which might mimic degenerative disease - and one of the most interesting antibodies in this regard is IgLON5, and you will be aware that it has been discovered in 2014 in patients who shared a characteristic sleep movement disorder (non-REM parasomnia). The spectrum has broadened a lot, and one possible manifestation is that it could come into the differential of Parkinsonian syndromes - so, for example, if you have axial Parkinsonism and a gaze palsy, you are in a PSP phenotype, but the red flag would be maybe if the eye movement disorders are not really fitting with the PSP phenotype. Also, in PSP patients, we don't expect parasomnias at night. If the bed partner is, for example, complaining that the patient is moving in his sleep and doing movements, then this would be a red flag, and in this context, you would think of IgLON5. IgLON5 could also give you Parkinsonism and cerebellar ataxia, and they might have dysautonomia, and, of course, with a sleep movement disorder, you are now in the ballpark of MSA phenotypes; however, if there are additional features (like, for example, fasciculations) which you don't expect in MSA, that would be, again, the red flag. So, typically, even in those differentials, there are some red flags on handles which would point you to the diagnosis - it is not that it completely mimics the phenotype of our default degenerative disease, but, sometimes, you need to hunt a little bit for those handles.   Dr Smith: So, Bettina, that's really interesting. I wanted to ask you about IgLON5, and in particular, the sleep phenotype, but, you know, I wonder whether there's a risk of just confusing this with REM sleep behavior disorder and a chronic Parkinsonian syndrome - what's the time course of this, and any other wisdom in terms of how to differentiate it from, you know, a more common neurodegenerative problem?   Dr Balint: So, the spectrum of sleep disorders in IgLON5 is actually a bit broad. The characteristic thing is the non-REM sleep parasomnia with the finalistic fine movements, but classic REM sleep behavior disorder has also been reported in these patients. And one of the tricky things is IgLON5 is a slowly progressive disease (some patients had symptoms for a decade prior to diagnosis), so it's really an important differential of autoimmune disease - but as mentioned, the features not fitting in, and they are typically also the cardinal features. So, gaze palsies are very frequent, ptosis, bulbar symptoms, vocal cord palsy, sleep movement disorders which might not fit to the original phenotype, and breathing problems (for example) so severe that they require a tracheostoma – so, these are some red flags which would alert you to this diagnosis of anti-IgLON5 disease.   Dr Smith: I'm curious, Bettina, how do you keep up on all of this and keep it all straight? Right, there's a lot of information, and as I was reading your article, you've got these wonderful tables - and in fact, this whole issue for our listeners feels that way. I've read several of these articles now, and I'm just curious what your strategy is to stay up to date and stay organized. You have to be very organized to be an autoimmune neurologist, it seems to me.   Dr Balint: And having a little bit of OCD helps clearly, as always, in neurology. I think it is just that I started to be interested in this area for a while and I have in my head the clinical phenotype to most important associated antibodies, and as the field continues, I just add up on that panel. But, I don't want people to be discouraged - you're right, many antibodies, but I think the point is not to know each and every antibody but to know in which scenario to think of an autoimmune syndrome and then to know where to look it up.   Dr Smith: Well, I think that's a great way of ending our conversation, Bettina. I think your article does a great job of that, and one of the things I love about Continuum is these articles serve as point-of-care tools. I think our conversation will also serve as a useful framework, because I think you've talked a lot about how to organize your thinking, and, you know, pearls for when we should be thinking about these disorders which are uncommon, but you certainly don't want to miss one because the therapy can be very effective. So, Bettina, thank you so much for joining me. This has been a really great conversation.   Dr Balint: Thank you so much, Gordon. Thank you very much for your good questions.   Dr Smith: So, again, today, I've had the great pleasure of interviewing Dr Bettina Balint, whose article on ataxia and other autoimmune movement disorders appears in the most recent issue of Continuum, which is on autoimmune neurology. Be sure to check out Continuum Audio episodes from this and other issues. And thanks to our listeners for joining us today.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Awareness of the specific clinical and MRI features associated with AQP4-NMOSD and MOGAD and the limitations of currently available antibody testing assays is crucial for a correct diagnosis and differentiation from MS. Growing availability of effective treatment options will lead to personalized therapies and improved outcomes. In this episode, Gordon Smith, MD, FAAN speaks with Elia Sechi, MD, author of the article “NMOSD and MOGAD,” in the Continuum August 2024 Autoimmune Neurology 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. Sechi is a neurology consultant in the neurology unit of the Department of Medical, Surgical and Experimental Sciences at the University Hospital of Sassari in Sassari, Italy. Additional Resources Read the article: NMOSD and MOGAD 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: @EliaSechi Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME.   Dr Smith: Hello. This is Dr Gordon Smith. Today, I've got the great pleasure of interviewing Dr Elia Sechi about his article on aquaporin-4 antibody-positive NMOSD and MOGAD, which appears in the August 2024 Continuum issue on autoimmune neurology. Dr Sechi, before we dig into this really exciting topic about NMOSD and MOGAD, perhaps you can tell our listeners a little bit about yourself, where you practice, how you got interested in this topic.   Dr Sechi: Hi, Dr Smith, and thank you for having me. So, my story begins here in Italy, actually - I did my med school and residency in neurology at the University Hospital of Sassari here in Sardinia. And after residency, I was lucky enough to be accepted at the Mayo Clinic in Rochester, Minnesota for a research fellowship - and that's where I spent the next three-and-a-half years, approximately. My fellowship was focused on autoimmune neurology, specifically demyelinating diseases of the CNS associated with antibodies – so, of course, NMOSD and MOGAD mostly, but also myelitis, MS, and autoimmune encephalitis – so, there's where I built most of my expertise in the field. And then, it was at the beginning of the pandemic (of the COVID pandemic) that I came back here to Italy to practice. And now, I work mostly as a neurohospitalist, and I also have my subspecialty outpatient service for patients with autoimmune neurological diseases.   