Continuum Audio

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

Posttraumatic Headache With Dr. Todd Schwedt 05/01/2024

Posttraumatic Headache With Dr. Todd Schwedt Posttraumatic headache is an increasingly recognized secondary headache disorder. Posttraumatic headaches begin within 7 days of the causative injury and their characteristics most commonly resemble those of migraine or tension-type headache. In this episode, Aaron Berkowitz, MD, PhD, FAAN, speaks with Todd Schwedt, MD, FAAN, author of the article “Posttraumatic Headache,” in the Continuum April 2024 Headache issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of neurology at the University of California San Francisco, Department of Neurology and a neurohospitalist, general neurologist, and a clinician educator at the San Francisco VA Medical Center and San Francisco General Hospital in San Francisco, California. Dr. Schwedt is a professor of neurology at Mayo Clinic in Phoenix, Arizona. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the Academy of Neurology: Social Media Host: Guest: 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 Berkowitz: This is Dr Aaron Berkowitz, and today, I'm interviewing Dr. Todd Schwedt about his article on post-traumatic headache from the April 2024 Continuum issue on headache. Dr. Schwedt is a Professor of Neurology at Mayo Clinic in Phoenix, Arizona. Welcome to the podcast today, Dr. Schwedt. Dr Schwedt: Well, thanks so much. It's a real pleasure to be here. Dr Berkowitz: Thanks. We're very happy to have you. So, head trauma is common, and headache following head trauma is also very common. Let's say you're seeing an otherwise healthy young patient in your clinic who had a minor car accident a few weeks ago with some head strike and whiplash, presenting now for evaluation of headache again a few weeks out from the accident. Walk us through your approach to the history and exam here when you're seeing one of these patients. Dr Schwedt: Yeah, absolutely. I'd be happy to do so. I'll start by saying, as you mentioned, this is such a common problem - patients that are coming in with post-traumatic headache). Of course, like almost everything in neurology, it's super important to get a detailed history to start with (so, doing the appropriate interview), and I usually like to start by getting some information about the injury itself - the mechanism of the injury, and the severity, and, of course, the symptoms that went along with the potential traumatic brain injury – so things we all know about. Then, of course, it's very important to understand how the patient felt prior to the injury because we know that, amongst people presenting with post-traumatic headache, oftentimes they might have had headaches even prior to their injury, and that's because having preinjury headaches is a risk factor for developing post-traumatic headache, as well as the persistence of that post-traumatic headache. If someone had headaches prior to their injury, then of course we want to know if that actually changed or not - is there a difference in the severity, or the frequency, or in the characteristics of the headaches they've been experiencing since their injury? Then, of course, you're going to ask about exactly what the symptoms are they're having now and what's concerning them the most, realizing that for a diagnosis of post-traumatic headache, it’s very important to understand the timing of the onset of these headaches in relation to the injury. By definition, post-traumatic headache should have onset within seven days of the inciting traumatic brain injury - so the diagnosis of PTH, I mean, really is dependent upon that timing - so, using ICHD (which is International Classification of Headache Disorders) criteria, it's got to start (or be reported to have started) within seven days. It's important to realize there are no specific headache characteristics that help to actually rule in or rule out post-traumatic headaches; the criteria themselves just say “any headache,” as long as it was within that seven-day period. Having said that, though, the vast majority of people who come into the clinic for evaluation - their post-traumatic headache is going to be very similar to migraine. So, like, in other words, if they didn't tell you and you didn't ask about when the headache started and you just asked about symptoms, it would seem a lot like migraines – so, very common for the headache to be moderate and severe in intensity, be associated with light sensitivity and sound sensitivity and nausea, be worse with physical and mental exertion (very much the migraine-type characteristics). As far as diagnosis, it's also, of course, important to think about other sequelae of traumatic brain injury that could be causing the headache. For example, if you're under the impression it's a mild traumatic brain injury, but in fact, there's an intracranial hemorrhage - it wouldn't necessarily be mild any longer, but of course, that could cause headaches. We should be thinking about whether there could have been injuries to the cervical spine or the musculature of the neck that could be causing more of a muscular, cervicogenic-type headache. Think about rare possibilities, like if there was a cervical artery dissection, or if there's actually a spinal fluid leak, or, again, other things that after an injury could be causing headache. Most of the time, that's not going to be the case and you would move forward with your diagnosis of post-traumatic headache. Dr Berkowitz: Fantastic. That's very helpful to hear your approach. You just mentioned, as you said, most patients who've had minor head trauma and are presenting with headache, fortunately, have not suffered a cervical artery dissection or CSF leak or have an evolving subdural. But when you're in this early stage (just a few weeks after the initial injury) and there is headache, what features of the history or exam would clue you into thinking that this patient does need neuroimaging to look for some of these less common, but obviously very serious, sequelae of head trauma? Dr Schwedt: So, it's things that, as neurologists, we all know about, right? But certainly, if you're concerned about a spinal fluid leak, then really someone who has a prominent orthostatic component to their headache (so, you know, much worse when they sit up or stand up, compared to lying down) could be concerning. With a cervical artery dissection, almost always you're going to have focal neurologic deficits in addition to the headaches. With intracranial hemorrhage - again, usually it's going to be fairly obvious, in that the symptoms that someone's presenting with are much more diffuse and more severe, and maybe they're actually having progression of symptoms over time rather than stability or even early improvement. Then, as we would always say, the exam is essential, right? I mean, certainly someone who's had a mild traumatic brain injury might have very subtle deficits in things like their cognition and memory of events around the injury itself - and perhaps some ocular motor deficits and some vestibular dysfunction - but they should be relatively minor compared to somebody who has one of these other etiologies for a postinjury headache. We'll point out, of course, not everyone requires imaging, again, as there's all these decision rules out there about who needs CT, for example, after an injury (and certainly not everyone does). But, you know, if people have red flags, then of course it makes sense to initially get a CT of the head, and then if symptoms persist, perhaps an MRI. Dr Berkowitz: So, once you're confident that this is a primary headache disorder - and presuming again (as in the example I gave to start us off here) that we're just a few weeks out from the initial trauma - and the patient’s presenting to you for evaluation of their headache, how do you approach treatment in these patients? Dr Schwedt: Yeah, so the specificity of your question, I think, is actually quite important - so considering the timing of when you're seeing that patient really is essential. So, if we're a couple weeks out or a few weeks out and the person is still having symptoms, that tells us something to start. The majority of people who have postconcussion symptoms are going to have resolution within a few days, or a week or two, so if someone's still having symptoms at, let's say, two weeks, three weeks, four weeks, well, then that’s an indicator that, unfortunately, they're likely to continue to have symptoms for some time - when we want to be a little more aggressive, if you will, with the diagnostics and management of that patient. So, like, very early on - let's say within the first few days, or even the first week or two - some patients won't require any treatment. So, if they're having mild headaches, and maybe they take something over the counter every once in a while as it gets a little more severe, that's oftentimes fine, actually. If someone's having much more severe problems with headache (even in that very acute setting), then maybe we would give them a prescription medicine just to take for their more severe headaches. But then as symptoms progress and persist, then we should of course be thinking about other ways to - in more of a preventive approach of how to - help the patient, because, unfortunately, we don't have high-quality evidence for how to treat both acute and persistent post-traumatic headaches. The recommendation for many years (and it continues to be) is that you determine the other headache type that the PTH most resembles and you treat it like that. For example, if someone has PTH and a lot of migraine symptoms, well, then you would treat it like migraine. That might mean actually giving people specific acute migraine medications. It might mean, perhaps, putting them on migraine-preventive medications. Certainly, using other forms of therapy besides medications - maybe physical therapy is needed if someone has a lot of muscular involvement of the neck. And if they're having vestibular dysfunction from the injury, maybe they need vestibular rehab. Cognitive behavioral therapies - there's some evidence, at least, to suggest that can be helpful after an injury - so, kind of the multimodal approach. We need to make sure that people are getting good sleep, or doing what we can for that to occur (we know that sleep problems, including insomnia, are quite common after a concussion, for example), and really making sure that we're treating the whole patient. The person who is still having headaches at multiple weeks after their injury - likely they're still having other symptoms, too (some of which I just named, but other symptoms as well), like symptoms of autonomic dysfunction are quite common (like orthostatic problems; autonomic type of orthostatic problems) after an injury, cognitive problems, emotional issues - people probably are anxious and not feeling well. A lot of these folks are quite healthy prior to their injury, and all of a sudden, they have, really, a significant problem, and maybe they’re missing work and missing school, and so we really have to treat the patient as a whole, of course. Dr Berkowitz: Along those same lines, I was wondering - at this early stage - the patient has had still relatively recent head trauma (they are a few weeks out from this initial injury) but still having symptoms which, as you importantly highlighted, can go well beyond headache and a number of other neurologic symptoms they might have. Very common for the patient to ask, “How long is this going to last? How long am I going to feel like this?” How do you counsel patients? Obviously, the outcomes are very variable. How do you counsel patients as an expert here, based on seeing so many of these patients a few weeks out - as you said, an otherwise healthy patient, minor head trauma, having headache, and potentially even other concussion symptoms as you mentioned - how do you counsel them on what to expect? Dr Schwedt: I'll start by saying that this is an area of really high interest to me and my research team, as well as my clinical team - so we're not good enough yet in being able to actually predict recovery and the timing of that recovery - but this is an absolutely essential point, and for multiple reasons. The main reason is based on the question you just asked. Of course, our patients want to know, “When am I going to get better? How long is it going to take? When can I get back to my normal life (whether that be work, or playing sports, or military, or other scenarios)?” – so, that's the most important reason. And it's important as well, because from the clinician’s standpoint, if you know (or if you think you know) based on prediction that someone's highly likely to continue to have symptoms – well, again, that might help you make the decision about how (you know, I'll use the word aggressive) to be with their treatment and how closely to have them follow up, and this type of thing. It’s also important for research. I already mentioned that, unfortunately, there really isn't decent quality evidence (for example, for what treatments to use for post-traumatic headache), and part of that reason for that is that there have been attempts at large clinical trials, and they've failed in a sense, and I think part of the reason for that is because there is, fortunately, such a high rate of natural resolution of symptoms that if you end up enrolling those patients into these prospective clinical trials, it makes it difficult to actually study any difference you might see between a treatment and your placebo. So, if we can have and develop good, clinically useful predictive models, that would really help in each of those domains. So what do I do now? I mean, basically, it's a little bit of a cop-out answer, but what I do is, I try to look at the trajectory that the patient has had thus far (and so, you know, this is all just logical and obvious), but if a patient is already having some degree of improvement - even if they still have symptoms, but they're having some improvement over those first three weeks - well, you would more or less consider the slope of that recovery to persist more or less at the same level. On the flip side, though, if someone's there and it's been multiple weeks - and they've just had absolutely no recovery and maybe they're even feeling worse - then I'm more concerned that this might be a longer-term issue. Dr Berkowitz: That's helpful to understand both your approach and the challenges in making a firm statement on counseling our patients and using (as has been a theme in many of your helpful responses today) just, sort of, the clinical trajectory and what information that patient's giving you to try to help with the prognosis (however ambiguous it may be) and just needing time to see how the patient does. Dr Schwedt: I might just add as well, though, that there are studies that have suggested there are certain risk factors for prolonged recovery from post-traumatic headache (and there's some limitations to these studies, so, really, validation is needed), but for post-traumatic headaches specifically, I mean, probably the biggest risk factor for persistence of the post-traumatic headache is having headaches prior to the injury. So, for example, people who have migraine before TBI that then are having an exacerbation or a new headache after the injury - unfortunately, they're less likely to have resolution during the acute phase. Other factors include the severity of the injury itself - so there are certain features of the injury that if, you know, it is seemingly more severe, maybe their likelihood for resolution in the acute phase is lower. And then there are multiple other factors that have been suggested as well, including the patient's own expectations for recovery, which I find to be quite an interesting one. Dr Berkowitz: Yeah - very important points. So, let's say that, unfortunately, the patient does continue to have headache now several months out after the trauma; how do you approach these patients with respect to treatment? Dr Schwedt: Yeah. Once someone's gotten to that point, they probably really are going to need more in the way of preventive measures (and, you know, I did mention some of these). So, if someone's having migraine-like PTH, well, then I'm probably going to end up putting them on medicines that I would use for prevention of migraine. You know, you do have to be especially careful, though, in these individuals who have had TBIs, because you want to make sure that the treatments you're starting aren't going to actually exacerbate their other symptoms, right? So, of course we know some of our migraine preventives can cause things like hypotension, or, you know, cause things like insomnia or cognitive problems, as side effects, and if people are already having those issues from their TBI, then we could actually make them overall feel worse even if we make some progress for their headaches. So, you know of course, we're always careful when thinking about side effects from these medications, but especially so, perhaps, in the patient with a concussion who's having some of these symptoms anyway. And then again - just to highlight, it's not all about medication - that's one small aspect here (one important, but perhaps small, aspect here). So, really, trying to get at lifestyle measures that can be helpful - so, again, sleep, and trying to help people to moderate their stress levels, and making sure that they have an environment that's going to facilitate the recovery (meaning, if they're having a lot of light sensitivity and sound sensitivity and these types of things, you know, doing what we can to help these individuals to be in environments that will allow them to recover). Dr Berkowitz: Yeah, all very important points - medication being just one part of treatment for these patients, as you said. But to just ask another question about medication so our listeners can learn from your expertise - I'm a general neurologist, and my experience with patients with post-traumatic headache and migraine and otherwise is that it's hard to predict who will respond to which medication (and some patients who failed many pharmaceutical medications will have an amazing response to riboflavin and vice versa) - in your experience (acknowledging that we are very limited in terms of data here), are there any migraine prophylactic agents that you feel, anecdotally, have been particularly helpful in patients with post-traumatic headaches or similar to the general migraine/tension headache population? It's very hard to predict, and it's trial and error and picking the right medication and finding the right dose (just depends on the patient). It requires the patient’s patience - and our patience as well - as we sort of go... /episode/index/show/continuumjournal/id/30596918

Cluster Headache, SUNCT, and SUNA With Dr. Mark Burish 04/24/2024

Cluster Headache, SUNCT, and SUNA With Dr. Mark Burish 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: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: 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,... /episode/index/show/continuumjournal/id/30631383

Acute Treatment of Migraine With Dr. Rebecca Burch 04/17/2024

Acute Treatment of Migraine With Dr. Rebecca Burch Most patients with migraine require acute treatment for at least some attacks. There is no one-size-fits-all acute treatment and multiple treatment trials are sometimes necessary to determine the optimal regimen for patients. In this episode, Teshamae Monteith, MD, FAAN, speaks with Rebecca Burch, MD, FAHS author of the article “Acute Treatment of Migraine,” in the Continuum April 2024 Headache issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Burch is an assistant professor in the Department of Neurological Sciences at Larner College of Medicine, University of Vermont, Burlington, Vermont. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: 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 turned after the episode to get CME for listening. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. Today I'm interviewing Dr Rebecca Burch on acute treatment of migraine, which is part of the April 2024 Continuum issue on headache. Dr Burch is an Assistant Professor at Larner College of Medicine at the University of Vermont in Burlington, Vermont. Well, hi, Rebecca - thank you so much for being on our podcast. Dr Burch: Thank you so much for having me. It's always such a pleasure to talk with you. Dr Monteith: You wrote a really excellent article on acute management of migraine - really detailed. Dr Burch: Thanks so much. I'm glad you enjoyed it. I had a lot of fun writing it. Dr Monteith: Why don't you tell our listeners, what did you set out to do in writing this article? Dr Burch: Whenever I write a review article on a topic, I aim for two things, and these were the same things that I was aiming for here with this one. One is practicality and just for it to be really applicable to clinical practice and every day what we do - the ins and outs - and that was the case here as well. I really love a good table in a paper like this. I spend a lot of time on tables. I want people to be able to print them out, use them as reference, bookmark them. So, that was one thing that I aimed for - was just for this to be really useful. The other thing is, I really wanted to instill a sense of confidence in people after reading this article. I think the management of migraine can be very overwhelming for people taking care of people with migraine. And there are so many acute treatment options, so I wanted to give a framework for how to think about acute treatment (how to approach it), and then within that framework, to really go into the nuances of all the various options, and how to choose between them, and what to do in specific circumstances. And I also really wanted to cover what to do when the first couple of options don't work. Because I think most neurologists, PCPs, are comfortable prescribing sumatriptan, and then the question is, what happens when that doesn't work or the patient doesn't tolerate it? What do you do for rescue therapy? What do you do for your fifth-line treatment? And I think that was an area that I really wanted to cover as well. Dr Monteith: Yeah, you got a lot done, for sure. So, I agree - there's been so many options, new options, even over the past five or definitely ten years. One of the things that excited me about going into headache medicine were all the options, thinking of migraine and other headache disorders as a treatable disorder. What made you interested in headache medicine? Dr Burch: Like so many other people who ended up going into headache medicine, I had a fantastic mentor in residency who was really great at treating headache patients - as Brian McGeeney at Boston Medical Center (he's now at Brigham and Women's). He was really passionate about headache medicine, and seeing patients with him was always such a delight because he always had something to try. And many other situations, it would be, like, “Well, this person, we've tried something; we don't know what else to do.” But when you work with a headache specialist as a mentor or as a preceptor, they have so many things they can do, and people largely get better. And they're so grateful - it changes people's lives to be able to treat their migraine, their other headaches effectively. So that was really inspiring. And then when I started doing headache rotations and sort of thinking about whether this was the right subspecialty for me, I quickly realized two things about headache medicine that ended up being what I really love about it to this day. One is the longitudinal relationships that we have with patients - we take care of people for a long time. And it doesn't always have to be that we're seeing people every three months and making tweaks - sometimes it's once a year. But we do get to know people. You know, I have two children. Many of my patients saw me through both of those pregnancies and ask about my kids, and it's just lovely to have that sort of personal relationship over time. And then the other aspect that I really love is that we can't see patients in isolation just as their migraine disorder or headache disorder; we really have to think about who they are as a whole person. What's going on in your life? What are your stressors? How's your job, how's your family? How are you sleeping? How's your mood? Are you exercising? What's your diet like? All of these things impact how someone's migraine disorder is going. And I like to joke, “I'm half life coach, you know, and half pharmacologist,” and I love that. I love that I bring my whole self every time I see a patient and see their whole self, too. Dr Monteith: I can just imagine how well you do that. You mentioned the power of mentorship, and that seems to be a theme when interviewing authors (that mentors are super important). And I know you've been an incredible mentor. Why don't you tell us a little bit about your academic journey? I mean, I see you in the halls at these major conferences, but I've never pulled you aside and said, “Hey, what's your journey - your academic journey – like, other than your great editorial work for neurology, of course?” Dr Burch: I did my fellowship at Brigham and Women's and then stayed on there as an attending, and ultimately took over as fellowship director before I took a break, which I'll talk about in a minute. In that time, I was doing clinical care and I had a research program and I was doing education - doing a lot of teaching for CME work, and teaching primary care and subspecialists about migraine - and I really love that piece of things - and precepting fellows. And then, I also had my editorial work on top of that. I have been a medical journal editor as long as I have been a headache specialist. We were talking about mentors, and I want to talk, at some point, about my fantastic mentor, Elizabeth Loder, who is also a research editor, in addition to being an outstanding headache medicine clinician and researcher and educator. But she got me started as an Assistant Editor for Headache in my fellowship year - the journal Headache - and I continued as an Associate Editor there. I worked as a Research Editor for the British Medical Journal for a while and then joined the journal Neurology, where I am one of the eight Associate Editors. I cover the general neurology portfolio, which includes a lot of things - includes headache medicine, includes traumatic brain injury, pain, spine, neuro-oncology, neuro-otology - there's a whole bunch of different things that I have learned a lot about since starting as an editor. So, I have always had a lot of different parts to my job, which keeps me interested. It's also a lot, and I do always talk about the fact that I ended up taking a year off because I think it's important to be real about the lives that we lead and our jobs as academic neurologist. So I ended up having a bunch of family health issues that came up in 2021, and combined with all of the other things that we're doing, I just couldn't keep it all going. And I ended up getting sort of burned out a little bit and was having trouble balancing all of that and the family health issues that were going on. And I ended up taking about a year off from clinical work. I continued with my editorial work and kind of got everything sorted out with my family, and then just started my current position in January. I'd just like to bring that up to show that – you know, not everyone's going to be able to take a year off - I recognize that. But I think it's important to normalize that just being “pedal to the metal” all the time is not feasible for anyone. And we need to recognize that it's okay to take breaks periodically. So, I'm kind of an evangelist for the “taking-a-break model.” Dr Monteith: Yeah, you took a break but you kind of didn't, because you've been doing a lot for us in neurology, and I certainly appreciate that. Speaking about all of that and feeling burnt out - what inspires you; what does keep you going? Because I know you keep going. Dr Burch: I do. Well, it's really funny - when I took my time off, I used that as an opportunity to really think about, “Okay, is this really what I want to be doing? Is this the right path for me? Do I want to rethink things?” And I ended up in the same job that I left, just in a different place. I'm still doing clinical care, and I'm the fellowship director of my current institution, and I still do all this education, and I'm getting my research program going, and I'm still an editor. So, I think the bottom line is, I have always loved what I do; it's just a question of making it all fit. So, you know, when I get up in the morning, when it's a clinic day, I am so excited to just go and talk to my patients and see how they're doing and see if there's something I can do to make them feel better. And it's just delightful to be able to play that role in people's lives, even if they're not getting better. You know, I think sometimes just being there with them is of service and is worth doing, and that feels very meaningful to me. And I have a fellow now. I love working with my fellow and teaching, and I love just talking about headache medicine and, you know, “What can we do to help people?” So, that really inspires me. On an editorial day, I'm interested in what research people are doing and seeing how neurology can publish the best research possible. We're all moving the field forward and it's just delightful to see what people are doing. I don't know - I like all of it. Dr Monteith: Yeah - you spoke about talking to patients and having that interaction. I'm thinking about migraine and patients going into status, having severe attacks. Is there any case that really moved you, made you think differently? Dr Burch: What really sticks out in my mind when I think about acute treatment, in particular, is what doesn't necessarily fit neatly into the algorithms that we develop. The situations where creativity and persistence and working together really make a big difference for a patient. I am the first person to tell you we do not know everything yet, and maybe we will never know everything. And I think sometimes we need to think outside the box. We need to “listen between the lines” to what people are telling us, and really work together to figure out a very individualized, well-crafted plan. I'm thinking about times that - for example, someone came to me and said, “I'm having these intermittent episodes where I get all of the symptoms of migraine but I don't get headache pain. You know, I get the nausea and I get the photophobia and I'm irritable and, you know, what do I do about this?” And we ended up saying, “Okay, well, take your triptan and let's see what happens,” after trying some other things. And it worked, and it turned out to be the only thing that worked. And that's maybe something we wouldn't think about because we talk about pain all the time and that was really key to improving that person's quality of life. Or, you know, trying to figure out - if there's a situation that provokes an attack pretty reliably, how do we decide when this person is going to take their acute medication ahead of time to try and prevent that from happening? So, for example, somebody who always gets a migraine when they get on the airplane - can we maybe think about doing that? Is it part of the algorithm that we all think of? No, but it's what's right for that person. I feel like I am doing my best work when I really sit with the person and their individual story and listen to how they describe their experience, and then partner with them to come up with something that really works for their specific situation. Dr. Monteith: Give us a few tips. You mentioned the use of triptans, even thinking about most bothersome symptoms, associated symptoms. Let's say they tried the triptan, they have a severe migraine, and still with pain two hours later - what do we say? Dr Burch: Yeah, and I think this is - like I said at the beginning, this is where people often start to feel a little anxious sometimes; you've tried the triptan, it's not necessarily working - what do you do? I think there's a couple of things. First of all, triptans are still first line for migraine - in the absence of vascular risk factors, that's still what we start with. The guidelines ask us to try two different triptans before we try switching to a different class. So, the first thing - most people start with sumatriptan (it’s the oldest one; it's usually covered well by insurance). So, first thing to ask is, what was the patient's experience with it? Was it not strong enough? Did it not work fast enough? Was it too strong? And then you think about - based on that response, are we going to go to eletriptan, which is kind of considered to be the strongest or most effective of the triptans? Are we going to go to rizatriptan, which is faster onset? Are we going to go to naratriptan or frovatriptan, which lasts longer? Then, if the second triptan doesn't work, we think about moving to a gepant - that's what the guidelines are currently recommending. The other thing to consider is whether someone needs an antinausea medication or an antiemetic, because if people are feeling queasy, they're worried about vomiting, then they may be reluctant to take medication. Or it could be that their GI system just isn't working as well, so we need to think about better absorption of the oral medications as well. There are lots of other tips and tricks also. I don't want to go through the whole list, but one of the things that I put in the article is a whole set of things to do if triptans are not effective or if your acute treatment is not effective. It's also things like making sure they're treating early, using combinations of medications - there's a whole list. Then that brings us to rescue therapy. And I think that's also essential; we don't talk enough about rescue therapy. We do think about it, but we think about it when we get the phone call to our clinic, where we get the message that says, “I took my treatment didn't work. And this is the second time this has happened. And I'm desperate, and what do I do?” That's not when you want to be managing this. You want to be managing this at the visit, before it happens. So, I think anybody who has an attack occasionally that doesn't respond to treatment needs a rescue plan. There's a bunch of different things you can do - I talk about this in the article as well - but some backup, like an injectable sumatriptan, might be helpful. Sometimes we use sedating medications to just try and help people go to sleep. I personally really like to give phenothiazine antiemetics because they have intrinsic antimigraine properties as well as being sedating and helping with nausea, so I sometimes use those. But there are a lot of different strategies and it's just worthwhile looking through them and getting comfortable with a few of them to give patients as a backup plan. Dr Monteith: I loved – I did love your tables. I love that you put the devices in the tables because usually when we think about neuromodulation, that's almost like usually a separate article. But you went ahead and combined it because all of the devices may have some acute benefits for patients. So, how do you think about devices? How do you talk to patients about devices? Dr Burch: Yeah, well, all of them were originally tested for acute treatment before their preventive indications. So, I think it's appropriate; if we're thinking about a plan, we want to have everything in one place, which is why I always include neuromodulation. The neuromodulation device that has the strongest evidence is remote electrical neuromodulation, which is the band that patient wears on their arm and uses as an acute strategy. The others may be helpful for individual patients, but I tend to lean towards the remote electrical neuromodulation as my acute treatment of choice just because of the strength of the evidence. I also haven't had as much trouble getting it for patients. The big barrier for all of these neuromodulation devices is cost because, relatively - I mean, they're not cheap and they're almost never covered by insurance (sometimes they are, but not always), and many of our patients are going to be able to access them and many of our patients are not. So, I'm always judicious in the way that I talk about them because I don't really want to put people in the situation of having to say, “I can't afford this thing that you think would be great for me.” Which, of course, comes up - not just with neuromodulation but with medication as well. But, you know, I think they're good for people who don't want to take medication or who are taking medications too often, and we need something to throw in there that is not a medication to prevent the development of medication overuse headache. Some people just prefer them. The evidence is not as strong for neuromodulation as it is for acute medications - and some of that just has to do with the challenges in blinding people to treatment arm in a clinical trial - but I think they have their place. Dr Monteith: When I'm just looking at the data, and then, as you mentioned, there are multiple options in terms of the latest developments. What are the things that you're most excited about in terms of either nonpharmacological, pharmacological interventions, or even patient populations like pregnant patients or patients with cardiovascular disease. Dr Burch: It is such an exciting time to be a headache specialist. I feel like things are coming out all the time, even in between writing this article and sending the final draft in, and now new things have come out. The zavegepant nasal spray is now FDA approved for acute treatment of migraine, and that... /episode/index/show/continuumjournal/id/30596808

