Management of stroke due to large vessel occlusion (LVO) has undergone unprecedented change in the past decade. Early identification and aggressive treatment are important in mitigating negative effects on patients’ prognoses.

In this episode, Allison Weathers, MD, FAAN, speaks with T. M. Leslie-Mazwi, MD, author of the article “Neurocritical Care for Patients With Ischemic Stroke,” in the Continuum June 2024 Neurocritical Care issue.

Dr. Weathers is a Continuum® Audio interviewer and an associate chief medical information officer at Cleveland Clinic in Cleveland, Ohio.

Dr. Leslie-Mazwi is a professor and chair in the department of neurology at the University of Washington in Seattle, Washington.

Additional Resources

Read the article: Neurocritical Care for Patients With Ischemic Stroke

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Transcript

Full transcript available

In neurocritical care, the initial evaluation is often fast paced, and assessment and management go hand in hand. History, clinical examination, and workup should be obtained while considering therapeutic implications and the need for lifesaving interventions.

In this episode, Aaron Berkowitz, MD, PhD FAAN, speaks with Sarah Wahlster, MD, an author of the article “The Neurocritical Care Examination and Workup,” in the Continuum June 2024 Neurocritical Care issue.

Dr. Berkowitz is a Continuum® Audio interviewer and a professor of clinical neurology at the University of California, San Francisco

Dr. Wahlster is an associate professor of neurology in the departments of neurology, neurological surgery, and anesthesiology and pain medicine at Harborview Medical Center, University of Washington in Seattle, Washington.

Additional Resources

Read the article: The Neurocritical Care Examination and Workup

Subscribe to Continuum: shop.lww.com/Continuum

Earn CME (available only to AAN members): continpub.com/AudioCME

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Host: @AaronLBerkowitz

Guest: @SWahlster

Full Episode Transcript

Sarah Wahlster, MD

Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by clicking on the link in the Show Notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the Show Notes. AAN members: stay tuned after the episode to hear how you can get CME for listening. 

Dr Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Sarah Wahlster about her article on examination and workup of the neurocritical care patient, which is part of the June 2024 Continuum issue on neurocritical care. Welcome to the podcast, Dr Wahlster. Can you please introduce yourself to the audience?

Dr Wahlster: Thank you very much, Aaron. I'm Sarah Wahlster. I'm a neurologist and neurontensivist at Harborview Medical Center at the University of Washington.

Dr Berkowitz: Well, Sarah and I know each other for many, many years. Sarah was my senior resident at Mass General and Brigham and Women's Hospital. Actually, Sarah was at my interview dinner for that program, and I remember meeting her and thinking, “If such brilliant, kind, talented people are in this program, I should try to see if I can find my way here so I can learn from them.” So, I learned a lot from Sarah as a resident, I learned a lot from this article, and excited for all of us to learn from Sarah, today, talking about this important topic. So, to start off, let's take a common scenario that we see often. We're called to the emergency room because a patient is found down, unresponsive, and neurology is called to see the patient. So, what's running through your mind? And then, walk us through your approach as you're getting to the bedside and as you're at the bedside.

Dr Wahlster: Yeah, absolutely. This was a fun topic to write about because I think this initial kind of mystery of a patient and the initial approach is something that is one of the puzzles in neurology. And I think, especially if you're thinking about an emergency, the tricky part is that the evaluation and management go hand in hand. The thinking I've adapted as a neurointensivist is really thinking about “column A” (what is likely?) and “column B” (what are must-not-miss things?). It's actually something I learned from Steve Greenberg, who was a mutual mentor of us - but he always talked me through that. There's always things at the back of your head that you just want to rule out. I do think you evaluate the patient having in mind, “What are time-sensitive, critical interventions that this patient might need?” And so, I think that is usually my approach. Those things are usually anything with elevated intracranial pressure: Is the patient at risk of herniating imminently and would need a neurosurgical intervention, such as an EVD or decompression? Is there a neurovascular emergency, such as an acute ischemic stroke, a large-vessel occlusion, a subarachnoid hemorrhage that needs emergent intervention? And then other things you think about are seizures, convulsive/nonconvulsive status, CNS infection, spinal cord compression. But I think, just thinking about these pathologies somewhere and then really approaching the patient by just, very quickly, trying to gather as much possible information through a combination of exam and history.

Dr Berkowitz: Great. So, you're thinking about all these not-to-miss diagnoses that would be life-threatening for the patient and you're getting to the bedside. So, how do you approach the exam? Often, this is a different scenario than usual, where the patient's not going to be able to give us a history or maybe necessarily even participate in the exam, and yet, as you said, the stakes are high to determine if there are neurologic conditions playing into this patient's status. So, how do you approach a patient at the bedside?

Dr Wahlster: So, I think first step in an ICU setting (especially if the patient has a breathing tube) is you think about any confounders (especially sedation or metabolic confounders) - you want to remove as soon as possible, if able. I think as you do the exam, you try to kind of incorporate snippets of the history and really try to see - you know, localize the problem. And also kind of see, you know, what is the time course of the deterioration, what is the time course of the presentation. And that is something I actually learned from you. I know you've always had this framework of “what is it, where is it?” But I think in terms of just a clinical exam, I would look at localizing signs. I think, in the absence of being able to do the full head-to-toe neuro exam and interact with the patient, you really try to look at the brainstem findings. I always look at the eyes right away and look at, I think, just things like, you know, the gaze (how is it aligned? is there deviation? is there a skew? what do the pupils look like? [pupillary reactivity]). I think that's usually often a first step - that I just look at the patient's eyes. I think other objective findings, such as brainstem reflexes and motor responses, are also helpful. And then you just look whether there's any kind of focality in terms of - you know, is there any difference in size? But I think those are kind of the imminent things I look at quickly.

Dr Berkowitz: Fantastic. Most of the time, this evaluation is happening kind of en route to the CT scanner or maybe a CT has already happened. So, let's say you're seeing a patient who's found down, the CT has either happened or you asked for it to happen somewhat quickly after you've done your exam, and let's say it's not particularly revealing early on. What are the sort things on your exam that would then push you to think about an MRI, a lumbar puncture, an EEG? You and I both spend time in large community hospitals, right, where “found down” is one of the most common chief concerns. In many cases, there isn't something to see on the CT or something obvious in the initial labs, and the question always comes up, “Who gets an MRI? Who gets an LP? Who gets an EEG?” - and I'm not sure I have a great framework for this. Obviously, you see focality on your exam, you know you need to look further. But, any factors in the history or exam that, even with a normal CT, raise your suspicion that you need to go further?

Dr Wahlster: It's always a challenge, especially at a community hospital, because some of these patients come in at 1 AM where the EEG is not imminently available. But I think - let's say the CT scan is absolutely normal and doesn't give me a cause, but as an acute concerning deterioration, I think both EEG and LP would cross my mind. MRI I kind of see a little bit as a second-day test. I think there's very rare situation where an acute MRI would inform my imminent management. It's very informative, right, because you can see very small-vessel strokes. We had this patient that actually had this really bad vasculitis and we were able to see the small strokes everywhere on the MRI the day later, or sometimes helps you visualize acute brainstem pathology. But I think, even that - if you rule out a large-vessel occlusion on your CTA, there's brainstem pathology that is not imminently visible on the CT - it's nothing you need to go after. So, I do think the CT is a critical part of that initial eval, and whereas I always admire the neurological subspecialties, such as movements, where you just – like, your exam is everything. I think, to determine these acute time-sensitive interventions, the CT is key. And also, seeing a normal CT makes me a little less worried. You always look at these “four H” (they're big hypodensity, hyperdensity, any shift; is there hydrocephalus or herniation). I think if I don't have an explanation, my mind would imminently jump to seizure or CNS infection, or sometimes both. And I think then I would really kind of - to guide those decisions and whether I want to call in the EEG tech at 2 AM - I would, you know, again, look at the history and exam, see if there's any gaze deviation, tongue biting, incontinence - anything leading up towards seizure. I think, though, even if I didn't have any of those, those would strengthen my suspicion. If I really, absolutely don't have an explanation and the patient off sedation is just absolutely altered, I would still advocate for an EEG and maybe, in the meantime, do a small treatment trial. And I think with CNS infection - obviously, there are patients that are high risk for it - I would try to go back and get history about prodromes and, you know, look at things like the white count, fevers, and all of that. But again, I think if there's such a profound alteration in neurologic exam, there's nothing in the CT, and there's no other explanation, I would tend to do these things up front because, again, you don't want to miss them.

Dr Berkowitz: Yeah, perfect. So many pearls in there, but one I just want to highlight because I'm not sure I've heard the mnemonic - can you tell us the four Hs again of sort of neurologic emergencies on CT?

Dr Wahlster: Yeah. So, it's funny; for ages - I'm actually not sure where that's coming from, and I learned it from one of my fellows, one of our neurocritical care fellows - he's a fantastic teacher and he would teach our EM and anesthesia residents about it and his approach to CT. But yeah, the four H - he was always kind of like, “Look at the CT. Do you see any acute hypodensities, any hyperdensities?” And hypodensities would be involving infarct or edema; hyperdensities would be, most likely, hemorrhage (sometimes calcification or other things). Then, “Do you see hydrocephalus?” (because that needs an intervention). And, “Look at the midline structures and the ventricles.” And then, “Do you see any signs of herniation?” And he would go through the different types of herniation. But I thought that's a very good framework for looking at the “noncon” and just identifying critical pathology that needs some intervention.

Dr Berkowitz: Yeah – so, hypodensity, hyperdensity, herniation, hydrocephalus. That's a good one – the four Hs; fantastic. Okay. So, a point that comes up a few times in your article - which I thought was very helpful to walk through and I'd love to pick your brain about a little bit – is, which patients need to be intubated for a neurologic indication? So, often we do consultations in medical, surgical ICUs; patients are intubated for medical respiratory reasons, but sometimes patients are intubated for neurologic reasons. So, can you walk us through your thinking on how to decide who needs to be intubated for the concern of depressed level of consciousness?

Dr. Wahlster: It's an excellent question, and I think I would bet there's a lot of variation in practice and difference in opinion. There was actually the 2020 ESICM guidelines kind of commented on it, and those are great guidelines in terms of just intubation, mechanical ventilation of patients, and just acknowledging how there is a lack of really strong evidence. I would say the typical mantra (“GCS 8, intubate”) has been proposed in the trauma literature. And at some point, I actually dug into this to look behind the evidence, and there's actually not as much evidence as it's been put forth in guidelines and that kind of surprised me - that was just recently. I was like, “Actually, let me look this up.” I would say I didn't find a ton of strong evidence for it. I would say, as neurologist – you know, I'm amazed because GCS, I think is a - in some ways, a good tool to track things because it's so widely used across the board. But I would say, as neurologists, we all know that it sometimes doesn't account for some sort of nuances; you know, if a patient is aphasic, if a patient has an eyelid-opening apraxia - it can always be a little confounded. I'm amazed that GCS is still so widely used, to be frank. But I would say there is some literature - some school of thought - that maybe just blindly going by that mantra could be harmful or could not be ideal. I would say – I mean, I look at the two kind of functional things: oxygenation and ventilation. I think, in a neuro patient, you always think about airway protection or the decreased level of consciousness being a major issue (What is truly airway protection? Probably a mix of things). Then there's the issue of respiratory centers and respiratory drive - I think those are two issues you think about. But ultimately, if it leads to insufficient oxygenation - hypoxia early on is bad and that's been shown in several neurologic acute brain injuries. I think you also want to think about ventilation, especially if the mental status is poor to the point that the PCO2 elevates, that could also augment an ICP or exacerbate an ICP crisis. Or sometimes, I think there's just dysregulation of ventilation and there's hyperventilation to the point that the PCO2 is so low that I worry about cerebral vasoconstriction. So, I worry about these markers. I think, the oxygenation, I usually just kind of initially track on the sats. Sometimes, if the patient is profoundly altered, I do look at an arterial blood gas. And then there are things like breathing sounds (stridor, stertor [the work of breathing]). And I think something that also makes me have a lower threshold to intubate is if I'm worried and I want to scan, and I'm worried that the patient can't tolerate it - I want an imminent scan to just see why the patient is altered, or seizing, or presenting a certain way.

Dr Berkowitz: All great pearls for how to think through this. Yeah - it's hard to think of hard and fast rules, and you can get to eight on the GCS in many different ways, as you said, some of which may not involve the respiratory mechanics at all. So, that's a helpful way of thinking about it that involves both the mental state, kind of the tracheal apparatus and how it's being managed by the neurologic system, and also the oxygen and carbon dioxide (sort of, respiratory parameters) – so, linking all those together; that's very helpful. And, related question – so, that’s sort of for that patient with central nervous system pathology, who we're thinking about whether they need to be intubated for a primary neurologic indication. What about from the acute neuromuscular perspective (so, patients with Guillain-Barré syndrome or myasthenic crisis); how do you think about when to intubate those patients?

Dr Wahlster: Yeah, absolutely - I think that's a really important one. And I think especially in a patient that is rapidly progressing, you always kind of think about that, and you want them in a supervised setting, either the ER or the ICU. I mean, there's some scores - I think there's the EGRIS score; there's some kind of models that predict it. I would say, the factors within that model, and based on my experience, often the pace of progression of reflex motor syndrome. I often see things like, kind of, changes in voice. You know, myasthenia, you look at things like head extension, flexion - those are the kind of factors. I would say there's this “20/30/40 rule” about various measures of, like, NIF and vital capacities, which is great. I would say in practice, I sometimes see that sometimes the participation in how the NIF is obtained is a little bit funky, so I wouldn't always blindly go by these numbers but sometimes it's helpful to track them. If you get a reliable kind of sixty and suddenly it drops to twenty, that makes me very concerned. But I would say, in general, it's really a little bit the work of breathing - looking at how the patient looks like. There's also (at some point) ABG abnormalities, but we always say, once those happen, you’re kind of later in the game, so you should really - I think anyone that is in respiratory distress, you should think about it and have a low threshold to do it, and, at a minimum, monitor very closely.

Dr Berkowitz: Yeah, we have those numbers, but so often, our patients who are weak, from a neuromuscular perspective, often have facial and other bulbar weakness and can't make a seal on the device that is used to check these numbers, and it can look very concerning when the patient may not, or can be a little bit difficult to interpret. So, I appreciate you giving us sort of the protocol and then the pearls of the caveats of how to interpret them and going sort of back to basics. So, just looking at the patient at the bedside and how hard they are working to breathe, or how difficult it is for them to clear their secretions from bulbar weakness. Moving on to another topic, you have a really wonderful section in your article on detecting clinical deterioration in patients in the neuro ICU. Many patients in the neuro ICU - for example, due to head trauma or large ischemic stroke or intracerebral hemorrhage, subarachnoid hemorrhage, or status epilepticus - they can't communicate with us to tell us something is getting worse, and they can't (in many cases) participate in the examination. They may be intubated, as you said, sedated or maybe even not sedated, and there's not necessarily much to follow on the exam to begin with if the GCS is very low. So, I'd love to hear your thoughts and your pearls, as someone who rounds in the neuro-ICU almost every day. What are you looking for at the bedside to try to detect sort of covert deterioration, if you will, in patients who already have major neurologic deficits, major neurologic injury or disease that we're aware of? I’m trying to see if there is some type of difference at the bedside that would lead you to be concerned for some underlying change and go back to the scanner or repeat EEG, LP, et cetera.