Dr Smith: I wonder if you might just give us a minute or two about what it was like training in Mayo? I went to medical school there, and, you know, at the time, I thought that was just normal healthcare and normal training, and, you know, it was only later that I realized how amazing that was. I mean, this is where aquaporin-4 was discovered - I mean, what was that like? It must have been really cool training there with that team.   Dr Sechi: Yeah. You know, it's the temple of autoimmune neurology. It's fantastic. It's a great environment, very stimulating. You know, I think the great strength is that they see many patients with rare diseases, so, you get really confident with MRI features and clinical features with the history of the diseases, and this is important to recognize the typical features and differentiate from MS to do a good differential. And, of course, you know, the team is fantastic - superstars in the field. It's very, very stimulating. So, it's something that I definitely recommend. It was a fantastic experience.   Dr Smith: Well, you know what's great is, I don't know if you follow sports, but, you know, like, in the United States and college football, people refer to Gator Nation – right, these are all people who are fans of the Florida Gators. Or, maybe it's AC Milan nation in Italy. I don't want to get there (Roma, whatever), but there are all these people who've trained at Mayo, and, uh, what's great is it's a small world, right? So, I'm super excited to meet you and talk about this, because - I'm going to add you to my Rolodex, because when I see these patients (I'm a neuromuscular guy, but I do a fair bit of inpatient time), I'm always calling a small number of people, so I'm really pleased to meet you so I can put you on speed dial and ask you questions about these patients. I wonder if, maybe, we can begin? You know, in our preparatory discussions, I shared that I just came off our hospital service, and we had several of these patients, you know, where we were thinking about NMO or MOGAD as a cause for their problem - and I wonder if you just have any pearls or pitfalls in when we should suspect this, right? Most of us recognize bilateral optic neuritis, longitudinally extensive myelitis - we need to be thinking about these. Any pearls or pitfalls for when we should or should not be looking for these disorders?   Dr Sechi: Yeah, I think this is a great question. I think the first thing to pay attention is the phenotype. So, the clinical MRI phenotype that are typically associated with NMOSD and MOGAD, they are quite characteristic - and it's important to be aware of those phenotypes and how they differ from MS, because in my experience, one of the common misinterpretation (misconception) in clinical practice is just to test for AQP-4 and MOG antibodies in any patient with new-onset demyelinating disease of the CNS, even if it's typical MS. And, this is quite wrong, because MS is way more common in clinical practice - it's sixty, eighty times more common than NMO and MOGAD - and so, if you test all those patients without filter (indiscriminately) for antibodies, you increase the risk of false positivity exponentially, even if you have a highly specific test. So, first of all, I think it's good to select the right patients to test. As you said, patients with LTM, extensive involvement of the optic nerves on MRI, ADEM - there's also patients with cortical encephalitis phenotype (which is a rare phenotype of MOGAD), but not definitely good to test the typical MS patients. This is the first thing.   Dr Smith: Yeah, I mean, that's an issue in all of neurology, isn't it, right? I mean, it's an issue in sort of just sending, you know, the Mayo panel, the autoimmune encephalitis panels - you need to select patients carefully, but I think this attention to prior probability is something that we need to really focus on in multiple areas. So, I wonder if you might expand a little bit on assays. I do a lot of work in myasthenia and I know which labs do a really good job with, you know, acetylcholine receptor antibody testing and those that maybe do not, and there are different methodologies for testing - do you have any wisdom in terms of how to select a lab, what to look for, and how to interpret the results you see based on the particular assay that's being used?    Dr Sechi: Yeah, that's a critical point. I agree. And especially if you work in myasthenia, you're very well aware of the differences between different assays, and nowadays, most of the high-quality assays are cell-based assays (either fixed or live) - it's the same in myasthenia, and people need to pay attention to some of the less-specific assays. Let's say ELISA, for instance - testing AQP-4 and MOG antibodies with ELISA is quite dangerous, because the risk of false positivity is quite high. So, it's good to know what assays to trust most and also good to know what's the right specimen to send for antibody test. For instance, with AQP-4, we know that serum testing is recommended only, and the CSF doesn't add much, but with MOG, we know that approximately 10% of patients have an isolated positivity in the CSF, which is interesting, because it means that when you have a patient with a strong diagnostic suspicion as a phenotype that is highly suggestive for MOGAD and the serum testing is negative, you may consider testing the CSF to increase your sensitivity. So, this is very important.   Dr Smith: So, I have a question for you that may seem a little naïve, but I bet other people are thinking it - can you tell us why it is that these disorders affect optic nerve and spinal cord preferentially? And I think, for NMO, the whole area postrema thing seems awfully specific to me. What's the deal? Why are these areas preferentially affected by these antibody-mediated disorders?   Dr Sechi: This is a tough question. For NMO, we know, probably, there is higher expression of some of the isoforms. Let's say there is a higher density of AQP-4 molecules that target the most affected regions - so, of course, AQP-4 is preferentially expressed in the subependymal regions around the ventricles and in the spinal cord and optic nerves, but you may have, also, solutions along the cortical spinal tracts in case of the brain involvement. The area postrema is kind of a different explanation, because there is a sort of permeability - increased permeability - of the blood-brain barrier there. So, there are several factors in MOGAD - this is not very clear, so, this is a great topic to study in the future, I think.   Dr Smith: This is a really interesting area, and one that's really benefited by significant therapeutic development. I wonder if you might look a little bit in the future and tell us, maybe, the agent, or perhaps the target, that you're most excited about therapeutically that's coming down the road these days?   