Approach to the Patient With Headache With Dr. Deborah Friedman 04/10/2024

Approach to the Patient With Headache With Dr. Deborah Friedman Headache medicine relies heavily on the patient’s history, perhaps more than any other field in neurology. A systematic approach to history taking is critical in evaluating patients with headache. In this episode, Katie Grouse, MD, FAAN, speaks with Deborah Friedman, MD, MPH, FAAN author of the article “Approach to the Patient With Headache,” in the Continuum April 2024 Headache issue. Dr. Grouse is Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Friedman is a neuro-Ophthalmologist and headache specialist in Dallas, Texas. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Dr 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 Grouse: This is Dr. Katie Grouse. Today, I'm interviewing Dr Deborah Friedman on approach to the clinic patient with headache, which is part of an issue on headache. Dr. Friedman is a neuro-ophthalmologist and headache specialist in Dallas, Texas. Deborah, I'd love if we could just start by you telling us more about you. How did you become interested in the diagnosis and treatment of headache? Dr Friedman: I guess one of the lessons in life that I have learned regarding this question is, “never say never.” I started as a neuro-ophthalmologist - that's what I did my fellowship in. My very first job was in Syracuse, New York, at Upstate Medical University, and there was no headache specialist in Syracuse at the time. And I started seeing neuro-ophthalmology patients and specifically told the person who did my scheduling for me, “Do not schedule headache patients. I am not a headache doctor; I'm a neuro-ophthalmologist.” Well, these people just snuck in the door. They got referred in for their visual disturbances, right - we know what that was - or for their, you know, transient loss of vision or some type of visual manifestation of migraine or eye pain, right? So, I started seeing the patients and I figure, “Well, I did a neurology residency; I can treat headache as well as anybody else.” And so I started treating their headaches. and they would come back to see me in follow-up and say, “You gave me my life back,” and I was pretty blown away by that. This was a few decades ago, and we didn't give very many people “their lives back” at the time in neurology, so I decided I should go learn more about headache medicine. And I started attending national meetings of what is now the American Headache Society. I found that I really, really loved treating headache, and it has a natural marriage with neuro-ophthalmology. As my career progressed, I ended up doing more headache medicine and less neuro-ophthalmology, but I still love both. Dr Grouse: Yeah, absolutely. I think the treatment of headache can be so satisfying and I'm so happy to hear that you were able to discover that love of treating headache in your own career. Why do you think it's important for neurology clinicians to read your article? Dr Friedman: Well, headache is the most common disorder seen in general neurology. It is actually the most common neurological disorder overall, by a factor of ten. And it is one of the most common causes of neurologic disability worldwide - like it's in (routinely in) the top five. So, it's an important problem, and patients are going to come see us, and we need to know how to effectively interview them so we can effectively manage them. I think, in a nutshell, that's why. Dr Grouse: You mentioned in your article the importance of making time to discuss the headache - so much so that, actually, you said that if they mentioned it offhand at the end of the visit that they have a headache, you really should be scheduling time for them to come back, to prepare and organize the information, and to have the time to really talk with them. I find this is such an important point and, in my mind, really gets to the heart of what you're trying to tell us in your article - that the way you take the history can make or break your ability to diagnose and treat the problem. Can you talk more about that? Dr Friedman: Sure. The history is absolutely the most important part of the office visit with headache medicine. I mean, they always say, “In medicine and in neurology, ninety percent of the diagnosis is made by history.” And that is more than true in headache medicine. So, you have to really get a good history. And it's a skill, but there's also kind of an art to it. So, there are certain questions you want to have answers to, but there's also this art of how to relate to the patient and how to really get them to tell you what you need to know, right? When I wrote the article, I really tried to convey that, because I think a lot of it can be learned. But there are a lot of nuances to taking a headache history, and I think that, for many people, it's helpful to have a guide to do that. Dr Grouse: Following up on what you just said - you mentioned, of course, the art of taking the good history for headache, which I completely agree is absolutely true. However, in your article, you also mentioned that things like various questionnaire tools, AI, can also be really helpful for diagnosis, which seems to be the opposite of the art of medicine. Tell me more about how you can incorporate that into taking your history. Dr Friedman: I find that questionnaires are incredibly helpful. I devised my own - it is one of the questionnaires that's available in the article (there's a link for it). It's not that I just read the questionnaire and I walk in the room knowing exactly what's going on - sometimes that's true - but at least I have a good idea of what I'm going to be facing when I walk into the room and start talking to the patient. The other reason (perhaps more importantly) that I think it's so helpful is because it gets the patient thinking about the details of their headaches and the details of their life and, you know, like, what medications they've taken in the past. And it really prepares the patient for the interview. In a lot of ways, I think that's more important than the information it gives me. But I do look at all the questionnaires, and I'll say, “Well, you know, you checked off this, and what did you mean by that? And you said this or that on your questionnaire.” And I kind of refer to it so they at least know that I looked at it - there's nothing more irritating than filling out a long questionnaire and then nobody ever looks at it - so, I do look at it and I do acknowledge in front of them that I have looked at it and am looking at it. But I think that they help in many ways. There are programs in AI that the patient will just enter information into online and the program will just spit out a narrative, as well as a diagnosis or a differential diagnosis. For clinicians that are really under a lot of time constraints, I think these can help considerably as well. Dr Grouse: That's really interesting, and that actually brings me to the next question I wanted to ask, which was - do you have any tips for the many busy neurologists out there (many listening to this podcast right now) who really want to do a good job gathering information and taking a careful history but are really limited on time to be able to do this? What other tools out there would you recommend for them, or tips? Dr Friedman: Yeah, I think that probably the questionnaires and the AI-based programs are very helpful. There is - I have no financial relationship with this company; I just happen to know about it and I know the people that developed it - but it's called BonTriage (as opposed to bon voyage), and it was developed by headache specialists. And I've seen the product and I've seen the output that can be used, and I think that one is incredibly helpful. It was really made for primary care, so that people could do this thing online and then just walk in with a piece of paper, hand it to their primary care doctor, and they'd have the whole history and the differential diagnosis. But it's equally as useful for neurologists. Dr Grouse: How about in history taking - any tricks to get the history you need and let the patient feel heard without necessarily taking lots of time going down the wrong pathway? Dr Friedman: Yeah, that can be really hard, and sometimes patients just want to bring you down what you would consider the wrong pathway (obviously, they consider it the right pathway). People have different styles of interviewing and people have different styles of answering the question. I find that it's often very obvious early on whether the patient is going to do better by asking closed-ended questions or asking open-ended questions. I always start with open-ended questions because the research says that that's more helpful, and that getting the patient to describe their headache disability is one of the most important things that you can do, so you should ask it right up front. But some people - when you ask them the questions (as you probably know), they just go on and on and on, and it's really not the way that you might process information. So sometimes I just have to take it back and ask them very specific questions – “Do you have this symptom? Do you have that symptom? How long does this last? What triggers your headache?” - that kind of stuff. It's very, I think, specific to an individual patient. Dr Grouse: Yeah, that absolutely makes sense. Your article highlights some important and frequently missed causes of headache, including hemicrania continua and intracranial hypotension, and specifically, you have some example cases that you talk about. I have to say, reading those certainly triggers my own latent fear of misdiagnosis of these important causes of secondary headache. Can you highlight some of the important questions to ask or situations to keep in mind in order not to miss these? Dr Friedman: Sure. You know, those examples in the article came from my practice. I had to alter them a little bit because they're not supposed to sound like real people, but the patient with hemicrania continua was a real - I wouldn't say necessarily “eye opener” - but it really hit home with me. I spent all this time taking the history from the patient. She'd seen numerous doctors beforehand; they all thought she had chronic migraine. I take her history and I think she's got chronic migraine too, but she's trialed several medications; they haven't really worked, so, you know, we kind of ended it. I said, “Well, I think you have chronic migraine.” She came back for her follow-up visit and looked at me and said, “Could I have hemicrania continua?” At which point, I panicked. It's like, “Oh my god - I think I take a pretty good history, but what did I miss?” I'm like, looking through the note from the last visit and trying to figure out where I went wrong. And where I went wrong was, I never asked her, “Are you ever completely headache free?” And that is such an important question to ask because most often, when people come in and they start talking about their headaches, they talk about their worst headaches, right? Those are the ones that are really interfering with their lives. They often will just totally neglect to tell you that they have a headache almost every single day, but it's just mild and they don't pay attention to it. That was like a big lesson for me, and I try - it's even on my questionnaire – “Are you ever headache free?,” because it's just so important to know that. Intracranial hypotension is also one that you really have to be a detective for. A lot of times, the imaging will help us, but about ten, fifteen, twenty percent of people with intracranial hypotension have normal imaging. Then it becomes like this whole quest of making a diagnosis based on your clinical impression, right? So, there are just a lot of different things that you can ask and there are a lot of different symptoms people can have. One of the important lessons I learned in there was asking about orthostatic headache; the common way to ask that is, “Does it get better when you lie down?” Well, with few exceptions, most people with headache prefer to lie down, right? People with migraine prefer to lie down. But their headache doesn't get better just because they were lying down. It gets better because they took medicine and maybe they went to sleep. So, it's not just, “Is it better when you're lying down?” Is not going to sleep is part of it? And conversely, we want to know like what they feel like when they first wake up in the morning before they get out of bed, right? So just asking about, “Well, what's your headache like in the morning?” - that's not going to necessarily get the answer you want. So there are, again, kind of fine points about asking some of these questions to really find out what you need to know. Dr Grouse: Absolutely - that makes sense, that the intracranial hypotension case was another one that really, you know, makes me go back and think, “Gosh, how many of these might I have missed in my own career?” You know, such an easy-to-miss case based on what was described. Dr Friedman: I go through the same thing. I think that, early in my career, I could think back to patients that I probably missed that diagnosis. One of them I even sent to (may he rest in peace) Dr Mokri, who described it, and I sent him the imaging. He said, “No, this patient doesn't have it.” But knowing what we know now, I think she probably did. Dr Grouse: Wow. Transition to some other types of questions - what's the most common misconception you've encountered in treating patients with migraine? Dr Friedman: I would say that a lot of people think that migraine has to be (as the name implies) hemicranial. A substantial proportion of adults and even a higher proportion of children have migraine headaches that affect both sides of the head. I think that's really the most common misconception. Dr Grouse: What's the easiest mistake to make (and potentially avoid) when treating patients with migraine, or headache in general? Dr Friedman: Studies have been done looking at this question in migraine. The first mistake is not giving the patient a correct diagnosis. And it is surprising in real life how many people walk out of the doctor's office and nobody's ever told them, “You have migraine with aura,” or “You have chronic migraine,” right, and giving them a very specific diagnosis. Second most common mistake in treatment is not offering them an acute treatment. So, many people are using over-the-counter medications that are not very effective, or even prescription medications that are not very effective. We have a lot of good treatments out now, and basically every patient with migraine should be offered an acute treatment. We also know that preventive treatment is massively underutilized. Again, studies (mostly by Richard Lipton and his group) have interviewed patients and done population studies, and people who clearly meet contemporary guidelines for offering preventive treatment are never offered it. So, I guess those would be my top three. Dr Grouse: Going on the theme of patients maybe not being offered the optimal treatments, what's the greatest inequity or disparity you see in treating patients with headache disorders? Dr Friedman: The first thing that contributes to that is - there is a shortage of headache specialists. There's also a shortage of neurologists, so that's a problem. There are certain groups that are less likely to seek care for headache. If people don't seek care, it makes it harder for us to treat them. African American males, in particular; Hispanics. I think that some of this might be stigma; some of this just might be cultural - I'm not sure. Women are more likely to seek care for migraine than men are. But there are what they refer to as, like, “islands of health-care disparity” throughout our country, where there are just not enough physicians, or even advanced practice providers working with physicians, to be able to take care of all these people. So, it's estimated that there are well over forty million people with migraine alone in the United States (not to mention all the other kinds of headaches), and there are really not enough of us to go around, and there are very long waiting times to get in to see us. So, some people will end up using the emergency room to treat their headaches, which is totally suboptimal and not a good experience for the patient, either. So, I think there are a lot of aspects to disparities in migraine care, and there is a group in the American Headache Society that actively focuses on this issue and has written papers about it. But I think it's multifaceted and it's going to take a lot of effort on both the part of us, as clinicians, as well as patients, recognizing that there is good treatment out there and people shouldn't have to live with these kinds of disorders. Dr. Grouse: Absolutely. This has been such an interesting article. I just wanted to end with one last question, which is, what do you think is the most important clinical message of your article that you hope our listeners take away from this podcast? Dr Friedman: I was really happy to be asked to write this article for Continuum. And I'm glad it is the lead article in Continuum because I think that taking the headache history is by far and away the most important part of the headache medicine evaluation. When I was asked to write it, I was specifically requested to write it from the perspective of a clinician seeing adult patients. And I just want to let the audience know that I did not neglect the pediatric patients - that there is a different chapter in Continuum that addresses the specifics of taking a history and what's important to ask from pediatric patients. It was really a joy to write the article. I hope that people read it and learn from it and enjoy it. Dr Grouse: I really thoroughly enjoyed this article - it was so interesting. Even as someone who does a lot of headache diagnosis and treatment myself, I learned a lot. I think it's such a rich source of information and I hope everyone takes advantage of the opportunity to read it and learn a little bit more about headache treatment and diagnosis. Thanks so much for coming to talk with us today. Dr Friedman: Thank you so much for inviting me. It was a pleasure. Dr Grouse: Again, today I’ve been interviewing Dr. Deborah Friedman whose article on Approach to the Patient with Headache appears in the most recent issue of Continuum on Headache. Be sure to check out Continuum Audio episodes from this and other issues, and thank you to our listeners for joining today. Dr. Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed... /episode/index/show/continuumjournal/id/30595328