Dr Wahlster: Yeah. I think that's an excellent question because that's a lot of what we do in the neuro ICU, right? And when you read your Clans, your residency, like, “Ah, QNR neuro checks, [IG1]  ” right? We often do that in many patients. But I think in the right patient, it can really be life or death a matter, and it is the exam that really then drives a whole cascade of changes in management and detects the need for lifesaving procedure. I would say it depends very much on the process and what you anticipate, right? If you have, for example, someone with a large ischemic stroke, large MCA stroke, especially, right, then there's sometimes conversations about doing a surgical procedure before they herniate. But let's say, kind of watch them and are worried that they will, you do worry about uncal herniation, and you pay attention to the pupil, because often, if the inferior division is infarcted, you know, you can see that kind of temporal tickling the uncus already. And so, I think those are patients that I torture with those NPi checks and checking the pupil very vigilantly. I would say, if it's a cerebellar stroke, for example, right, then you think about, you know, hydrocephalus. And often patients with cerebellar stroke - you know, the beauty of it is that if you detect it early, those patients can do so well, but they can die, and will die if they develop hydrocephalus start swelling. But I think, often something I always like to teach trainees is looking at the eye movements in upgaze and downgaze because, often, as the aqueduct, the third ventricle gets compressed and there's pressure on the colliculi – you kind of see vertical gaze get worse. But I would say I think it's always good to know what the process is and then what deterioration would look like. For example, in subarachnoid hemorrhage, where you talk about vasospasm - it's funny - I think a really good, experienced nurse is actually the best tool in this, but they will sometimes come to you and say, “I see this flavor,” and it's actually a constellation of symptoms, especially in the anterior ACA (ACom) aneurysms. You sometimes see patients suddenly, like, making funky jokes or saying really weird things. And then you see that in combination with, sometimes, a sodium drop, a little bit of subfebrile temperature; blood pressure shoot up sometimes, and that is a way the brain is sometimes regulating. But it's often a constellation of things, and I think it depends a little on the process that you're worried about.

Dr Berkowitz: Yeah, that's very helpful. You just gave us some pearls for detecting deterioration related to vasospasm and subarachnoid hemorrhage; some pearls for detecting malignant edema in an MCA stroke or fourth ventricular compression in a large cerebellar stroke. Patients I find often very challenging to get a sense of what's going on and often get scanned over and over and back on EEG, not necessarily find something: patients with large intracerebral hemorrhage (particularly, in my experience, if the thalamus is involved) just can fluctuate a lot, and it's not clear to me actually what the fluctuation is. But you're looking for whether they're developing hydrocephalus from third ventricular compression with a thalamic hemorrhage (probably shouldn't be seizing from the thalamus, but if it's a large hemorrhage and cortical networks are disrupted and it's beyond sort of the subcortical gray matter, or has the hemorrhage expanded or ruptured it into the ventricular system?) And yet, you scan these patients over and over, sometimes, and just see it's the same thalamic hemorrhage and there's some, probably, just fluctuation level of arousal from the thalamic lesion. How do you, as someone who sees a lot of these patients, decide which patients with intracerebral hemorrhage - what are you looking for as far as deterioration? How do you decide who to keep scanning when you’re seeing the same fluctuations? I find it so challenging - I'm curious to hear your perspective.

Dr Wahlster: Yeah, no - that is a very tricky one. I mean, unfortunately, in patients with deeper hemorrhages or deeper lesions - you know, thalamic or then affecting brainstem - I think those are the ones that ultimately don't have good, consistent airway protection and do end up needing a trach, just because there's so much fluctuation. But I agree - it's so tricky, and I don't think I can give a perfect answer. I would say, a little bit I lean on the imaging. And for example - let's say there's a thalamic hemorrhage. We recently actually had a patient - I was on service last week - we had a thalamic hemorrhage with a fair amount of edema on it that was also kind of pressing on the aqueduct and didn't have a lot of IVH, right? But it was, like, from the outside pushing on it and where we ended up getting more scans. And I have to say, that patient actually just did fine and actually got the drain out and didn't need a shunt or anything, and actually never drained. We put an EVD and actually drained very little. So, I think we're still bad at gauging those. But I think, in general, my index of suspicion or threshold to scan would be lower if there was something, like, you know, a lot of IVH associated, if, you know, just kind of push on the aqueduct. It's very hard to say, I think. Sometimes, as you get to know your patients, you can get a little bit of a flavor of what is within normal fluctuation. I think it's probably true for every patient, right? - that there's always some fluctuation within the realm of like, “that's what he does,” and then there's something more profound. Yeah, sorry - I wish I could give a better answer, but I would say it's very tricky and requires experience and, ideally, you really taking the time to examine the patient yourself (ideally, several times). Sometimes, we see the patient - we get really worried. Or the typical thing we see the ICU is that the neurosurgeons walk around at 5 AM and say, like, “She's altered, she's different, she's changed.” And then the nurse will tell you at 8 AM, like, “No, they woke up and they ate their breakfast.” So, I think really working with your nurse and examining the patient yourself and just getting a flavor for what the realm of fluctuation is.

Dr Berkowitz: Yeah - that's helpful to hear how challenging it is, even for a neurocritical care expert. I'm often taking care of these patients when they come out of the ICU and I'm thinking, “Am I scanning these patients too much?” Because I just don't sort of see the initial stage, and then, you know, you realize, “If I'm concerned and this is not fitting, then I should get a CT scan,” and sometimes you can't sort it out of the bedside. So, far from apologizing for your answer, it's reassuring, right, that sometimes you really can't tell at the bedside, as much as we value our exam. And the stakes are quite high if this patient’s developed intraventricular hemorrhage or hydrocephalus, and these would change the management. Sometimes you have these patients the first few days in the ICU (for us, when they come out of the ICU) are getting scanned more often than you would like to. But then you get a sense of, “Oh, yeah - these times of day, they're hard to arouse,” or, “They're hard to arouse, but they are arousable this way,” and then, “When they are aroused, this is what they can do, and that's kind of what we saw yesterday.” And yet, as you said, if anyone on the team (the resident, the nurse, the student, our neurosurgery colleague) says, “I don't think this is how they were yesterday,” then, very low threshold to just go back and get a CT and make sure we're not missing something.

Dr. Wahlster: Exactly. Yeah. I would say the other thing is also certain time intervals, right? If I'm seeing a patient that may be in vasospasm kind of around the days seven to ten, for the first fourteen day, I would be a little bit more nervous. Or with swelling - acute ischemic stroke says that could peak swelling, when knowing which [IG2]  , I would just be more anxious or have a lower threshold to scan. Yeah.

Dr Berkowitz: Yeah - very helpful. Well, thank you so much for joining me today on Continuum Audio.

Dr Wahlster: Thank you very much, Aaron.

Dr Berkowitz: Again, today we've been interviewing Dr Sarah Wahlster, whose article, “Examination and Workup of the Neurocritical Care Patient” appears in the most recent issue of Continuum, on neurocritical care. Be sure to check out Continuum Audio episodes from this and other issues. And thank you so much to our listeners for joining us today.

Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practice. And right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024 or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members: go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.

In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Ariane Lewis, MD, who served as the guest editor of the Continuum® June 2024 Neurocritical Care issue. They provide a preview of the issue, which published on June 3, 2024.

Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota.

Dr. Lewis is a professor of neurology and neurosurgery and director of the Division of Neurocritical Care at NYU Langone Medical Center in New York, New York.

Additional Resources

Continuum website: ContinuumJournal.com

Subscribe to Continuum: shop.lww.com/Continuum

More about the American Academy of Neurology: aan.com

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facebook.com/continuumcme

@ContinuumAAN

Host: @LyellJ

Full episode transcript 

Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the Show Notes.

Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr Ariane Lewis, who recently served as Continuum's guest editor for our latest issue on neurocritical care. Dr Lewis is a Professor of Neurology and Neurosurgery at NYU, where she serves as the Director of the Division of Neurocritical Care. Dr Lewis, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners? Tell us a little bit about yourself.

Dr Lewis: Thank you so much for having me, Dr Jones. It was a pleasure to be an editor of this issue, and I'm really excited for it to come out. As you mentioned, I'm a Professor of Neurology and Neurosurgery at NYU. I'm also a fellow of the American Academy of Neurology and a fellow of the Neurocritical Care Society. I serve on the Ethics Law and Humanities Committee for the AAN. I was a past chair of the Ethics Committee for the Neurocritical Care Society and also the past chair of the Ethics Committee at NYU.

Dr Jones: So, pretty diverse professional interests. And I was going to ask you about the ethics - that feels like something that ties in pretty well to neurocritical care. I imagine that expertise comes in handy, right?

Dr Lewis: Yes, absolutely. My area of expertise is related to brain death and ethical, social, and legal complications related to brain death determination.

Dr Jones: Got it. And when we were talking before we started recording here, you're from the New York area and a lifelong Yankees fan, is that right?

Dr Lewis: Yes, that's correct.

Dr Jones: How are they going to do this year?

Dr Lewis: We're hoping we're going all the way.

Dr Jones: Okay.

Dr Lewis: In a while.

Dr Jones: Our listeners heard it here first. So, the issue – let’s get into the neurocritical care topics – phenomenal issue, full of detailed diagnosis and management strategies for patients with, you know, all manners of severe neurologic disorders requiring critical level of care. With your perspective (which is a unique perspective) - you've just edited a full issue on neurocritical care, you got to delve into all the topics - what were you most surprised to learn, Dr Lewis?

Dr Lewis: Well, you know, I think that one of the most exciting things about this issue is the fact that, in addition to dealing with the typical topics related to neurocritical care - like hypoxic ischemic brain injury and stroke and intracerebral hemorrhage and subarachnoid hemorrhage, of course - the issue delves into some very unique topics related to neurocritical care. There's an article written by Dr Barry Czeisler that focuses on emergent management of tumefactive and aggressive demyelinating disorders, Dr Casey Albin wrote about neuromuscular emergencies, and doctors Maciel and Busl wrote about neuroonc emergencies – and I think that these areas are really important areas for neurologists and trainees to know about, and they’re not talked about all that often. And these topics are often focused on, of course, by other subspecialties, but the perspective of a neurointensivist related to these topics is infrequently addressed. So I think that these are really the most exciting aspects of this issue, because it’s something so unique in terms of the spin on these topics.

Dr Jones: Fantastic. And what else can we look for in this issue? What other topics can our listeners and readers expect to find there? 

Dr Lewis: So, the issue starts off with the examination and workup of the neurocritical care patient. Dr Sarah Wahlster and Nick Johnson from the University of Washington did an awesome job really bringing the reader into the topic of neurocritical care as they address an overview of neuroemergencies, red flags related to life-threatening conditions, herniation syndromes, vascular territories, and mechanisms and management of acute neurodeterioration, and they summarize monitoring modalities in neurocritical care and clinical and radiographic scales and scores that are commonly used in neurocritical care – and that’s a really nice overview to introduce the reader to this issue. The rest of the issue focuses on a wide range of topics pertaining to the emergent management of neurocritical care issues, including hypoxic ischemic brain injury (which was addressed by Dr Steinberg from the University of Pittsburgh),  management of stroke due to large vessel occlusion (which was addressed by Dr Leslie-Mazwi from the University of Washington), management of ICH (addressed by Dr Murthy from Weill Cornell), and then also management of spontaneous subarachnoid hemorrhage (addressed by Dr Soojin Park). Dr Clio Rubinos addressed emergent management of status epilepticus. Emergent management of TBI and spinal cord injury was addressed by Dr Podell and Dr Morris from the University of Maryland. And then neuroinfectious emergencies – which, again, is another unique topic in this issue – was  addressed by Dr Reynolds from Mount Sinai. And then the issue concludes with a paper that focuses on prognostication and neurocritical care by Dr Susanne Muehlschlegel from Johns Hopkins University. 

Dr Jones: Yeah. And what a great list of authors and expertise. And really, you know,  having seen these articles, really just phenomenal guidance on a lot of different subtopics. And I imagine – you know, this is a dynamic area, there’s a lot of evidence – but, you know, sometimes, there are controversies or debates or unresolved questions in the field. Having just reviewed and edited the issue, what do you think the biggest debate or controversy is in neurocritical care right now? 

Dr Lewis: So there’s definitely a lot of controversies that are addressed in each of these individual articles. For example, in the paper on subarachnoid hemorrhage, Dr Soojin Park provides a summary that compares the guidelines on management of subarachnoid hemorrhage that were written by the Neurocritical Care Society and the American Health Association / American Stroke Association in 2023 and really walks through what’s similar and what’s different between these guidelines. For the most part, they are very similar, but there are areas of differences. Additionally, in terms of management of acute neuroemergencies related to neuromuscular issues (in some cases, it’s not clear whether to treat patients with IVIG or with plasmapheresis), Dr Casey Albin creates a nice summary addressing these issues in terms of what are the pluses and minuses associated with each of these medications. Additionally, there are a number of novel therapies that are not traditionally considered for various neuroemergencies that are walked through in each of the individual articles. For example, in the paper that focuses on management of status epilepticus, Dr Rubinos addresses alternative therapies, like immunomodulatory agents or neuromodulation, for management of super-refractory status epilepticus. So, I think, in addition to addressing the more traditional therapies for various neuroemergencies, the issue really goes above and beyond to address novel interventions. 

Dr Jones: That’s fantastic. And obviously, it continues to be a rapidly evolving area.  When you look out to the horizon – and the next generation of care for patients with critical neurologic illness – what do you see on the horizon? What should our listeners and readers be aware of to watch out for? 

Dr Lewis: I think one thing that is really important to be aware of related to patients with neuroemergencies is the Curing Coma Campaign (which is organized by the Neurocritical Care Society), which focuses on research in terms of improving the clinical management, the prognostication, and the care of patients and addresses the goals for  improving recovery for patients who are comatose. And obviously, coma can be due to a wide range of different etiologies (many of which are described in this issue), and so I think that their work as we move ahead will be incredibly important and interesting to see how things evolve in that domain.

Dr Jones: We will be on the lookout for the Curing Coma Campaign – sounds like a great initiative. And, I think, medicine is a team endeavor, right? We were talking about the Yankees earlier (baseball) as a team sport – so is medicine. When you think about the importance of teams, it’s hard to imagine a setting where it’s more critical to have, you know, well-functioning teams than in the neuro ICU. But there’s also parts of the team (people on the team) who are outside the neuro ICU – and I’m thinking of other neurologists, our listeners and readers who might work in the inpatient setting, but not in this really specialized environment. When you think about those neurologists, is there a key message for those hospitalist neurologists or inpatient neurologists that you would want to share from your perspective as a neurocritical care specialist? 

Dr Lewis: So, I think it’s imperative for all neurologists to have an understanding of the existence of various neuroemergencies and the identification of when a patient is  having a neuroemergency so that they can escalate the management if it’s something beyond their skills or expertise to somebody who is capable of appropriately managing the patient. Each of these articles walks through the differential diagnosis, the identification of the neuroemergency, the first steps in terms of management, the laboratory workup, and then the subsequent steps as well. And I think that, you know, for all neurologists, really, the key things to know about (even if you’re not specializing in  neurocritical care) is how to identify a neuroemergency and what needs to be done as the first steps in terms of intervening and diagnosing these emergencies.

Dr Jones: Great message, and that’s one of the key things we learn in training, right,  is when to recognize that someone’s sick and you need to escalate their level of care. What about – you know, I imagine the neurocritical care field is a relatively small community, and you know a lot of these folks – any key message that you would want to share with that audience?

Dr Lewis: So, I think that this issue is still really important for all neurointensivists (in addition to for general neurologists and trainees), because of the fact that every article  really addresses in depth each of these aspects of neurocritical care and provides tidbits of information that not every neurointensivist would know. So, I think that the issue is beneficial both for trainees, general neurologists, and people who have expertise in the field of neurocritical care.

Dr Jones: That’s a great point. I think the fact that it is such a rapidly changing and broad field (you mentioned all the different article topics that are in the issue), it’s a challenge to stay up to date on everything. And I think that’s what this issue really brings  to the neurointensivist – is, you know, this is all (as of what’s the latest in 2024) for the care of patients with critical illness. It’s all there, right? 

Dr Lewis: Absolutely. I think, you know, the issue is unique because neurocritical care is unique in that our role involves taking care of patients with a wide range of different neurologic disorders. So, the issue touches upon stroke (both ischemic and hemorrhagic). It touches upon seizure management. It touches upon management of traumatic brain injury. It addresses demyelination (so types of aggressive MS and other demyelinating disorders), neuromuscular issues, neuroonc issues – so I think that, really, there are so many subspecialties within neurology that it’s important for them to have awareness of the emergencies that can emerge within their individual field.

Dr Jones: So, we know that neurocritical care is pretty specialized work, and I imagine the expertise and the resources are not necessarily going to be available in every community. Are you aware, Dr Lewis, of any disparities in access or outcomes to neurointensivist expertise? 