Dr Sechi: There are trials ongoing for MOGAD, which is the real need in terms of treatment, because for NMO, we already have three, four drugs that have been approved and which efficacy have been demonstrated by randomized clinical trials, and those are B-cell depleting agents, IL-6 inhibitors, and complement inhibitors. For MOGAD, this is still a gray zone, because the optimal treatment strategies remains to be defined. There are ongoing trials that are quite promising on IL-6 inhibitors and the inhibitors of the neonatal Fc receptor (which is also used in myasthenia gravis as you know). And something that seems to be quite effective - a good option for long-term treatment in these patients and relapse prevention - is also the periodic administration of IVIG (intravenous immunoglobulin), which is a nice option, for instance, in the children where you want to avoid immunosuppressants of other types. So, I think IL-6 is going to show to be very effective in the end. We'll see. We'll see.   Dr Smith: So, I wonder if I might just give you a vignette and get your thoughts about, kind of, acute management, right? I just took care of a patient who had a longitudinally extensive myelitis and she was essentially paraplegic and actually came in progressing fairly rapidly, and we, of course, started her on IV methylprednisolone, sent off the proper diagnostic testing - the question I have is, how quickly do you advance therapy and go to IVIG or plasma exchange when you're encountering these, right? It takes, you know, I think the turnaround time is, you know, often about a week to get these tests back (at least several days) - I mean, should we be going very quickly to plasma exchange in someone who has a severe phenotype? Is it okay to do three to five days of IV methylprednisolone and wait for the results to come back? What's the right approach?   Dr Sechi: I think this is a great question, actually. You know, management of the acute attacks probably is the most important thing, you know, to allow a good recovery, and I think timing of PLEX administration should be very short - so, the threshold for PLEX should be low, especially when the attack is severe, and this has to be done regardless of antibody testing results, which is typically not available before one or two weeks (at least a year in Italy), I think, in many hospitals. So, I think the risk-benefit ratio of administering PLEX is in favor of treatment in these patients, because the side effects (the potential side effects) are very rare and can be prevented. Some diseases, they can mimic NMO or MOGAD - they're very rare, and they can really worsen with PLEX. As an example, we can say spinal cord infarction can worsen, maybe, because of hypotension due to PLEX. Or some very rare infections, like one case, a bad case of intramedullary spinal cord abscess that looked really similar to an AQP-4 IgG-related LTM - and it was bad, because the patient had no fever, no signs of infection, the CSF culture was negative initially, so we ended up doing a biopsy after failure of PLEX and steroids. So, it is recommended to start within the first three to five days, preferentially, in severe cases, and this is great for the outcome of the patient, so, I do recommend PLEX as a second treatment option. And I'm not sure about IVIG acutely. There is some data on MOG, but it's still controversial - it works a lot when PLEX fails, but it can be considered after PLEX, of course. And there are some very rare patients that do not improve, even after IV methylprednisolone, PLEX, or IVIG, and so, you need to consider some rescue therapies. In those patients, it's kind of complicated, because there are some options, like IL-6 inhibitors seem to be quite effective and quite fast-acting for MOGAD attacks, and also eculizumab and complement inhibitors can be an option in patients with AQP-4 - but maybe less in patients with MOG. So, these are the possibilities (very quickly).   Dr Smith: So, you mentioned FcRn inhibitors a moment ago, and I wonder, do you see a future where - and I think you were mentioning them as maybe more chronic therapy? Correct me if I'm wrong.   Dr Sechi: Yeah, yeah.   Dr Smith: Do you foresee a role for these agents in acute management? I mean, there are some that, you know, very quickly lower immunoglobulin levels, though just looking out in the future, you think that these sort of infusion therapies that we think about chronic therapy (you mentioned, you know, complement inhibitors) are going to be useful in acute management?   Dr Sechi: Yeah, it depends. It's a good option to try. I'm not sure about the time to action. It's very dependent on that, because IL-6 inhibitors and complement inhibitors are very fast-acting (I think they can be effective already within twelve hours, 24 hours, which is good), but it's reasonable that, also, Fc inhibitors can be an alternative in the future. As far as I know, there is not much in the literature, but it's good to try in the future in case, acutely.   Dr Smith: Well, exciting times indeed. Elia, thank you so much for a great discussion. I thoroughly enjoyed this. I look forward to visiting you soon, and I want to congratulate you on a really great article that's very interesting and very clinically useful.   Dr Sechi: Well, thank you, Dr Smith. This is my pleasure, and thank you for great questions. I had a great time and hope the readers of Continuum will like the article and the nice figures we have put together. So, thank you, thank you very much.   Dr Smith: Well, again, congratulations. And for our listeners today, I've been interviewing Dr Elia Sechi, whose article on aquaporin-4 antibody-positive NMOSD and MOGAD appears in the most recent issue of Continuum, which is on autoimmune neurology. It's a very exciting issue. Please check out Continuum Audio episodes from this and other issues of Continuum. And thanks to you all for joining us today.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Send us a Text Message.Come voyage with us as we learn about evidential mediumship with internationally trained medium, astrologer, and spiritual teacher Michael Mayo. Michael's journey from a chance encounter to becoming a respected medium and teacher will inspire you to explore your own potential. Through his unique approach at the Oakbridge Institute, Michael shares the foundational principles that can guide anyone towards spiritual awakening and mediumistic development.Learn how passivity and neutrality can enhance psychic awareness as Michael reveals practical steps to quieting the mind and recognizing subtle energetic sensations. From his studies with renowned mediums like Eileen Davies and Gordon Smith to his personal experiences of clairaudient communication, Michael offers a detailed roadmap for anyone interested in mediumship. We also tackle the common fears surrounding the spirit world and explore how personal development and healing trauma can play a crucial role in enhancing spiritual practices.Whether you're a seasoned practitioner or just starting your spiritual journey, Michael's insights will provide valuable guidance and inspiration for developing authentic mediumship skills. Support the Show.-- SUBSCRIBE in your preferred podcast app!-- Follow @clairvoyagingpodcast on Instagram.-- Send us an email: clairvoyagingpodcast@gmail.com-- Become a Clairvoyager and get access to exclusive extras!Looking to book a distance Reiki session with Lauren?https://www.hellolaurenleon.com/