April 2024 Headache Issue With Dr. Amy Gelfand 04/03/2024

April 2024 Headache Issue With Dr. Amy Gelfand Headache is among the most common neurologic disorders worldwide. The differential diagnosis for primary and secondary headache disorders is broad and making an accurate diagnosis is essential for effective management. In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Amy Gelfand, MD, who served as the guest editor of the Continuum® April 2024 Headache issue. They provide a preview of the issue, which publishes on April 3, 2024. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Gelfand is an associate professor at Benioff Children’s Hospitals, University of California San Francisco in San Francisco, California. Additional Resources Continuum website: Subscribe to Continuum and save 15%: More about the American Academy of Neurology: Social Media Host: Guest: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by clicking on the link in the Show Notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the Show Notes. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum Lifelong Learning in Neurology. Today, I'm interviewing Dr Amy Gelfand, who recently served as Continuum's guest editor for our latest issue on headache disorders. Dr. Gelfand is a child neurologist at the University of California, San Francisco, where she is an associate professor of neurology, and she also happens to be Editor-in-Chief of the journal Headache. Dr Gelfand, welcome, and thank you for joining us today. Dr Gelfand: Thank you so much for having me. Dr Jones: Dr Gelfand, this issue is full of extremely helpful clinical descriptions and treatment strategies for headache disorders. With your perspective as the editor for this issue - and you've just read all these wonderful articles and edited these articles - what were you most surprised to learn? Dr Gelfand: I would say that the medication overuse headache article I think is where you'll find the most surprising content. This is an area in headache medicine that has been controversial. I think what we've got is new data - relatively new data, published in Neurology (in the Green Journal) in 2022 - the MOTS trial, showing that what we all thought was not necessarily true. In headache medicine, there was this mantra that, if somebody is overusing (too frequently using) a certain kind of headache acute medication, you've got to stop them; you've got to have them stop it completely before you can get them on a preventive treatment if you expect it to work. Turns out, in this trial, that's not the case. People were randomized to either stopping the overused acute medicine and starting a preventive versus continuing it and starting a new preventive, and they did equally well. I think that's really taught us that that dogma was not based in evidence (was not true), and what really matters is getting a patient started on an effective migraine preventive treatment. Dr Jones: Wow, that is really – that is kind of ground shaking, isn't it? That's going to change a lot of practices for a lot of neurologists out there. Do you think that's going to be well received, or has it been well received so far? Dr Gelfand: I think it has. I want it to get out there further, so I hope everybody will read in that chapter and really pick up on that piece. I think it's helpful for patients, too - that we don't necessarily need to disrupt what makes them feel like they're getting some acute, in-the-moment relief. We just need to make sure we're getting a good-quality migraine preventive therapy started. That's the most important thing. We don't necessarily need to ask them to change something about their acute treatment. Dr Jones: That's fantastic, and it certainly could make things a little more straightforward, I think for people who are helping patients manage this. To be honest with you, the term, “medication overuse” almost sounds like it's putting the onus on the patient a little bit. Dr Gelfand: It very much does sound that way. It is a very challenging term for a lot of reasons. And I agree with you that that's a problematic part of this whole terminology. Dr Jones: Well, just three minutes into the interview here and, Dr Gelfand, you've already changed people's practice. I think that's wonderful, and we'll look forward to reading that specific article in the issue. Again, from your view as a headache specialist and a leader in the field, what do you think the biggest debate or controversy is in headache medicine right now? Dr Gelfand: I think where we're really a little bit stuck in trying to figure out how to move forward is how to take care of patients who have continuous headache. It's not even really a fully defined term, but if you imagine a person who - they wake up, headache is present; it continues to be present throughout the entire day; they go to bed- it's still present; if they happen to wake up in the middle of the night to go to the bathroom, it's there then - it's just there all the time. It can be hard to imagine that situation is real - that somebody could have a headache that is continuously present for weeks, months - but this is true of some of our patients who have chronic migraine, our patients who have new, daily, persistent headache, certain other headache disorders. This entire group of patients who have continuous headache have historically been excluded from treatment trials, so our existing data don't necessarily generalize to how to treat their condition. And we need to change that, because this is a group that is arguably most in need of research, most in need of effective therapies. The question is how? Who exactly should be included in the inclusion criteria? And then, what are your outcome measures? Historically, in migraine treatment trials, we use headache days per month or migraine days per month. Days of headache per month may or may not be the right primary outcome measure for somebody who's starting from a point of continuous headache. Maybe more appropriate is, how many severe headache days you're having in a month, or how much disability you have from your headache disease. It's an area that's evolving and really does need to evolve, because this is a patient population that has been underserved in research thus far. Dr Jones: I learned that, I think, in reading one of the articles talking about continuous headache at onset – so, the headaches that are continuous from day one, which is, as I understand it, pretty uncommon. But really very little of the clinical trial data speak to how to care for those patients - is that right? Dr Gelfand: That is exactly right. And, epidemiologically, maybe not as common. But in a headache clinic, we certainly see patients who have had these headache disorders where it starts on one particular day, it becomes continuous within twenty-four hours of onset and has now been going for at least three months, and we would call that new, daily, persistent headache. Or equally commonly, people with chronic migraine where it ramped up over maybe a short to medium-long period to daily and continuous. And now they have been experiencing continuous headache for some number of months, if not longer. Dr Jones: This question may be a little bit of an unfair question. One of the challenges with headache is that, unlike some other areas of a diverse specialty of neurology, there aren't as many biomarkers as you might have for dealing with patients who have cerebral ischemia or neuromuscular disease. Do you find that that leads to more differences of opinion or more variability in diagnosis and management than you might see in other areas? Dr Gelfand: I'm so glad you asked that question. What I find that leads to is more stigma. Many of our patients are not believed, including by medical professionals who they've met before. People might think they are faking their symptoms, or that there's some sort of secondary gain, or this is something related to - they just don't know how to manage stress. This is a real problem for patients with migraine to be encountering so much stigma. As a headache medicine clinician, when I'm meeting a patient, oftentimes I need to make sure to acknowledge that, almost certainly, they've encountered that before. I need to reassure them that they're not going to be experiencing that in our headache clinic, and really try to undo some of that harm to be able to build trust that we're going to have a collaborative relationship moving forward - we're going to be a team; we're going to be determining the next steps in treatment together - and that I 100% believe them that the symptoms they are experiencing are real, are very challenging. Because migraine and other primary headache disorders are real neurologic diseases that can be quite severe. But because we have a paucity of biomarkers, it's hard for some people outside the field to recognize that. And that, I think, has been really difficult for patients historically. Dr Jones: So, a challenge for clinicians has become really more of a burden for patients. Dr Gelfand: Yes - well said. Dr Jones: Yeah. That's too bad, and maybe someday that will change, and probably can be approached from a couple of different directions, right? - from educating clinicians’ perspective and also pursuing the science. This might be a related question, Dr Gelfand - what do you think the biggest misconception you've encountered in - I'm thinking mostly from the provider of the clinician community - what do you think the biggest misperception or misconception there is about patients who have headache and the management of those patients? Dr Gelfand: Well, I think it is tied in, in some way, to this notion that the patients are somehow causing their problem; that it's something about - well, I'm a child neurologist; I see adolescents and children – so, their parent is causing their problem because they're a helicopter mom or whatever it is, or they're just not managing stress in an appropriate way. I think that that is really an issue that patients are sort of handed from the medical community. Whereas if I step back and think about it, before 2018, no migraine-specific preventive therapies existed. We were borrowing from all other corners of medicine. We were borrowing from antihypertensives, antiseizure medicines, antidepressant medicines, but there was no actual migraine-specific therapy. Then came the monoclonal antibodies targeting CGRP (calcitonin gene-related peptide) - they're targeting either the ligand or the receptor. We now also have the oral forms that target the receptor, the gepants. So, we do have this one or two classes, depending on how you break that out, that are migraine-specific preventive therapies. But that's not enough for a complex disease like migraine - we need twenty of them. Look at epilepsy; there are probably twenty-plus antiseizure medicines, and yet, some patients still seize. Is that because they're anxious or stressed, or their mothers are too stressed? No - it's because some people have terrible epilepsy. And yet that same explanation has not been afforded to people with difficult migraine disease, that with just one class of migraine-specific preventive (or two, if you break out the monoclonals and the gepants) - that, somehow, they're supposed to have magically stopped with this treatment. That really doesn't make any sense. It's because we don't have enough effective therapies that they're still having difficult migraine - it's not because they're causing their disease. Dr Jones: Thank you - that's a great example. That is important to understand - that misconception about causation. And we may come back to causation here in a moment. It really doesn't make any sense that there are few specific, disease-modifying therapies for migraine, which affects tens of millions of people in the United States alone, right? Why is that? Why are there so few? Dr Gelfand: First of all, Dr Jones, I love it that you called it disease-modifying therapy, because that's how I think about it, too. The term, “preventive migraine therapy,” which is the more commonly used therapy, is not always really useful because - some people who have continuous headache will say, “Well, what are you trying to prevent? I've got headache all the time.” But this is really just treatments that are designed to dampen down disease activity in any form - how frequent, how long of duration, how intense - and I think it is really better conceptualized as disease-modifying therapy, so I love that you use that term. Why have there been so few? I think that it comes down to a paucity of research. Historically, NIH has underfunded migraine and other primary headache disorder research quite a bit, compared to how much disability those diseases cause in Americans each year. Hopefully, that will be getting better soon; I think there are some positive signs that that could be moving in a more positive direction. But I think, because migraine and other primary headache disorders are “invisible” illnesses - can't show you an x-ray with a broken bone; can't show you a lab readout with what your disease activity is; like you said, there's not a lot of biomarkers. Because of that, it's been hard for funders to really get behind it, and I think that's put us a little bit behind where we need to be. More research will lead to more therapies. Dr Jones: Let's hope so. It certainly is very common and affects, again, millions upon millions of people and leads to impaired quality of life and disability, as you point out. You are also the editor-in-chief of a leading journal in your field, Headache. I know many of our listeners who are neurologists and perhaps interested in editorial work as a career path might be curious - what led you to that, and how has it helped you as a clinician (being in that role)? Dr Gelfand: Yeah - I love being the editor of Headache. It's the journal of the American Headache Society. I think it's where the most interesting new science and work in headache medicine is coming out of. I have always found that reading helps me learn. If I want to learn about a topic, I need to read about it and I need to synthesize everything I read about. Being an editor makes that so accessible and fun. I really enjoy reading all of the articles that are coming in. It really helps me to think about everything I know, and thought I knew, in the field. And keeps my mind really questioning – do I really know that that's true or did I just think that's true? - and now this new data shows me that, actually, it's something else. And I really enjoy being challenged that way, on a daily basis, by new science that's coming in. So for anybody out there who has an interest in editing and playing an editorial role, I definitely encourage you to pursue that. There are programs - I know that the Green Journal has a resident and fellow section; that's where I started out, and I really had a wonderful experience in that. And then in our journal, in Headache, we have an assistant editor program for junior people - residents, fellows, postdocs - people who want to learn more about how to be an editor. I think that you learn so much about how to be a better writer, how to be a better scientist, how to communicate your findings in the most effective way. It's just invaluable and it's very fun. Dr Jones: It is kind of selfishly fun, isn't it? Dr Gelfand: Right, right. Dr Jones: Yeah, and it's important work, obviously - to put good information out into the world. At Continuum, we also have - on our editorial board, we have two residents and fellow positions, again, for that career development. I have to ask you a really hard question here, Dr Gelfand. You mentioned you read to learn; if you had to make a choice - electronic or print - what would it be? Dr Gelfand: Electronic. I know that many journals, including ours, are having to make some of these decisions right now. But I read my PDFs and I store them so that I can come back to them and search for them, and make sure, when I'm citing them, that they actually say what I thought they said because sometimes I need to look back at that. So, I am an electronic person. How about you? Dr Jones: I think I'm print. Dr Gelfand: Uh huh. Dr Jones: And I'm just sitting here thinking, there are so many people listening to this interview, and they're screaming at their device, saying, “Electronic is the answer,” or “Print is the answer.” Like you, we want to meet our subscribers where they are, and I think neurologists are very clear in their preferences. Let's just say we'll agree to disagree, and no one is right and no one is wrong – how about that? Dr Gelfand: Fair enough - I can respect that. Dr Jones: All right. I have one more question for you. This might sound like a strange question in an interview between two neurologists talking about headache - what can you tell us about chicken farming? Dr Gelfand: Well, I'd be delighted to tell you about chicken farming. As you know, because they were squawking earlier in our chat, I've got a little flock of chickens in our backyard and they are an absolute joy in my life. One thing I can tell you is that chickens respond to the photo period (how long the daylight is in a year). Now that it's November, it's the time of year when they don't get a lot of light, so they stop laying very much. I find that between Thanksgiving and about Valentine's Day, we actually start to need to buy eggs, which makes me very sad because I love having our egg supply come completely from our chickens. But we want them to rest and so that's what they're doing. Chickens will not lay very much at this time of year. During the summer and the spring and the fall (in the earlier part of the fall), they will lay almost daily, depending on which breed and how old they are. But at this time of year, it's really quiet - really, just one or two a week, I would say, right now. Dr Jones: It sounds like a fun hobby. Hopefully the chickens don't mind that you're buying chickens in the winter, and they don't feel offended by that or jealous. Dr. Gelfand: I worry that they do. I try not to show them the grocery bags. Dr Jones: Well, Dr Gelfand, thank you so much for joining us today, and thank you for such a thorough and fascinating discussion on headache disorders from your unique position as a guest editor for Continuum, I do encourage all of our listeners to check out that issue. It's really full of phenomenal pointers on practice-changing tips and tricks for managing patients who have headache disorders. I'm really grateful for your time today. And thank you for telling me a little bit about chicken farming. Dr Gelfand: Thank you so much for having me. It was really fun. And thank you for your interest. Dr Jones: Again, we've been speaking with Dr Amy Gelfand, guest editor for Continuum's most recent issue, on headache. Please check it out and thank you to our listeners for joining today. Dr. Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant... /episode/index/show/continuumjournal/id/30595173

Symptomatic Treatment of Myelopathy with Dr. Kathy Chuang 03/27/2024

Symptomatic Treatment of Myelopathy with Dr. Kathy Chuang Regardless of the underlying cause of spinal cord disease, we have many tools at our disposal to improve symptoms and function in these patients. Even better, technology in this area is advancing rapidly. In this episode, Lyell Jones, MD, FAAN, speaks with Kathy Chuang, MD, author of the article “Symptomatic Treatment of Myelopathy,” in the Continuum February 2024 Spinal Cord Disorders issue. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Chuang is an instructor in neurology at Harvard Medical School and assistant in neurology co-director at Paralysis Center, Massachusetts General Hospital and Spaulding Rehabilitation Hospital in Boston, Massachusetts. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Transcript Full transcript available on Libsyn 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 exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum Lifelong Learning in Neurology. Today, I'm interviewing Dr Kathy Chuang, who has recently authored an article on symptomatic management of myelopathy in the latest issue of Continuum, on spinal cord disorders. Dr. Chuang is a neurologist and physical medicine and rehabilitation specialist at Mass General, where she serves as Co-Director of the MGH Paralysis Program and Chief of the Neuromuscular Rehabilitation Program. Dr Chuang, welcome, and thank you for joining us today. Would you introduce yourself to our listeners? Dr Chuang: Hi, my name is Kathy Chuang. As you said, I'm a neurologist at Mass General Hospital specializing in neuromuscular medicine, also physiatry, physical medicine, and rehab. And I'm glad to be here. Dr Jones: Thank you for joining us. Basically, if we want to know more about managing spinal cord disorders, we have come to the right person, right? Dr Chuang: I try to do my best with all patients - yep. Dr Jones: For our listeners who are new to Continuum, Continuum is a journal dedicated to helping clinicians deliver the highest quality neurologic care to their patients, and we do this with high-quality and current clinical reviews. For our long-time Continuum Audio listeners, you'll notice a few different things with our latest issue and series of author interviews. For many years, Continuum Audio has been a great way to learn about our Continuum articles. Starting with our issue on spinal cord disorders (this issue), I'm happy to announce that our Continuum Audio interviews will now be available to all on your favorite open podcast platform, with some exciting new content in our interviews. Dr. Chuang, your article is absolutely full of extremely helpful and clinically relevant recommendations for the treatment of myelopathy, regardless of the cause. If there were one single most important practice-changing recommendation that you'd like our listeners to take away, what would that be? Dr Chuang: I think the most important thing to take away is that spinal cord injury of any type spans so many organ systems, it is good to get people - or multidisciplinary care - involved early on. There's eighteen model systems for spinal cord injuries scattered across the US. Those can be great avenues of resources for patients and for practitioners, for people around. Physical medicine and rehab specialists (our physiatrists or spinal cord injury specialists) can be very useful. And then, also for each individual organ system, there are specialists involved. And so, having that multidisciplinary care is probably the most important thing for a patient that's suffering from myelopathy because every patient is different and coordinating that care is so important to them. Dr Jones: So, teamwork is probably the most important thing, and I think most of our listeners who have taken care of patients with spinal cord disorders realize that that's really key. Your article - it leads off with such a great review of one of the big problems with myelopathy, which is spasticity management. From a medication perspective, I think many of us struggle with the balance between controlling the spasticity and some of the side effects of those medications, like sedation. How do you walk that fine line, Dr. Chuang? Dr Chuang: Spasticity management, like everything else, is patient directed. It depends on what the patient is most complaining of. If a patient has spasticity but they're not actually having any complaints from it, we don't need to treat, because of fear of side effects. I tend to try to use focal procedures (like botulinum toxin injections) earlier on, in order to try and spare side effects of antispasticity medications. Use of other conservative therapies, like bracing, stretching, is very essential. Another thing to consider is that dantrolene doesn't usually have side effects - cognitive side effects, at least - and actually can be monitored pretty closely for hepatotoxicity, which is its major side effect. Other possibilities are the baclofen pumps, which can be very useful in patients with spinal cord injury because their spasticity is often more in their lower limbs than in their upper limbs. By using multimodality approaches, we can definitely limit the amount of cognitive side effects of medications. Dr Jones: That's fantastic. Do you start with that multimodal at the beginning, or do you step into it with one, then the other, then the other? Dr Chuang: I usually start off with a low-dose baclofen because they usually have generalized tone - first, in order to see if they have cognitive side effects with it and if so, at what dose. Also, so that insurers have a trial of some medication before we proceed to something as expensive as botulinum toxin injection. But yes, if there's significant focal spasticity, especially, I try to bring in botulinum toxin injections as early as possible, just because of the possibility of minimizing the effect. Dr Jones: That's a great point - that you can start these from multiple angles and start them early. And great point about dantrolene - I think the hepatotoxicity makes many of us nervous. But it’s a key point there - that it can spare some of the cognitive side effects. Dr Chuang: Yes, and actually, it can be monitored pretty closely. As long as a patient has access to labs, we can check liver function tests weekly or every two weeks until you're on a stable dose, and after that, only at intervals. And it can be weaned off just as quickly. Dr Jones: Fantastic. Another issue that you cover really nicely in the article, that I think is an underrecognized complication of spinal cord diseases - neuropathic pain. What's your approach to that problem, Dr. Chuang? Dr Chuang: Neuropathic pain is very, very tough to treat a lot of times. I usually give the chance of gabapentin, pregabalin, and duloxetine early, just to see if we can start managing their pain early and to try to prevent potentiation of pain. But I also tend to try to get pain management specialists on early, and also keep in mind that there can be other causes of pain other than just the actual spinal cord injury itself. Because of deafferentation and reafferentation, patients may think of neuropathic pain, and it could be something as simple as appendicitis. If there's a change in pain, there always needs to be a workup for acute causes. Again, multidisciplinary treatment, especially with pain specialists, can be really helpful. Dr Jones: Great point about thinking of other causes, including appendicitis or the musculoskeletal things that I'm sure can be pain generators in this pain population, right? Dr Chuang: Yeah, it's very common. Patients can often fracture themselves just with a simple transfer and that can cause a huge flare-up of pain. So, not all pain should be just dismissed as being neuropathic or just from the spinal cord injury itself. Dr Jones: Great point - thank you. Another topic that you cover - that I think is mystifying to many of us - is the neurogenic bladder problems that occur in patients with myelopathy. You talk about the different types - how do you tell them apart? Dr Chuang: It's hard to tell them apart from a patient perspective because a patient will just say that they have difficulty with urination. With a spastic bladder or detrusor sphincter dyssynergia, oftentimes, patients will complain of a short stream and having to force things out. And with an atonic bladder or flaccid bladder, they have difficulty initiating a stream. What can be useful are postvoid residuals - where, if a patient is in the hospital, or if you have access to an ultrasound, or if they see a urologist - after they void, you measure the amount of urine left in their bladder. You can see whether it's a smaller amount, which is suggestive of a spastic bladder, versus a large amount, or an atonic or flaccid bladder. The standard procedure that's done to measure these are also urodynamic studies that are done, oftentimes, by urologists, where they can actually measure pressure volumes and oftentimes get EMG recordings of the actual bladder - the sphincters. Dr Jones: Perfect. When you do those postvoid residuals (easiest done with ultrasound), what's the general cutoff you use to say - that's a small amount that might be suggestive of a spastic bladder? Dr Chuang: I would say, probably less than a hundred. And then, if it was flaccid, more than five hundred. If there's in between, it may fall into either category. Dr Jones: Got it. When you think about neurogenic bladder, what are the treatment options? How do they vary between the different types that patients may have? Dr Chuang: If you have an atonic or flaccid bladder, the main possibilities for patients just are, oftentimes, Credé maneuvers (or pressure on the bladder) in order to try and help with the bladder to squeeze urine out. But a lot of times they need clean intermittent catheterization or maybe placement of a suprapubic catheter long term. For patients who have a spastic bladder or detrusor sphincter dyssynergia, we can use anticholinergic medications, like bethanechol, tolterodine - those medications - in order to try to relax the sphincter a little bit and then allow the urine to pass through. You can also have BOTOX injections to these sphincters of the bladder as well, which can be useful to relax them so that they can allow the urine to pass through. But a lot of times, a mainstay of treatment is intermittent catheterization, also for patients with severe detrusor sphincter dyssynergia, so that we can maintain small bladder volumes and not develop hydronephrosis, urinary tract infections, and complications of holding urine in the bladder. Dr Jones: Thanks for that, Dr. Chuang. Another part of your article that I thought was really fascinating, and probably will cover some new ground for our readers and listeners, is the use of nerve transfers or surgical treatment of weakness, basically. Tell us about that and how it's used in patients with myelopathy. Dr Chuang: For patients with myelopathy, it's used often in the upper extremities. If a patient has voluntary control of either elbow flexion or elbow extension (usually, elbow flexion), you can oftentimes have the ability to transfer nerves into the finger flexors and allow voluntary hand closure. If there's supination or wrist extension, you can oftentimes allow transfers of branches of the nerve - for example, from the supinator, or from the branch to the extensor carpi radialis brevis, into the finger extensor - so that, over a period of nine to twelve months, we'll be able to slowly regrow the nerve back in and allow the denervated muscle to become reinnervated with a voluntary controlled muscle and then restore voluntary finger extension, which can be extremely beneficial - just being able to voluntarily open and close their hands. Dr Jones: Right. And it sounds like the goal is really that functional use of grip and use of the upper limb. Not really so much for transfers, I imagine - is that not so much the goal? Dr Chuang: If there's less than antigravity strength of elbow extension and reasonable external rotation strength, you may be able to get elbow extension strong enough antigravity, and at that point a patient may be able to transfer independently - with a lot of training. Dr Jones: Wow, that's fantastic - thank you. There's lots of therapeutic options, really, for many of these complications, which I think is an important point for our readers and our listeners to take home. When you look into the future, Dr. Chuang, what do you see on the horizon as the next generation of care for patients with spinal cord disorders? Dr Chuang: I see a huge, expanding field, both of therapeutics - there are stem cell trials all over the world; there are neurorestorative hormones that are being tried. I'm very excited about the advent of robotics, with motors being basically shrunk down to the size of millimeters, and exoskeletons becoming lighter and lighter. I suspect that, long term, we’ll be able to have robotic exoskeletons to be able to help patients walk and move their limbs normally. I know there are clinical trials right now involving orthoses that are controlled with brain interfaces that will hopefully help restore function in patients who need it. Dr Jones: It sounds like science fiction, but a lot of that technology exists now, right? Dr Chuang: Yes, it does. We definitely have prototypes of multigear hands with multiple directions. Now, the problem is trying to find the way to control these motors and to control these robotic hands and legs. Dr Jones: Caring for patients with myelopathy I imagine can be challenging, but I imagine it can also be quite rewarding. Tell us, Dr. Chuang, what drew you to this work specifically, and what do you find most exciting about it? Dr Chuang: I want to help people move better. I'm a physiatrist by training, and our job as physiatrist is to try to get people back to their activities of daily living as soon as possible; to try to remove any barriers to becoming active, independent people in their society. And so, I think that spinal patients that suffer from myelopathies or other spinal cord injuries have a lot of potential in the amount of activities that they can do and the way that they can contribute. I've seen patients who have been paralyzed and unable to move their hands at all develop tenodesis scripts, initially in order to just pick up things and then later obtain voluntary control of opening and closing their fingers. And it's huge in terms of what they can do in their everyday lives. Just being able to see that is just really rewarding. And even being able to help patients navigate society around them is just a hugely rewarding experience. Dr Jones: I imagine that must be really fantastic to see folks regain those milestones. Dr Chuang: Yes. Dr Jones: It's pretty unusual for someone to have done a neurology and a physiatry residency. So, between me and you and all of our listeners, which residency was better? Dr Chuang: Wouldn't trade one without the other. Probably wouldn't have done the one without the other, either! Dr Jones: What a great, diplomatic answer. Okay, good. Dr Chuang: It's true. Dr Jones: Yeah. You avoided offending all the neurologists and physiatrists out there. And really fascinating discussion, Dr. Chuang. It's an outstanding article. I think it's a must-read for anyone who takes care of patients with spinal cord disorders. I want to thank you Dr. Wang for joining us and for such a thoughtful, fascinating discussion on symptomatic management of spinal cord disorders. Dr Chuang: Thank you, Dr. Jones for having me today. Dr Jones: Again, we've been speaking with Dr. Kathy Chuang, author of an article on symptomatic treatment of myelopathy in Continuum's most recent issue on spinal cord disease - please check it out. And thank you to our listeners for joining today. Dr. Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, please consider subscribing to the journal. There's a link in the episode notes. We'd also appreciate you following the podcast and rating or reviewing it. AAN members, go to the link in the episode notes and complete the evaluation to get CME for this episode. Thank you for listening to Continuum Audio. /episode/index/show/continuumjournal/id/29863543