Dr Lewis: Yeah, absolutely. Unfortunately, as you look internationally, first, there are many places that don’t have neurointensivists, so patients with neuroemergencies are being taken care of, in some cases, not even by general neurologists, but by specialists just in medicine. Additionally, the resources are often not available in terms of having an intensive care unit, having nurses with a good ratio to care for neurocritical care patients, having access to therapists who can participate in rehab and promote rehab, for patients having access to medications that are necessary, having access to various interventions (such as access to neurosurgeons who can do neurosurgical procedures or placement of an external ventricular drain), or other monitoring modalities are not available and accessible. So, all of these issues – in terms of resources, in terms of funding, in terms of other issues related to the existence of protocols as to how to  manage patients in the neuro ICU – all impact the outcome for patients in neurocritical care. Additionally, social issues and cultural issues can impact the outcome for patients in the neuro ICU. So, there’s a lot of issues pertaining to equity in terms of the management of neurocritical care patients around the world. 

Dr Jones: Those are great points. I know you and I both work with trainees in our field,  and when I talk to residents who are interested in neurocritical care, I think part of what draws them in is when they are exposed to it and they see how much, you know, the value of what their expertise brings to the outcome for that patient. I mean, it really does make a difference to understand the brain when you’re caring for people with these critical neurologic disorders – and I think that’s part of the appeal, right? 

Dr Lewis: Yeah, absolutely. I think that people who are interested in going into the field of neurocritical care are interested in the more fast-paced aspect of neurology, rapid decision making, dealing with emergencies, also dealing with prognostication,  discussions (unfortunately, at end of life) – so that’s really the kind of individual who turns to the field to specialize in.

Dr Jones: And what about you, Dr Lewis? What drew you to this, you know, pretty high-pressure, intense, dynamic environment? 

Dr Lewis: So I think, actually, you know, all the buzzwords you just used are really the things that made me want to go into neurocritical care. I am interested in much more  fast-paced management of patients, and, you know, unfortunately, obviously emergencies happen, and I find them to be exciting to be able to manage patients in that setting. And, you know, as you mentioned earlier, in the neuro ICU, it’s a very multidisciplinary team, and I really enjoy being able to work with nursing, social work, care management, therapists, a variety of consultants – and addressing very acute issues with these individuals as a team in the ICU setting is really very rewarding. 

Dr Jones: Yeah, and I hear that from others who are drawn to the field, and I think you really have to have kind of a broad skill set to manage actively, you know, critically ill patients, but also do the communication competencies and other things that are necessary. So, anecdotally, I would say I see more interest among trainees in this field. I don’t know if you’ve seen the same thing in your world.

Dr Lewis: Yeah. I think that, you know, as you mentioned, it’s really important to emphasize that being a neurointensivist does not  just require expertise in the medical aspects of care for these patients, but really, also it’s very important to ensure that we  promote education related to communication and neuroprognostication. So, our last article on this issue (by Dr Susanne Muehlschlegel) addresses prognostication and includes a variety of different details about how to address uncertainty, how to implement family and patient-centered prognostication and promote shared decision-making – and these topics are so important for everyone to know about when they’re communicating with patients and families to address goals of care and to prognosticate.

Dr Jones: Yeah. Thank you. And before we wrap up our discussion here, Dr Lewis, in addition to being a neurointensivist and being an expert on ethics and all of your clinical and research work, you do editorial work. You have editorial responsibilities not only for this issue of Continuum, but also at Seminars in Neurology and at “The Green Journal”.  For our listeners who might be interested in that career pathway, how did you get into that? 

Dr Lewis: I very much enjoyed writing, and so I published a lot. And then I think that, you know, making connections is incredibly important and really looking out for those types of opportunities. Once you build a semblance of expertise in an area, then that often tends to lead to opportunities. So, I’m a Deputy Editor for the Disputes and Debate section of the Neurology journal. I’m also a Deputy Editor of Seminars in Neurology. I edited a book with Dr Jim Burnett on advances in neuroethics related to death determination by neurologic criteria, areas of controversy and consensus. And then I’ve also been a Guest Editor for a number of other journals, like the AMA Journal of Ethics that focused on socially situated brain death, a neurosurgical focus issue on primary and secondary infections of the brain, and a issue of Seminars in Neurology focused on ethics in neurology.

Dr Jones: You must have like a twenty-eight or twenty-nine-hour day, Dr Lewis. I don’t know how you do all that. I wasn’t even aware of all those things that you do, but I can tell you, having looked at this issue, your editorial skills are off the charts. I really want to thank you not just for a wonderful issue, but for joining us today and for such a thoughtful, fascinating, and thorough discussion on the field of neurocritical care.

Dr Lewis: Thank you so much. I'm so excited for all the readers to look at our issue and learn about all of these different topics. 

Dr Jones: Again, we've been speaking with Dr Ariane Lewis, Guest Editor for Continuum’s most recent issue on neurocritical care. Please check it out. And thank you to our listeners for joining today. 

Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practice - and right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024, or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. Thank you for listening to Continuum Audio.

Indomethacin-responsive headache disorders are rare conditions whose hallmark is an absolute response to the medicine and include paroxysmal hemicrania and hemicrania continua.

In this episode, Gordon Smith, MD, FAAN, speaks with Peter Goadsby, MD, PhD, FRS, author of the article “Indomethacin-Responsive Headache Disorders,” in the Continuum® April 2024 Headache issue.

Dr. Smith is a Continuum® Audio interviewer and professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia.

Dr. Goadsby is a professor of neurology at King’s College London in London, United Kingdom and professor emeritus of neurology at the University of California, Los Angeles in Los Angeles, California.

Additional Resources

Read the article: Indomethacin-Responsive Headache Disorders

Subscribe to Continuum: continpub.com/Spring2024

Earn CME (available only to AAN members): continpub.com/AudioCME

Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud

More about the American Academy of Neurology: aan.com

Social Media

facebook.com/continuumcme

@ContinuumAAN

Host: @gordonsmithMD

Transcript

Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the Show Notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the Show Notes. AAN members: Stay tuned after the episode to hear how you can get CME for listening.

Dr Smith: This is Dr Gordon Smith. Today, I've got the great pleasure of interviewing Dr Peter Goadsby on indomethacin-responsive headache disorders, which is part of the April 2024 Continuum issue on headache. Dr. Goadsby is a Professor of Neurology at King's College London, in London, United Kingdom and a Professor Emeritus of Neurology at the University of California, Los Angeles, which is located in Los Angeles, California. Dr Goadsby, welcome to the podcast. Well Peter, I'm super excited to have the opportunity to talk to you. And I think, before we begin, we probably ought to expand on your introduction. I think there may be three or four neurologists who don't know who you are, and I think they should know who you are because you've got a really amazing story. These are exciting times in headache, right? And a lot of that's because of your work and you've been widely acknowledged for that; you received the appropriately named “Brain Prize,” which (if I'm correct) is the largest neuroscience award in the world; got to meet Danish royalty; you’re - more recently, the ABF Scientific Breakthrough Award, which is super excited. So, particularly interested in hearing about your Continuum article. But before we get there, I think it would be really great to hear your story. How did you get into this in the beginning, and what's inspired you along the way to the many achievements you've had?

Dr Goadsby: Why, it's a very kind introduction. People have been nice to me. It has to be said, Danish royalty were very nice, I have to say, and the very jolly chap, the Prince of Denmark. I got into neurology - I guess it's all about mentoring for me. I got into neurology because I got into medical school pretty much by accident. I really wasn't that interested and heard a lecture by James Lance, who was Professor of Neurology, University of New South Wales, at the time. He was talking about a nondominant parietal lobe. I'd seen the case as a medical student; it sort of just seemed weird to me and I wasn't that interested. But he set out this way of thinking about things to try and understand why a clinical presentation is what it is - what he described as a physiological approach to clinical neurology. He described a number of things, but he described that in this lecture and then gave a reference to some work that Mountcastle did on nondominant parietal recordings from awake behaving monkeys in the Journal of Neurophysiology. And I thought to myself, “Wow, this is really interesting - you could really get to the bottom of something,” and had that sort of “puzzle-y” thing going on. And I thought Lance was just wonderful, so I became interested in that. And then eventually I asked him about research - actually, I asked him about research after a lecture he gave on migraine, and the explanation of the time was some circulating substance - probably just as silly now. I went up to him afterwards and said to him, I thought the explanation he was giving was wrong. Like, here was a global person - he described Lance-Adams syndrome; this was someone who trained at Mass General, trained at Queen Square; was the first professor of neurology in Australia. I was just – like, it was a stupid thing to do. But I couldn't resist myself - I told him I thought it was wrong. And he's very polite, and he said, “Well, perhaps you could come and help us by doing some research.” And I thought, “Okay, that's a very nice response.” Interestingly, his daughter described him as unfailingly polite at his funeral. Of the many things you'd say about him, he was a kind person. Whether it's science or just the way you practice - that word (kind) - you can know as much about a subject as you like, but if you're not kind to patients, you're probably in the wrong game. He taught me to be curious about a problem and got me interested in headache, and to be kind in clinical practice - just kind – and I think they were very important lessons. So, I got into it because of excellent mentoring, and I’d like to think I've helped some others along the way.

Dr Smith: Well, you certainly have helped a lot of people, Peter, and what a great story. I'm reflecting - I think the first vignette in The Man Who Mistook His Wife for a Hat was a right parietal syndrome - wasn't it? You've read that book?

Dr Goadsby: Yes, I have. And I've met Sacks. When Sacks came to Australia, he wanted to see Lance, and Lance said, “Fine, but you have to meet me between the morning round and the afternoon clinical meeting.” And he got him to come and have lunch with him in the hospital cafeteria at the Prince Henry Hospital and invited me to this lunch. And I sat there and watched them chat. But it was a measure of Lance and how people were interested in him that Oliver Sacks had to get in a taxi and come out to a hospital cafeteria to have lunch if you wanted to have a chat. Because it was - it was a privilege to train with the person. You know, I've done okay, but I only do okay if you've got – you know, you can work with patients, you've got great collaborators, and you've got someone you can get advice from (a great mentor).

Dr Smith: Yeah, that's actually really great words of wisdom for the residents and fellows and junior faculty listening to this. Maybe we should actually talk about your article, which was really great. Your article was on indomethacin-responsive headaches - and we can maybe talk about some specific questions - but what's the main take-home point? If our listeners needed to take or were to take home one point from your article, what would it be, other than it's indomethacin-responsive (that's in the title)?

Dr Goadsby: Yeah, it's what it says on the jar. Well, I think the one thing to take home is that there are forms of headache that seem relatively pedestrian, like one-sided headache that feels like it ought to be migraine that's strictly one-sided, and a small percentage of them respond almost like switching a light off to indomethacin. So, I think you have to have a high index of suspicion. And I’m sure I give indomethacin to ten, twenty times as many people - or thirty - who end up (or even more, probably) who end up having a response. But we do it for a short period of time. For those who get the response - I can tell you, when they come back, they're crying, their partners crying, or the other day I saw one, their child's crying, because all of a sudden, you've basically fixed the problem up. So, the message would be, if you've heard about something and it feels a bit “maybe, could be” - you've heard this indomethacin thing - just do it for a couple of weeks. The worst thing that can happen is nothing (nothing happens). For a couple of weeks, they're not going to have a problem with the tummy (and I'm not advocating taking people with a active gastric ulcer, trying to bump them off). But you cover them properly, you give them a short trial, and occasionally in your practice, you will be so rewarded by that - you will dance home.

Dr Smith: Well, this is going to be my next question. There are very specific criteria, right, for defining cluster, SUNCT, SUNA (and there was a really great Continuum Audio conversation I had with Mark Burish I'll refer our listeners to about cluster, SUNCT, and SUNA), but the indomethacin-responsive headaches - and even migraine - that sounds to me, as someone who's not a headache person, like, that could be challenging to sort out. If you see someone who has consistent, unilateral headache, do you just do an indomethacin trial, or do you select based on other criteria from the classification system?

Dr Goadsby: I'd like to think I was aware of the criteria, and I am. But the longer I practice, the more I'm inclined simply to give the indomethacin and get the question off the table because I don't think there's a sine qua non; there's nothing that will - apart from the indomethacin effect - there's nothing that will convince me 100% to be able to not do it. I've seen enough people who haven't clearly read the classification in detail (patients, I mean) and took indomethacin, and got a response where you wouldn't have predicted it, and they're very happy and the story ends well. So, I would advise people not to worry too much about whether it ought to or not respond, but find out if it does.

Dr Smith: So, the obvious next question is, how does this work? It's pretty unusual in medicine, certainly in neurology, to have something that's so dramatically effective. What's the mechanism?

Dr Goadsby: Well, that's the easiest question - we don't understand it. It is particular to indomethacin - it's weird. Some patients will say, “We'll give you a little bit of a hint by telling you (maybe) that ibuprofen was useful,” but most don't give you that much of a hint (some will even say aspirin is useful). But we haven't really gotten to the bottom of it. What are the current thoughts? It must be something that's not simply cyclo-oxygenase because other cyclo-oxygenase inhibitors don't do that – so, that's helpful. The other broad things people think about are whether there's a nitrergic aspect to it. We've got some basic science work that can show that nitrergically induced changes in experimental animal model of these trigeminal autonomic cephalalgias can be modified by indomethacin in one part of the model, where naproxen (for example) can't. So, we think there may be a nitrergic component to it. The other thing is the structure of the molecule makes you think about melatonin, if you put the two up – it's a work in progress. Of the things I would like to do in my life, I'd really like to get to the bottom of it, I have to tell you, because if we could work out what it is that's great about indomethacin and then get rid of the GI thing . . . Then, if you talk about cure - because when people get a response to this (you know, the oldest reported case with a response took it for thirty-seven years; they died of something else) - and continue to respond. It's one of the sort of upsides and downsides when you diagnose it - you can tell a person that they're going to continue to respond (take a breath) until they die basically, because unfortunately, the problem doesn't tend to settle down - at least the treatment stays consistent. If we could get rid of the tummy problem, that would be real progress.

Dr Smith: So, what do you do with the patient who has the tummy problem? Is there another approach?

Dr Goadsby: Well, there's a range of things you try and do; you use PPIs (proton pump inhibitors) and H2 blockers pretty liberally; you try to get the lowest dose, and that's usually best done by the patient. I give them the ordinary-release indomethacin; it's an impression that I have, over the years, that the slow-release indomethacin is not as efficient (just as a recommendation). I let patients - they take it three times a day, or twice - I let them work out what the littlest amount is that they need, having given them a regime to iron it out, because they can work it out for themselves. It's a partnership. It'll be very individual. If someone wants to take two in the morning and one at night and feels happy, have at it. If they want to take one three times a day, if they want to take one at lunchtime - whatever they - let them work out the minimal amount. And the other thing that we found useful - small percentage (maybe one in five) will find the coxibs useful (like celecoxib), but that's not universal at all; it generally takes the edge off. A palpable percentage will find adding melatonin in can be indomethacin sparing. Then the other (probably most important) thing is that the noninvasive vagal nerve stimulator can be very useful in reducing indomethacin dosing or even getting patients entirely off indomethacin dosing. How that works, of course, is as mysterious in the sense of these problems as is indomethacin. But that's something really worth thinking about - can be very, very useful in getting the doses down.

Dr Smith: You've been doing this for a while, right? And you've seen a lot of –

Dr Goadsby: Let's not emphasize that “for a while” side, right, okay?

Dr Smith: For a while – just a little while, Peter.

Dr Goadsby: A little while.

Dr Smith: I’m just thinking - and I'm a neuromuscular guy, so give me a little latitude - but when I was a resident, our concept of headache was pretty simple; it was migraine, classic or common, and we knew a little bit about cluster. And no one talked about SUNCT or SUNA or all these other things, and wow, what an amazing several decades it's been. What's the future look like? And - maybe think big – so, is a cure for migraine in the foreseeable future? What's coming next?

Dr Goadsby: If you think really big (and I'll think really big), if “cure” means that we could control it sufficiently that you wouldn't notice it, I think that's very much - it's almost here, for some. Now, I think of it like cholesterol - someone's got high cholesterol; they take a statin, and if they don't get any problems, the cholesterol normalizes. I'm simplifying things (I'm not a cardiologist), but you take your cholesterol tablet - you take it once a day; everything's fine and dandy. You never get “cured,” as such, but the effect is an effective cure from manifestations of the problem - and I am simplifying things a little bit. If I look at it like that, then I think we're getting to a place where some patients, we can treat them so well, and the problem is so suppressed, and they have so few problems with side effects (and some have none), that we're really getting there. We saw a study of the promontory phase of migraine using a gepant (ubrogepant), and we saw the ability (if you recognize the attack early enough) to treat and never have pain. Never have pain. Well, that's pretty close. It might sound crazy to think about it as a cure because someone will say, “Well, they've still got their genes,” and so on. Fine. But migraine is about disability, and if you can stop the disability and give a person full function in their life, well, you're pretty much there. And we're getting there, as we understand the disease.