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.

Soccer analyst Gordon Smith on England unable to breakthrough again at the EURO, CanMNT finish to Copa, impact of manager Jesse Marsch and the fans taking over Hard Rock Stadium in Florida.

Soccer analyst Gordon Smith on Spain winning EURO 2024 and the chaos at Copa and the Redblacks with a huge win on the road.

Soccer Analyst and Commentator Gordon Smith talks all things Copa America with Canada set to face Argentina tomorrow night in the semi-finals.

JR gets Kenny's assessment of the Sens offseason moves thus far, Henry Mews drafted by the Sharks, and Gordon Smith joins the show to talk all things Copa America and Canada Soccer.

AJ Jakubec is joined by former Atlético Ottawa GM and CEO Fernando López, to talk about his decision to join Real Zaragosa in Spain. Then he takes a look around the world of soccer, including Copa and Euro, with Gordon Smith

Welcome ye Freeloaders of the interweb....to another edition of my new Podcast season.

AJ's joined by Gordon Smith to talk Euros and Copa America. Then AJ replays some of his and Graham Creech's interview with Matthew Scianitti talking about Canada's Men's National Team and their performance at Copa

Our soccer analyst Gordon Smith joins Graham and Matt on The Drive to talk Copa America and set up Canada's big match tonight against Peru.

Graham and Matt recap Game 7 of the Stanley Cup Final, Cats avoid all-time choke job, Oilers devastation, Sens trade for Linus Ullmark, and Gordon Smith talks Copa America.

Episode Notes Destinations across Europe are grappling with extreme heat, with soaring temperatures contributing to the deaths of five tourists in Greece. Authorities on the continent are struggling to develop strategies to combat the heat, writes Travel Experiences Reporter Jesse Chase-Lubitz.  Chase-Lubitz notes policy experts in the European Union believe governments are unprepared for the heat despite having access to information about possible heatwaves. European Climate Pact Ambassador Cinzia de Marzo said countries are responding to emergencies instead of putting plans in place to deal with extreme heat.  The World Meteorological Organization released data recently showing that five of the most severe heat waves since 1950 took place in just the past three years. Next, a large number of Asian sports fans have traveled to Europe for the Euro 2024, the continent's soccer championships, reports Asia Editor Peden Doma Bhutia. Online travel company Trip.com Group reported a 125% increase in bookings to Germany from Asian tourists. Bookings from Chinese tourists have registered the largest jump — 132%. A Trip.com executive cited a growing Asian middle class with disposable income as one reason Asian fans are interested in traveling to Germany for the tournament.  In addition, flying to Germany has gotten easier for Chinese travelers, in particular. The number of direct flights from China to Germany has increased by 70% compared to last year.  Finally, JetBlue is making a big change to its baggage policy. From September, the airline will allow all passengers — even those on its most restrictive ‘Blue Basic' fare — to bring a carry-on bag for no extra charge. Airlines editor Gordon Smith gets into the impact.  The policy change brings JetBlue in line with most of its peers. American, Delta, Southwest, and Alaska all allow ‘free' carry-on bags, plus a smaller underseat personal item, across all fare categories.  The move leaves United Airlines as the only major U.S. network carrier to charge its Basic Economy passengers for a carry-on. Come September, United will find itself squeezed on two fronts. Along with all of its more upscale counterparts offering complimentary carry-ons as standard, even ‘ultra-low-cost airlines' are making big customer service improvements.  Get more travel news at https://skift.com.

Season 7 Premiere - Episode 1Greetings, seekers of the supernatural!We're back with a brand new season, and oh boy, do we have some tales to tell.Join me, Clinton Baptiste, your spiritual guide and purveyor of paranormal wisdom, as we embark on a journey filled with revelations, mysteries, and maybe even a dash of the unexpected.But before we dive into the depths of the unknown, let's meet Harry, my trusty tour manager and all-around sidekick. From rubbing elbows with the stars to navigating the quirks of life on the road, Harry's got stories that'll make your head spin.Back in the studio, we catch up with Linda Pollock, refreshed and ready to regale us with her holiday escapades. From airport mishaps to unexpected baggage discoveries, Linda's adventures will have you in stitches.Now, let's delve into the mysterious letter from Rachel Jevons. A childhood encounter with the supernatural resurfaces, revealing secrets long buried in the depths of memory. Prepare for chills as we uncover the truth behind Rachel's haunting experience.But that's not all – we've got heartwarming tales, spiritual insights, and even a bit of ghostly mischief from Gordon Smith to keep you entertained. And don't miss our exclusive interview with Estelle and Ian Chorley, where CCTV takes on a life of its own. See Patreon for Video.Join us on Patreon for access to behind-the-scenes footage, exclusive content, and more spine-tingling stories from the world of the paranormal. And if you want to catch me live, be sure to check out my RollerGhoster tour – coming soon to a venue near you! www.clintonbaptiste.com/tourClint.xCredits:Harry my tour managerKathrine BoyleRacheal JevonsSteve and ryan gardnerChorley Little Theatre Estelle and IanSinger and musician Glowe and ArchieProduced by Alex Lowe and Laurie Peters at PETERS-FOXShare your own spooky stories at clinton@clintonbaptiste.comFind more Clinton Baptiste merchandise at https://ko-fi.com/clintonbaptiste/shop Get bonus content on Patreon Hosted on Acast. See acast.com/privacy for more information.