BONUS EPISODE: Continuum 2024 and Beyond 03/23/2024

Metabolic and Toxic Myelopathies with Dr. Kathryn Holroyd 03/20/2024

Metabolic and Toxic Myelopathies with Dr. Kathryn Holroyd Too much, or not enough? A wide range of nutritional deficiencies and toxic exposures may cause spinal cord dysfunction. To make matters even more confusing, the clinical presentations for these disorders may overlap. In this episode, Teshamae Monteith, MD, FAAN, speaks with Kathryn Holroyd, MD, an author of the article “Metabolic and Toxic Myelopathies,” in the Continuum February 2024 Spinal Cord Disorders issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Holroyd is an instructor in the Department of Neurology at Yale School of Medicine in New Haven, Connecticut. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media facebook.com/continuumcme Host: Transcript Full transcript available on Libsyn Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you’re not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. Today, I'm interviewing Dr Kathryn Holroyd on toxic metabolic myelopathies, which is part of the February Continuum issue on spinal cord disorders. Dr. Holroyd is an instructor in the Department of Neurology at Yale School of Medicine in New Haven, Connecticut. Katie, thank you so much for being with us on the podcast, and thank you so much for your excellent article. It was filled with a lot of really great tips. Dr Holroyd: Thank you - happy to be here. Dr. Monteith: I want to start off with knowing, how did you gain expertise in spinal cord diseases? Dr Holroyd: Yeah, I have a fairly diverse clinical background. My primary work now is as a neurohospitalist. But after residency training, I did two one-year fellowships: one in neuroimmunology and one in neuroinfectious diseases. I think, with those things together – you know, a lot of these, especially acute-onset myelopathies, tend to present inpatient for diagnosis – so, we see a lot of those in my hospital practice. Then, I think, specifically for toxic metabolic myelopathies - to identify these, you often have to know what it's not. So, my experience with some of the other autoimmune and infectious disorders really comes into play. Then finally, I kind of focused on global health work, which is why I primarily do neurohospitalist work - to allow for travel. I spent the past year working at a neuro HIV research site in Thailand, and I've done some work (mainly with education) in Zambia. But I've seen that, kind of, all how people's environments and local areas can really affect what disorders are more common, and I think it's really important to take that into account with especially this topic, as well. Dr Monteith: Well, your work in global health could be a whole other area, a whole other podcast that I would really want to record with you. But let's start with, what did you seek to accomplish when writing your article? Dr Holroyd: I think, when I was writing the article along with Dr. Berkowitz, the co-author, we really wanted to focus on things that would be clinically relevant, not just for neurologists, but for clinicians all over who may not have access to a subspecialist neurologist. We tried to focus less on metabolic pathways or disturbances and focus more on clinical pearls. I tried to think, “When I see these patients, what are the questions that I have that are not easily answerable from Google or UpToDate or a textbook? And how can we really use primary evidence to answer some of those questions? For example, what percent of patients with B12 deficiency actually have an abnormal MRI? Those are the things we were asking ourselves and, hopefully, that we were able to answer through the article. We focused on three main categories of toxic metabolic myelopathies, as you can see from the work. Dr Monteith: So, specifically, you've been writing about nutritional deficiencies, environmental and dietary toxins, drug abuse, medical illnesses, and oncological treatments. When you wrote your article and, comparing it to even, like, five or ten years ago, what has changed? Dr Holroyd: It's a great question because, I think, even when I started writing the article, it's easy to feel like not much has changed in these particular disorders. But if you go deeper, I think that's not the case. The main ways in which things have changed, I think, on the nutritional front, is there’s been an increase in weight loss and weight-loss surgery, which is one of the main contributors to all nutritional deficiencies. The second main category is - in some of these toxic myelopathies - is the increasing rates of drug use, particularly heroin, which we talk about in detail in the article. Additionally, along those lines, with climate change - we often don't think about the way that climate change can really affect disorders that are related to nutrition or the way that certain foods are prepared, especially with increasing rates of drought, and that really relates to konzo. Finally, there's been great advances in the treatment of all sorts of cancers, particularly with immunologic therapy. The one immunologic complication we talk about is with immune checkpoint inhibitors, and I think there's been a huge increase in clinicians seeing these as complications of checkpoint inhibition. So, those are the three main ways that I think these have evolved in the past decade. Dr Monteith: Great. You spoke about your interest in clinical pearls - can you describe some essential points that you wanted readers to take away with when diagnosing and managing patients that are presenting with myelopathies thought to be due to toxic or metabolic etiologies? Dr Holroyd: Yeah, and a lot of these are so different it's hard to find overarching themes, but I think there are a few that come through in the article. The first is that a lot - not all, but a lot - of these are reversible. Diagnosing them early is important and can really make a difference in patient outcomes. The second is a real clinical principle of all neurology that I learned from Dr Berkowitz, my co-author - is that neurology really is time course and localization. Amongst these, I think it's important to look at the time course, whether it's acute or subacute, and the location in the cord, whether it's a subacute combined degeneration or a more dorsal-column-only-predominant myelopathy - that can help you narrow the differential. A couple other small things is that, overall, these toxic myelopathies tend to be more thoracic cord-predominant and affect the legs more than the arms. In the majority of cases, the MRI will actually be normal, which is a big difference from a lot of the other autoimmune or infectious myelopathies. I think those are some main takeaways. And finally, you really have to be careful when you're interpreting the lab tests and make sure that the clinical picture fits with the lab tests that you're measuring - for example, the vitamin or other cause - and make sure that you really are correlating the diagnosis with that test. Then, I think the cause of the deficiency will affect your treatment choice; whether you're dosing supplements orally or IV, and what dose you choose - those are the major things to take into account. Dr Monteith: I really like what you say because, I think, as neurologists, we are always thinking about localization, localization, localization, but that time course also matters for a number of diseases. Dr Holroyd: And to that point, I think the clinical diagnosis is particularly important in resource-limited settings, where advanced diagnostics, such as MRI or lumbar puncture, may not be available. For example, konzo - the WHO has very clear clinical criteria of how to define this disorder, given that in most of the regions where cassava root is primarily eaten, there are not these diagnostics. I think we can apply that globally or even in our own practice in areas of the US or other places - to really rely on your clinical judgment and the time course and the localization of the . Dr Monteith: Yeah. What was that like when you were practicing in Zambia? Dr Holroyd: I worked primarily with Dr Deanna Saylor, who is there funding and working with neurology residents, and we would see a wide variety of clinical cases but have very little real-time information. So, I really admire the residents who train and work in Zambia and have to make clinical decisions with very little information. In those settings, the history – so, asking people about recent ingestions, any drugs, diet at home, any exposures that might cause increased risk of these conditions - is very important. And sometimes you have to rely on empiric treatments, such as vitamin B12, in cases where you may not be able to send for those tests - especially more specific tests, such as methylmalonic acid or homocysteine. Dr Monteith: With your hospitalist experience, can you think of some cases, or like, one case that stands out that made you lose sleep at night, that you cracked the puzzle? Just so that we have this on our radar. Dr Holroyd: Yeah, I think that there's some more unusual causes of toxic myelopathies. We saw a young woman who came in with a very acute, very severe myelopathy after studying for a test. She had a dorsal column-predominant hyperintensity, but all of her other diagnostics - lumbar puncture, everything else - was completely normal. We weren't really thinking of nutritional deficiencies because it was such an acute onset in such a young woman; we are really thinking this must be autoimmune or something else. And it actually came out that she had been ingesting whippets – so, inhaled nitric oxide, which came out a bit later in the history. And we checked for a B12, which was very low, and it turned out to be a nitric oxide-induced vitamin B12 myelopathy, which can be seen but is relatively rare and really stuck out in my mind. Thankfully, she made a full recovery with the supplementation of vitamin B12 and cessation of drug use. Dr Monteith: Wow, that is an impressive story. I'm glad that was on your mind and you figured it out. Dr Holroyd: Thanks. Yeah - team effort. Dr Monteith: What should we take away about nutritional deficiencies? Dr Holroyd: Nutritional myelopathies – I think there are kind of the four main ones that we speak about in the article - vitamin B12, folate, vitamin E and copper - and I think these really have more similarities than differences. They all present clinically very similarly, with the subacute combined degeneration of the cord (the dorsal columns and the corticospinal tracts) - that's going to give you, basically, spasticity and upper motor neuron signs, as well as sensory symptoms (loss of vibration and proprioception). Weakness can be a part of it, but that's usually a bit later in the course. Secondly, they all have similar diagnostics. As I mentioned, the MRI is going to be normal in over 50% of cases of all of these, but when it's abnormal, generally they'll be a T2/FLAIR hyperintensity in the dorsal column, and that will be the most common finding. Often, we don't have a lot of lumbar puncture data from these conditions, but generally, when lumbar puncture is performed, it will be relatively normal or noninflammatory. So, those are some of the similarities. Some of the differences are the risk factors. Vitamin B12 - the risks are going to be mainly bariatric surgery, a vegan diet, or autoimmune pernicious anemia. Folate deficiency from nutritional causes is very rare, so that's usually going to come from someone with an increased folate requirement (sickle cell anemia or certain hematologic malignancies). Vitamin E often comes from malabsorption, as seen in cystic fibrosis, or abetalipoproteinemia, or hepatobiliary disorders. And then finally, copper generally comes from gastric surgeries or from excessive zinc intake, the classic example of being denture cream. I think one way to differentiate these is by looking at the person's risk factors. Finally, I think I tried to categorize them in my head in a few different ways with clues that might give you a specific clue. So, if someone comes in with a subacute myelopathy and they also have a macrocytic anemia, that would push you more towards vitamin B12 or folate. However, if they're presenting with a myeloneuropathy (so, that's upper motor neuron signs) but also a peripheral neuropathy on exam, you might think more vitamin B12 or copper. Then finally, if someone comes in with a myelopathy as well as ataxia, you might think more likely vitamin E deficiency. Those are some ways to categorize these that may otherwise appear very similar. But I think, at the end of the day, and someone with a subacute myelopathy and a nutritional risk factor, you'll end up sending all four of these blood tests to evaluate for appropriate treatment. Dr Monteith: Well, let's move on to climate change. It's not often that we see climate change in a neurology article, but yet it's a thing that affects patients. Can you talk about konzo? I wasn't familiar with the term before reading your article, so thank you. Dr Holroyd: Yeah, it's one of these that we debated - should we include this in the article (because it is relatively rare). But I think it is important to keep a global perspective. Konzo and lathyrism are the two nutritional toxic myelopathies that we talk about, but I'll just focus on konzo for brevity. This occurs in populations that rely on the cassava root for nutrition and generally occurs in times of drought, and that's because drought increases the cyanide content in the cassava root. After higher rates of ingestion, especially in people with protein malnutrition (so, a lot of children and young women), you can actually get a toxic myelopathy from cyanide. And the mechanism is not totally understood, but it tends to be quite acute onset, primarily with spasticity, impaired gait, and weakness. It will self-stabilize, but there really is no way to improve symptoms after it's occurred. It is relatively permanent. There really isn't a lot of data on MRI findings or CSF findings, but the few case reports that have been published, they tend to be normal. I think what's important is that there are very easy public health interventions to prevent these toxicities – so, by simply increasing the wetting time of the cassava root (so, soaking it for longer), you can reduce the cyanide content and really effectively prevent this condition. So, I think the big picture takeaway that can be connected to a lot of other neurologic disorders globally is that we need to be aware of how climate change will affect our environment - and dietary changes, environmental exposures - and focus on early public health interventions to prevent these. So, how can we help prevent these rather than treat them once they happen. Dr Monteith: Are we seeing more of it, or is it just better diagnosed? Dr Holroyd: There's not great public health data on the rates throughout areas. It (so far) has only been reported in the African continent. There have been increases and decreases in numbers based on, I think, both the climate (so, times of drought or worse, malnutrition), but also, I think the reporting - I think it fluctuates not only with the weather but also with the amount of ability to publish on cases. So, I don't think we have a good grasp on whether, globally, their rates of konzo or lathyrism are increasing or not. Dr Monteith: Then, heroin - we have to talk about heroin, right? It's just simply remarkable that close to a million individuals in the US over the age of twelve use heroin in 2020. So, now you just have to talk to us about heroin myelopathy because it's something that we could see. Dr Holroyd: Absolutely. It's not something that I think most clinicians are familiar with as the complication of heroin use. But I'm sure that heroin touches all of our lives as clinicians in any field. There are two types of myelopathy related to heroin. There can be a slower, subacute myelopathy with chronic use. But what's more common, actually, is in people who have a long history of heroin use and then abstain for days to weeks and then use heroin again. This causes a very acute-onset longitudinal myelopathy that often has MRI abnormalities as well and can affect both the cervical and the thoracic cord and be quite severe, affecting all modalities (sensation as well as weakness). The mechanism really is not well understood for this and, therefore, the treatments really aren't well understood, either. Some case reports have trialed IV corticosteroids, but really, there's an unclear benefit for this. Most people will regain some recovery of function, but often it's not full recovery, and some may have no recovery. I think the follow-up question to this is, as we see the composition of drugs change – so, now there's a predominance of fentanyl, actually, whereas most of these case reports were from more traditional heroin. I was actually looking into it - this isn't covered in the article - but there has been one case report in 2019 about fentanyl use in someone who primarily used heroin, was abstinent for eight days but continued to use fentanyl patch, and developed an acute-onset, severe cervical myelopathy quite similar to this traditional heroin myelopathy. So, it seems like fentanyl will probably still have the same risks, but it's slightly less well understood at this point. Dr Monteith: And important also for chronic pain – just, like, poorly managed chronic pain that we might see, as you do during a hospital consultation. Dr Holroyd: Absolutely, yes - especially because this was from a fentanyl patch itself. Dr Monteith: Great. So, why don't you wrap up the most important clinical takeaways from your article? Dr Holroyd: I think one takeaway that we haven't really focused on is that, actually, most of the primary literature on a lot of these topics, especially the nutritional topics, are twenty to thirty years old, and I think updated case series would really inform clinical practice. When it came down to it, actually - folate deficiency - we really only found four to five case reports in all the literature, which I really think is disproportionate to how much we learned about it in medical school and residency. I think, really, a better understanding of (in this era) what the prevalence of these disorders are, how they're presenting, and effective treatments, is really needed. I think that a lot of the exciting work will also occur in the field of oncology, with new treatments, with immune checkpoint inhibitors, and better understanding of how we can mitigate the risks of neurologic complications while still allowing patients the benefit of their cancer treatment. So, I think diagnosing toxic metabolic myelopathies early is very important. And in someone with a... /episode/index/show/continuumjournal/id/29872618

Immune-Mediated Myelopathies with Dr. Michael Levy 03/13/2024

Immune-Mediated Myelopathies with Dr. Michael Levy The explosion in diagnostic tools to identify immune-mediated myelopathies has led to much more precise diagnosis and treatment of these patients, but also created gaps in knowledge. In this episode, Kait Nevel, MD speaks with Michael Levy, MD, PhD, FAAN author of the article “Immune-Mediated Myelopathies,” in the Continuum February 2024 Spinal Cord Disorders issue. Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana. Dr. Levy is an associate professor at Massachusetts General Hospital and Harvard Medical School in Boston, Massachusetts. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Transcript Full transcript available on Libsyn 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 episode notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. Dr Nevel: This is Dr Kait Nevel. Today, I'm interviewing Dr Michael Levy on immune-mediated myelopathies, which is part of the February 2024 Continuum issue on spinal cord disorders. Dr Levy is an Associate Professor at Massachusetts General Hospital in Harvard Medical School in Boston, Massachusetts. Welcome to the podcast. Thank you so much for being here today and chatting with me about your article. I really enjoyed reading your article. I read through it, and it felt like, you know, just really enjoyable. I had no concept of time when I was reading it. I encourage all of the listeners to read the article, too. I'll start with just a really broad question, with - what is the most important, clinically relevant thing from your article that you'd like the neurologist listening today to know? Dr Levy: I would say that the group of conditions in which the immune system can attack the spinal cord are growing. We're getting better at identifying the specific antigens, like in the case of NMO neuromyelitis optica and in MOG antibody disease. We're getting better at identifying targets for treatment, like with neurosarcoidosis - identifying those biologics that seem to help. And then, we're even beginning to characterize some of the idiopathic forms, some of which follow covid, or vaccines, or other conditions. I think the message is that we're getting a lot better out there, and if you have a case of inflammation in the spinal cord, then this is something that has a good workup now (and people should be paying attention to articles like this that give them an idea for how to work this up), and then the most appropriate treatment. Dr Nevel: Right. And not to get too much “in the weeds,” but in your article, you really outlined very nicely an algorithm or stepwise approach in evaluating patients with suspected immune-mediated myelopathies. Could you just briefly go through the general principles of that evaluation and stepwise approach, and what you would consider really necessary tests to order for these patients? Dr Levy: Sure. I would say that the first thing that you want to do is to make sure that it's inflammatory. And to do that, we have – the blood tests are few and far in between. If you're dealing with inflammation in the spinal cord, the few ways that we have to convince ourselves that there's truly inflammation - there are MRI and spinal fluid - and those objective tests need to be considered in the appropriate clinical context. The order of events is: patient comes in, reports certain neurological functions that localize to the spinal cord - that's step one, Step two, neurological exam that confirms that there's a neurological problem that localizes to the spinal cord. And then, numbers three, four, five are objective workups, including MRI of the spinal cord and other parts of the neuraxis, CSF testing, and blood testing, all of which then support your differential diagnosis. For each diagnosis, that order is the same, and it should always result in an answer for you, which ultimately may all be negative (and then we have a plan for that, too). If all your workup is negative, you don't know what caused it - at least a plan to deal with that as well. Dr Nevel: Building off of that - in your article, you mentioned that there are shared features between the different immune-mediated myelopathies. We have some tests that can help us differentiate, but what are some of the limitations or strengths of our currently available diagnostic evaluations - our clinical clues to help us differentiate between the different types? Dr Levy: The biggest limitation, of course, is that it's hard to access the spinal cord. We're not going to biopsy almost any patient unless we really have to rule out cancer. Otherwise, we don't want to take a punch out of a very small spinal cord that's carrying a bunch of fibers going in and out of the brain. So, that is our biggest limitation. We can't physically see it under the microscope, so we have to infer what's going on with MRIs and spinal fluid. And of course, spinal fluid isn't necessarily directly in touch with the inflammation - it could just be around it and bathing it. But we're hoping that there are clues from the spinal cord that shed into the spinal fluid that we can detect by lumbar puncture. I do think that we're getting better and also we're identifying things in the bloodstream that could also impact the spinal cord. And of course, blood tests are much easier to do, and some of these blood tests look for antibodies, which we know last for months and months. So, even if a person is having trouble getting their workup done on time, these antibody tests are still useful, even months after onset. Dr Nevel: Yeah. In your opinion, what have been some of the bigger breakthroughs? And I know there's been a lot in immune-mediated myelopathies over, let's say, the past five to ten years. That's a long timeframe, and I know a lot of things have happened during that timeframe – but what do you think has made the biggest impact in either evaluation and/or treatment for these patients? Dr Levy: When I was training, everything in the spinal cord was always MS. It was just - everything was multiple sclerosis in this big bucket of MS that we thought was heterogeneous. Now we're identifying the biomarkers that actually are distinguishing these patients from MS. We know what the immune system is targeting now in many of these conditions. Then, based on that immunological pathway, there are drug targets that have been developed. So, for even a very small disease, with 20,000 people in the US (one in 100,000) who have neuromyelitis optica, we now have three FDA-approved drugs because the science is so well worked out. And now there are two trials in MOG antibody disease, for example. As we identify new biomarkers based on the antigen specificity of the disease, I think we're going to have more and more specific therapies for each of these conditions, even if they're rare diseases. Dr Nevel: Yeah, that's great. Thanks for mentioning those, and I urge the listeners to check out the article to read a little bit more about some of those treatments for NMO spectrum disorder and MOG antibody disease that are in trials. What's the most common mistake that clinicians can make when evaluating or treating patients with immune-mediated myelopathies. What should we watch out for or to try to avoid doing? Dr Levy: I would say, at the beginning, there might be an urge to overtreat because we know that “time is spinal cord” - we don't want to waste time; we don't want to lose time. Some clinicians might just be inclined to give high doses of steroids, even in cases that they're not sure are inflammatory. The big overlap here is especially in older people who might have vascular myelopathy, where steroids might make things worse and it might delay their care. So that's the first problem – is, when physicians rush to judgment. Then the other big problem is when they take their time, and they say, “Well, this is just multiple sclerosis, probably. And we know that, in the end, MS patients do the same whether they're treated or not treated, and so we can take our time with this.” Whereas if we know that this is actually NMOSD, time is spinal cord and destruction is ongoing and potentially irreversible. I would say that there's problems on both sides of the time window. My approach is to be aggressive very early on and try to identify whether or not it's inflammatory. And then if it's not, then you can take a step back and go to the other chapters in this continuum - try to figure out what this is – and if it is inflammatory, then you definitely want to get on top of the treatment. Dr Nevel: Yeah, finding that sweet spot; making sure that you're not waiting too long but that you're not treating inappropriately or the wrong thing. So, what do you think - let's say you have a patient with an immune-mediated myelopathy; you've diagnosed them, they're undergoing treatment. What's the most challenging part of ongoing management of a person who has an immune-mediated myelopathy? Dr Levy: I would say that one of the most satisfying parts of my career lately has been that we're good at preventing the next attack once we know what the disease is. So, for NMO and for MOG and MS, we're good at that. We can suppress the immune system or modulate it in a way that we're preventing the next attack from occurring, and patients are excited about that. But when they come into clinic and I say, “Great job, no new attacks,” then they look at me and they go, “But how do I get out of my wheelchair now?” Because the damage done from prior attacks is not touched by any of these meds. So, there's a huge unmet need in that area of regeneration and recovery of function because, while it's all great that we can prevent the next attack and with all these great drugs that are approved, patients are still suffering. They have mobility problems, bowel/bladder problems, and pain, especially neuropathic pain, that really causes a lot of disability, and that's from damage that's already done. It's the same as spinal cord injury from trauma or from tumors or whatever - the spinal cord injury is the same and there's still a huge unmet need in that area. Dr Nevel: On that note, who else do you usually consider part of the team, if you will - who else should be involved in the management of these patients? Dr Levy: A lot of people. We have urologists involved for bladder, we have physical therapists involved for mobility, and occupational therapy for things related to hand and hand function. We have psychiatrists related to mental illness and also just dealing with these issues, because even if you don't have clinical depression, you still have an adjustment from the disease process and from all the treatments. Social workers, because this is a huge financial burden for a lot of people. An often rheumatologists, because NMO, for example, has about 25 percent overlap with other diseases. We don't want to double treat - we’ll often choose a treatment that's applicable to both the rheumatologic disease and the neurological disease. So, I'd say that we don't work alone in almost any case; it’s usually quite a big team involved. Dr Nevel: One of the questions that I always like to ask is, what do you think the next big breakthrough is going to be in immune-mediated myelopathies? What's most exciting to you - what do you think is on the horizon here? Dr Levy: I think probably the most exciting area is in multiple sclerosis, where we're starting to understand the role of the Epstein-Barr virus in triggering the disease, and potentially, even in driving the disease. Up to now, we've been suppressing immune systems in people with MS. But maybe we should be looking more at how can we prevent MS from occurring in the first place. And in cases where MS has already started, how does the virus play a role, and can we potentially modulate the outcome of disease with something like antivirals against EBV? So, I think that's the huge, exciting area. It's dominating a lot of the conversations at neuroimmunology conferences. But I think it's well worth the investigation because if MS turns out to be just an Epstein-Barr virus infection, I think a lot of what we've been doing up to now might not be as relevant. So, this is something that's very important. Dr Nevel: Yeah - to have a way to prevent disease rather than treating it after, too, would be a super powerful thing. Dr. Levy: And there are lots of Epstein-Barr virus vaccines that are being developed. But then the question comes up, “Well, are we going to prevent one in a thousand people from getting MS by vaccinating all thousand kids?” Is that really worth it? Can we pick out the ones who are more high risk for developing MS and just vaccinate those kids? A lot of ethical questions involved in that, too. Then what happens if we don't let our population get infected with EBV? We've evolved with that virus for hundreds of thousands of years. What if we abolish it all of a sudden - what does that do? Does it have any implications? I don't know. Dr Nevel: Yeah, lots of really complicated things to think through, with exciting potential but a lot of unknowns. Dr Levy: A lot of unknowns. Dr. Nevel: Talking about patients with seronegative relapsing transverse myelitis - what's your general approach to those patients? When you feel like you've exhausted the extent of your workup but they have a relapsing transverse myelitis, how do we approach those patients and take care of them? Dr Levy: “Seronegative” refers to patients who test negative for aquaporin-4, which is NMO, and test negative for MOG antibody disease (so they are double seronegative), but they have a recurring disease that looks an awful lot like one of the two. We generally stratify these patients into the “aquaporin-4-like,” “MOG-like” or “MS- like.” So, we try to put them into a category even if they're seronegative because we think that the treatments would be the same. So, for the MOG-like, for example: these are patients who have recurring attacks; they're not necessarily all long, but they do tend to remyelinate, and they can be severe at first but then they do get better over time. That's “MOG-ish,” so we treat those people with MOG treatments. Whereas people who have this sort of aquaporin-4 type, they have severe attacks and they really don't get better, and they have a lot of necrosis if you look at it under the microscope. And those people we tend to treat with aquaporin-4 NMO drugs. And then we have the MS type that kind of lingers or is more focal white matter lesions. Even if they don't have a lot of brain lesions, they might be oligoclonal band-positive; we put them in the category of MS. But we have a very active research effort to identify new antibodies in case any of these diseases that are seronegative and don't fit into any category - it's certainly possible that there's an antigen of their own that they're attacking, so we'd like to try to identify that in these novel assays that we’re doing in the lab. Dr Nevel: How do you counsel patients on what to expect in the future, who you're seeing in the hospital with their first episode of transverse myelitis, for whatever the cause? Because one of the biggest questions I suspect most patients ask is, “Am I going to get better? Is this going to happen to me again?” How do you navigate those tough discussions, and what do you tell patients? Dr Levy: In the hospital, it's tough, because a lot of our testing takes time - it takes ten, fourteen days. So, in the hospital, I say, “Look, we're going to focus on here and now - we're going to suppress the inflation; we're going to try to get you better from this event.” It could have been a severe optic neuritis or transverse myelitis, or brain stem injury, or whatever - we're going to try to focus on that. And then I say, “When you come back to my clinic, we'll have the results from all of your testing and we’re able to talk about the future and how to prevent the next one, if we have to.” It does take time, unfortunately, to get all that data back, and it is a little bit suspenseful for patients, but that's what we have at the moment. Dr Nevel: Yeah, the most honest answer that you can give them is always the best one. And that's the scenario when you're in the hospital - that there just isn't full answers. Dr Levy: Yeah. One of the reassuring things I can say is, “We have a lot of medications that target different parts of the immune system, so no matter what you have, we can probably treat it.” Dr Nevel: Right. Obviously, really important to give people a sense of hope and reassurance that you're there and you're going to help find a treatment that's going to help them in the future. Well, thank you so much for chatting with me today. I really enjoyed our conversation and reading your article and learning more about immune-mediated myelopathies. Dr Levy: It's been a pleasure. Thank you. Dr Nevel: Thank you, Dr Levy, for joining me on Continuum Audio. Again, today we've been interviewing Dr Michael Levy, whose article on immune-mediated myelopathies appears in the most recent issue of Continuum, on spinal cord disorders. Be sure to check out Continuum Audio podcasts from this and other issues, and thank you to our listeners for joining us today. Dr. Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, please consider subscribing to the journal. There's a link in the episode notes. We'd also appreciate you following the podcast and rating or reviewing it. AAN members: go to the link in the episode notes and complete the evaluation to get CME for this episode. Thank you for listening to Continuum Audio. /episode/index/show/continuumjournal/id/29863443