Dr Smith: Really amazing. I have another question that I've actually been really dying to ask you. I'm a peripheral nerve guy, and you may not be aware of this, but those of us who are interested in therapeutic development in peripheral neuropathy, or advocacy, or recognition of neuropathy as a substantive, meaningful entity, are inspired by the work of you and your colleagues in headache. Examples might be advocacy for federal funding or having CDMRP funding - things like this. But an area where - I'm just curious - we spent a lot of effort (and it seems like it's been really transformational for you guys) is having taxonomy, which isn't a particularly sexy topic. But maybe you can talk about the power of having a taxonomic classification and getting towards a cure. Because looking through this Continuum issue - it's really remarkable – it’s just all sorts of things that I never would have thought of twenty years ago, and each of them is treated a bit differently.

Dr Goadsby: Yes. As with all things in medicine, if you don't get the diagnosis, you can't get to the base - you've got to be able to get a diagnosis. And our taxonomy, the International Classification of Headache Disorders, has gone through three editions. We're working on the fourth. I have the privilege of being the chairman for the fourth edition (the first three were chaired by Jes Olesen). I do think it's one of the absolute achievements of our field (and Olesen needs to be really feted for doing this) that we have a definition system - it's operational; it's reasonably straightforward; it's been translated into, like, forty languages; that every government on the planet that I know of - and I'm talking about (I think I'd better mention no governments) but every big government you can think of, without exception, has adopted (‘cause I'll just get in trouble with the ones I’ve mentioned) have all adopted this classification; all the health technology assessments (the FDA, for example; the European Medicine, for another example), the Chinese government (People's Republic), Taiwan. Just, all over the world, people use one thing. So, if we do a randomized control trial - there's one recently came out; it doesn't really matter which gepant it is - but you look at the results in North America, and then you look at the results that were done by the Chinese and the South Koreans in a study, and the placebo rates and the active rates are more or less identical. Because what we've been able to do is homogenize who gets into clinical trials and understand what's happening. So, if I get up and talk about whatever we're going to talk about now, like, in rural India, people will know what we're talking about; all the neurologists will be on the same page and so we can make progress. And when we make progress, it's global progress because we sing from the same hymn sheets. I think the taxonomy has been really important for this. And, of course, if you get the diagnosis right, then you can start to begin to get the treatments right and you can bring all the knowledge from randomized controlled trials. There's no point having a whole lot of data if you can't apply it, and what's great about our taxonomy is we can apply it everywhere in the world.

Dr Smith: Wow, what a cool answer. So, I have a follow up question for you, Peter, which has to do with reproducibility. This is a huge issue, right? In reproducibility and clinical trial evidence and in many fields, this has been a big issue - in psychiatry and other areas of neurology, where trials are nonreproducible. To what extent do you think this problem in other fields is a taxonomic problem, or a internal validity problem, in terms of the populations being recruited? I'm really impressed to hear that you don't have that problem in headache.

Dr Goadsby: I do think one of the advantages that the International Classification of Headache Disorders has given us (International Headache Society being the proponent of that) is that there's clinical homogeneity, relatively speaking, in our clinical trial populations. This comes back to the clinic; good clinical trials are as much about the clinicians who are involved and the care they take in recruiting patients, and so on. Which is not to say that psychiatrists are not careful - not at all. But I do think that if you want to just test a question, everyone in the laboratory will tell you that you need to have - say you're doing work with rodents, for example; you want about the same weight, you want the same strain, they're eating about the same, they're up and down at night - everything is about the same. If you want to do good clinical trial work, you have to tidy up as much as you can so the only thing that's really impacting upon the question is the medicine, or the placebo, or whatever that you're testing. So, I think you're right. I think sometimes the pain people struggle with this because, as you say, a painful neuropathy can come from a lot of places. Well, if you just take all of those etiologies, you throw them into one study, and you test it against something, it doesn't surprise me that that's not so useful, compared to taking an individual thing that's really well defined - where you've understood the clinical side, you've understood the pathophysiology as much as you could - and just test that, one at a time. I think that's been a good lesson for us. And that's why there's nothing that's ever failed in a migraine clinical trial (a properly designed one) that ever was useful, and nothing that was ever successful that didn't continue to be successful. Now, some things were successful, and they produced, like, liver enzyme problems - so, that's “no win-no foul” situation. But the homogeneity's been quite important, I think. And it comes back to good clinical practice.

Dr Smith: Well, thank you for the roadmap - that's really, really interesting. I'd like to finish up with another shift in gears, and to talk about workforce. Obviously, we have a national shortage of neurologists in the United States. We're never going to be able to train enough headache neurologists to take care of all headache patients, and we need to think about systems of care, which I guess we could talk about. But my question for you is, what would you say - a lot of residents listen to Continuum Audio, and hopefully, more medical students in the future and now - what do you say to them about a career in headache? Listening to this, I kind of feel like I want to go do a headache fellowship - it's pretty exciting. What's your pitch to them?

Dr Goadsby: I’ll tell you one small thing first before I say that; I did do twelve months in clinical neurophysiology, doing nerve conduction, muscle biopsies, evoked potentials. I actually did over ninety muscle biopsies (needle muscle biopsies) when I was training, so I understand your feeling. But I just got the feeling many years earlier than you've had it. What do I say to residents? Well, headache is an area where you can make a diagnosis, you can manage the patient, and you can make them better. I'd say to the resident, “Ask - just look in the mirror and ask yourself, why did you get into medicine?” You got into medicine to help people, and headache is an area where you can really help them. Plus, there's tens of millions of people with the problem, so you will always be in demand. And one of the great things about headache (I think it's probably true of neuromuscular) is it's also a very good lifestyle choice because our problems are generally with primary headache disorders - are not emergent (people don't tend to ring you up at night), and it's not really an on-call issue. You can have a proper balanced existence (work-life balance), and you can do it in a way that's really enjoyable. And then there's an extra bonus: there's all the wonderful neuroscience and neuropharmacology that's going on in headache. I just think if a resident looks in the mirror and says, “Why am I doing this?” most of them are going to look back at themselves and say, “Because I want to do good.” And they also want to do good in a way that they can have a proper life themselves. And if they're the two answers you got back when you look in the mirror (“I want to do good” and “I want to have some life myself”) - headache - that's the place to go, because there's plenty of room and you can do both.

Dr Smith: Well Peter, that's great - sign me up. And I think people know where to find you to call for a recommendation. What a great conversation and a really great article. And again, I'll refer our listeners to Mark Burish’s article on cluster, which is a really great companion to your article ‘cause it gives you the full spectrum of trigeminal autonomic cephalgias (which is pretty cool), and the rest of the issue is equally amazing. Peter, you don't disappoint. The next time you see the Danish Crown Prince, say “Hi” from me (I love Denmark - it's a lovely place to be). And thanks again for doing this.

Dr Goadsby: Well, thank you, and thanks for the Academy for organizing. And the other thing about residents - if you want to stay in touch with neurology, stay in touch with the Academy; they're a pretty good bunch.

Dr Smith: Couldn't agree more, couldn't agree more. Again, today we've been interviewing Dr. Peter Goadsby. His article on indomethacin-responsive headache disorders appears in the most recent issue of Continuum, on headache. Be sure to check out our Continuum Audio podcasts from this and other issues. And listeners, thank you very much for joining us today.

Dr. Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practice. Right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024, or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members: go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.

Cranial neuralgias comprise a distinct set of disorders typified by short-lasting attacks of intense pain in the distribution of a particular nerve in the cranium. Cranial neuralgia syndromes are rare but can be debilitating and go undiagnosed or misdiagnosed for years.

In this episode, Lyell Jones, MD, FAAN, speaks with Stephanie J. Nahas, MD, MSEd, FAAN, MD, an author of the article “Cranial Neuralgias,” in the Continuum® April 2024 Headache issue.

Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota.

Dr. Nahas is an associate professor of neurology at Thomas Jefferson University and assistant director of the Headache Medicine Fellowship Program at Jefferson Headache Center in Philadelphia, Pennsylvania.

Additional Resources

Read the article: Cranial Neuralgias

Subscribe to Continuum: continpub.com/Spring2024

Earn CME (available only to AAN members): continpub.com/AudioCME

Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud

More about the American Academy of Neurology: aan.com

Social Media

facebook.com/continuumcme

@ContinuumAAN

Host: @ LyellJ

Guest: @stephanieJnahas

Full transcript available here 

Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. 

Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr. Stephanie Nahas, who has recently authored an article on cranial neuralgias in the latest issue of Continuum on headache. Dr. Nahas is a neurologist at Thomas Jefferson University where she is an Associate Professor of Neurology and serves as Assistant Program Director of the Headache Fellowship program there. Dr. Nahas, welcome, and thank you for joining us today.

Dr Nahas: Thanks for having me. Glad to be here.

Dr Jones: So, for our listeners who are new to Continuum, Continuum is a journal dedicated to helping clinicians deliver the highest possible quality neurologic care to their patients, and we do so with high quality and current clinical reviews. Dr. Nahas, your article is a perfect example of that - it's full of really helpful (and I think clinically relevant) recommendations for neurologists who take care of patients with cranial neuralgias. And now that at this moment (during this podcast interview), you have the attention of a huge audience of neurologists - what's the one most important practice change that you would like to see in the care of these patients? 

Dr Nahas: I would like to see the recognition of these cranial neuralgias and related syndromes as distinct and overlapping with other primary headaches much more often. I think far too often, clinicians will try to pigeonhole these headache and facial pain diagnoses and try to make just one diagnosis the main one, and any other symptomatology that comes along with it – “Oh, that's just a weird part of your primary syndrome, right?” I know I've fallen into this trap a number of times, because mostly what we see in a headache clinic is going to be migraine, so we kind of have a laser focus towards migraine-type symptoms (and we know migraine can do just about anything). So then when we hear a little bit about a facial pain, a little bit about some sort of neuralgia, we just try to wrap it up into migraine - but that's not always necessarily the case. You know, we know that any person on the planet can have as many diseases as they darn well please, so why not ascribe two diagnoses when it's appropriate? That can lead to better treatment outcomes, in fact. If you are focusing your treatment on two distinct, but overlapping, entities, you tend to get better results, because the treatments may not be identical (and they rarely are).

Dr Jones: And that's a great example of it's Occam's razor on one side (there's one problem) versus - what is it, Hickam’s Dictum?

Dr Nahas: Something like that.

Dr Jones:  - where you can have as many problems as the patient wants to have, so I think that's a great example of that. And, earlier, in the same issue on headache, we do have a wonderful article by Dr. Deb Friedman, who walks through that really important history component of trying to, you know, determine which headache syndrome the patient is dealing with (which is obviously a prerequisite for the diagnosis and management) - so that's a great point. So that's the one takeaway - recognition of cranial neuralgias as a distinct entity. Keep it in mind – otherwise, we'll miss it. Is that right?

Dr Nahas: You got it.

Dr Jones: Okay, good. If we learn nothing else, we'll take that away. So, speaking of the history, Dr. Nahas, for many pain syndromes (including these), the history is really paramount in establishing the diagnosis for patients, specifically with trigeminal neuralgia. How do they usually describe that pain to you? 

Dr Nahas: The whole spectrum of descriptors for trigeminal neuralgia-form pain is, actually, maybe broader than you would think, and I actually find that, sometimes, patients have a real hard time verbalizing and describing the way it feels, because it's so unusual - it doesn't remind them of anything they've necessarily felt before.  Sometimes, it can. For example, a patient who's no stranger to having lots of dental work - that pain that when they drill in or if they hit an irritated part of the tooth or the gums, that's usually kind of neuralgia form-like. But at the same time, patients will say, “It's still not quite like that. You know, it's really hard for me to explain. It's sharp and it's terrible like that, but it has a different quality.” And I think they just don't necessarily have the terminology, but I encourage them to try to be creative. You know, some of my patients will personify the pain - they'll describe as if there's some little creature in there that's clawing, or scraping, or pulling, or stabbing. Or they might use other descriptors, such as burning like a fire (like a blow torch is there). Or they may even use colors. You know, some of my patients are really creative, and I don't know if they actually have synesthesia or they're just bordering on that, but they'll describe different colors for the qualities of pain. (“Is it more red? Is it more like icy blue? Is it black or white?”) I don't hear that too often, but I do like to just open the door and let my patients describe for themselves in their own words - and if they can't have any words, I give them some examples and that usually gets the ball rolling.

Dr Jones: So, a combination (like we usually do) with some open-ended questions, and then some directed ones to kind of clarify. That's really interesting, and it gives you some immediate empathy and sympathy for the discomfort these patients have to deal with, right (as when they describe it in those burning, clawing kind of terms)?

Dr Nahas: Exactly, and they'll also put it into context for you - so not just describing what the quality of the pain is like, but they'll give you good examples of when they feel these symptoms, what brings them on, what alleviates them, how the symptoms may change from day to day depending on the situation or circumstance. And again, it just gives them an open door to express themselves, and it really does help to strengthen that alliance you're trying to create and maintain with your patient. You do get useful and valuable information when you just let them go on and describe things.

Dr Jones: So, there are, I think, misconceptions in the popular world and also in the clinical side of care that, you know, folks will have a perception of a disorder that maybe doesn't really match reality. What do you think is a common misconception you've encountered in taking care of patients with cranial neuralgias? 

Dr Nahas: The patients that I see tend not to have the clear-cut textbook descriptions  (like it's almost as if they're reading the criteria when they tell you your symptomatology) - because those cases are a little bit easier, they get identified more readily, they get appropriate treatment sooner, their disease doesn't necessarily progress and become complicated by, you know, any number of things that can happen with unmanaged neuralgia-form craniofacial pain. The ones that I see - they've been around the block several times, because maybe their syndrome isn't quite so typical. Maybe they didn't really have the terminology to be able to describe their symptoms. Maybe nobody really opened that door for them and invited them to just talk about what it is. Perhaps they, or whoever they were seeing, were more focused on diagnostic testing, and so their focus is more on, “Why is my MRI not showing anything? Why is my x-ray completely normal? You know, I have these symptoms. There must be an explanation.” Because that's what patients want - they want solutions. They have a problem, they want to know why they have it, and they want a solution to it. And they can get too focused on the hard data and ignore that it's a subjective experience that really guides us to help treat their symptoms, especially when we don't have necessarily an anatomic target to go after. (When we do, that's great.) But again, these straightforward cases tend not to come to me, because they’re easier to take care of.

Dr Jones: Still, just as legitimate a diagnosis, even with a normal MRI, right? I do find it's sometimes hard to kind of get around that with a patient, isn't it?

Dr Nahas: Absolutely, it is. You know, they're both relieved and disappointed. I often find if we order imaging for an unusual syndrome (or even a typical syndrome) and they see that, “Well, there's nothing on this report to go for. What does that mean? Does that mean that I'm crazy? Does it mean that this is all in my head, that I'm imagining it, that I'm amplifying my symptoms somehow? Is this my fault?” You know, all this self-doubt comes in, and you have to reassure these patients that, “Yes, your symptoms are real. They are in your head, because your brain is in your head, and your brain is the source of your perception and your experience. So, let's take your symptoms at face value and let's give you treatments that are directed at those symptoms.”

Dr Jones: Well said, and that's where we like to keep it, the brain inside the head. I think that was day one of neuroanatomy. I know that the treatment for many of these cranial neuralgias overlaps, right? There's some common approaches to several of these. There are some things that we put in our academic writing, but there are some things that we just kind of learn from experience. Do you have any tips or tricks that you would like to share with our listeners about the management of the cranial neuralgias? 