In this episode of "Chachi Loves Everybody," Dave "Chachi" Dennis sits down with broadcasting titan Steve Newberry. With a career spanning over four decades, Newberry shares remarkable stories and valuable lessons learned from his journey in the radio industry. From acquiring his first radio station at 21 to navigating the complexities of the NAB and leading innovative ventures at Quu, Newberry's experiences are both inspirational and educational.Newberry delves into his early career, recounting tales of entrepreneurial grit and the supportive mentorship he received from industry giants. He reflects on the challenges and triumphs of growing Commonwealth Broadcasting Corporation and the invaluable lessons from his tenure at NAB, including his relationships with influential figures like Gordon Smith. Listeners gain a deep understanding of the strategic decisions and leadership qualities that have defined Newberry's exceptional career. The episode also explores Q's groundbreaking work in enhancing listener experiences through visual radio technology, highlighting the future of broadcasting in the era of digital innovation.Here are a few highlights from the episode: Steve Newberry's journey from small-town radio to industry titanEntrepreneurial struggles, family support, and lessons learnedBuilding a radio station from scratch in KentuckyA partnership with a former governor leads to 35 radio stationsLessons learned from managing radio stations in small marketsNavigating leadership roles and mentorship in the NABLeadership and trust in the broadcasting industryFrom consultant to full-time EVP at NAB navigating political relationships and advocacy in Washington DCManaging construction costs and team dynamicsTransitioning from NAB to CEO of Quu amid COVID-19 challengesEnhancing radio ads with visuals for better retentionThe vital role of radio in community safety and healingThe importance of mentorship and paying it forwardA tribute to leadership and radio industry excellencePeople Mentioned in this EpisodeAntonin ScaliaBill McElveyBrayton JonesCaroline BeasleyCarrie NewberryCharles WarfieldChris ArnellisChuck AndersonDale ThornhillDan MasonDavid KennedyDoug CombsEd ChristianEddie FritzFreddie TravisGene CollinsGordon SmithHoward BermanJack SanderJames NewberryJeff SmulyanJim SpectorJinny MorrisJoe D'AngeloJohn DavidJohn DilleyLou DickeyLyle LovettMark MaysMel CarmezonMichael FiorelliMike NovakMitch McConnellRandall MaysRandy GravleeRuss WithersRuth Bader GinsburgSenator Rand Paul Enjoyed this episode of Chachi Loves Everybody? Let us know by leaving a review!

Welcome to Episode 165 of The Darlington Podcast! In this special Commencement episode, listen to Gordon Smith ('71), chairman of the Board of Trustees and retired executive director and chief operating officer of the United States Tennis Association, give his Commencement address on May 18. Smith reminds graduates that the tools they've received at Darlington enable them to change the world and become the people they most want to be, noting that his own Darlington story didn't end when he graduated, but that it had only just begun.Click here for complete show notes >>

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.

Today on Sense of Soul podcast we have back Phill Webster he is a writer, actor, a knowledgeable confident speaker and spiritual teacher. After living abroad for 20 years, he returned to the UK and ventured into acting. He has since gone on to appear in movies alongside Sylvester Stallone, Benedict Cumberbatch, and Elle Fanning, among others. Last year Phill came on Sense of Soul to share his book Letting Glow which was his first book, and a profoundly personal account of grief after losing his mother in 2021. Phill realised that he had been dismissing spiritual calls to action his entire life.  Phill has trained with Indigenous Shamans from North and South America, as well as world-renowned mediums such as James Van Praagh, Gordon Smith, and Claire Broad. Phill has also studied Female Spirituality In The Middle Ages at the University of Barcelona, and is a trained meditation teacher as well as a personal trainer. He joined me again to share his newest book Glowing Deeper, from ancient teachings of indigenous shamans to Celtic folklore, right up to modern-day mediumship, he expands on the teachings of his first book Letting Glow and takes a practical approach to demystifying the mystical, enabling us to implement ancient esoteric truths in our daily lives. https://phillwebster.com www.collectiveinkbooks.com/o-books/our-books/glowing-deeper-letting-glow-trilogy Learn more about Sense of Soul at www.senseofsoulpodcast.com
  

With earnings season well underway, Gordon Smith and Jay Shabat examine the key trends and finer details from JetBlue and Volaris - two of the largest low-cost carriers in the Americas.