Genetic Myelopathies with Dr. Kara Stavros 03/06/2024

Genetic Myelopathies with Dr. Kara Stavros While collectively uncommon, the clinical presentation of genetically-mediated spinal cord disorders frequently overlaps with other neurologic conditions. Our understanding of these disorders has grown considerably. In this episode, Kait Nevel, MD, speaks with Kara Stavros, MD, FAAN, author of the article “Genetic Myelopathies,” in the Continuum February 2024 Spinal Cord Disorders issue. Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana. Dr. Stavros is an associate professor of neurology and clinician educator at Warren Alpert Medical School of Brown University in Providence, Rhode Island. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Transcript Full transcript available on Libsyn 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 of the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by clicking on the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you’re not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the episode notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. Dr Nevel: This is Dr Kait Nevel. Today, I'm interviewing Dr Kara Stavros on genetic myelopathies, which is part of the February 2024 Continuum issue on spinal cord disorders. Dr Stavros is an Associate Professor of Neurology and Clinician Educator at Warren Alpert Medical School at Brown University in Providence, Rhode Island. Welcome to the podcast. What is the biggest takeaway from your article that you'd like the neurologists listening to this to know? Dr Stavros: I would have to say that there's maybe two big takeaways that I would want to highlight. One would be that, generally speaking, in a nutshell, the genetic myelopathies can present with chronic and progressive symptoms, oftentimes (but not always) a family history of similar symptoms, and involvement of other structures outside of the spinal cord. Exclusion of the more treatable causes of myelopathy is a really key and important step in the diagnostic process. And because there are many different causes of genetic myelopathies, in some cases, the symptoms can overlap. I think this really underscores the utility of doing genetic testing to really confirm the precise underlying neurologic condition. The second takeaway that I would want to highlight is that, while treatment for most of these conditions is typically supportive, there have been a number of recent therapeutic breakthroughs for treatments in ALS, spinal muscular atrophy, adrenal myeloneuropathy, and Friedreich ataxia. While these aren't cures, it's really exciting and gratifying to see new therapeutics emerge via different mechanisms for patients with conditions that we've had very little treatment options for in the past. Dr Nevel: Yeah, I really enjoyed reading that in your article - about these treatments that have been coming out over the past several years. The one with Friedreich’s ataxia, too - that looked like it was really just recently approved this year. Dr Stavros: Yes. Dr Nevel: And so, kind of jumping off of that topic - there have been these exciting treatments that have been coming through. What do you think is going to be the next big thing? Or what do you think is the next thing that might come through? Or what's going on in research in genetic myelopathies that might help our patients? Dr Stavros: That's a really great question. I think that, as far as the future in this area, genetic testing has definitely grown in terms of being able to identify more genes now that are implicated in these disorders than ever before. But this is still an area where our knowledge is continuing to evolve. So, I think the future holds further advancements in our ability to successfully diagnose patients who have these conditions and provide them with the sense of closure that having a definitive diagnosis brings, as well as opening the door to potentially targeted treatment options once a specific diagnosis is made. Another thing I think the future holds is continued development of expanded treatment options for patients with these conditions, both in terms of advancing our supportive care capabilities and then also providing more disease-modifying therapies. Again, as I mentioned, in recent years, new disease-modifying treatments have actually become available for several of these conditions. And I think that's just the beginning. There's going to be more to come, for sure. Dr. Nevel: Yeah, that would be great. Going back to the genetic testing and how things are - we're finding more and more and more genes. When you decide that genetic testing is indicated, how do you counsel your patients about genetic testing and walk them through that process? Dr Stavros: Okay - I would say that it usually starts with having a conversation with the patient about whether they want to pursue genetic testing or not for the particular condition or conditions that are suspected. Genetic testing is really helpful to, again, confirm the diagnosis once the initial diagnostic workup perhaps has given you some clues as to what the underlying condition might be. Again, because sometimes the clinical symptoms can overlap in different genetic myelopathies in particular, the genetic diagnosis can be really important as far as getting a definitive, final diagnosis. Usually testing is pretty carefully considered and the risks versus the benefits are explored with the patient. Oftentimes, this is done in conjunction with a genetic counselor or with genetics clinic. So, there's a lot of teamwork there in working with the genetics department, at least in my experience. There's a lot of options that might include testing a panel of genes for the suspected condition, to up to whole-exome sequencing. Again, this is really like an evolving landscape. So, we have a current understanding of the genes that are implicated in some of the genetic myelopathies, but there's still so much that we don't know. So, a lot of times, testing can result inconclusive or may be falsely negative, and it can be tough because a negative test doesn't necessarily exclude a potential genetic etiology. It becomes a very nuanced, I think, conversation and journey with the patient. Dr Nevel: Yeah, and in your article you mentioned some of the health care disparities that exist around genetic testing and access to genetic testing, specifically. How do we, as clinicians, try to mitigate inequities in regard to access, or in regards to being able to offer our patients genetic testing - is there anything that we can do? Dr Stavros: I do think there are some resources available, where free or sponsored testing can be utilized from nonprofit organizations or pharmaceutical companies. But you're right that this is a real area for potential health care disparities. And making sure that we have equitable access to genetic testing is really important. Some of the issues that come up are: limited access due to location; due to socioeconomic factors; a lack of awareness on the part of the patient or sometimes the provider about testing that's available; cost, of course, being a big issue, oftentimes; and sometimes, distrust of how the medical information, the genetic information, might be used or protected. Dr Nevel: What do you think is one of the most challenging things about managing patients with genetic myelopathies? Dr Stavros: I think one of the more challenging aspects of the care is the diagnostic journey. I think that some of these conditions - most of them are not terribly common – and they may not always be at the top of our differential diagnosis in the course of a workup for myelopathy. The first step, I think, is really continuing to be aware of these conditions and not letting them become a “blind spot” when we're formulating a differential diagnosis for a patient with myelopathic symptoms. I think it can really take some time to reach the ultimate diagnosis for most of these conditions. Another challenging aspect, which I alluded to earlier, is sometimes when genetic testing might come back inconclusive or nonrevealing, and there remains some diagnostic uncertainty despite best efforts and a thorough workup -that can be frustrating as well, sometimes. Again, our knowledge of these genetics and the genetic mutations underlying these disorders is still really evolving. But on the flip side, there's a lot of rewarding aspects as well. I think one of the most rewarding aspects is trying to help patients identify interventions that improve their quality of life, and working with the patients and their families (who oftentimes become very expert in their own rare conditions in their own right), and working amongst the interdisciplinary teams. So many of these conditions are associated with extraneurologic manifestations, and so patients need coordination of care with other specialists. Hereditary spastic paraplegia is a great example, as well as Friedreich ataxia, where you often work closely with the cardiologist and of course, ALS, where there are a lot of multidisciplinary needs. Dr Nevel: Yeah, I'm so glad that you mentioned that because, in neurology in general (and specifically in this area), I can imagine the benefit to patients when there are multiple specialists involved in their care who are experts in the various aspects that are impacted from their underlying condition. Shifting gears a little bit - but going back to something that you've mentioned a few times, about making sure that we don't have a blind spot to genetic myelopathies, and that we consider this in part of our differential diagnosis when we're evaluating patients - in the patient who doesn't have an extensive family history of the exact same neurological symptoms, when should we consider genetic testing for patients that we're seeing in clinic? Like, at what point should we say, “Okay, we've done the other tests and now is the time to consider genetic testing.” Because I think, unless somebody has that really strong family history, it's probably not on the top of your list to do it right away, for a variety of reasons. Dr Stavros: I think you make a great point. Family history is tricky because, typically, we use that as a really strong clue of an inherited disorder of any type. But it can be tricky because, for a variety of reasons, it might be negative. Sometimes there is a de novo mutation, or there's variable phenotypes within the family, variable penetrance within the same family. Autosomal recessive inheritance can actually be, sometimes, hard to pick out. Or sometimes, patients don't have knowledge of their family members’ medical histories. For all of these reasons, there may be information lacking in the family history. But I would say one of the most important things to exclude when you're working up patients initially is, of course, acquired causes of myelopathy, because you wouldn't want to miss a more treatable cause. And so, things like structural causes, nutritional, vascular or demyelinating causes (things that are explored more deeply in some of the other articles in this issue) are important. But if you've excluded acquired causes despite lacking a strong family history, I think, at that point, it's worth broadening your differential diagnosis to consider whether you might have reason to suspect a genetic myelopathy, particularly if you have some extraneurologic manifestations, some systemic symptoms that might be a clue towards a more systemic process. In genetic myelopathy, sometimes imaging can actually be quite helpful. It helps you exclude - MRI of the spine can help you exclude acquired causes, but it also helps you sometimes get clues toward a genetic cause. Typically, the finding might be either normal or show some spinal cord atrophy (but typically without signal change, so that can sometimes be a clue). Dr Nevel: What's one mistake that is made in managing patients with genetic myelopathies? Maybe “mistake” is too strong a word; maybe “misconception” about treating patients with genetic myelopathies. Dr Stavros: That’s a great question. I think that one of the, maybe, misconceptions might be that these are homogeneous entities, these different diseases. But one of the things that surprised me anew in going back to research this topic and prepare this article was a reminder of just how variable both the genotypes and the phenotypes are within what we consider sometimes just one diagnosis, like hereditary spastic paraplegia, for example, spinocerebellar ataxia. There's so many different presentations and genotypes associated with these. It's really a family of different conditions. You could say the same thing about ALS as well. So, the spectrum of disease, I think, is important to recognize. Dr Nevel: Yeah, and I can imagine because of that spectrum of disease, just having an open mind in considering genetic testing and not excluding a potential genetic cause because it doesn't fit into what we think is the most typical presentation of that genetic condition. Dr Stavros: Yes - I'm in total agreement. Dr Nevel: I've asked you about what some of the misconceptions are and what some of the challenges are, but what's the most rewarding part about taking care of patients with genetic myelopathies for you? Dr Stavros: I think one of the most rewarding parts has to be working with the patients and the families. Like I mentioned earlier, sometimes they become so expert in their own conditions - it's amazing. And, working with them, working with the interdisciplinary teams, is a really rewarding process. I think that the more I've encountered patients with some of these rare conditions, the more I've learned from their stories and experiences, and so, that's, I think, been the most rewarding aspect to me. Dr Nevel: You've mentioned the multidisciplinary team a couple of times that we've talked about this, but who specifically do you usually include or contributes to the care of these patients? Dr Stavros: It may depend on the condition in question. So, for example, for Friedreich ataxia, there's always going to be a cardiologist involved in the patient's care. For ALS, there's going to be a larger team. For those who are familiar with ALS multidisciplinary clinics, this often includes physical therapy, speech therapy, nursing, pulmonary, and many others. And so, it really depends. I think in most cases though, genetics evaluation and genetic counseling is a really important piece. Dr Nevel: How do you work with the genetic counselors in counseling families about testing other family members? Because that's something that's really challenging in genetic conditions, especially for people with children that may be underage, and this is a really complicated topic. But how do you approach that? Dr Stavros: I think that it may depend on your particular institution. Where I'm at, typically, that's something that our genetics department will take the lead on and they will meet with the patient first and then also meet with and bring in any interested family members who are hoping to pursue the possibility of testing themselves. There's a bit of controversy or differing opinions around genetic testing, specifically for presymptomatic individuals for inherited ALS, because - certainly, there's pros and cons for being tested for any condition, but some special considerations come into play when someone is presymptomatic. There's actually been studies done, in particular, on patients who have a family history of ALS who are presymptomatic, and generally, the studies have shown that those patients are usually - the majority - in favor of being tested. But it does certainly bring up some ethical implications. Of course, any discussion is going to be undertaken with the goal of informing the patient and discussing the risks versus the benefits in detail. There's actually recommendations on the principles and the practice of presymptomatic testing for ALS, which is available and referenced in the article. Dr Nevel: Do you think as - hopefully, in the future, as more treatments become available - that presymptomatic genetic testing could play a role in how we manage patients? Dr Stavros: I think that's a great thought. I think it may, especially as more treatments become available, I think there may be a greater interest in demand for finding out early whether you might have a likelihood of developing a certain condition so that you can plan accordingly and perhaps even pursue treatments early on. Dr Nevel: You know, you mentioned this (and this isn't maybe quite exactly the same thing), but in SMA - you mentioned newborn screening for SMA and new treatment for SMA, and that newborn screening is not always a standard, and that there's controversy around that, now that we have treatment for it. Dr Stavros: Yes. That's another area where some controversy comes up as well, as far as cost and treatment, for sure. Dr Nevel: Thank you, Dr Stavros, for joining me on Continuum Audio. Again, today we've been interviewing Dr Kara Stavros, whose article on genetic myelopathies appears in the most recent issue of Continuum on spinal cord disorders. Be sure to check out Continuum Audio podcasts from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, please consider subscribing to the journal. There's a link in the episode notes. We'd also appreciate you following the podcast and rating or reviewing it. AAN members, go to the link in the episode notes and complete the evaluation to get CME for this episode. Thank you for listening to Continuum Audio. /episode/index/show/continuumjournal/id/29872573