Dr Nahas: First and foremost (and I think this kind of goes for any of the disorders in the spectrum of headache and facial pain) is you need to be patient, and you need to set up appropriate expectations that, by and large, this is a trial-and-error process where we need to introduce a therapeutic intervention gradually and titrate the dose gently to effect while following for clinical response, but also keeping an eye on what our guardrails are. What do I mean by that? Let’s say, for example, we’re using oxcarbazepine for some sort of neuralgia-form disorder (I mean, take your pick for any of them – it’s fair game for most of these as a good initial trial).

Dr Jones: Sure. Yeah.

Dr Nahas: So, you want to start it at a low dose, start building it up slowly, and in addition to following for their clinical response - which I counsel them it may take a while  (even once we hit a target dose, it may take several more weeks, we've got to give it time) - you can monitor a serum level of oxcarbazepine and certain other antiseizure medicines for that matter. So, that can help guide you to know how high you can go. This is a little bit different from the situation with epilepsy, where you're checking levels to ensure that it's in a therapeutic range to make sure that it's not toxic - maybe to assess for adherence - but here, we're using it as a guide to know how much farther can we push the dose on this drug. And, of course, also, you want to be monitoring for any adverse events that can occur with that drug (such as hyponatremia, or changes in the CBC, et cetera) - so I do monitor these folks a little bit more closely than I otherwise ordinarily would, especially when I have a therapeutic intervention where I can actually monitor the drug level of it and be very, very precise in trying to maximize and optimize their treatment.

Dr Jones: Got it. So, patience with each trial, and then patience that there might be (and I mean patience with a ‘c’ that there might be) multiple trials – I think that's a good takeaway for all of these cranial neuralgias with pretty much all of the medication treatments, right?

Dr Nahas: Yes, and I do find that in some cases, one treatment is not quite enough. Because most of the treatments we draw from our antiseizure medication category, it can get complex trying to balance two, or even three, antiseizure medicines and finding the optimal dose for each. Do we push all of them to the max? Do we say this one is the undercurrent (we just want to keep it at a low level) and these other two are going to be doing the lion's share of the work? It becomes kind of fun if you like uncertainty and if you like to be creative. If you're the type of person who likes checkboxes and checklists and cut and dried results, you know this is not the game that you want to play - but that's one of the reasons that I enjoy doing this, because I have so much freedom to be creative and really finely tailor and tune the treatment specifically to the individual patient’s needs.

Dr Jones: That's fantastic, and in a minute, I think we can come back to maybe what drew you to this - I'm curious to hear that. But before we get to that, you know, when we think about the medications that are available (and again, your article does a phenomenal job summarizing the therapeutic approaches to the cranial neuralgias) - what do you see on the horizon, Dr. Nahas, for the care of these patients? 

Dr Nahas: I want to see a lot more research being done in this population of patients and across this spectrum of disorders. What makes it so hard is because they are somewhat rare, and because they very often co-occur with another primary headache disorder - so that makes it extraordinarily difficult to create a research study on a population that's so heterogeneous, right? That's, I think, the biggest challenge - is that we have so little to guide us other than our own clinical experience. There are not a ton of clinical trials for any of these disorders. I think one in particular that can be both underdiagnosed and overdiagnosed is occipital neuralgia - and I mentioned before that I, myself, have found myself falling into this trap of once I see a signal for migraine, I just call everything migraine, right? And, sure, with migraine, there can be allodynia in the scalp, and oh, sure, we all hear that if you push on something sore, you can have some lancinating pain. Oh, that occipital neuralgia that somebody told you about? No, no, that's just part of your migraine. You don't actually have occipital neuralgia. Well, you know, if you look at clinic-based studies (there's one in particular that I cited), most of the presentations of occipital neuralgia actually co-occurred with another headache diagnosis (either primary or secondary), and very commonly, it was migraine or probable migraine or chronic migraine. And why this is important is because you need to validate for these patients that they do have more than just migraine. They have a separate problem that, yes, it's interrelated, it's interconnected, they can influence each other - but we might have to treat them both differently. So, you have your suite of migraine treatments which might not include an antiseizure medication. Then, for the occipital neuralgia, maybe you are pulling in an antiseizure medication, or maybe you're focusing more on peripheral nerve blockade or physical therapy - or even considering a surgical referral, because as surgical treatments for nerve decompression or ablation or other interventional procedures also continue to evolve, that helps to give us some more hope in giving  these patients more relief with fewer complications. I'd also like to see some more creative solutions, not just more antiseizure medicines, not just more targeted anatomic interventions. But, hey, is there a role for some other peptides or neurotransmitters that we just haven't identified yet? Might some novel treatment approaches actually be useful for some of these patients? And, you know, again, how do we get at those answers? It's going to be challenging, because the patients - while they're out there, they're not really a homogeneous group, and the results from a particular study might not be so generalizable.

Dr Jones: And we've seen such great success in the world of migraine, right (looking for novel targets) And so it would be nice to transport that over to the cranial neuralgias, right?

Dr Nahas: Yes, absolutely.

Dr Jones: Yeah. We should always be mindful of disparities in care of patients who have neurological problems. Are you aware of any literature around the care of these patients related to health care disparities that our listeners should be aware of?

Dr Nahas: Nothing focused specifically on disparities in this population or subpopulations within this population (based, for example, on ethnicity, or race, or socioeconomic status). You're looking for subpopulations within a huge population, almost like a needle in a haystack - not quite that difficult, but again, it takes a lot of effort and diligence to try to find these individuals and then to get them to agree to enroll in some sort of research study, even if it's just a survey study or doing interviews with them trying to understand their symptomatology better. It can be quite challenging. And then again, let alone designing a rigorous clinical trial for these folks - who, again, such a heterogeneous presentation - and the willingness to participate in a placebo-controlled trial for pain that can be so heinous can be very, very challenging. You know, we've seen this as a challenge with cluster headache, too - not just because of the nature of the disease (when the cycles come and go somewhat unpredictably). But these folks aren't necessarily willing to forgo treatment for the purposes of a clinical trial - I mean, many are, and I thank them - this is another one of the reasons that research is really lacking in some of these rarer syndromes.

Dr Jones: So, another part of the rationale for more investigation for these uncommon and probably underserved disorders. So, Dr Nahas, I know caring  for patients with craniofacial pain, I imagine it can be challenging. I can imagine it's also pretty rewarding as well. What drew you to this work, and what do you find most exciting about it? 

Dr Nahas: Well, what brought me to headache to begin with was kind of random chance, and really, it revolves around mentorship. When I very first started as a neurology resident, Dr. Silberstein took me under his wing and wanted to turn me into a headache specialist (that was one of his goals). And, thankfully, he was successful, although he didn't really have an easy job of it, because back then, I didn't really see or understand how studying headache and facial pain could really satisfy that hunger that I have to understand the brain and the nervous system. I mean, that's why I became a neurologist in the first place, right? (I think that's why most of us did.) You know, not only are we drawn to medicine to help people and be altruistic and to study a fascinating topic, but particularly with the brain and the nervous system - I mean, this is what makes us human. This is what's so fascinating to me. And until I started to learn more about headache, I thought the best way to really learn about brain function is through disease (such as stroke or epilepsy, or movement disorders, cognitive disorders, degenerative disorders). This is how we learn, right? This is what I was taught, at least in college and med school. And then you get to the real world of actually practicing medicine or being in training. You start talking with these folks, and you hear their stories and how distinct they are from the textbooks. And again, when you invite them to really describe their experience, you see the human side of it, and you listen to them describe their symptoms - and you start to imagine yourself, what's really going on in their brain and their nervous system for them to experience that? So you start reading a lot of the literature about cortical spreading depolarization and how that can activate the trigeminal system and sensitize it - how that might be linked to the expression of aura (for example) - then, you can actually really parse out the anatomy and understand why somebody experiences those symptoms when you understand the anatomy. And there are just countless examples of this - about how studying the symptoms and what brings them about, what the pathophysiology is, and then what the treatment is, how that really informs our understanding of how the brain functions - that's really what's kept me excited about this. That, and again, forming relationships with patients and sometimes being the first person who ever just sat down and listened to them and let them talk, and they really feel like they're cared about and like they're important - because they are. I think far too often, patients with headache and facial pain disorders are stigmatized, and they're left feeling like it's not worth it trying to get better, that there is no solution. Society has beat them down, the medical system has let them down, and they just want to give up. Then, when we can finally sit and listen and give them some hope, and they see some improvement - the transformation that occurs right before your eyes is extraordinarily gratifying.

Dr Jones: So, it's fascinating, and you can help people - and I can't think of a better advertisement for headache fellowship for all those neurology trainees out there.  Well said, Dr Nahas. So I've got one more question for you before we close. And I know that the headache community, including yourself, are very strong advocates for your patients and for more research (as we've talked about today) into headache disorders, understanding the pathophysiology, developing better treatments. What is it about purple hair? I've seen several headache specialists (and maybe someone on this call) post online some purple hair. What's the story behind that?

Dr Nahas: A number of years ago, as part of advocacy efforts, we recognized there's got to be a way to really improve the awareness of such a common condition, of headache in general. It affects so many people, it almost becomes, again, brushed off. We say headache, it's just a nuisance. Well, no it's not. It's actually fascinating as part of the human condition. One of the things we needed was a color - our signature color - and we chose purple. We know that we share this color with other advocacy groups, but it's a great color, it's eye-catching, and you can utilize it in a number of different ways. One of the early ways was people dressing up in all kinds of purple garb - putting purple makeup on, purple sunglasses, purple tutus, purple T-shirts, and even purple wigs. A lot of us have been donning purple wigs for advocacy and for awareness efforts, particularly for events (such as Miles for Migraine, for example) - but some of us have been so bold as to not just put on a purple wig, but to actually go to a salon, bleach the hair, and dye it bright purple. I have at least one male colleague who also did this to his beard. Last year, we did it together at the same salon, took a bunch of pictures to post about. It really created a big splash online and for our social media efforts and outreach, and it caught on. Lots more people now are thinking about dying their hair purple. One of our current fellows actually did it this year. At our center, we have about 30 different purple wigs that we bought with some funds that we procured, and on the Shades for Migraine Day (June 21), we all went out parading around Center City, Philadelphia wearing our purple T-shirts and our purple wigs, and handing out flyers trying to raise awareness. We got a lot of strange looks, but we also got a lot of good feedback. And I think we actually reached some people who didn't realize that there's such a thing as a headache center that they could actually come and see us and get relief for this problem they thought was just a part of everyday life. That was kind of a long-winded answer, but -

Dr Jones: No, that's great, and it worked. It got me to ask you about it, right? And I will say I admire your commitment and dedication. The best I could do today, Dr Nahas, was wear a purple tie, but I'm sure your patients appreciate that level of investment, too. It’s really, really cool. Really impressive.

Dr Nahas: Yeah. A lot of them this past year have asked me, “Where's the purple hair? I thought you were going to do it every year around this time.” And, you know, it is a bit of a commitment.

Dr Jones: It's a commitment, yeah.

Dr Nahas: And there's some upkeep that is required and you're kind of stuck with it for a while (unless you want to go to the trouble of reversing the process, but that's really just covering it up). I said, "We've moved beyond dying the hair. We're doing wigs, and we're thinking of the next thing.” 

Dr Jones: Good for you. Dr Nahas, thank you so much for joining us, and thank you for such a thorough and fascinating discussion on symptomatic management of cranial neuralgias and such a wonderful article in the latest issue of Continuum.  Really appreciate you being here today.

Dr Nahas: I can't thank you enough. It's been my pleasure.

Dr Jones: Again, we've been speaking with Dr Stephanie Nahas, author of an article on cranial neuralgias in Continuum's most recent issue on headache. Please check it out, and thank you to our listeners for joining today. 

Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal which is full of in-depth and clinically relevant information important for neurology practice - and right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024, or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members, go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.

The majority of children and adolescents experience headache, with pooled estimates suggesting that approximately 60% of youth are affected. Migraine and tension-type headache are the leading cause of neurologic disability among children and adolescents 10 years and older.

In this episode, Allison Weathers, MD, FAAN speaks with Serena Orr, MD, MSc, FRCPC, author of the article “Headache in Children and Adolescents,” in the Continuum® April 2024 Headache issue.

Dr. Weathers is a Continuum® Audio interviewer and an associate chief medical information officer at Cleveland Clinic in Cleveland, Ohio.

Dr. Orr is an assistant professor in the departments of Pediatrics, Community Health Sciences, and Clinical Neurosciences at Cumming School of Medicine, University of Calgary and a pediatric neurologist at Alberta Children's Hospital in Calgary, Alberta, Canada.

Additional Resources

Read the article: Headache in Children and Adolescents

Subscribe to Continuum: continpub.com/Spring2024

Earn CME (available only to AAN members): continpub.com/AudioCME

Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud

More about the American Academy of Neurology: aan.com

Social Media

facebook.com/continuumcme

@ContinuumAAN

Guest: @SerenaLOrr

Transcript 

 Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. 

Dr Weathers: This is Dr. Allison Weathers. Today, I'm interviewing Dr. Serena Orr on pediatric headache, which is part of the April 2024 Continuum issue on headache. Dr. Orr is an Assistant Professor at the University of Calgary, and a Pediatric Neurologist at Alberta Children's Hospital in Calgary, Alberta, Canada. Welcome to the podcast. So, thank you, Dr. Orr, for taking the time to speak with me about this fantastic article that covers such an important topic – headache in the pediatric population, in children and adolescents. First, I'd love to start by learning a little bit about you. Where do you practice, and how did you get interested in this topic? I love learning more about the authors of these incredible articles and how they became interested in their fields. So, you know, pediatric neurology is already a pretty subspecialized area of medicine – how did you become interested even further subspecializing in headache?

Dr Orr: Well, thank you for the invitation. Nice to meet you, Dr. Weathers. I’m Serena Orr. I’m a clinician-scientist, pediatric neurologist, and headache specialist based in Canada at the Alberta Children’s Hospital in Calgary, Alberta, just outside of the Rockies. I’m really passionate about headache medicine. I think I came to it because it allowed me to marry my interests in neurology and psychology together. I did my undergraduate studies at McGill in psychology and really wanted to take a biopsychosocial approach to my practice. The first child neurology patient I ever saw was a child who was experiencing migraine and having a lot of disability from it, with lots of impacts on her life - and I really saw an opportunity to take a holistic approach to the patient and marry my interests in neuroscience, neurology, and psychology together. So, I'm very excited to talk to you today about this topic that I'm really passionate about and that I think is underserved – um, hopefully get more people excited about it.

Dr Weathers: But so great, and I'm sure we will do that just based on how excited I was just reading your article. So, I always like to start, actually, with what you feel is the most important clinical message of your article. What is your biggest takeaway you want to leave our listeners with?

Dr Orr: Yeah, well I think this is a really big topic in neurology. So, if you look at the reasons for consulting a child neurologist, headache falls into the top three. 60% of youth experience headache in youth. If we look at what presents to neurology in terms of headache, the majority is migraine – and so that’s a big focus of this article, because anywhere between a half to 88% of headache consultations in neurology are for migraine. And as I kind of alluded to in discussing my interests in this area, you know, it's really important to take a biopsychosocial approach to managing any chronic pain disorder, including migraine and headache disorders. Another big takeaway point from the article is that - specific to pediatric headache - there's really high placebo response rates that we're still trying to understand and grapple with in the field, and I think this underscores the importance in really doing patient-centered care and ensuring that you're educating patients and families about the level of evidence that we have about the placebo response rates and engaging in shared decision-making when you're choosing treatments together. So, I think those would be the main take-home points.

Dr Weathers: I think both really critical. And I think even without – I’ll put my plug in – even without the placebo effect, I think that shared decision-making is such an important concept for all of us in neurology to think about - but I think you make such the important point that with it, it becomes absolutely critical. I want to expand on a concept that you were just talking about. Pediatric headaches are so incredibly common, and you make the point in the article so well that they're one of the leading causes of neurological disability in pediatric patients. They have such a significant impact that really touches all aspects of these children's lives - both at school, how they impact their hobbies - pretty much everything that they do, and these long-reaching impacts. But then you go on to say that pediatric headache remains the most underfunded pediatric disease category when you take into account allocated public research dollars, which was just staggering to me. Why do you think this is?