The trigeminal autonomic cephalalgias are a group of headache disorders that appear similar to each other and other headache disorders but have important differences. Proper diagnosis is crucial for proper treatment.  In this episode, Gordon Smith, MD, FAAN, speaks with Mark Burish, MD, PhD author of the article “Cluster Headache, SUNCT, and SUNA,” 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. Burish is an associate professor at UT Health Houston in Houston, Texas. Additional Resources Read the article: Cluster Headache, SUNCT, and SUNA Subscribe to Continuum: continpub.com/Spring024 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 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'm interviewing Dr. Mark Burish on cluster headache, which is part of the April 2024 Continuum issue on headache. Dr Burish is an Associate Professor of Neurology at the University of Texas Health Science Center at Houston, which is located in Houston, Texas. Mark, thanks so much for joining me today on Continuum Audio. I was really excited to be asked to talk with you about this article. When I recertified from my boards the last time (and actually, it will be the last time I have to take the exam), I did the AAN course on all of neurology. And I'm a neuromuscular guy, right, and so I was actually kind of worried about the headache part because I thought, “How interesting could that be?” And I was blown away at how fascinating headache has become, and in particular, your topic (cluster, SUNCT, SUNA, the trigeminal autonomic cephalalgias) - such a great topic. But before we start talking about them, I'd love to just hear more about how you got interested in this area - both headache, this topic in particular. What's your story, Mark? Dr Burish: Well, thank you very much for having me. I'm honored to be part of this. I got into headache probably the way many people do; is, in residency, you figure out what you like, and your residency clinic tends to start collecting patients that you like (not that you're trading them with other residents, but you see certain patients). And mine (by the end of residency) had a lot of headache and pain patients into it. Then, I was very fortunate and had the opportunity to do some research as part of my career. I'm an MD-PhD, and I spend about half my time now doing research on cluster headaches, so I'm very fascinated by these types of diseases. Dr Smith: Can you tell us really briefly what you're working on in your research? Dr Burish: Cluster headache is such a poorly researched area. There's not a lot of people in it, so we do a little bit of everything: we have a clinical trial going; we do some basic science on the circadian mechanisms (cluster gets this very weird timing to it, where the headaches happen same time every day); and we do a little bit of starting to wade into the genetics. Dr Smith: Well, super exciting. I was actually blown away by the statistics on cluster (as common as multiple sclerosis), and the severity of pain I was amazed to learn is above that of childbirth (it was, like, between nine and ten out of ten, which is really crazy). And I'm worried that I missed these patients in my neuromuscular clinic. So, maybe we can begin by - just tell us what you think our listeners need to know. If they have to drop off right now, what message do they need to remember from our conversation? Dr Burish: I think there's two things. First of all, the first-line treatments for these headaches have not changed recently. For cluster headache, you still treat it with oxygen, the triptans (the faster triptans; not the oral ones, but the injectables and nasals), and you prevent them with verapamil. For SUNCT and SUNA, you use lamotrigine. So, those have not changed over time. There are some new treatments, which we'll talk about later. Then the second point is, there are four different types of headaches in this family and they all look very, very similar (one-sided pain, autonomic features, ipsilateral lacrimation, rhinorrhea - that type of thing). They differ in the treatments and how long they last. If you get them wrong (if you misdiagnose them), you're probably not going to give them correct treatment. Indomethacin works very well for two of them (the ones with hemicrania in the name, so not the ones we're going to discuss today). And then SUNCT, SUNA, and cluster headache - indomethacin does not work very well. So, it's important to distinguish them and get them right. Dr Smith: Maybe we can start there, Mark. I mean, I was kind of appalled to learn that the average delay in diagnosis is four to nine years in your article, and given the severity of pain and the impact it has on these patients, that's clearly a challenge. What's so hard about this? And do you have pearls on how we can recognize these patients? And how do you sort this out practically in clinic? Dr Burish: For cluster headache patients especially, it is a lot more common than we would think it is, but it still goes misdiagnosed, partly because most cluster headache patients are episodic. So, there's an episodic version where you get them every day for a few weeks and then they might go away for a year. So, I think what happens is that patients start to get into a cycle and they either get confused for sinusitis (because it happens in the spring), or they schedule a visit with a neurologist or somebody else, but the headaches are over by the time they see them, and they cancel the visit. So, I think they get misdiagnosed partly because it's either confused or they don't see doctors fast enough. I think a little bit more awareness of what this disease is and then, somehow, a mechanism to get these patients in a little bit more urgently is probably what's necessary. Dr Smith: Well, Mark, access is a real issue in neurology more broadly, and I'd love to talk to you about that in a moment, but I wonder if we could go back. You talked about how similar these are to one another, yet the treatments are different. How do you sort out the diagnosis when you're seeing a patient? Let's say you have someone who comes in who has episodic, unilateral, very severe pain and some of these autonomic features. What are the pearls for differentiating cluster, SUNCT, and SUNA from each other? Dr Burish: The big difference between all these different headaches is the timing. As a general rule, SUNCT and SUNA attacks last seconds (they're very similar to trigeminal neuralgia); paroxysmal hemicrania (that's one of the hemicrania ones, where indomethacin helps) - those attacks last minutes; cluster headache attacks last about an hour; and the hemicrania continua is constant (that's the other hemicrania one where indomethacin works). The other part is how often they happen. Again, SUNCT and SUNA - very similar to trigeminal neuralgia, may happen hundreds of times a day; paroxysmal hemicrania - dozens of times a day; cluster headache - maybe a handful of times; and then, hemicrania is constant. Based on how long the attacks are and how frequent the attacks are, you can generally separate them out. And if you're not sure, just try indomethacin. And then if it doesn't work, you're trying to distinguish between SUNCT and SUNA, which lasts seconds, and cluster headache, which lasts an hour, so fairly easy to distinguish those. Dr Smith: How long does it take to medicine to work in a patient with hemicrania continua or paroxysmal hemicrania? I'll remind our listeners - there's a separate article in the same issue of Continuum on that topic - but for our purposes, let's say you try that; how long do you need to try it? Dr Burish: Yeah, there's a great, another article about how much to give and how it works. It is generally pretty quick. I have noticed with most patients that the onset is twenty-four to forty-eight hours. And then, if you stop the medicine, the same thing - offset is kind of twenty-four to forty-eight hours. So, patients know pretty quick whether it's going to work. Dr Smith: Wow - that's awesome. One of the things I was interested in was so-called “secondary cluster.” So, you've seen your patient and let's say you've diagnosed them with cluster (primary cluster). Do you do additional testing? Do they need imaging or other laboratory workup? Dr Burish: Yeah. The differential for cluster (and cluster is the one that we know the most about; it is the most common of all the trigeminal autonomic cephalalgias) - it's a fascinating differential. If you don't know much about them, migraine is probably the most common. If you do know a lot about them, hemicrania continua and paroxysmal hemicrania are very common. But there's all these secondary headaches that can look identical to cluster headache; these pituitary hormone-secreting tumors (prolactinomas) - things like that. So, because all these other secondary causes can happen, they generally recommend everybody gets an MRI of the brain, with or without contrast. If that is normal and the patients continue to not respond to the medicines like you expect them to (verapamil doesn't work, oxygen doesn't work, and so forth), then you might do some additional testing for pituitary bloodwork. So, just kind of a panel of hormones, looking at blood vessels (because there are some cases that dissections or AVMs can cause cluster headaches). And then sometimes get imaging of the apex of the lung because there's some data that - with the Horner syndrome - that that might be relevant. Dr Smith: I'll refer our listeners to your article, just in general, because they really need to read it. It's fantastic. But your discussion about the neuroanatomy is really cool, and probably more than we want to get into right now, but the intersection of the neuroanatomy with therapeutics, and some of these other potential etiologies. So, one thing I was really amazed by (or appalled by, frankly) was the frequency with which these patients have suicidal ideation, given the severity of the pain and, I assume, the long time it often takes to get this sorted out. How do you handle that in clinic? Do you have conversations with people about this? How often do you appreciate it? And any words of wisdom for those of us who might encounter these patients? Dr Burish: Yeah. It's not hard to imagine why patients would be suicidal with this. When you have pain that is a ten out of ten - and patients who have also had childbirth and cluster, they consider childbirth more around a seven - so you can imagine how painful this is and what thoughts might be going through people's heads. It tends to be (in my personal experience and some emerging data) that they are suicidal during a cycle. So, for these episodic patients (most patients are episodic with cluster headache for a few weeks), they are suicidal during those weeks. And when the headaches go away, much less risk of suicide. So, during the cycle, I try to get my patients in as fast as possible, get the medications in as fast as possible, but basically just be there to let them know that we have options, and so that they consider me as their first option, rather than something darker. Dr Smith: How successful is first-line therapy in these patients and what's your success rate with your initial attempt at treatment? Dr Burish: On the acute side, the as-needed medicines (sumatriptan, oxygen) - if you give an injection (not the oral; that takes too long) - incredibly effective; for most patients, one or both of those will work. We usually prescribe both because the injections - usually you can't get that many (they can be quite expensive, realistically speaking). But also, just practically speaking, patients can have headaches up to eight times a day and you're not really supposed to be taking sumatriptan eight times a day, so we also give oxygen (but then again, oxygen is not very portable, so that's where the sumatriptan comes in). On the preventive side - not great. There's been some studies suggest maybe fifty percent is as good as any preventive is going to work for you, and that's not considering side effects and other things that patients might stop them. So, we do need to have a few different preventive options and you may have to go through a few different things. Chronic cluster headache (which is the more rare version, where patients have them year-round) is anecdotally much more refractory to treatment. Dr Smith: Can you talk a little bit about bridge therapy? You differentiate bridge from prophylactic therapy in your article. Dr Burish: Yeah. When you're approaching one of these patients - let's say they're completely naive to any medications - usually we will give them a couple of as-needed, acute medications (sumatriptan injections and oxygen). We'll give them a preventive like verapamil, but the verapamil takes a few weeks to kick in. So, the obvious question is, “What am I supposed to do in the meantime, while you're ramping it up and it's kicking in?” So, we use these short-term preventives, which we call bridge therapies or transitional therapies. These are short-acting preventives; they kick in quick, but you can't take them for very long. The most common by far is prednisone. Or an occipital nerve block with some sort of steroid (so, steroids in some sort of fashion). We will usually give them right at the beginning of a cycle (right at the beginning of a flare for chronic cluster headache patients) while we are uptitrating something like verapamil. Dr Smith: This may be a really silly question, but the next time I see one of these folks and I want to start oxygen, how do I do it? What are the logistics of giving someone oxygen for this, and how do patients navigate that, right? If you're having eight attacks a day during a cluster and you work as a nurse in the headache clinic, you probably have oxygen there. But you get where I'm going, right? - it's logistically challenging. How do you order it, and do you have words of wisdom to make it easier for patients to use? Dr Burish: There's a whole kind of system of oxygen, durable medical equipment - stuff that I've had to learn. To boil it down, there are basically two types of oxygen. There's a concentrator - kind of just a machine that takes room air and turns it into about ten percent oxygen - that is sometimes effective for patients. But sometimes ten liters per minute (which is the highest that can give) is not enough and you need fifteen liters per minute. In that case, you need an oxygen tank (the big metal cylinders that you see with a extra device on top called a regulator, that can crank it up to fifteen liters a minute. For both of these - fifteen liters a minute - you're going to need a mask. The nasal canula is just - it doesn't get up to fifteen; it's not going to be enough, so we give you this bag mask (the non-rebreather mask, or the bag hanging out below it). You really need high dose, pure oxygen for these things to work, so you have to write orders that say, “fifteen liters a minute, with regulator and non-rebreather mask.” Dr Smith: I'll refer our listeners to your Continuum article. I know a lot of our listeners use Continuum at point of care. And, of course, you can access it electronically, so there's really great pearls there. Another question for you: CGRP agents have really transformed migraine; what role do they play, if any, in management of these headaches (cluster, SUNCT, and SUNA)? Dr Burish: I think this is a fascinating emerging area of cluster headache research. One of the studies in the last three years came out that it was successful for episodic cluster headache, called galcanezumab, and it did not work for chronic cluster headache. Meanwhile, a couple other CGRP companies have tried them and they were unsuccessful, at least according to the data on ClinicalTrials.gov. And some other CGRP studies are still emerging. We know that both migraine and cluster headache work on the trigeminal system (I mean, this is a trigeminal autonomic cephalalgia - it's in the name) and CGRP is involved in the trigeminal system. That's probably where the commonality between migraine and cluster headache come from - they both work on