Spinal Cord Neoplasms with Dr. J. Ricardo McFaline-Figueroa 02/28/2024

Spinal Cord Neoplasms with Dr. J. Ricardo McFaline-Figueroa Tumors affecting the spine are fortunately uncommon, and may arise within the spine or metastasize from malignancies elsewhere. Effective treatment is determined by tumor type, location, and urgency. In this episode, Allison Weathers, MD, FAAN, speaks with J. Ricardo McFaline-Figueroa, MD, PhD, author of the article “Spinal Cord Neoplasms,” in the Continuum February 2024 Spinal Cord Disorders issue. Dr. Weathers is a Continuum® Audio interviewer and the associate chief medical information officer at Cleveland Clinic in Cleveland, Ohio. Dr. McFaline-Figueroa is a physician at Dana-Farber Cancer Institute and instructor in neurology at Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Transcript Full transcript available on Libsyn Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you’re not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. Dr Weathers: This is Dr Allison Weathers. Today I'm interviewing Dr Riccardo McFaline-Figueroa on spinal cord neoplasms, which is part of the February Continuum issue on spinal cord disorders. Dr McFaline-Figueroa is a physician at Dana Farber Cancer Institute in Boston, Massachusetts, an instructor in neurology at Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts. Welcome to the podcast. You do a really fantastic job in the article providing a comprehensive overview. But if you had to come up with the most important clinical takeaway from the article that you want our listeners to walk away with, what would that be? Dr McFaline-Figueroa: I think the most important thing to remember about tumors of the spinal cord is, one, that there is no specific diagnostic feature on imaging that can be used to determine what a neoplasm of the spinal cord is or even if it is a neoplasm - I think, going in broadly, when you're looking at a mass lesion of the spinal cord, is very important. Then the second is just to know that there's just such a wide range of cancer possibilities that can do this, that getting an appropriate diagnosis becomes very important. Dr Weathers: I think two really salient points right there. I want to explore something that you said a little bit more. You talk about the concept that there's no one diagnostic feature of the MRI, and actually, I was thinking about this as I was reading your article. What struck me, too, is that that holds true, actually, for the patient’s presenting signs and symptoms, right? As a neurohospitalist, I'm constantly struggling with always how to balance not missing a diagnosis such as this (a diagnosis of spinal cord tumor), versus putting a patient through what can be an often unnecessary and very costly workup, right? So, this is such a rare diagnosis, but the presenting symptoms and signs, just back radicular pain and weakness, are shared by so many common conditions. What's your approach to distinguishing between them, and what are some of the red flags you look for to know when further workup really is indicated? Dr McFaline-Figueroa: Certainly. I think there's not one way to decide whether you need to go down the route of exploring a neoplasm of the spinal cord, but there are certainly things that would clue someone into this needing to be the case. I think, one, as opposed to a lot of the monophasic illnesses that we see in neurology, certainly it's something that is progressive; is certainly something that increases the certainty, and it's different from ischemia of the spinal cord or an acute demyelinating event. I think another important feature is also just the context. I think, even though these are rare, when you're dealing with a patient with a known history of cancer, that's when “the rare” becomes common, and that's when you have to really start thinking about it being a neoplasm of the spinal cord. It's still not perfect; it covers some of the side effects of treatment that can look a little bit like a spinal cord neoplasm. But certainly, that should increase the level of suspicion for something going on in that compartment that's neoplastic. Dr Weathers: I think that's such a great take-home quote for our listeners to think about - when the rare becomes common. You actually hit on the point that I wanted to ask you about next. In neurology, we always talk about how important the history and the exam are - it's kind of our core of what we do. But it feels especially true when talking about neoplasms of the spinal cord. You mentioned, obviously - the big one is that if they have a history of cancer, especially in active history, that's a pretty big clue that something more serious could be going on. But what else is key in the history? Why are the history and the exam so especially important when you're concerned about or dealing with neoplasms of the spinal cord? Dr McFaline-Figueroa: When we're dealing with the spinal cord, we're dealing with a lot of different compartments. I think, to your question, the one where thinking about history and physical becomes the most important is when you're thinking about the possibility of leptomeningeal involvement, right? The leptomeningeal space is not easily imaged, right? We can't really see much what's going on in the CSF. And so, we rely on - imaging-wise - on there being deposition of cancer cells along the dura or along the direct surface of the cord. But oftentimes, that's not the case. That's when knowing exactly what someone's cancer history is, what their stage in the natural history is, whether they're progressing or not progressing, have some knowledge of what the oncologic medications that they're on are (because brain penetration is different for several of them), and then really hearing for those signs and symptoms that are connected to that compartment - signs of increased intracranial pressure, signs of cranial neuropathy that may or may not be evidence on imaging, radiculopathies. So those are the things that are very important in all investigations of spinal cord tumors. But certainly for leptomeninges, it's often the case that, really, history and physical are all you have to try to get the diagnosis right. Dr Weathers: You make, actually, a really great point in the article that I think it bears mentioning here. Because I was embarrassed when I read it, because I said, “I have been guilty of that” - that the history of, kind of, these very generic histories of cancer; you know, “Oh, they had lung cancer” - is probably not sufficient, right? That there's value in getting really specific. Why is that? Dr McFaline-Figueroa: That's certainly why we all specialize in different things, right? For a neuro-oncology standpoint, it sounds very different to me to hear the same history in a patient with melanoma versus the patient with bladder cancer. You think of melanoma from a neuro-oncologic standpoint, you're thinking of a cancer that is incredibly trophic for the brain and spinal cord, probably because it's derived also from ectoderm (so it's kind of the same origin of the cells), and it just makes your level of suspicion go so much higher when you are in that mind space. Thinking of a melanoma patient versus someone with a tumor, that very rarely (if it all) goes to the central nervous system. I think that's something that's really important. And those are two big extremes. But even - like I mentioned - even in lung cancer, certainly, small cell versus non-small cell are very different in terms of when and how they can affect the spinal cord or any part of the central nervous system. So, that one is a little bit more nuanced and, being a neuro-oncologist - but still, it’s specific as you can be when you're discussing with your neuro-oncology colleagues or medical oncology colleagues, and the better for trying to figure these things out. Dr Weathers: An excellent pro tip right there. You were very gracious about it - about that we all have different specialties. I was reflecting on that, too - this is such an important yet definitely pretty specialized topic; how did you become interested and develop your expertise in it? Dr McFaline-Figueroa: My clinical work is on all sorts of tumors of the central nervous system. Actually, in neuro-oncology, we also do a little bit of peripheral nervous system tumors, depending on how they present. And it's all a continuum. Not to use that - well, we just happen to be on Continuum. But it's all a continuum: brain, spinal cord - it's all one big compartment. And it forces you to be really familiar with all of those. And I think it's an interesting topic - we don't talk about it as much as we do for some of the other – you know, cancers of the brain, for example. In terms of becoming an expert, for me, I mean a lot of it is just, at this point, experience. And I will say, a lot of reading, because you don't see all of these. I cover some topics, like primary glioneuronal tumors of the leptomeninges, which are incredibly rare - I've never seen a patient with one. But it's one of those things where you should know the basics of these, at least for my field, and certainly beyond. Dr Weathers: What about neuro-oncology in general? How did you decide that you wanted to specialize in that? Dr McFaline-Figueroa: Well actually, me, personally - I spent a lot of my residency trying to decide between being a neurointensivist and being a neuro-oncologist. I think, for me is that I like taking care of patients who are potentially very sick. I think I just enjoyed the process of the more longitudinal relationship you have as a neuro-oncologist - seeing people in clinic, walking them through all these treatments and difficult disease courses – and that, to me, I just found really fulfilling, while still having lots of internal medicine to think about, lots of interesting neurology, just in a different context. Dr Weathers: It's such an interesting field. And I was also really thinking about this - that while neurology overall has had so many incredible advancements in terms of diagnostic and therapeutic capabilities in the last several years, neuro-oncology, in some ways, is almost like an entirely different field since I was in residency training, which wasn't all that long ago. How have these changes impacted how you diagnose and manage spinal cord tumors? Dr McFaline-Figueroa: Certainly, there's been a lot of changes in technology that I think have been helpful. And then, certainly, slowly but surely, we are coming up with better treatments for patients. When I speak of technologies, one thing that, for example, comes to mind is - historically, it's just so difficult to diagnose. I keep coming to the same anatomic compartment, but it's so difficult to diagnose leptomeningeal carcinomatosis or leptomeningeal involvement by a tumor, even more so, I think, in the spinal cord, because it's just difficult to catch on imaging. But over the last few years, so many advances in, like, molecular testing of cerebral spinal fluid to be able to look for cell-free DNA; to be able to enrich for rare cell populations and then identify them, which really, kind of, have changed that “we need to do three LPs” mentality. We have things that are sensitive enough that are rolling out. And in terms of treatment, certainly, the field is changing. There's so many now targeted therapies emerging for tumors as we understand the biology, which is probably the biggest roadblock to better care for the primary spinal cord tumors - it's also a very exciting time to be in neuro-oncology because of that. Dr Weathers: On perhaps a less positive note - the fields change so quickly; has this led to any controversies in the field? Dr McFaline-Figueroa: I think the biggest controversies are less so controversies in the traditional sense, in that I don’t think anyone's fighting with each other. But it's become really difficult to know, particularly as those therapies that I mentioned come out, what is the right first step. Is the right first step for somebody to have, for example – well, actually, this is less controversial now - but for example, someone with von Hippel-Lindau, who might have multiple hemangioblastomas. We're reaching a point that, with approvals of targeted therapies for that disease, you might not necessarily go for surgery (which could be quite morbid in some instances) or radiation for progressive disease. So, I think one of the issues there is that we're not necessarily at the point where we are sure that, you know, definitely the intervention with the longest survival is targeted therapy first, and then maybe surgery, and then maybe radiation, versus the other. I think the order at which we treat these tumors is just a little bit in flux. Dr Weathers: Hopefully, with time and more evidence, that will become more definitive and clear. You just mentioned - just in that answer alone - surgery and radiation. The other really fascinating thing about this topic (about neoplasms of the spinal cord) is how truly a multidisciplinary effort the management of patients with spinal cord tumors is. What other specialists do you work with to diagnose and manage this patient population, and what's everyone's role in these cases? Dr McFaline-Figueroa: Certainly, neurosurgery still plays a huge role, particularly because even when you are relatively sure that it's a tumor of the spine (particularly if you think it's a primary tumor of the spine), there's really no - again, just no diagnostic test; that's just imaging. The only way that we have to establish the diagnosis is through tissue examination. In neurosurgery, in a lot of diseases, still plays a huge role. For example, ependymoma is one where, really, gross total resection is one of the biggest (if not the biggest) prognostic factor in treatment. Radiation oncology - there are still histologies that we have no good systemic therapies for. For example, for diffuse midline gliomas, most of them are not very sensitive to the therapies that we have that are systemic. So, for these tumors, it becomes important to do radiation as the most significant step in management that we have - we just don't have anything efficacious for those tumors, at the moment, although we're learning a lot about the biology. A lot of these have histone mutations that people are trying to target for more effective treatments. So, radiation oncology, again, still plays a huge role in the treatment of our patients. Certainly, when you're dealing with patients with metastatic cancer to the spine, medical oncology is huge. And that's where - me, as a neuro-oncologist, I'm less of an oncologist and more as a person who the medical oncology can bounce ideas from. We talk about - sit down and talk about - their expertise in how to treat these tumor types. And then, me bringing in what might be brain-penetrant, what things may or may not be toxic to the nervous system - stuff like that. It's really a group effort, and that's not even mentioning nurses, nurse practitioners, amazing people who coordinate care, and stuff like that. And like I mentioned early on, one of the most important things is to know exactly what type of tumor or cancer these are before proceeding with any conversation about treatment. And that's where our neuropathologists really drive the direction of what we're doing. Dr Weathers: Even as I was thinking about this question, in my mind, what I thought your response point may be - that was even more of a complex team than I think I had envisioned, and it really speaks to, again, the true multidisciplinary effort, the “team of teams” that's needed to provide care for these patients. And I think I heard you say this in your - that wonderful answer, but that as things are evolving and as we are better understanding the biology, that we're getting better with our targeted treatments. But that could possibly include, at some point, even targeted therapies for midline gliomas, which would be incredible. I know that's always been one with, not only especially poor prognosis, but given the population it tends to affect (younger patients), it can be quite devastating. That definitely struck me as I heard you say it. So, I think this is a field where we're going to continue to see so many breakthroughs. And that leads me, actually, into my last question. I always like ending these on a hopeful note, and I think that certainly does it. But we've talked about so many changes already, and again, I know even more to come. What do you think the next big breakthrough will be? Did we cover it already? Is there anything else that you're excited about that's coming down the pike? Dr McFaline-Figueroa: I think we covered some of it, which is really being able to bring more systemic therapies (more oral therapies or intravenous therapies) that treat these tumors, as opposed to things like aggressive surgery or radiation, which are effective. But the hope here is that we can delay those so that we can have people living longer with these cancers, or cured of these cancers, and trying to spare them as many side effects of treatment as we can - which historically, in the spinal cord, is quite significant because it's a difficult space to do surgery on and it tolerates only a certain amount of radiation before coming into toxicity. So, I think it's a really exciting time to be on the medical side of things as a neuro-oncologist and see all these treatments coming in that really improve people's quality of life. Dr Weathers: Definitely an exciting time to do what you do. Well, again, thank you for the incredible article, for taking the time to speak with me today. Any last thoughts for our listeners? Dr McFaline-Figueroa: Just be mindful when working up those spinal cord tumors. There's a lot to think about, but there's also a lot of good can be done by doing good diagnostic workup. Dr Weathers: Thank you, Dr McFaline-Figueroa for joining me on Continuum Audio. Again, today we've been interviewing Dr. Riccardo McFaline-Figueroa, whose article on spinal cord neoplasms appears in the most recent issue of Continuum, on spinal cord disorders. Be sure to check out Continuum Audio podcasts from this and other issues. And thank you to our listeners for joining today. Dr. Monteith: This is Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, please consider subscribing to the journal. There's a link in the episode notes. We'd also appreciate you following the podcast and rating or reviewing it. AAN members: go to the link in the episode notes and complete the evaluation to get CME for this episode. Thank you for listening to Continuum Audio. /episode/index/show/continuumjournal/id/29872548

Structural Myelopathies with Dr. Ligia Onofrei 02/21/2024

Structural Myelopathies with Dr. Ligia Onofrei Compressive myelopathy caused by degenerative spine disease is common, but the pathophysiology is surprisingly complex and there are potential surprises in the evaluation of these patients. In this episode, Katie Grouse, MD, FAAN, speaks with Ligia Onofrei, MD, author of the article “Structural Myelopathies,” in the Continuum February 2024 Spinal Cord Disorders issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Onofrei is an associate professor of neurology and neuromuscular medicine at the University of Utah in Salt Lake City, Utah. Additional Resources Read the article: Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): American Academy of Neurology website: Social Media Guest: Transcript Full transcript available on Libsyn 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 of 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 Grouse: This is Dr. Katie Grouse. Today, I'm interviewing Dr. Ligia Onofrei about our article on structural myelopathies in the February 2024 Continuum issue on spinal cord disorders. Dr Onofrei is an Associate Professor of Neurology in neuromuscular medicine at the University of Utah, in Salt Lake City, Utah. Welcome to the podcast. Just to kind of get started, I wanted to ask you, the topic of your Continuum article is cervical and thoracic structural myelopathies - what are these and how common are they? Dr Onofrei: So actually, structural myelopathies are the most common myelopathies that we encounter clinically. I know in neurology we tend to focus on things like MS or NMO or transverse myelitis as the myelopathies that we talk about most commonly, but we actually see them a fair bit. As you will see in my article, it's really hard to actually give you a precise number as to how common they are. We know they're common because we encounter them a lot, but there are also a lot of patients out there who have them who are undiagnosed. Structural myelopathies really refer to both the symptoms of myelopathy but also having compression of the spinal cord. That's what you have to have in order to have a structural myelopathy. Dr Grouse: How did you become interested in this area of neurology? Dr. Onofrei: It’s a bit of a different kind of story in neurology than the usual career trajectory. Actually, when I was a resident, there was a patient at the VA who had Parkinson's disease and myelopathy, and he went undiagnosed for months because people kept blaming his dexterity issues and day changes on his Parkinson's. But, in fact, he really had a cervical myopathy that was actually quite severe. When we got him diagnosed. I remember thinking to myself, “I really want to learn more about it.” And I was asking around and what I saw, even though my attendance at the time were super smart and very well versed in neurological issues, they just weren't comfortable with degenerative disorders of the spine. I wanted to learn more. I read what was available and I actually went to the AAN Spine Course, which at the time was a full day. I met Dr JD Bartleson, who was my mentor - who became my mentor, I should say. He gave me some really terrific advice about how to learn more. When I finished my residency at the University of Utah, I went on to do a neuromuscular fellowship, also at the University of Utah. But during that fellowship, I actually had two months to spend as additional training time outside of neurology, and I chose to spend it with the spine and musculoskeletal physical medicine and rehabilitation specialists at the University of Utah. They taught me a lot about degenerative spine issues, musculoskeletal issues, and I felt I really, for the first time, had a really good grasp of the diagnosis, and also the interplay between degenerative spine issues and neurological disorders. And then after that, I did something even less typical for neurologists. After I graduated fellowship, I actually went on to have a clinic embedded within the neurosurgery department at our institution. I evaluated patients – like, a day a week - patients who had spine issues and were referred for surgical evaluation. I would evaluate the patients in conjunction with one of the neurosurgeons, and then we would decide together if they needed surgery. It was a really great education to understand the interplay between degenerative spine issues and neurological disorders. Dr Grouse: That sounds like a circuitous but very interesting path, and very fruitful in the end. You mentioned that even very adept clinicians can miss this important and actually common diagnosis. What are some early signs that are easily missed? Dr. Onofrei: I think, with myelopathy, the most important part is actually just thinking about it as a diagnostic possibility. If you think about it, then you will essentially ask the questions that are really important diagnosis. I think it can be especially difficult if it's a patient who has a preexisting neurological disorder because we get stuck in asking the kind of things we usually ask our patients with MS or Parkinson's, or whatever else they may have. But it's really important to understand the trajectory of symptoms always. If they're having dexterity changes, “Did that happen all of a sudden? Was there something else happening?” Asking about dexterity changes to start with is a super helpful, important part of the diagnosis. And then also asking about gait changes. Again, if they have a preexisting neurological diagnosis, asking them if they've had a big change, a rapid progression, if something else happened in their disease - that's the beginning step. It's actually very, very basic information, but asking about these changes is super important. Then, once people have identified those changes, then you can delve into the more specific questions that are really unique to myelopathy, like manipulating small objects, manipulating utensils - for example, zippers or buttons. That's a really sensitive way to ask for dexterity changes for myelopathy. For gait abnormalities, it’s a little bit less unique to myelopathy. A lot of the symptoms overlap phenotypically with, like, peripheral neuropathies. For example, having difficulty on uneven ground or getting your toes caught on something. But identifying a shift in your gait is usually that key initial diagnostic clue. Dr Grouse: Really, really helpful. And, I think, always a great reminder with almost anything - you don't think of it, you won't diagnose it. Sounds like for myelopathies - structural myopathies – this could be especially true. Thinking about this article, what do you think would come as the biggest surprise to our listeners who read the article? Dr. Onofrei: It’s a really great question. I think there can be a lot of different surprises in each little section. But, to me, the thing that stands out is how complex the pathophysiology of myelopathy actually really is. There's so much more than just direct compression of the spinal cord. When you have compression of the spinal cord, you are stretching the spinal cord; you are inducing changes to the gray matter, the white matter. But you're also changing the actual biology of the cells. When you're causing compression of the spinal cord, you're inducing hypoxic or ischemic injury, and that triggers a neuroinflammatory cascade and it causes apoptosis of the neurons and the oligodendroglia. I think what was really interesting to learn is that, when you're decompressing the spinal cord with surgery, that reduces that cascade of neuroinflammation but it doesn't eliminate it. You will still have some residual apoptosis of the cells even after decompression. This actually is probably one of the pieces of information that supports the idea that we really should be intervening at an earlier stage for these patients. Dr Grouse: Does this mean that, even after decompression, patients can continue to deteriorate or do worse as a result of that apoptosis and those changes? Dr Onofrei: I think that the way I would interpret that, more in practice, is that those patients might not improve. They might not have any improvement post surgery. In fact, any surgeon who is an ethical surgeon will tell you that they cannot promise improvement with decompressive surgery, but we do notice improvement in a significant proportion of patients. While you can never promise that there's actual hope for these patients, it's just that some patients may not improve and we don't have a great way to predict who will improve and who will not improve. Dr Grouse: I was also curious, when you mentioned about what chronic compression looks like, why does chronic compression look so different from acute compression of the cord, both how it presents and how the patients can look? Dr Onofrei: That's a really fantastic question. I think part of it is that, just like with other degenerative disorders of the spine – like, for example, lumbar stenosis with neurogenic claudication and cauda equina, there's an element of time and adaptation. When you have acute compression, you do not have those adaptive mechanisms in place, and you will have to deal with just acute loss of function. That's how I would think about it. The time component allows for some adaptive changes, and also for specifically degenerative myelopathies. When you have chronic compression, you usually have less compression than with an acute traumatic myelopathy. Dr Grouse: I want to ask, as well, what do you think is the biggest debate or controversy in this particular area - whether it comes to the underlying pathophysiology of what's going on, or else the management or treatment of it? Dr Onofrei: I would say, without a doubt, the biggest controversy is when to intervene. Obviously, that is a hugely important question for patients and physicians alike. There's a lot of debate because there are patients who remain stable with mild myelopathy for many years, and then there are people who decline. There is a yearly rate of decline for these patients. But right now, we don't have good ways to predict who will decline and who will remain stable. I think there's a huge potential for more research, especially in the field of imaging - and especially with diffusion tensor imaging - to see if that can be used as a way to predict who will be declining or who might respond better to treatment. Dr Grouse: That makes a lot of sense, and certainly, I think, something that a lot of our listeners grapple with as they try to counsel patients with these types of conditions. I was struck by another point you made in your article - which I thought was really interesting - which was that a common misconception is that pain is a significant manifestation of spinal cord dysfunction. And this made me think that this could definitely fall in the category of an easy mistake that you could make in this diagnosis. Tell us more about that. Dr Onofrei: Yeah, so we are very used to using pain as an alarm signal. I think it's important, again, at a provider level, to remind ourselves that, actually, function is a better proxy for dysfunction than pain for a lot of patients. But pain, again, continues to be a really important reason why patients come to us. From one perspective, even though pain is something that we worry about and patients think potentially has really bad consequences, pain can actually be reassuring in some ways. But for myelopathy, pain is usually an incidental finding, in the sense that, usually, pain with myelopathy will happen because you have axial pain – you know, pain because your posture is poor, or you might have a superimposed radiculopathy. Pain will be sometimes the symptom that will bring the patient to attention, but it's very unlikely to be a symptom of how bad the problem is or to actually tell you if there is underlying myelopathy. Dr Grouse: Thank you - that's a really important review, I think for all of us. Often we’ll ask that as almost one of the first questions, when we're thinking about it. Tell us a little bit more. I was reviewing some of the common signs of cervical myelopathy and - it's funny - a lot of them, especially the early signs, may not even be the ones you first think of. I think you've mentioned it before - the gait dysfunction and slight loss of dexterity. I also was interested in (and this maybe may not be quite as an early one) myelopathic hand - if you wouldn't mind telling us a little bit more about that as well. Dr. Onofrei: Of course. Assessing function is very important, just by asking the patient what they do that requires dexterity. So, starting there and then moving on to trying to understand if there’s any particular issues that would confound the patient's ability to perform these activities. Like, if they have arthritis of their hands or a painful finger (like a trigger finger, or something like that), that will change the way they can handle the types of activities that require them to be dexterous. That's the initial phase. Once they have had progression of their myelopathy, they will usually have more frank weakness. I think a lot of people will say they drop more objects, but that's probably the least helpful, from a clinical perspective, just because it happens with so many different pathologies. But really paying attention to loss of actual strength and then visually examining the hand – so, looking for loss of muscle for the hand and looking for loss of strength on exam. So, finger abduction is your most sensitive exam maneuver that you can do to assess for that. And even very subtle weakness can be a really good indication of myelopathy. And then, in patients who have more advanced pathologies, you'll see more significant atrophy of the hand - actual frank, like, muscle wasting and potentially fasciculations in the hand. I talk about the myelopathic hand from a pathophysiology perspective. I thought it was really interesting that you can see this myelopathic hand with compression at any level in the spinal cord. So, even if it's high cervical compression, you can still see the hand atrophy and weakness. So, it is important to visually inspect the hand, do the strength examination, and like I said, really ask the patient about their function. Dr Grouse: Thank you. That was really helpful. Being a neurologist, of course, I think, like many of our listeners, I'm a big fan of checking reflexes, and in your article, you mention some really interesting, different ones that we don't check every day. Do you have favorite or a few favorites that you'd like to call out for us to pay attention to? Dr. Onofrei: As I mentioned my article, hyperreflexia is a really common manifestation of myelopathy. While it's not always present, if you can elicit hyperreflexia, it's really helpful. I think you can do whatever reflexes are your favorites, as long as they're a measure of hyperreflexia. I do like the finger flexor reflex, and I included that in the paper. It's just one that people use less often, but it's super easy to do. And if it's asymmetric, in particular, it's a really helpful tool. But, again, I don't think it matters which ones you do as long as you do a complete exam and then you look at the presence of hyperreflexia. Dr Grouse: That's great, and I encourage everyone to check out the article and take a look at some of those reflexes that she referenced are very interesting. What role does DTI play for imaging of degenerative myelopathies, and what promise do they hold going forward? Dr Onofrei: Diffusion tensor imaging is a really interesting imaging modality for the spine. It's not as commonly used for the spine as it is for things like stroke, right? We all are super familiar with its amazing role in stroke and early diagnosis of stroke. In the spine, it's much more complicated. The spine is a much more difficult structure to image, in general. So, while it's not being used right now on a clinical basis routinely, there's a lot of active research in that arena to try to understand what the best protocol might be, and how to use it to either predict which patients might deteriorate or which patients might need to have earlier surgical intervention. I think the promise of it is really tremendous, but to date, there hasn't been a unified protocol. But I think that, as we have more sensitive imaging modalities, better software algorithms to analyze the images, we might actually be really able to have excellent sensitivity. Dr Grouse: Well, very interested to see how that develops over time. Just to finish up, is there any last sort of important key points you hope that our listeners will take away as they go forward into the world and look for patients with structural myelopathies? Dr. Onofrei: I think the most important things that I want people to remember from this article, number one, is that diagnosing myelopathy starts by thinking about myelopathy, first of all. If you're thinking about myelopathy, you're more likely to ask the questions to elicit myelopathies. And then, I do want people to think about the phenotypic overlap between myelopathies and other neurological disorders. Third, I think people just need to remember that they are already doing the work of discovering myelopathy, which is asking the questions, doing a really good history and a really good exam. Really, the key for the diagnosis is having a really good history, is understanding the function of the patient, and is doing a really good neurologic exam, especially in patients who have a preexisting neurological diagnosis. Having those serial neurologic exams is really, really important to understand if the patient has a new myelopathy or to give the patient a better understanding of how they might respond to surgery, or what proportion of their symptoms is really attributed to a neurological disorder versus a myelopathy. Dr Grouse: Thank you so much for coming to talk with us about this really important topic. Again, I can't encourage everyone enough to read this article. I think it was so helpful, so interesting, and just gets back to all the things I think we all love about neurology. Dr. Onofrei: Thank you for having me. Dr. Grouse: Again, today I've been interviewing Dr. Ligia Onofrei, whose article on structural myelopathies appears in the most recent issue of Continuum, on spinal cord disorders. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, please consider subscribing to the journal. There's a link in the episode notes. We'd also appreciate you following the podcast and rating or reviewing it. AAN members, go to the link in the episode notes and complete the evaluation to get CME for this episode. Thank you for listening to Continuum... /episode/index/show/continuumjournal/id/29863408