Dr Orr: I think there's a few reasons. So, one of the main reasons, I think, is that headache medicine has been underserved - there haven't been enough people who have gravitated to this field. I think this is rapidly changing as we train more people and show the world how important this topic is and how much exciting translational research is going on. But, historically, this has been a very small subspecialty that's been underserved relative to disease burden (so not enough scientists equals less research funding) - but there's another aspect to this as well. There was a paper published in 2020 by Mirin – who actually looked at research dollars in NIH based on disease burden and whether the diseases were male or female dominant - and found that there's a significant gender bias in research funding. Male-dominant diseases tend to be significantly overfunded relative to female-dominant diseases when you look at disease burden - and if you look at the female-dominant disease table, headache disorders and migraine are in the top three most underfunded disease categories amongst the underfunded female-dominant diseases. That data has been replicated looking at NIH dollars on the pediatric side as well. They didn't look at gender breakdown in the pediatric paper that was published a couple of years ago, but found, actually, that pediatric headache disorders are the most underfunded in terms of NIH research dollars to pediatric diseases – so, top underfunded relative to disease burden. So, yeah, being underserved as a field - and then, I think, gender bias has also played a significant role in what gets funded over time.

Dr Weathers: Wow, that is hard to think about. And I think those are really insightful points and ones we really need to think about as we think about the bias in our research and our funding. Why is access to care and treatment for these children and adolescents so important? I know this seems like a super obvious one, but it feels like the answer is actually really much more complex.

Dr Orr: Well, there's data to show that earlier diagnosis can lead to better long-term outcomes for youth with migraine - and this is really important, because if you look at the incidence curves for migraine, you see that at least a third, if not more, of incident cases occur before adulthood. We also know there's some GWAS data to show that youth-onset migraine has a higher genetic loading when looking at polygenic risk scores than adult-onset migraine, so people who have migraine onset in youth may be more genetically loaded (that may be important). And we also know that early access to diagnosis and treatment gives them a better long-term prognosis. We know that headache disorders and migraine are associated not only with long-term potential for disability on the physical side, but also increase the risk of psychiatric comorbidities developing over time, so there's really a huge opportunity in accessing a diagnosis and treatment early to improve long-term function - both on the medical side, but also potentially avert poor mental health outcomes - and also diagnose and treat a subset of people with the disease that may be more genetically loaded. We don't know if that impacts outcomes, but potentially, it does. So there's lots of reasons, I think, that we can get in there early and make a big impact – and even for those who it takes a while to find effective treatment for, really having access to education early so that they understand their disease and also ways that they can engage in self-management strategies, I think, is really empowering to the patient and really important (even if we're struggling to find the best medical therapy).

Dr Weathers: You laid out a lot of really important reasons, and again, it goes back to the arguments made at the beginning about why it's so important to increase the funding so that this is no longer an area that's underserved, so that we are able to increase the access, and that everybody who needs this kind of care is able to get it. I want to shift a little bit and think about how we diagnose and work up patients who present with a headache. So as a neurologist - and also as a parent - one of the scariest considerations for me is figuring out if a headache is just a headache or if it's a sign of something else (you know, what we think of as a secondary headache disorder). What is your approach to distinguishing between the two?

Dr Orr: We take a very clinical approach to diagnosis. We don't have specific biomarkers for different headache disorders, so we're still, you know, relying on a really detailed history and physical exam in order to sort out the diagnosis. As I discussed in the article, really the key first branch point (like you say) is, is this a primary headache disorder or a secondary headache disorder? There's some tools that we can use in practice to try to get at that, I think the most useful of which is the SNOOP tool - it's an acronym that goes over headache, red and orange flags. Every time I write an article where I discuss this, it's expanded to include more red or orange flags (it’s in its probably third or fourth iteration now), but there's a nice table in the article that goes over some of these red and orange flags. It includes things like systemic feature (like headache, nuchal rigidity), if there's a history of cancer, if there's associated, you know, headache waking child up in the morning with vomiting - and a variety of features. I have to say the level of evidence for some of the features is relatively low, and our understanding of some of the red flags has changed over time. As one example, we used to think occipital headaches in youth were almost always associated with a secondary headache disorder, but now there's more emerging data to show that it's actually relatively common for youth with migraine to have an occipital location. So, really, using the tool is about kind of putting the whole picture together to try to risk stratify. In the majority of youth who present with recurrent headaches, who don’t have any red or orange flags, and who have an unremarkable neurological examination without focal deficits, it typically is such that we don't have to do further investigation - but any red or orange flags (or a combination of them), any focal deficits on exam, would typically be where we would be considering neuroimaging. It's very unusual that we have an indication to do an EEG or large amounts of blood work in youth with headache, but it is context specific - for example, a case presenting with recurrent hemiplegia (you may have Todd's paralysis on the differential and you may want to do an EEG), or in a youth who also has GI symptoms (I picked up some youth with celiac disorder who have chronic headaches as well). So there are specific circumstances where blood work, EEG may be indicated (or obviously lumbar puncture in the case of suspected infection, et cetera), but for the most part, we're really relying on a very thorough history and physical exam to sort out our pretest probability of a secondary headache disorder and whether we need to do neuroimaging and further investigations.

Dr Weathers: I think keeping in mind that systematic approach and really working through the algorithm is really reassuring and makes sense that, one, you won't miss something kind of worrisome, but on the other hand, that you're also not doing unnecessary testing, either. Along those lines, what do you think is the easiest mistake to make when treating children and adolescents with headache, and how do you avoid it?

Dr Orr: I think the easiest mistake to make is undertreatment. Both for acute and preventive therapies, I often see undertreatment. I think families are often hesitant to give medication to their children, and so I have a lot of families say, “Oh, well, you know we typically wait the attacks out until they get more severe, we try to avoid medication, we use cold compresses, et cetera.” So, explaining to families that acute treatment (of course, we don't want to overuse it) and overusing simple analgesics (NSAIDS) more than three days a week can increase the risk of higher frequency of attacks and medication overuse headache - but undertreatment is a risk, too. And the way I like to explain it to families is in the scientific basis of pain chronification - so I'll say to families, “You know, we have these pain pathways in our brain. If we let them go off for long periods of time, they get stronger (and so that's where we want to get medication in quickly to try to shorten the exposure of the attacks). When you don't do that, those pain pathways may start out like a dirt road - and maybe then you have lots of long attacks, and then it gets paved, and then it becomes a highway.” I find it's a useful way to help families understand the concept of pain chronification and why we want them to treat attacks. The same thing goes for undertreatment on the preventive side. If you know a youth is having frequent attacks that are impacting their life and their ability to function, we really should be thinking about a daily preventive treatment, because we know that pill-based interventions will result in a significant reduction in headache frequency in at least two-thirds of youth - and again, allowing the youth to have frequent attacks contributes to that pain chronification (and explain it to families in a similar way to what I just explained for acute treatment) - but there can be a lot of hesitancy to engage with pill-based treatments, even though we know that they can be helpful.

Dr Weathers: I think that's a really powerful point - and I think something we also, frankly, probably tend to do on the adult side as well – but, especially, I could see where there's even probably more hesitancy in children and adolescents (this concern that we're going to overtreat them and then end up inadequately treating, which leads to increased problems). And also goes back to the concept you were talking about earlier about the importance of shared decision-making and really engaging with the patient and their families in the discussion early on to help avoid that, as well to have everybody aware of the benefits and the side effects of all of the different options, I think is so critical. I was also really excited to see you (in the article) write about the importance of a trauma-informed care approach. This is an area I'm really passionate about in my work as a clinical informaticist and how we can leverage the electronic health record to support trauma-informed care and raising awareness of what a patient's triggers may be. Can you explain to our listeners who may not be knowledgeable about this approach what it means, and why you think that this might be applicable to children adolescents with headache?

Dr Orr: Thanks for bringing that up. I think it's really important as well. We've done some work in my lab (and many others have as well) to show that there's a relationship between adverse childhood experiences and the development of headache disorders in youth and adults. By adverse childhood experiences, I mean exposure to highly stressful (like toxic stress) environments in early childhood, such as experiencing death of a parent, divorce, abuse, neglect. So, we know that adverse childhood experiences are associated with higher risk of developing migraine and headache disorders, and knowing that and how common these are amongst our patients - really think it's important to advocate for screening all children, adolescents coming in with recurrent headaches for adverse childhood experiences and exposure to trauma, because it really will impact not only how you interact with the patient, but also potentially what you will screen them for on the mental health side. And so providing trauma-informed care, I think - of course we want it to be targeted - but really taking this approach with all patients is actually a good way to think about it, because trauma is very common in our society, and some of the ways that we've measured trauma in the past (like some of the examples that I gave, divorce, death of a parent) are really narrow and don't encompass broader aspects of trauma (like systemic racism and other things that people are experiencing that haven’t been adequately measured). So what trauma-informed care is - you know, there's a few core aspects, and one is screening all patients for trauma. The way I do that in clinic is just asking them if they've had any major stressful life events (and then I give a few examples), but there are standardized questionnaires that can be used for this as well. And then really trying to develop a nurturing rapport with the patient - an open listening strategy, asking open-ended questions, being empathic with patients and families - I know we all try to do this, anyway, but really focusing on that, especially in the context of trauma. And then thinking carefully about not only how you're talking to the patient, but how you're approaching them during the physical exam (so, for example, asking permission before touching the patient rather than just diving into the exam to be sensitive to that). And then also recognizing, like I said, that some of the ways that we've conceptualized trauma have been a little bit narrow, and that trauma may occur in context outside of what we traditionally think of.

Dr Weathers: Again, I think that's so important and could be certainly much more broadly applied than even just to this one field, but thrilled to see that you're incorporating it into your work and your research (and again, it was discussed in the article) - and, absolutely, I think that the more that we incorporate it as well here, I think, that the better off for all of our patients and the improved care we provide. Moving on from that, I always like to end my interviews on a positive and hopeful note, and so I'd love to hear from you what you're most excited about in the field of pediatric headache. What breakthroughs do you think are coming, or what's giving you the most hope?

Dr Orr: There's so much, there's so much exciting stuff going on in our field (and so, you know, I'll have to rein in myself in here), but one thing is there's been an explosion of novel treatment options on the adult migraine side in the last five to ten years, including agents targeted at the CGRP pathway, calcitonin gene-related peptide, some monoclonal antibodies, and receptor antagonists. There's been an explosion of neuromodulation options with now five devices that have various levels of FDA clearance for use in adults and/or youth with migraine. And there are, for most of these devices and novel drugs, either published studies or ongoing research into how they may be used in youth, so I'm hopeful that we will have more treatment options that are evidence based for youth going forward. This is in part due to the Pediatric Research Equity Act that came out a couple of decades ago now that has put requirements for pediatric studies when new drugs are approved by the FDA for adults - so I think that has had an impact, and I'm hopeful that we'll have an expanded treatment landscape in the years to come. There's also a lot of really exciting, more kind of fundamental research going on that I think will help us move the pediatric field forward more rapidly. In the past, we have really often borrowed from what the adult neurologists are doing for adults with headache disorders without really understanding some of the fundamental biological and psychosocial differences between headache disorders onset in youth versus adulthood, and so there is more and more research going on to understand the biology of migraine in youth and some of the risk factors at this age and some of the features that may make youth a little bit different, because it's very rare that youth are just little versions of adults for any disease or problem. And then, you know, I've seen a really large expansion in the number of trainees who are interested in headache medicine since I've entered this field (I've even got one of our residents who's going to do a headache fellowship, which is exciting), and seeing the growth and interest in headache medicine and the number of people being trained really gives me a lot of hope for the future, because there's so much work to be done in this area, and, really, that's where we're going to have the largest impact - is in mentoring and fostering the next generation of headache neurologists. So, there's lots of reasons to be excited, and I would say to the trainees listening that if you want an exciting career where there's lots of opportunity to make impact both clinically on your patients and in terms of educating the next generation and spearheading research initiatives, headache medicine is for you.

Dr Weathers: I think that is incredibly inspiring and will hopefully get a lot of our listeners excited about joining this incredible field. Well, thank you for, again, this great article and for all of your time this evening, I've learned so much and really enjoyed speaking with you.

Dr Orr: Thank you. Likewise, it was great to have this opportunity. I really enjoyed it.

Dr Weathers: Again, today, we've been interviewing Dr. Serena Orr whose article on pediatric headache appears in the most recent issue of Continuum on headache. Be sure to check out Continuum Audio podcasts from this and other issues. And thank you to our listeners for joining today.

Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you’ve enjoyed this episode, you’ll love the journal, which is full of in-depth and clinically relevant information important for neurology practice. And right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/ Spring2024, or use the link in the episode notes, to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members: go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.

New daily persistent headache is a syndrome characterized by the acute onset of a continuous headache in the absence of any alternative cause. Triggers are commonly reported by patients at headache onset and include an infection or stressful life event.

In this episode, Aaron Berkowitz, MD, PhD, FAAN, speaks with Matthew Robbins, MD, FAAN, FAHS, author of the article “New Daily Persistent Headache,” in the Continuum® April 2024 Headache issue.

Dr. Berkowitz is a Continuum® Audio interviewer and a professor of clinical neurology at the University of California, San Francisco

Dr. Robbins is an associate professor of neurology and director of the Neurology Residency Program at New York-Presbyterian/Weill Cornell Medical Center in New York, New York.

Additional Resources

Read the article: New Daily Persistent Headache

Subscribe to Continuum: continpub.com/Spring2024

Earn CME (available only to AAN members): continpub.com/AudioCME

Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud

More about the American Academy of Neurology: aan.com

Social Media

facebook.com/continuumcme

@ContinuumAAN

Host: @https://twitter.com/AaronLBerkowitz

Guest: @ @mrobbinsmd

Full Transcript Available:

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 Matthew Robbins about his article on new daily persistent headache, from the April 2024 Continuum issue on headache. Dr Robbins is an Associate Professor of Neurology and Director of the Neurology Residency Program at New York-Presbyterian/Weill Cornell Medical Center, in New York. Welcome to the podcast.

Dr Robbins: It's great to be with you, Dr Berkowitz.

Dr Berkowitz: Well, thanks so much for joining us this morning. To start, what is new daily persistent headache? I think it's an entity maybe that might be new to some of our listeners.

Dr Robbins: Yeah - it's an entity that also struck me when I was in training. I didn't hear much of it as a neurology trainee until I did a fellowship in headache, where, all of a sudden, we were seeing patients with this syndrome (and labeled as such) all the time. And that actually inspired me to begin a research project to better characterize it - a clinical project that ended up helping to broaden the diagnostic criteria. New daily persistent headache really is just defined by what it says - it's new; it's every day; it persists; it's a headache. It can't be from some other identifiable cause, which includes both secondary disorders (you know, something that, where headache is a symptom of) or a primary headache disorder; distinguishes itself from, say, migraine or tension-type headache because there's no real headache history and there's an abrupt onset of a daily and continuous headache that has to last for at least three months since onset. And the onset is typically remembered - it's usually acute or abrupt; there may or may not be some circumstances that surrounded the onset that might have some diagnostic or causal or associated implications that we can explore.

Dr Berkowitz: Okay. So, I always find it challenging in headache medicine and some other areas where we don't have a biomarker, per se - an imaging finding, a lab finding; we have an eloquent and detailed clinical description - to know how comfortable to be making a diagnosis like this. In this case, particularly, right - you said it has to be going on for three months. What if I see a patient one month into something I think could be this, but I can't technically say, per the criteria, right (it's three months)? When do you start thinking about this diagnosis in patients, and what are some of the main considerations in confirming the diagnosis, and what needs to be ruled out or excluded for making the diagnosis?