the same pain system. But why all of them seem to work for migraine and only some of them – you know, some of these medicines work for cluster headache - is a fascinating thing. Does that mean that we don't have the dose right? Does that mean that we don't have the timing of these clinical trials right? Does that mean it's just not as effective? And there's other things that are involved in cluster headache - it's an interesting mechanism that we can start to explore. Dr Smith: I wanted to learn more about the circadian aspects of this - I found that really interesting, and you commented that you're interested in that in a research perspective. Can you describe that phenomena a little bit and just tell us what your thoughts are? Dr Burish: The interesting thing about cluster headaches, specifically, is that the headaches happen, for most patients, the exact same time every day – so, within an hour each day. So, my patient usually will say, “They're at two AM.” Across different time zones, every study that's been done - well, not every study, but many studies have been done - two AM is the most common time of day. But if you ask an individual patient, patient number one will say, “They happen every day at two AM; patient number two will say, “They happen every day at three in the afternoon.” I had a patient who was, I think, kind of getting fed up with all the questions I was asking about his headaches, and he said, “Dr Burish, it's three o'clock; if you want to wait until three fifteen, I'm going to get a headache - you can see what it's like.” That's how sure he was about when the headaches were going to happen. And other than maybe hypnic headache, there are a few other headaches that have that level of circadian predictability. So, it's just an odd, curious, unique thing to these headaches and we don't quite understand why yet. Dr Smith: So, I'm curious if the time of day patients get their headaches is in any way correlated with other aspects of sleep phenotype, right? There's broad variability in your sleep phase - the length of it, when it starts and ends. Is there any relationship, in your experience, between the time of day (two AM, ten PM) and other aspects of their sleep? Dr Burish: We haven't seen that, to my knowledge. People have looked, for example, at sleep studies while patients are having attacks. These attacks occur out of REM sleep, non-REM sleep - it doesn't seem to matter. Anecdotally, patients will say, “My cycle last year - I had headaches every day at two AM. But my cycle this year - I have headaches every day at five in the afternoon.” So, even a same patient who, theoretically, is not having big sleep changes over different years, has different timing of attacks. Dr Smith: Mark, what's the latest thing? What's most exciting in the field that you can tell our listeners about? Dr Burish: There are a lot of new treatments for cluster headache. There's the galcanezumab, which we discussed a little bit. There is a new dose for prednisone. We weren't sure how effective it was; now we're using kind of neuroimmunology-level doses of prednisone (100 milligrams daily; kind of titrating down from there). And then there's an occipital nerve stimulator for the chronic cluster headache patients. Since the last Continuum review on this topic, these three trials have been successful, and I think what gets lost is how impressive each one of these is in different ways. The prednisone study is impressive because you had to study that medicine (which we thought worked but didn't have a good clinical trial), and it's really hard to enroll patients in a placebo-controlled study where you already think it works. Another was done by a large pharmaceutical company. This is not an advertisement for or against, but these companies have rarely ventured into studying cluster headache until recently. The third study, the stimulator study, was a ten-year, multisite study involving surgeons and neurologists - just a monumental effort. It's because of these impressive studies that we now have data on how to treat the patient. Dr Smith: Just so interesting. I tell you what - I mean, if you told me twenty years ago I would be this interested in headache, I would have said, “You're crazy.” But now I see why our residents are so interested in it and why you are. This is fascinating. I could keep going for another hour or two asking you questions, Mark, but maybe we can pivot back to where we began. You told us your story about enriching your resident clinic - and for those residents listening, those are words of wisdom right there, my friend. But here's my question for you: we've already talked about access to care and how you manage access for these patients, but we have a huge access issue in neurology broadly and we desperately need more neurologists. As you're probably aware, there are some of our colleagues that don't think pain is neurology (I'm not one of them, but I know some of them and respect them otherwise). If there's an access issue for neurology, there's a access crisis for pain neurologists. And you don't just see headache, as I understand it; you see other patients with pain. So, I want to give you the last few minutes of our Continuum Audio episode to do your pitch, right? What do you have to say to the residents that are listening to us (or students) about why you find managing pain so rewarding and why they should consider this as a field? Dr Burish: Yes - I also did a fellowship in pain medicine, in addition to my headache research, so I see a little bit of both. For me, the patients are very appreciative because you are talking with them about what they are interested in. They are not interested in the change in the MRI between last time - I mean, they are interested in it, but not as much as, “I hurt today.” So, patients are more than happy - they're very grateful that you are addressing their primary concern, the thing that they're going home with that day that they're worried about. For me, seeing these patients has been very rewarding. From the research side. I think it's fascinating that there's just not enough research in this area - you can create your own niche; you can look into your own mechanisms - there's just not a lot of people in this field. And then, I think from a clinical side, other than the rewarding nature of it, there's a lot of options that we have. There's all of these neuropathic medications; there's all these different headache medications. If you want to wade into the procedural side of things (which I did with pain management), you can get into fluoro-guided procedures and spinal cord stimulators and all these different options that we have for these patients that help them, in addition to whatever they're going through. I have patients that then come back and say, “Well, by the way, I have these seizures; do you mind helping me kind of just go through my antiepileptics.” And they're generally well controlled and they consider me kind of a general neurologist for them. So, I've found it extremely rewarding and I wouldn't do anything different. Dr Smith: Well, that's really great information and I hope our resident listeners will take that to heart. Your article is truly amazing, Mark. I can't tell you how much I was impressed with it, and for our listeners - you gotta check it out. I've got a list of ten other things on my piece of paper here I could ask Mark about, but I think we're probably at time. So, Mark, thank you so much. Congratulations on an amazing article and really fascinating and exciting area of neurology. Dr Burish: Thank you. Thank you very much for having me. Dr Smith: Again, today we've been interviewing Dr Mark Burish whose article on cluster headache - appears in the most recent issue of Continuum, which is on headache. Be sure to check out Continuum audio podcasts from this and other issues, and thank you very 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. 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.

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