Traumatic Spinal Cord Injury with Dr. Saef Izzy 02/14/2024

Traumatic Spinal Cord Injury with Dr. Saef Izzy Traumatic spinal cord injury is a potentially devastating disorder. Best practices in clinical care for these patients has evolved, with implications for long term outcomes. In this episode, Aaron Berkowitz, MD, PhD, FAAN, speaks with Saef Izzy, MD, author of the article “Traumatic Spinal Cord Injury,” in the Continuum February 2024 Spinal Cord Disorders issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of neurology at the University of California San Francisco, Department of Neurology, a neurohospitalist, general neurologist, and clinician educator at the San Francisco VA Medical Center and San Francisco General Hospital in San Francisco, California. Dr. Izzy is an assistant professor of neurology at Harvard Medical School and an associate neurologist in the Department of Neurology, Divisions of Neurocritical Care and Cerebrovascular Diseases at Brigham and Women’s Hospital in Boston, Massachusetts. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): American Academy of Neurology website: Social Media Host: Guest: 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 of the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by clicking on the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the episode notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. Dr Berkowitz: This is Dr. Aaron Berkowitz. Today, I'm interviewing Dr. Saef Izzy about his article on traumatic spinal cord disorders from the February 2024 Continuum issue on spinal cord disorders. Dr. Izzy is an Assistant Professor of Neurology at Harvard Medical School and an associate neurologist at Brigham and Women's Hospital in Boston, Massachusetts. Welcome to the podcast, Dr. Izzy. So, let's say a patient comes to the emergency room with an acute spinal cord injury due to a car accident. Walk us through your approach. What's going through your mind when you hear this pager go off and you're walking down to the emergency room; what are you thinking? Dr Izzy: Yeah, great question. So, one of the first question is, what's the medical status of the patient? And, starting from, “How sick is the patient? (looking at the ABCD - basically, airway, breathing, circulation), make sure the patient is stable from that perspective, with the specific focus then going to be the injury level and the injury severity. And with that, once the patient is clinically stable, we try to pay very close attention to that aspect, especially since we know the patient is coming with a spinal cord injury from the prefield assessment. So, having a very close assessment to the spinal cord using a standardized tool (such as the ASIA, which is the American Spinal Injury Association Impairment Scale) will be very helpful to communicate the level of injury to the rest of the team, which usually is going to be a multidisciplinary team approach from the emergency room into neurosurgery, neurology and other disciplines where we'll be involved. So, having a standardized tool will be a key. ASIA, as a scale - it starts with a letter “A” - and to be A when there is a complete injury, with loss of motor and sensory, and E is basically normal exam (a neuro exam with normal motor and sensory examination). And between B to D, they have some preserved voluntary anal contraction and some of the reflexes, such as the bulbocavernosus reflexes, with a various degree of motor and sensory. Having an early introduction into this scale will be super helpful to communicate with other services. Then will be the decision about who I should image, and also, whether I should clear the C-collar or not. And this is also another sort of decision making, comes into the patient mental status, the injury severity, the level of injury, as well as ability to perform a reliable neurological examination - all plays a role into this decision. In this article, we have elaborated on the clinical decision making - an approach in the acute setting - and we provided, in Figure 1, a comprehensive approach about patient we should think about imaging and what modality of imaging, as well. Dr Berkowitz: Perfect, that's so helpful. So, you're thinking through the ABCDs, as you mentioned. And then a detailed neurologic exam to get a sense of the degree of injury. And then you mentioned the decisions about imaging. Tell us a little bit about how you think about who to image, what to image, how to image, after you've done your neurologic exam. Dr Izzy: So, the imaging in general, as we know, that previously used to be an x-ray. But the recent literature really focus on utilizing the utility of high-quality CAT scans as it's provide more comprehensive characterization of vertebral fractures. And that will be very helpful to identify the level and severity of radiographic injury. However, MRI will always be superior, as it also provides the extent of the cord compression, signs of cord injury, as well as could help us rule out ligamentous injury within, especially, the first 48 hours post the event. In addition to that, we have to pay attention to a patient at risk of having vascular injuries, as many spinal cord, especially the cervical and skull-based injuries, can associate with blunt cerebrovascular injuries, which often missed in the emergency room, and even in the acute stay, as no one would have thought about that aspect. That's why, in this article, we have highlighted the role of Memphis criteria, which is a very valuable tool to identify patients at risk to be scanned. And also the Biffl Scale, which used to be known at the Denver, and modified Denver Scale, to assist classifying the level of vascular injury. Dr Berkowitz: Great. So, I want to pick up on a number of the things you mentioned there. So, let's talk about injury to the bony structures that could result in impingement on neurologic structures, such as the nerve roots or cord or cauda equina. So, Often, neurology and neurosurgery are consulted together in these patients, right? And both arrive at the bedside in the emergency room. Tell us a little bit about working with our neurosurgical colleagues to figure out who should go for surgery, what type of surgery they should go for, and the neurologist’s role in helping in that decision making. Dr Izzy: I believe the neurologists have a significant role in the acute setting, especially with performing a very thorough, refined neurological examination when it comes into assessing the cranial nerve, because often traumatic spinal cord injury could associate with traumatic head injury. In addition to that, perform a very thorough motor and sensory exam, with a specific look into reflexes, as well as anal reflexes. And documenting that, in conjuncture with the neurosurgery colleague, will be super helpful. We have to know that doing neurological assessment, or also relying on them, the ASIA scale is a key, but also could be confounded in the acute setting with other multisystemic events, including respiratory failure, using some pain medication, traumatic brain injury, hypotension, which all could confound the initial exam. That's why having a repeated exam for this patient throughout the hospital stay will be a key, especially when we are using some of these examination in the acute setting to guide our prognostication. Also, when it comes into the neurological assessment, looking into, not only the level of injury, but paying attention into the levels below. And documenting this exam is also a very critical aspect of assessment. One of the early decisions we share - many times when we, as neurologists, get consulted on these patients who should go to surgery, and that's a whole topic by itself discussed thoroughly in this article about the literature on a patient who should basically pursue surgery. And, one of the main highlight of the literature that, pursuing surgery in less than 24 hours has been associated with improved outcomes. Yet the literature on that still need further evaluation, especially now the most common practice that patients with worsening exam, mass effect, and epidural mass takes priority. But further studies on this area definitely require further exploration. Dr Berkowitz: Another aspect you mentioned is blunt cerebrovascular injury - so, injury to the carotid or vertebral arteries in the neck or in the skull base. So, are CT angiograms part of the standard neuroimaging now for patients with spine injury, or on a case-by-case basis, or perhaps should they be? Dr Izzy: Great question. It's not. That's why paying specific attention for a patient at risk, and that's where the Memphis screening protocol takes place. And we encourage our colleagues from neurology and neurosurgery, as well as emergency department, to try to keep this sort of screening, helpful protocol handy when approach traumatic spinal cord injury. More specifically patients, who have basilar skull fracture with involvement of the carotid canal; the one with a basilar fracture with involvement of the petrous bone; the cervical spine fracture with neurological exam that doesn't necessarily explained by imaging; having a Horner syndrome on neurological exam; fractures pattern involve LeFort II or III fractures; as well as neck soft injury; the seatbelt sign - these are all signs that could really raise the red flag that there is a possible underlying vascular injury that require evaluation by CT angiogram in the emergency room to further identify. Once we identify the vascular injury, there is another helpful and valuable score, which is the Biffl Scale, or the - what also well known to be Denver or the modified Denver. And that one will further characterize the injury from level 1 to 5, 1 involving the luminal irregularity and dissection with less than 25% luminal narrowing - that's the 1. And 2, more than 25% narrowing. The 1 and 2 carries different prognostication and management, because these two we can always think about starting antiplatelet or anticoagulation on the first two, while 3 is aneurysm or pseudoaneurysm in the artery, while 4 is occlusion or thrombosis, and 5, usually transection of the vessel, the free extravasation. Grade 3 and above, usually, medical treatment has not much of a big role and discussion with the vascular neurosurgery or neuroendovascular colleague will be super helpful. Dr Berkowitz: You started alluding to the next question I was going to ask you related to these. As neurologists are often consulted when there's vascular injury, traumatic vascular injury, about the questions of the risks and benefits of starting antiplatelets or anticoagulation. You mentioned that, in extreme cases - obviously if the vessel is transected or there's extravasation - there'll probably be great danger in starting those types of agents. But often we're consulted for the lower grades, such as a dissection or a luminal irregularity. And the question comes up, what is the extent of the benefit of antiplatelet and anticoagulation when balanced with the risk? – that these are often patients with polytrauma, not just affecting the nervous system, but often systemic organs as well. How do you balance the risk and benefit of treating these traumatic vascular injuries with antiplatelets or anticoagulation, to wanting to reduce the stroke risk related to these, on the one hand, and taking into account the extensive injuries that often accompany these? Dr Izzy: Yeah, absolutely. Very clinical relevant question. The short answer: there is no randomized clinical trials that compared antiplatelet therapy with anticoagulation, whether it's unfractionated or low-molecular-weight heparin, for the treatment of blunt cerebrovascular injury- not even compare the timing to start. That's why it comes into the clinical judgment when it comes to answer this question. As far as level of injury defined by Biffl Scale, Grade 1 and 2, when there is a dissection less than or more than 25%, it's reasonable to start either or. And that comes into the context of the patient. In general, most of these patient comes with other multisystemic event. Could be having a traumatic brain injury with contusion, and the size of the contusion maybe also play a role in this decision where there is risk of contusion expansion or bleeding in other parts of the body, which makes anticoagulation very critical and dangerous with these patients. Maybe starting aspirin could be reasonable and safe, as that comes into a multidisciplinary discussion with our colleague from neurosurgery, ortho (if they are involved), as well as the primary ICU team. Having a thorough discussion about the pros and cons of this decision is a key. Most specifically, it's about balancing the risks and benefits in management. When it comes into high grade (3 and above) involving pseudoaneurysm, we know that antiplatelet or anticoagulation might play a lesser role; might be beneficial to some extent (not very well studied in this cohort of patients). But having a discussion when it comes into vascular malformation involving arteriovenous fistula or near occlusion of a vessel with our neuroendovascular colleague and vascular neurosurgeon will be always a key. Just one more point to make - that if it's too risky to start in the acute setting because of other multisystemic involvement, having a repeat imaging in a few days might be also helpful in assessing the progression of the vascular injury - could also be helpful from that setting. If the patient start developing new neurological symptoms, rather than just blaming it on the cervical or thoracic spine, thinking about new-onset strokes that happen would be a key to elaborate there, as we know the duration - for how long. If we end up starting patients on anticoagulation, or antiplatelets such as aspirin, for how long we should keep it for? It's still controversial, but the common approach is to start when it's safe from clinical standpoint and consider keeping it for three to six months. And repeat follow up imaging in the outpatient setting to assess that vascular injury and determine the duration of treatment will also be a key. Dr Berkowitz: Shifting gears again here - you're involved in the acute setting here, diagnosing and managing these patients, often otherwise healthy patients who've suffered a devastating accident. How do you begin the conversation about communicating the prognosis, often probably the first question from the patient's family, “Are they going to walk again?” Obviously, a lot of factors go into this and it can be hard to prognosticate from the first moments of injury. But how do you begin to have that conversation when that question is asked for the first time, often in the emergency room? Dr Izzy: As a neural intensivist, commonly involved in the acute management of traumatic spinal cord injury patients, we try to focus on the acute management of patient, try to inform families that it’s too early to provide an accurate prognostication of the long-term outcome. Especially, that the acute course of the disease could associate with so many other clinically relevant variables that could have an impact on the long-term outcome, such as respiratory failure, hypotension, in terms of neurogenic or spinal shock, in addition to rate of infections. In such acute, early, or superacute stage of the disease, there's still not much known about the correlation with the very-long-term outcomes. As I mentioned earlier, even the very first ASIA scale, the first neurological assessment could be easily confounded by many of these factors. Once we address the hypotension, treat the infection, or even try to control the respiratory failure, we have seen that might improve the neurological assessment - could be in the acute setting. That's why we try to provide the families with the clinical status of the patient and postpone any discussion on neuroprognostication until the patient in a stable clinical state and when we have a better assessment of the neurological and hemodynamic state. Dr Berkowitz: Tell us now, in closing, what does the future hold for the treatment of these patients with acute spinal cord injury? Dr Izzy: Despite all the unknowns about the course of the disease, when it comes into the long-term outcomes and the increasing rate of early and delayed mortality in this disease and poor outcome, there are many ongoing attempts to test various pharmacological and nonpharmacological interventions to achieve neuroprotection and enhanced functional outcome after traumatic spinal cord injury. There are many promising attempts for transplantation of neuronal embryonic mesenteric stem cells, as well as oligodendrocyte precursor cells. Two or three clinical trials now ongoing, trying to assess the benefit for long-term outcome. The future is still optimistic that some of these initiatives might eventually transition to the bedside application and potentially leading to significant improvement in the long-term outcomes of our patient. However, many of these initiatives are still investigational but carries the hope. Our role as a clinical team - always satisfying taking care of traumatic spinal cord injury patients and their family and guide them through the journey to recovery. Dr Berkowitz: Dr. Izzy, thanks so much for taking the time to speak with us today. I encourage all of our listeners to read your phenomenal article. We could only scratch the surface today in our discussion on this very complicated, challenging area of neurologic practice, but your article lays out a lot of very helpful, practical clinical elements in the diagnosis, treatment, and prognostication in patients with spinal cord injury. Dr Izzy: Absolutely. My pleasure. Dr Berkowitz: Again, for our listeners, I've been interviewing Dr. Saef Izzy, whose article on traumatic spinal cord disorders appears in the most recent issue of Continuum on spinal cord disorders. Be sure to check out other Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, 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. /episode/index/show/continuumjournal/id/29863338