Dr Robbins: I think traditionally, in headache, the term “chronic” has that three-month time period. The reasons are twofold: one is that, typically, if there's some secondary disorder that might have some distinguishing feature (something that really evokes the headache or some other neurological accompaniment that develops in addition to headache), it would pretty much be likely to declare itself by the three-month mark. Or if it was something that was very self-limited, it would probably go away before three months have elapsed. Or if it resolved after some days or weeks but then declared itself as a more episodic disorder, then we might say someone who begins with continuous headache that might, for example, resemble migraine (maybe it presented a status migrainosis but then it devolved into a more episodic disorder that might just be migraine overall). So, I think that's pretty much why the three-month mark has been so prevalent in the International Classification of Headache Disorders, including how new daily persistent headache is diagnosed. But at the same time, there's lots of disorders that might mimic (or might be misdiagnosed as) new daily persistent headache, and they really are a secondary disorder. Probably the most common one that we think about is a disorder of intracranial pressure or volume, mainly because routine MRI features could be normal or could be easily missed if they had subtle abnormalities. The defining symptom of those disorders are also continuous headache, often from onset, with an abrupt and remembered nature. So, that's often the main category of secondary headache that might be misdiagnosed as primary headache. I think, probably, idiopathic intracranial hypertension as the prototypical disorder of high pressure often declares itself with visual symptoms, pulsatile tinnitus, and other abnormalities. And nowadays, there's much more increasing recognition for MRI abnormalities or even MRV abnormalities with such patients. But spontaneous intracranial hypotension (despite increasing recognition of CSF leaks in the spine that lead to intracranial hypotension or hypovolemia) really remains an underdiagnosed entity. I think that's one disorder where - for example, if I'm seeing a patient with new daily persistent headache and there's no orthostatic or positional nature to their headache - I will still do an MRI, with and without contrast, to be sure. But that the chances of them having a spontaneous CSF leak are low if that scan is unremarkable.

Dr Berkowitz: That's very helpful. Yeah. It's interesting; when you talked about the criteria for this condition - that it has an acute onset, which is a red flag, right, and it is persistent for months, which for a new headache would also be a red flag. So, this is a condition - correct me if I'm wrong – that, if you're considering it, there's no way that you're going to make this diagnosis without neuroimaging because there are two red flags, in a way, embedded in the criteria before we get to the other diagnoses being excluded. Is that right? So, this would only be a diagnosis made clinically but after neuroimaging is obtained, given that two red flags are part of the criteria – isn’t that right?

Dr Robbins That's absolutely right. So, I can't imagine there's anyone who has new daily persistent headache who hasn't had appropriate neuroimaging, and that typically should include an MRI, with and without contrast, unless there's some compelling reason to avoid that. There's some other workup that could be done that's not universal but - for example, in clinic-based studies of patients who have new daily persistent headache versus those who may have, say, chronic migraine or chronic tension-type headache, you may find more abnormalities. The biggest and more compelling example of that is hypothyroidism, which presumably would be somewhat subclinical if it hadn't been brought to someone's medical attention earlier. It doesn't mean that hypothyroidism is the cause of new daily persistent headache, but it could be some type of triggering or priming factor that leads to headache perpetuation in some patients. Sometimes, if that hasn't been done already, that would be a blood test I might think about sending. And, of course, the context of onset; if someone lived in a place where tick-borne illnesses are endemic, if there are other neurological symptoms, that might prompt looking for serological evidence of Lyme disease, as one example.

Dr Berkowitz: We see a lot of headache. I'm a general neurologist; I know you're a headache specialist; we all see a lot of patients with headache. You and I both work closely with residents. Often, residents will come to present a headache patient to me and they'll say, “The patient seems to have a new daily persistent headache. They haven't been imaged yet. They have a completely normal exam. The history fits.” And I always ask them, “Okay, we have to get neuroimaging, right? There's at least one red flag of the chronicity, maybe the red flag of something beginning relatively abruptly. Even though you're looking at the patients - I’m pretty sure that imaging is going to be normal, but we've got to do it.” But I always encourage residents, “Try to predict - do you think the imaging is going to be normal (this is a rule out) or do you think you're going to see something (this is a rule in)? - just to sort of work on calibrating your clinical judgment.” I'd love to ask you - as a headache specialist, when you're looking at the patient and say, “I know I need to get neuroimaging here to fully make this diagnosis of exclusion,” or you've heard something that sounds like a red flag; you know you're obligated to image, but your clinical suspicion of finding anything more than something incidental is pretty low. How often are you surprised in practice in a sort of enriched tertiary headache population?

Dr Robbins: That's a great way to frame such a presentation on how a resident would present to you the case and whether it's a rule in or rule out. I totally agree with your approach. I think much of it depends on the clinical story. I think if it was just a spontaneous onset of headache that kind of resembles migraine that just continued, then likely the MRI is being done to just be sure we're not missing anything else. However, if the headache started – really, say someone coughed vigorously or bent over and the headache started, and there was some clear change that you could perceive in - that was, say, the Valsalva or a transiently raised intracranial pressure, or some other maneuver; then you might really say, “Well, this really could be a spontaneous CSF leak,” for example. Even if the MRI of the brain, with and without contrast, is totally normal, I'm not really sure I'm convinced - that you might even take it further. For example, you might do an MRI of the total spine, with a CSF-leak-type protocol, to see if there's some sign of a spontaneous CSF leak or an extradural collection. So, I think in the cases where the preclinical suspicion is higher for a secondary headache, it might not stop at an MRI of the brain (with and without contrast) that's normal. Patients with spontaneous CSF leaks - about eighty percent of them have abnormal brain MRIs, but twenty percent don't. We found, from some observational studies, that a newer cause of intracranial hypotension, such as a CSF venous fistula in the spine, is more likely to present than other causes of CSF leak - with say, Valsalva-associated headache or cough-associated headache. That might prompt us to really take a workup more deeply into that territory, rather than someone where it really just sounds like chronic migraine that switched on. And maybe in those patients, when you dig around, they were carsick as a kid, or they were colicky babies, or they used to get stomachaches and missed school as a teenager here and there, and you think migraine biology is at play.

Dr Berkowitz: So, if you're thinking of this diagnosis before you can make it, these patients are going to get an MRI, with and without contrast. And it sounds like the main things you're looking to make sure you're not missing are idiopathic intracranial hypertension or intracranial hypotension from some type of leak. Any other secondary headaches you worry about potentially missing in these patients or want to rule out with any particular testing?

Dr Robbins: Yeah - I think sometimes we think of other vascular disorders, especially - when these patients come to medical attention, it's often a total change from what they're used to experiencing. They may present to the emergency room. So, it depends on the circumstance. You might need to rule out cerebral venous thrombosis. Or if there was a very abrupt onset or a relapsing nature of abrupt-onset headaches with sort of interictal persistent headache, we might think of other arteriopathies, such as reversible cerebral vasoconstriction syndrome. There's the more common things to rule out - or commonly identified conditions to rule out - like neoplasm and maybe a Chiari malformation in certain circumstances; those usually would declare themselves pretty easily and obviously on scan or even on clinical exam.

Dr Berkowitz: Another question I'd love to ask you as a headache specialist, in your population - sometimes we see this type of new daily persistent headache presentation in older patients, and the teaching is always to rule out giant cell arteritis with an ESR and CRP, in the sense that older patients can present with just headache. Again, my clinical experience as a general neurologist - I wanted to ask you as a headache specialist – is, for the countless times I've done this (older patient has gotten their neuroimaging; we've gotten ESR and CRP), I've never made a diagnosis of giant cell arteritis based on a headache alone, without jaw claudication, scalp tenderness, visual symptoms or signs. Have you picked this up just based on a new headache, older person, ESR, CRP? I'm going to keep doing it either way, but just curious - your experience.

Dr. Robbins: Yeah. We're taught in the textbooks (I'm sure we're taught by past Continuum issues and maybe even in this very issue) about that dictum that's classically in neurology teaching. But I agree - I've never really seen pure daily headache from onset, without any other accompaniments, to end up being giant cell arteritis. Then again, someone like that might walk in tomorrow, and the epidemiology of giant cell arteritis supports doing that in people over the age of fifty. But almost always, it's not the answer; I totally agree with you.

Dr Berkowitz: Good to compare notes on that one. Okay - so let's say you're considering this diagnosis. You've gotten your neuroimaging, you've gotten (if the patient is over fifty) your ESR and CRP, and you ruled out any dangerous secondary causes here. You have a nice discussion in your article about the primary headache differential diagnosis here. So, now we're sort of really getting into pure clinical reasoning, right, where we're looking at descriptions (colleagues like yourself and your colleagues have come up with these descriptions in the International Classification of Headache Disorders). Here again, we’re in a “biomarker-free zone,” right? We're really going on the history alone. What are some of the other primary headache disorders that would be management changing here, were you to make a diagnosis of a separate primary headache disorder, as compared to new daily persistent headache?

Dr Robbins: I think the two main disorders really are chronic migraine and chronic tension-type headache. Now, what we're taught about chronic migraine and chronic tension-type headache is that they are disorders that begin in their episodic counterparts (episodic migraine, episodic tension-type headache) and then they evolve, over time, to reach or culminate in this daily and continuous headache pattern, typically in the presence of risk factors for that epidemiologic shift we know to exist but that may happen on the individual level, which does include things that we can't modify, like increasing age, women more than men, some social determinants of health (like low socioeconomic status), a head injury (even if it didn't cause a concussion or clear TBI), a stressful life event, medication overuse, having comorbid psychiatric or pain disorders in addition to the headache problem, having sleep apnea that's untreated, and so on. New daily persistent headache - by definition, it should really be kind of “switched on.” Many years ago, Dr Bill Young and Dr. Jerry Swanson wrote an editorial where they labeled new daily persistent headache as the “switched-on headache.” Then, we're taught in headache pathophysiology that this chronification process happens over time because of, perhaps, markers of central sensitization that might clinically express itself as allodynia in trigeminal or extratrigeminal distributions. So, we're not comfortable with this new daily persistent headache, where we think the biology is like chronic migraine that gets switched on abruptly, but in so many patients, it seems to be so - it behaves like chronic migraine otherwise; the comorbidities might be the same; the treatments might still work similarly for both disorders in parallel. So, I think those are the two that we think about. Obviously, if there's unilateral headache, we might think of a trigeminal autonomic cephalalgia that's continuous, even if it doesn't have associated autonomic signs like ptosis or rhinorrhea (which is hemicrania continua) - and in those patients, we would think about a trial of indomethacin. But otherwise, I think chronic migraine and chronic tension-type headache are the two that phenotypically can look like new daily persistent headache. In patients with new daily persistent headache, about half have migraine-type features and about half have tension-type features. When I was a fellow, the International Headache Society and the classification only allowed for those who have more tension-type features to be diagnosed as new daily persistent headache. But we (and many other groups) have found that migraine-type features are very common in people who fulfill rigorously the criteria for new daily persistent headache otherwise. And then the latest iteration of the classification has allowed for us to apply that diagnosis to those with migraine features.

Dr Berkowitz: That's very helpful. So, we've ruled out secondary causes and now you're really trying to get into the nuances of the history to determine, did this truly have its abrupt onset or did it evolve from an episodic migraine or tension-type headache? But it could be described by the patient as migrainous, be described by the patient as having tension features The key characteristics (as you mentioned a few times) should be abrupt onset and a continuous nature. Let's say, now you (by history) zeroed in on this diagnosis of new daily persistent headache. You've ruled out potential secondary causes. You're pretty convinced, based on the history, that this is the appropriate primary headache designation. How do you treat these patients?

Dr Robbins: Well, that's a great question, Dr Berkowitz, because there's this notoriety to the syndrome that suggests that patients just don't respond to treatments at all. In clinical practice, I can't dispute that to a degree. I think, in general, people who have this syndrome seem to not respond as well, to those who have clear established primary headache disorders. Part of that might be the biology of the disorder; maybe the disorder is turned on by mechanisms that are different to migraine (even though it resembles chronic migraine) and therefore, the medications we know to work for migraine may not be as effective. In some, it could be other factors. There's just a resistance to appreciating that you have this headache disorder that - one day you were normal, the next day you're afflicted by headache that's continuous. And there's almost this nihilism that, “Nothing will work for me, because it's not fair - there's this injustice that I have this continuous headache problem.” And often people with new daily persistent headache may be resistant to, say, behavioral therapies that often are really helpful for migraine or tension-type headache because of this sort of difficult with adjustment to it. But at least there's observational studies that suggest that most of the treatments that work for migraine work for new daily persistent headache. There's been studies that show that people can respond to triptans. In my clinical experience, CGRP antagonists that work for the acute treatment of migraine may work. There is evidence that many of the traditional, older medicines (like tricyclic antidepressants, topiramate, valproate, beta-blockers, probably candesartan) and others that we use for migraine may work. There's observational studies specifically for new daily persistent headache that show that anti-CGRP therapies in the form of monoclonal antibodies and botulinum toxin can work for the disorder. Are there anything specific for some of the new daily persistent headache that might work? Not that we really know. There's been some attempts to say, “Well, if you get these people in the hospital early and try to reduce the risk of headache persistence by giving them DHE, or dexamethasone, or lidocaine, or ketamine, will you reduce the chances of headache persistence at that three-month mark or longer?” We don't really know (there's some people who believe that, though). Maybe there's good reason to do some type of elective hospitalization for aggressive treatment because we know that, notoriously, the treatment response is very mixed. There's been specific treatments that people have looked at. There's been some anecdotes about doxycycline as a broad anti-inflammatory type of treatment that might be used in a variety of neurological disorders, but there's really nothing in the peer-reviewed literature that suggests that is effective or safe, necessarily. And I think a lot of people in new daily persistent headache do develop a profile that resembles chronic migraine (they can develop medication overuse very easily). Often, goal setting is really important in the counseling of such patients. You really have to suggest that the goal for them might be difficult to have them pain-free at zero and cured, but we want this to be treated so the peaks of severity flatten out a bit, and then the baseline level of pain diminishes so that it devolves into a much more episodic disorder over time that looks like regular migraine or regular tension-type headache.

Dr Berkowitz: I see. So, in addition to starting a migraine-type prophylactic agent based on the patient's comorbidities and potential benefits of the medication (the same way we would choose a migraine prophylactic), do you do anything, typically, to try to, quote, “break the cycle” - a quick pulse of steroids as an outpatient or a triptan in the office - and see how they do, or do you typically start a prophylactic agent and go from there?

Dr Robbins: I think, like all things, it kind of depends on the distress of the patient and how they are functioning. If it's someone who's just out of work, cannot function - and someone like that might be very amenable to an elective hospitalization or some parenteral therapy, or maybe an earlier threshold to use a preventative treatment than we would be doing otherwise in someone with migraine overall - I think that it really depends on that type of a disability that's apparent early. I think it's compelling that, with new daily persistent headache, about a third of people report some antecedent infection that was around at the time. When new daily persistent headache was first described by this Canadian neurologist, Dr Vanast, in the 1980s, it was described in the context of Epstein-Barr virus infection, or at least a higher rate of serologies that are positive for, perhaps, recent Epstein-Barr exposure. And we know that Epstein-Barr is obviously implicated in lots of neurological diseases, like multiple sclerosis. And I mean, I think about these things all the time, and especially with COVID now. So, it's compelling - as a postinfectious disorder, do we, as neurologists (who are so comfortable with using pulse-dose steroids, IVIG) - do we use these things for a new daily persistent headache? But there's no great evidence that enduring inflammation in the dura that would spill into CSF analyses is really present in such patients. There was one study that looked at markers, such as TNF-alpha, in the CSF, but the rates of seeing that were the same in new daily persistent headache and chronic migraine, so there isn't really a specificity to that. Many people we see with new persistent headaches since 2020 may have it as part of a long COVID syndrome (or postacute COVID syndrome), and in those cases, often it's more like “new daily persistent headache-plus.” They might have something that resembles POTS (postural orthostatic tachycardia syndrome); they might have something that resembles fibromyalgia, chronic fatigue. Often in those patients, it takes management of the whole collection of neurological syndromes to get them better, not just the headache alone.

Dr Berkowitz: Well, this sounds like such a challenging condition to treat. How do you counsel patients when you've made this diagnosis - what to expect, what the goals are, what this condition is, and how you developed your certainty? It's often challenging (isn't it?) sometimes with patients with headache disorders, when we're not relying on an MRI or lab test to say, “This is the diagnosis”; telling them, it's just our opinion, based on their collection of symptoms and signs. So, how do you give the diagnosis and how do you counsel patients on what it means to them?