Clinical Approach to Myelopathy Diagnosis With Dr. Carlos Pardo 02/08/2024

Clinical Approach to Myelopathy Diagnosis With Dr. Carlos Pardo The spinal cord is a fragile network containing hundreds of millions of neurons, all passing through a conduit about the size of a dime. A consistent, organized approach to the diagnosis of spinal cord disease is necessary to give patients the best possible care. In this episode, Teshamae Monteith, MD, FAAN, speaks with Carlos Pardo, MD, author of the article “Clinical Approach to Myelopathy Diagnosis,” in the Continuum February 2024 Spinal Cord Disorders issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Pardo is a professor of neurology and pathology at Johns Hopkins University School of Medicine and director of the Johns Hopkins Myelitis and Myelopathy Center in Baltimore, Maryland. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): American Academy of Neurology website: Social Media Host: 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 of the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. Today, I'm interviewing Dr Carlos Pardo about his article on an Integrative Clinical Approach to Myelopathy Diagnosis, which is found in the February 2024 Continuum issue on spinal cord disorders. Dr Pardo is a professor of neurology and pathology at Johns Hopkins University School of Medicine in Baltimore, Maryland. Welcome to the podcast. Carlos, thank you so much for this wonderful article. I think it was great! Dr Pardo: Thank you very much for the invitation and, particularly, to continue to write about myelitis and myelopathy - that is one of my passions in my activities as a clinical neurologist. And I think that this is basically one of the areas in which I thought, after finishing my residency training here, to focus, because there was absolutely no good understanding of the biology, clinical profile – particularly, understanding of the pathophysiology of myelitis and myelopathies, and what was called (at that time) transverse myelitis. So, that is what I have spent the past 25 years is try to understand that concept and apply what I was trained, as a neurologist and neuropathologist, to be translated in the clinical practice. Dr Monteith: Great. Well, I definitely want to know - how did you get into this area? Dr Pardo: That's a very nice question. Dr Monteith: I'm going to give you an easy one. Dr Pardo: I was trained as a clinical neurologist, but at the same time was trained as a clinical and experimental neuropathologist. When I finished my residency training, along with some of my co-residents and colleagues in my residency training, we took the challenge to take a neurological disorder that was called at that time transverse myelitis, to investigate diagnosis, clinical neurology of those patients, and investigate the etiological factors contributing to that. Very soon, we discovered that that group of patients that we call transverse myelitis was a very heterogeneous group of patients. And that basically put us in the situation to expand our approach to investigate what were those etiological factors contributing to those pathologies that we call, at that time, transverse myelitis. Since then, we have been focused on that. We have been focusing on characterizing patients with inflammatory myelopathies, with vascular myelopathies, with patients with infection disorders associated myelopathies. That is one of the main messages of the paper, and is - we need to think in a very etiological approach, because the variety of etiological factors that may contribute to spinal cord disorders is quite broad - it's very extensive. We need to be extremely careful when we approach those patients. There are very common myelopathies, there are very rare myelopathies. So, obviously, we always look for the commonalities and common pathologies, but we shouldn't basically forget about those myelopathies that may be rare but are present. I will say, frequently, we ignore the possibility of metabolic-associated myelopathies because we don't see those too much. But after we do an analysis of that equation - the clinical profile, temporal evolution, lesion topography, and biomarkers in imaging, blood, spinal fluid - and we don't find a clear explanation, we need to stop a little bit and think more about other things that we are missing. And frequently, metabolical disorders of the spinal cord are missed, or other type of pathology. That the reason the clinician need to have open mind and, occasionally, need to think out of the box, particularly when there is no clear answer to the search for etiological factors. Dr Monteith: I mean, when we think about spinal cord lesions, they can obviously be devastating because they affect patient's ability to ambulate. Why don't you tell us the most important takeaways from your article? Dr Pardo: Yeah, so this is a very important aspect of the article. The first thing is, if we are going to treat the patient, if we are going to focus in the management of a clinical problem, we need to understand first, what is the clinical diagnosis? What is the cause of the problem? Importantly, what is the etiology or the etiological factors contributing to that problem? The first thing that I always emphasize is, we are not able to treat a patient with a neurological condition if we don't have a very precise diagnosis, regardless what we are investigating in that patient. Specifically, for spinal cord disorders, there is a multitude of etiologies and pathogenic factors and other causes of the disease that may be involved. For that reason, the clinician, the health care provider, need to be aware about how to approach that question; is, we need to answer first the cause and the profile of the spinal cord disorder. And when we need to answer the cause, we need to focus first in evaluating clearly what has been the evolution of the symptoms, how is the neurological exam, how the evolution of the symptoms are going to help us to identify those etiological factors that we are looking for. For that reason, in the approach that I am suggesting to take in patient with the spinal cord disorder, the first critical element of that approach is to sit down and talk very well with the patient about what is going on - what are the main symptoms that are present, what has been the temporal evolution of those symptoms, and what has been basically the pattern of progression of those symptoms - because those are the clinical elements that will facilitate the clinician a much better understanding for the clinical diagnosis. Evaluating the clinical profile of symptoms and evaluating the temporal profile of symptoms is probably the first step for solving that critical equation about the diagnosis of spinal cord disorders. The main target is to establish a diagnosis. Dr Monteith: And that's really the bread and butter of neurology, because we have a global audience and we have some neurologists that practice in areas with very limited resources. But you do speak of some very cool things that I want to also touch on, such as precision medicine, the advances in biomarker development and neuroimaging, as well as investigating different viral etiologies in the pathology of spinal cord disease. So, can you just speak to some of that? You've been in this field now - you said, 25 years - how that evolution has helped you better treat patients. Dr Pardo: That's a very important question, because in 25 years we have learned tons about myelopathies, myelitis, and noninflammatory myelopathies - and it's quite amazing. I think that one of the most important aspects of spinal cord disorders is that, in the past 25 years, we have learned about mechanism of the disease in spinal cord disorders. Back in the 20th century we used the term transverse myelitis, and one of the main messages that I have for the clinicians who are reading the article is, please stop using that terminology. We have now capability to establish a more precise diagnosis, a more etiologically oriented diagnosis. If you can take a look at what happened in the past 25 years, understanding spinal cord disorders is quite amazing. We have a better understanding of the immunological factors that contribute to myelopathies. We are able to diagnose myelopathies associated with aquaporin 4 disorders, or MOG-associated disorders, or demyelinating diseases, or infectious disorders. So, in the past 25 years, with a combination of different tools in laboratory studies, studies of spinal fluid analysis, studies of the blood, we have basically able to identify biological markers that may guide us to treat more precisely those patients that are suffering from immune-related disorders. In the same way, imaging has contributed dramatically to improve our understanding of myelopathy. We are able to use neuroimaging studies to differentiate in better way, what are the myelopathies that are associated with vascular etiology, versus myelopathies that are associated with inflammatory etiology. In other words, the 25 years have provided all set of tools (assays, imaging techniques) that allow us to establish a better and precise diagnosis that facilitate etiological diagnosis. And in that way, we avoid the use of the term, transverse myelitis, that I frequently say is a basket diagnosis that is not taking us anywhere, because we are not using properly the etiological diagnostic approach. Dr Monteith: In the setting of all of this evolution, what do you still find challenging, and as well, rewarding in treating these types of patients? Dr Pardo: The best reward that we obtain when we establish this type of diagnosis is that we are able to facilitate better recovery, we are able to identify the factors associated with the problem, and eventually, to target, in a better way, those factors that are contributing to the problem and identify potential avenues for full recovery of the spinal cord. If we are dealing, for example, with patients with suspected inflammatory myelopathies, and we are able to identify an antibody that is contributing to that inflammatory myelopathy - like in the case of neuromyelitis optica - I think that the reward is that we are going to avoid a very long process that is going to decrease our ability to rescue that spinal cord and facilitate improvement of that patient. If we identify a vascular myelopathy and we are able to establish promptly a precise diagnosis of a stroke of the spinal cord, that will avoid that the patient goes in a very long road of treatments that even may be more harmful for that patient. And in that way, we are able to contribute the recovery and facilitate improvement of those patients with vascular spinal cord disorders. This is the reward: the reward is that we are able to facilitate a much better recovery of those patients and, in that way, to improve outcomes in those patients that are suffering myelopathies. Dr Monteith: What's been some of the more surprising cases in your practice, in terms of patient presentations, surprise recoveries, or whatever? Dr Pardo: One of the best rewards that we have seen in our research (clinical research) in the past several years is to be able to provide a much better framework for evaluating patients. The other aspect is to be able to identify patients that have very specific pathologies, like strokes of the spinal cord - ischemic pathology of the spinal cord that may be acute ischemic pathology or even chronic evolving pathology. In that way, actually, we have been able to establish much better protocol for assessment of those patients. That is actually one of the major aspects of our progression in terms of understanding the spinal cord disorders. And that is the reason - once again, I emphasize that when we use the term transverse myelitis and we erroneously diagnose patients with transverse myelitis when they are experiencing vascular pathologies of the spinal cord, we are basically not serving well those patients. That is one of the emphasis that I always include in the manuscript is, it is much better to spend time establishing a diagnosis (etiological diagnosis) rather than treating empirically diagnosis that probably are not going to be very well served by using treatments that probably are not going to benefit the patient. For example, when we deal with patients that have vascular myelopathies associated with chronic venous abnormalities, like happen in dural arteriovenous fistula, we are deserting those patients by treating them with IV methylprednisolone or treating them with IVIG, or treating them with immunosuppressive treatments. This is a critical element of the precision approach to establish a better diagnosis in patients with myelopathy. Dr Monteith: And then, your article spoke a little bit about recent outbreaks of infectious etiologies - viral etiologies. Can you talk a little bit about that? Because sometimes we send off these tests and they come back nonspecific or negative, and we have a sense that this was an infectious process. Maybe there was a prodromal phase, or something like that. Can you speak about your excitement in the area of advances in these methodologies? Dr Pardo: Yeah - this is an important aspect of the clinical conversation. Our patients may provide initial clues for identification of potential risk factors, such as infections, as etiological factors contributing to spinal cord disorder. When you are discussing with patients about specific symptoms that emerge after they have experienced either illnesses or systemic symptoms (like fever, chills, rash, or anything that look like an infection disorder) it’s extremely important for the clinician to try to characterize that in much better way so we can use those elements of the investigation to determine if infection disorders may be involved as etiological factors in those myelopathies. We were trained to think about transverse myelitis as either an immunological-mediated disorder or an infection-mediated disorder. That's the reason I think that the clinician need to be open-minded when he's interviewing the patients to acquire, as much as possible, elements of the clinical history that may focus or avoid that the clinician pay too much attention to things that are not involved as etiological factor. Infection disorders frequently may produce neurological problems, and, obviously, spinal cord inflammation is one of those neurological problems. However, it's very important that the clinician be critical in the assessment of those potential risk factors. I frequently discuss with the students and residents in our ward that it's okay to think about West Nile myelitis when we are in the summer, but we are not able to discuss specifically about West Nile myelitis in middle of the winter, and particularly because those are etiological factors that are associated with seasonality and those are etiological factors that are associated with some risk factors that include, for example, mosquito transmission of a virus. When we talk about acute flaccid myelitis with our pediatric patient population, we need to think about circulation of viruses, and we need to think about if that is the right period of circulation of the virus that we are suspicious that is producing that spinal cord disorder. Again, the clinician need to be aware about the particularities of some infection disorder - seasonality, modes of transmission - to think about what is going on in terms of etiological factors, particularly infections, as part of causes of spinal cord inflammation. Dr Monteith: Let's talk a little bit about some controversies - things that maybe lead to overdiagnosis or underdiagnosis. Dr Pardo: It's a very good question, and I appreciate the controversy, always. One thing that is going back to the basis of the article is the precise diagnosis is strictly dependent of equation that involves different factors. We are not able to diagnose spinal cord disorders just using one factor of that equation. This is something that is extremely important for the clinician and health care provider. We are not able to establish a precise diagnosis just when we use only neuroimaging studies. We need to bring the clinical profile of that patient, the neurological examination, the neuroimaging studies, the spinal fluid analysis to the same equation. That is one of the controversies, because in the past, we relied heavily on neuroimaging studies for establishing a diagnosis of myelopathies. But I believe that has been a little bit of a mistake because we have been ignoring major elements of the clinical history and neurological examination. And probably the best example of that is the example of spinal cord strokes. When patients show up in the emergency department with acute onset of weakness and sensory problems, and an MRI show a lesion in the spinal cord, that is not automatically a myelitis. That is an acute spinal cord disorder in which the clinician has the responsibility to establish the precise diagnosis. This is one of the major messages that I want to give to our colleagues in the clinical setting is, we need to interview the patient; we need to characterize the clinical profile and make sure that what we see in the spinal cord MRI fits the clinical profile, the neurological examination, and even the spinal fluid analysis of that patient. One of the controversies that we have frequently is to diagnose patients with spinal cord strokes, because there is no gold standard for those diagnosis, unfortunately. It's a diagnosis that is comprised by several layers of assessment. In that way, we need to reach, basically, a consensus how to deal with those patients and how to manage those patients correctly. Dr Monteith: So, of course, we have a broad, I guess, “background” of listeners - from residents, medical students, even lay audience, as well as, of course, from neurologists. But why should a resident go into spinal cord disease as a subspecialty? Dr Pardo: It’s a very important aspect of the central nervous system function. I always equate the spinal cord as the major avenue for the neurological function in the human body. If there is a very good connectivity in our brain and brain hemispheres, that connectivity is not going to be effective if there is not a healthy and very good function in the spinal cord. The spinal cord is the best avenue for execution of many of the function of the central nervous system. And in that way, a clinician who is working in neurology need to be aware about the spinal cord - need to be aware about the pathophysiology of the spinal cord. Because even if there is not any element of cognitive function in the spinal cord, we have all of the major avenues that facilitate the human function in the spinal cord - motor function, autonomical function, sensory function – so,... /episode/index/show/continuumjournal/id/29827703

February 2024 Spinal Cord Disorders Issue With Dr. Shamik Bhattacharyya 02/07/2024

February 2024 Spinal Cord Disorders Issue With Dr. Shamik Bhattacharyya Spinal cord disorders are common and frequently disabling. Despite advances in our ability to diagnose and treat patients with spinal cord disease, many are underserved by their health care systems due to gaps in knowledge and care. In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Shamik Bhattacharyya, MD, FAAN, who served as the guest editor of the Continuum® February 2024 Spinal Cord Disorders issue. They provide a preview of the issue, which publishes on February 8, 2024. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Bhattacharyya is the Anne M. Finucane Distinguished Chair in Neurology and chief of the division of spinal cord disorders at Brigham Women's Hospital and an assistant professor of neurology at Harvard Medical School in Boston, Massachusetts. Additional Resources Continuum website: Subscribe to Continuum: American Academy of Neurology website: Social Media Host: Guest: Transcript Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today I'm interviewing Dr. Shamik Bhattacharyya, who recently served as Continuum’s Guest Editor for our latest issue, on spinal cord disorders. Dr. Bhattacharyya is a neurologist at Brigham and Women's Hospital, where he serves as Chief of the Division of Spinal Cord Disorders and as an Assistant Professor of Neurology at Harvard Medical School, in Boston, Massachusetts. Dr. Bhattacharyya, it's great to see you - welcome. Thank you for joining us today. Dr Bhattacharyya: Good to see you, Dr. Jones. I look forward to speaking. Dr Jones: So, for our listeners who are new to Continuum, Continuum is a journal dedicated to helping clinicians deliver the highest neurologic care to their patients. We do so with high-quality clinical reviews and content in our journal and in our audio format. For our long-time listeners to Continuum Audio, you'll notice a few different things with our latest issue and our latest author interviews. For many years, Continuum Audio has been a great way to learn about Continuum articles. Starting with this issue on spinal cord disorders, I'm happy to announce that our Continuum Audio interviews will now be available to all on your favorite open podcast platforms. We'll hear some exciting new content in our interviews, and we're also going to introduce interviews with our guest editors, like Dr Bhattacharyya, who are really indispensable in putting these issues together. In this issue, specifically, Dr. Bhattacharyya is full of extremely helpful clinical descriptions and treatment strategies for patients with spinal cord disorders. As the editor, you got really a broad view of the whole range of spinal cord disease. What was the most surprising thing when you were reviewing these articles? Dr Bhattacharyya: I think as a field, neurology - the knowledge base in neurology - grows bigger and bigger and bigger each day and in fields hard to keep up and how to integrate all of it together, right? I think all of us deal with it. And that's the hope of Continuum, is that you can provide these periodic refreshers. I got refreshed myself! Even though I see the patients day in and day out, when you actually read about the advances, for example, in hereditary spastic paraplegias, or the nuances of how neoplasms in the spinal cord are now classified- you say “wow”, I didn't actually know that. The knowledge spreads and grows, and I think that's the beauty of being an editor of some of these issues - is that you get to learn yourself and maybe perhaps even apply them in the clinical situation. Dr Jones: You and I are both educators. And that's, I think, one of the secret joys of teaching is that you end up learning a lot, sometimes from the people you're teaching, right? I guess maybe that's not a surprise - that you learn something by reading it. I guess it was probably pretty nice, huh? Dr Bhattacharyya: It was very good. I think the authors all come from different geographic backgrounds, even from different training backgrounds. In spinal cord disorders, there are trials in some aspects, but in other aspects it's really opinion-based practice, right? So, it was good to also see how other institutions do it. And I imagine it's the same for readers when they see how they do it at their institution and also get a viewpoint of how it's done at other places. That's the valuable perspective piece for putting together a different of authors and see how people do it at different places. Dr Jones: Always nice to learn from others. And speaking of learning - for our clinicians who are listening to our interview today, Shamik, tell us a little bit about the basics of how spinal cord disorders present. I know as an educator, sometimes for, especially junior learners, it's a little mysterious and I'm not really sure why that is, but what are some of the basic clinical tenets of how spinal cord disorders present? Dr Bhattacharyya: I'm glad you brought this up, because in some ways, spinal cord is the orphan child of neurology, right? I think for most neurology trainees, the nervous system stops at the brainstem and then progresses again at the nerves. The spinal cord is really just viewed as this conduit of tracts up and down, and that's all it does is a big set of wires, which is not true, right? A lot of primary neurological processing happens at the level of the spinal cord, and it really is a continuation of the central nervous system. And I hope, with this issue, people get a sense of that. For spinal cord disorders (also called myelopathy; the name goes, synonymously, hand in hand), I think one of the principal functions of the spinal cord is balance. A lot of the program - the neural programming of balance on postural reflexes are hard wired into the spinal cord. I think one of the key aspects of spinal cord disorders is imbalance. I think that people should think of this as a core feature of myelopathy. If you take an example for cervical spondylotic disease, people think, is it going to be off your hands? Well, I think most patients with cervical spondylotic myelopathy actually complain of gait imbalance as one of the early features of the disease. So, imbalance, bilateral weakness, and/or bilateral numbness, tingling, paresthesia - those aspects are suggestive of spinal cord disorder. Bowel and bladder dysfunction can be, but it's not universally true. Now, there’s some specific symptoms that I think are especially suggestive of spinal cord disorders I think that are kind of fun to ask about, and if true, can help you localize. One is the Lhermitte sign; you ask people to flex their neck and say, like, “Do you feel sharp, shooting thing, like, down your hands or your back?” In your legs? If true, you have something, right? That's a spinal cord disorder. The other sign that I think is clinically helpful is weakness on one leg and numbness on the other, like Brown-Séquard syndrome or hemicord syndrome. If you find that to be true - and you often see that with multiple sclerosis lesions or other traumatic lesions - that is a spinal cord disorder. I think those clues can come out in history and on exam, and can help you localize it better. Dr Jones: It's nice to know those specific features - in other words, those things that, when you do see or hear them, really should make us think about spinal cord disorders, right? Again, they might not be the most common way they present, but it's good to have those in your pocket, right? Dr Bhattacharyya: Right. Dr Jones: You mentioned this - spinal cord pathology occupies kind of an interesting place in the neurological world, right? There really aren't “myelopathists,” but you direct a division on spinal cord disorders, which is - I think is pretty uncommon. Tell us a little about that. How does that work at your institution? Dr Bhattacharyya: Maybe I can start with the history of this, right - of how this actually came about. I was graduating as a fellow and entering as a faculty in our neurology department. Initially, my interest was in autoimmune neurological disorder - it still is in autoimmune neurological disorders. And yet, when they saw patients who came in for myelitis and turned out they didn't have an inflammatory myelopathy, there really was no home for them, right? - it's a strange space. And that includes even for garden-variety, cervical spondylotic disease that's causing myelopathy - there is no good neurology home for those patients. After the first year of seeing patients, I felt that we need to do better for that. That's why we ended up opening the spinal cord disorders clinic, which was actually the only neurology-based one in our system. There are plenty run by physiatry, surgery, pain management, and other services. But the only neurology one in our system focused specifically on neurologic management of patients with any type of spinal cord pathology. Dr Jones: That's a distinctive way that it came about at your institution and in your own career. It sounds like this does need to be a team effort. Who are the other disciplines or specialists who need to be involved in the care of these patients? Dr Bhattacharyya: Our spinal cord clinic itself is a part of the comprehensive spine center in our hospital. In that center are pain management doctors, physiatry, as well as different spine specialties, including orthopedics and neurosurgeons and interventional radiologists. So, it's kind of a multidisciplinary group effort to take care of these patients. Dr Jones: I know it'll vary according to the problem with the spinal cord, right? There's dozens or hundreds of different diseases that can affect the spinal cord. So, treatments are different for different diseases, right? But what do you see, therapeutically, as being some of the next big things on the horizon for patients with spinal cord disease? Dr Bhattacharyya: I think one of the common, unifying aspects is pain from spinal cord injury. Especially if there's interruption in the spinothalamic tracts, the pain can be a very severe thing that ranges all the way from neuromyelitis optica, the tonic spasms, to spinal cord infarcts, chronic sequelae of pain, to trauma (spinal cord trauma) - pain is such a big aspect. And our both interventional and oral neuropathic pain medicines don't do a good job with it. I think there's a wave of new medications that are in trials for neuropathic pain and I'm hopeful that they will be helpful and that they will improve pain control and quality of life for our patients. The medication approaches to pain also come with side effects that all of the medicines have. Some of our patients are on high doses of multiple medicines and have cognitive impairment, right? I think that was also the motivation behind our getting a specific section in this issue on symptomatic management of spinal cord injury. Because I think no matter where you are in the spectrum of spinal cord disorders, whether you’re a vascular doctor or a family doctor, you will be prescribing gabapentin and baclofen, right - as for helping the patient, and it's good to know how to do it. The other aspect that I'm really hopeful about are sort of second-generation prosthetic devices. These are some of the electrostimulation devices where there's intelligence built into the device that detects you moving your leg and then artificially stimulates a peroneal nerve. This is much better than foot braces, for example, for foot drops. And there are now multiple companies who make these devices, and for some of our patients who have had spinal cord disorders and had difficulty walking or tripping, these have actually made a big difference. I think prosthetic and electric stimulation also has potential of helping a broad range of patients with spinal cord disorders. Dr Jones: And I'm glad you mentioned that article on the symptomatic management of the problems with spinal cord disease, regardless of the cause. And it's a wonderful article that will encourage our listeners to seek out. To go back to the pain, this is something that - many of us who care for patients with spinal cord problems - we encounter is this. And I think it's underrecognized (the pain complications of spinal cord disease). Medications on the horizon - what about devices and neuromodulation? This is another thing I get asked about a lot. Dr Bhattacharyya: Exactly. I think the - for example, spinal cord stimulators for pain management - I think it's been controversial in the sense of who are the best people for it. The history of neuromodulation in spinal pain in some senses has been unfortunate because it was first approved for so-called “failed back syndrome,” right? And the name is terrible. The patient population is heterogeneous. And it has come to a point where it was unclear who it was helping and what the right indications were. I think for neuropathic pain and, in particular, for spinal cord injury pain, I think there is now a renewed push to study neuromodulation, both implantable devices and external devices, to see if those aspects can help. I think they're part of the new wave of things. I think the question patients often ask me is, “Can you regrow my spinal cord?” - right? “Is there something on the horizon yet?” As far as I know, right at this moment, there is not, that's clinically applicable, but perhaps in the future that might be true. But I think, short of regrowing the spinal cord, we can help function and help pain in meaningful ways. Dr Jones: We’ll be hopeful about cell therapies and other regenerative therapies down the road. I don't think it's in our immediate future, but we maintain hope. You know, I know this is an area that, again - spinal cord problems are common, spine disease is common - but it does kind of fall between the cracks clinically. If there were one point, Dr Bhattacharyya, that you would want to make to our listeners about the one thing not to miss, or the thing that you most commonly see being missed in the clinical evaluation and/or care of these patients, what would that one thing be? Dr Bhattacharyya: I think the time to clinical evolution of myelopathy probably has the biggest value in determining the cause of it. I think this was beautifully brought out by the article by Dr. Pardo, where he talks about an integrative approach to myelopathy, and in contrast to prior conceptions of whether it's inflammatory based on your CSF cell count or your MRI features, it's actually based on time - time from onset of symptom to nadir of symptom. Is it a few hours, is it days, is it months, right? And having that diagnostic framework is, I think - I go back to it time and time again - is key in trying to figure out, because none of the measures we use, both on imaging or CSF or laboratories, are very sensitive or specific, and actually do not outperform just categorizing by time alone, right? So, I think the one take-home message is, if you have sudden, rapid-onset myelopathy that evolves over minutes, it's probably a vascular process. Even if you find ten cells in the CSF, it's still vascular, right? If it's something that evolves over days, maybe 7, 8, 9 days, and then you find diffusion restriction in the spinal cord on imaging, it's probably still an inflammatory process rather than a sudden spinal cord infarct, right? So, I think that the time aspect cannot be ignored and should play a central role in decision making. Dr Jones: That's very helpful. And I think maybe the corollary to that is - there are chronic spinal cord disorders, right? And I think clinicians, especially if you're not familiar with spinal cord disease, it’s terrifying, right? As soon as you start to think, “Wow, this patient's telling me a story and I'm worried this could be a spinal cord problem - should I send them to the emergency department?” - right? They have some bladder dysfunction; they have some gait disorder. But if it has been going on for years, the emergency department is probably not the best place to evaluate that, is it? Dr Bhattacharyya: I'm glad you mentioned it because we see that in the emergency room, right? Someone clearly has a myelopathy; you asked him how long it's going on – it going for months or even years sometimes, right? And it was first noticed and sent out. So, yes - there are multiple causes of chronic myelopathies. They range all the way from structural causes, where you can have things like, for instance, webs, of arachnoid webs, that cause slow progressive myelopathies, to vascular malformations of myelopathies, to nutritional causes (even that can cause a slow, progressive myelopathy), Not to speak of infections; I think we often think of infections as causing fast myelopathies, but especially with HTLV-1-associated myelopathy, the usual clinical progression is slow and progressive. I think across all categories of disease, there are instances of slow, progressive myelopathies that really require thoughtful workup but doesn't require an emergency workup. Dr Jones: Yeah, it's good to know that not every spinal cord problem is an emergency. I think it does terrify clinicians, right? I mean, this is the broadband connection between the brain and the body, and it's fragile, and it's unforgiving, and it's every command sent to the body - every piece of information sent back to the brain, all traveling through a billion neurons with a maximum diameter slightly larger than a dime, right? I think that's why it creates consternation. But I imagine it's also - on the clinical side - it's probably in part challenging and in part rewarding to care for these patients. When you think about what's most rewarding about the care of patients with spinal cord disorders, what comes to mind for you? Dr Bhattacharyya: I think, a couple of aspects. And just thinking back to my last clinic - I put it on Fridays, just because I get the most joy out of this clinic, right? The first is that there's no single piece of test that gives you the answer totally, right? It's usually about putting the history together, the labs, the imaging, and talking about it together, right? And I think it's that integrated piece that, as clinicians, I think that brings us joy; it’s that figuring something out, that's more than saying, “Is there diffusion restriction or not on the brain MRI?” – right? The second piece that I think is helpful is that, that patients really want to learn, and for spinal cord disorders in particular, there's easy anatomic things that you can point to patients and say, like, “This is why you are weak in the arm and maybe numb in the leg, and that's causing your problem, and this is what we're going to do about it.” And I think, the ability to communicate that with the patient through images is, I think, unique in the sense that patients understand it - that this is the connection and there's something wrong here and that's why I'm having these symptoms. I think those are... /episode/index/show/continuumjournal/id/29827523

Welcome to the New Continuum Audio 01/31/2024

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