Dr Robbins: Yeah, it's a great question because it's high stakes, because people will read online, or on social media, or on support groups that this is a dreadful condition - that no one gets better, that they're going to be afflicted with this forever, and the doctors don't know what they're doing, and, “Just don't bother seeing them.” And the truth is not that; there's so many people who can get substantially better. I tell people that it's common; in some epidemiologic studies, one in one thousand people in any given year develop new daily persistent headache, and most of those people get better (they don't seek medical care eventually, or they do, just in the beginning, and then they don't have follow-up because they got all better) - and I think that really happens. I think the people who we see in, say, a headache clinic (or even in general neurology practice) are typically the ones who are the worst of the worst. But even amongst those, we see so many stories of people who get better. So, I really try to reset expectations - like we mentioned before about assessing for treatment response and understanding that improvement will not just mean one day it switches off like it switched on (which seems unfair), but that the spikes will flatten out of pain (first), that the baseline level of intensity will then improve (second); that we turn it into a more manageable day-to-day disorder that really will have less of an impact on someone's quality of life. Sometimes people embrace that and sometimes people have a hard time. But it does require, like many conditions in neurology, incremental care to get people better.

Dr Berkowitz: Fantastic. Well, Dr Robbins, thanks so much for taking the time to speak with us today. I've learned so much from your expertise in talking to you and getting to pick your brain about this and some broader concepts and challenges in headache medicine. And I encourage all our listeners to seek out your article on this condition that has even more clinical pearls on how to diagnose and treat patients with this disorder.

Dr Robbins: Thanks Dr. Berkowitz - great to be with you.

Dr Berkowitz: Again, for our listeners today, I've been interviewing Dr Matthew Robbins, whose article on new daily persistent headache appears in the most recent issue of Continuum, on headache. 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, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practice. Right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024 or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members: go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.

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 a professor of clinical neurology at the University of California, San Francisco

Dr. Schwedt is a professor of neurology at Mayo Clinic in Phoenix, Arizona.

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Read the article: Posttraumatic Headache

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Host: @AaronLBerkowitz

Guest: @schwedtt

Full Transcript Available

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 through some trial and error.

Dr Schwedt: Yeah, I guess. You can hardly even imagine how much I want to answer this question by saying, "Yes, with my experience, I've found that it's these two classes of medications that really work the best for folks with acute or persistent post-traumatic headache,” - but that would be disingenuous. It's so much like it is in migraine, where there is some trial and error, and, you know, again, as you say, it's so difficult to predict exactly which one is going to be the right pharmacologic agent for which patient. If access was no issue, I would go to medications that have the least side effects (which tend to be some of the newer medicines that we have for migraine), but we all know the realities of practice, and oftentimes, that's not a possibility due to access issues. Almost all of our patients that have significant postconcussion symptoms are also being managed by our neuropsychologists - and so, again, they're getting things like cognitive behavioral therapy and getting things like cognitive rehab, and they also are very helpful when it comes to workplace or school-place recommendations and accommodations. Many of our patients are being seen by our vestibular audiologists, as well, to work on their vestibular dysfunction, and vestibular rehab with physical therapy and occupational therapy. And so, you know, as you say, once you get out to multiple months, this is really a multidisciplinary, comprehensive type of treatment approach. 

Dr Berkowitz: Let's say the patient has now gone one to two years out from their initial injury and you had started them on a prophylactic agent (or found the one that works for them maybe after a few trials), and they're doing great (no headaches for several months; otherwise young, healthy person), and they ask you, “Well, do you think I can just go ahead and try coming off these medications now? My injury is a long time ago. While those first few months were awful - thank you for helping me to get these headaches under control - do you think if I go off this medicine, that my headaches will come back, or am I sort of in the clear now?” How do you think about tapering patients off of preventive medications when they've had a good response at a year or so out?

Dr Schwedt: That's so important, right? I mean, I think we all see patients that we inherit that end up kind of being left on medications that perhaps aren't even needed anymore, and it's certainly a mistake we wouldn't want to make. Post-traumatic headache - unlike primary headaches like migraine that tend to be present for decades - they can go away; they can resolve, and they usually do. I mean, we can't lose sight of that, right? Usually, it's going to go away on its own (as I mentioned, you know, within the first few days or weeks), and even after it's become persistent, if you can get a good treatment response, then, absolutely, after several months of that good treatment response, we should be tapering people off. Just like with any headache patient who's on a preventive, I would recommend tapering off of the effective treatment slowly, so if that's a medication, I'm usually very slowly just reducing the dose over several weeks or months (depends on how long they've been on it), usually not because I'm concerned about side effects of withdrawing the medication, but you're just testing it to make sure that the headaches aren't starting to creep back as you reduce the dose of that medication. So, it's a test, and if headaches do start to come back as you're lowering the dose, well, then, presumably you can more quickly get control of it again by elevating the dose back to where it was previously effective. For medications and treatments that don't really have dosing, the other way of doing it - so, you know, some of our medicines, of course, are given at one dose but given at intervals (like, let's say, each month or every three months) where you can't really reduce the dose - you can increase the interval between treatments. So, if you're supposed to have a treatment every month, well, if someone's doing really well, then maybe you say, “You know what? Give it an extra week.” Maybe do it in five weeks instead of four or six weeks. In that same way, you're kind of testing whether or not the medication is still really needed.

Dr Berkowitz: Yeah, that makes sense as an approach here. In addition to your clinical expertise, Dr Schwedt, you're also a researcher in this area. Tell us, what's on the horizon for the future of diagnosis and treatment of patients with post-traumatic headache? 

Dr Schwedt: There's a lot of exciting things on the horizon. It's really encouraging that despite, for example, the lack of evidence currently that we have for treatment, and perhaps not as much preclinical and clinical research into post-traumatic headache as we need, the exciting part is that there's a lot going on. Fortunately, the funding environment for such research has been decent over the past so many years, and so, again, there's almost certainly going to be meaningful breakthroughs here in the near future. Some of our own work - for example, we do a lot of neuroimaging research of post-traumatic headache. One of the main areas of controversy in the headache field is whether or not post-traumatic headache and migraine are really the same thing or are they truly distinct headache disorders? And so, like, a lot of our work has gone towards addressing that - both through neuroimaging, as well as just examining outcomes and symptoms and whatnot - to see where there are similarities and differences. And I'm absolutely biased when it comes to addressing this, but I feel strongly that they really are distinct headache disorders. And that's important, because that means that we need to continue to study them as distinct disorders and we can't just fall back to the idea of saying, “Well, PTH of a migraine phenotype is migraine, and we already have migraine therapy, so let's just use those,” because I think all of us that see patients with PTH in clinical practice realize that our migraine treatments don't work as well for PTH as they do for migraine. So, we really need to continue down the path of understanding the mechanisms underlying PTH, the mechanisms of what makes PTH persist (you know, why it persists in some people and not others), and then what we can do to intervene. I think a major topic, I believe, in determining best treatment approaches is also kind of related to the way you were asking me these questions - it's related to the timing of the intervention. Much of what's been done in studying treatment of PTH is done after it's already persistent, and so in some of these studies, including ours (I mean, it's not a criticism; including ours) - sometimes, these people have had post-traumatic headache for five years or ten years at the time that you enroll them into a study. And, you know, at that point, that's probably a very different population as far as mechanisms and who might respond to which treatments (compared to if you were studying those folks, let's say, in the first few weeks or in the first couple months). There's preclinical evidence (from rodent models of mild traumatic brain injury and post-traumatic headache) that the earlier you intervene, the more effective that intervention is going to be in treating that headache and preventing its persistence, and I would think we could logically presume that's probably the case in people as well. But, of course, we don't want to expose everybody early on to treatments if they don't need it (I mean, if they're going to have natural resolution, then that would actually be inappropriate [to expose them to treatments]). And that's where the prediction comes in. If we had good predictive models of - oh, you know, even though they're only a week into their headache, based on their pre-TBI factors and other characteristics, that they're very likely to have persistence - well, maybe that's the patient where they should have an earlier intervention, and, you know, in another patient, maybe not. 

Dr Berkowitz: It's great to hear about your work and the work of others to help us understand this very, very common condition (and that’s been a theme in many of our questions), one in which we do our best, but are often limited by, our scientific understanding and the data on how to best manage these patients’ headaches. I've learned a lot from our discussion - both clinically, and I’m excited to have learned more about your work and what's on the horizon to help us take care of these patients. Thank you very much, Dr Schwedt, for joining me on Continuum Audio today. Again, for our listeners, I've been interviewing Dr Todd Schwedt, whose article on posttraumatic headache appears in the most recent issue of Continuum on headache. Be sure to check out other Continuum Audio podcasts from this and other issues. Thank you so much to our listeners for joining today. 

Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practice. And right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024, or use the link in the episode notes, to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members: go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.

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.

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Host: @gordonsmithMD

Full Transcript Available

Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the Show Notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the Show Notes. AAN members: stay tuned after the episode to hear how you can get CME for listening.

Dr Smith: This is Dr Gordon Smith. Today, I'm interviewing Dr. Mark Burish on cluster headache, which is part of the April 2024 Continuum issue on headache. Dr Burish is an Associate Professor of Neurology at the University of Texas Health Science Center at Houston, which is located in Houston, Texas. Mark, thanks so much for joining me today on Continuum Audio. I was really excited to be asked to talk with you about this article. When I recertified from my boards the last time (and actually, it will be the last time I have to take the exam), I did the AAN course on all of neurology. And I'm a neuromuscular guy, right, and so I was actually kind of worried about the headache part because I thought, “How interesting could that be?” And I was blown away at how fascinating headache has become, and in particular, your topic (cluster, SUNCT, SUNA, the trigeminal autonomic cephalalgias) - such a great topic. But before we start talking about them, I'd love to just hear more about how you got interested in this area - both headache, this topic in particular. What's your story, Mark?

Dr Burish: Well, thank you very much for having me. I’m honored to be part of this. I got into headache probably the way many people do; is, in residency, you figure out what you like, and your residency clinic tends to start collecting patients that you like (not that you're trading them with other residents, but you see certain patients). And mine (by the end of residency) had a lot of headache and pain patients into it. Then, I was very fortunate and had the opportunity to do some research as part of my career. I'm an MD-PhD, and I spend about half my time now doing research on cluster headaches, so I'm very fascinated by these types of diseases.

Dr Smith: Can you tell us really briefly what you're working on in your research?

Dr Burish: Cluster headache is such a poorly researched area. There's not a lot of people in it, so we do a little bit of everything: we have a clinical trial going; we do some basic science on the circadian mechanisms (cluster gets this very weird timing to it, where the headaches happen same time every day); and we do a little bit of starting to wade into the genetics.

Dr Smith: Well, super exciting. I was actually blown away by the statistics on cluster (as common as multiple sclerosis), and the severity of pain I was amazed to learn is above that of childbirth (it was, like, between nine and ten out of ten, which is really crazy). And I'm worried that I missed these patients in my neuromuscular clinic. So, maybe we can begin by - just tell us what you think our listeners need to know. If they have to drop off right now, what message do they need to remember from our conversation?

Dr Burish: I think there's two things. First of all, the first-line treatments for these headaches have not changed recently. For cluster headache, you still treat it with oxygen, the triptans (the faster triptans; not the oral ones, but the injectables and nasals), and you prevent them with verapamil. For SUNCT and SUNA, you use lamotrigine. So, those have not changed over time. There are some new treatments, which we'll talk about later. Then the second point is, there are four different types of headaches in this family and they all look very, very similar (one-sided pain, autonomic features, ipsilateral lacrimation, rhinorrhea - that type of thing). They differ in the treatments and how long they last. If you get them wrong (if you misdiagnose them), you're probably not going to give them correct treatment. Indomethacin works very well for two of them (the ones with hemicrania in the name, so not the ones we're going to discuss today). And then SUNCT, SUNA, and cluster headache - indomethacin does not work very well. So, it's important to distinguish them and get them right.

Dr Smith: Maybe we can start there, Mark. I mean, I was kind of appalled to learn that the average delay in diagnosis is four to nine years in your article, and given the severity of pain and the impact it has on these patients, that's clearly a challenge. What's so hard about this? And do you have pearls on how we can recognize these patients? And how do you sort this out practically in clinic?

Dr Burish: For cluster headache patients especially, it is a lot more common than we would think it is, but it still goes misdiagnosed, partly because most cluster headache patients are episodic. So, there's an episodic version where you get them every day for a few weeks and then they might go away for a year. So, I think what happens is that patients start to get into a cycle and they either get confused for sinusitis (because it happens in the spring), or they schedule a visit with a neurologist or somebody else, but the headaches are over by the time they see them, and they cancel the visit. So, I think they get misdiagnosed partly because it's either confused or they don't see doctors fast enough. I think a little bit more awareness of what this disease is and then, somehow, a mechanism to get these patients in a little bit more urgently is probably what's necessary.

Dr Smith: Well, Mark, access is a real issue in neurology more broadly, and I'd love to talk to you about that in a moment, but I wonder if we could go back. You talked about how similar these are to one another, yet the treatments are different. How do you sort out the diagnosis when you're seeing a patient? Let's say you have someone who comes in who has episodic, unilateral, very severe pain and some of these autonomic features. What are the pearls for differentiating cluster, SUNCT, and SUNA from each other?

Dr Burish: The big difference between all these different headaches is the timing. As a general rule, SUNCT and SUNA attacks last seconds (they're very similar to trigeminal neuralgia); paroxysmal hemicrania (that's one of the hemicrania ones, where indomethacin helps) - those attacks last minutes; cluster headache attacks last about an hour; and the hemicrania continua is constant (that's the other hemicrania one where indomethacin works). The other part is how often they happen. Again, SUNCT and SUNA - very similar to trigeminal neuralgia, may happen hundreds of times a day; paroxysmal hemicrania - dozens of times a day; cluster headache - maybe a handful of times; and then, hemicrania is constant. Based on how long the attacks are and how frequent the attacks are, you can generally separate them out. And if you're not sure, just try indomethacin. And then if it doesn't work, you're trying to distinguish between SUNCT and SUNA, which lasts seconds, and cluster headache, which lasts an hour, so fairly easy to distinguish those.

Dr Smith: How long does it take to medicine to work in a patient with hemicrania continua or paroxysmal hemicrania? I’ll remind our listeners - there's a separate article in the same issue of Continuum on that topic - but for our purposes, let's say you try that; how long do you need to try it?

Dr Burish: Yeah, there's a great, another article about how much to give and how it works. It is generally pretty quick. I have noticed with most patients that the onset is twenty-four to forty-eight hours. And then, if you stop the medicine, the same thing - offset is kind of twenty-four to forty-eight hours. So, patients know pretty quick whether it's going to work.

Dr Smith: Wow - that's awesome. One of the things I was interested in was so-called “secondary cluster.” So, you've seen your patient and let's say you've diagnosed them with cluster (primary cluster). Do you do additional testing? Do they need imaging or other laboratory workup?

Dr Burish: Yeah. The differential for cluster (and cluster is the one that we know the most about; it is the most common of all the trigeminal autonomic cephalalgias) - it's a fascinating differential. If you don't know much about them, migraine is probably the most common. If you do know a lot about them, hemicrania continua and paroxysmal hemicrania are very common. But there's all these secondary headaches that can look identical to cluster headache; these pituitary hormone-secreting tumors (prolactinomas) - things like that. So, because all these other secondary causes can happen, they generally recommend everybody gets an MRI of the brain, with or without contrast. If that is normal and the patients continue to not respond to the medicines like you expect them to (verapamil doesn't work, oxygen doesn't work, and so forth), then you might do some additional testing for pituitary bloodwork. So, just kind of a panel of hormones, looking at blood vessels (because there are some cases that dissections or AVMs can cause cluster headaches). And then sometimes get imaging of the apex of the lung because there's some data that - with the Horner syndrome - that that might be relevant.

Dr Smith: I'll refer our listeners to your article, just in general, because they really need to read it. It's fantastic. But your discussion about the neuroanatomy is really cool, and probably more than we want to get into right now, but the intersection of the neuroanatomy with therapeutics, and some of these other potential etiologies. So, one thing I was really amazed by (or appalled by, frankly) was the frequency with which these patients have suicidal ideation, given the severity of the pain and, I assume, the long time it often takes to get this sorted out. How do you handle that in clinic? Do you have conversations with people about this? How often do you appreciate it? And any words of wisdom for those of us who might encounter these patients?

Dr Burish: Yeah. It's not hard to imagine why patients would be suicidal with this. When you have pain that is a ten out of ten - and patients who have also had childbirth and cluster, they consider childbirth more around a seven - so you can imagine how painful this is and what thoughts might be going through people's heads. It tends to be (in my personal experience and some emerging data) that they are suicidal during a cycle. So, for these episodic patients (most patients are episodic with cluster headache for a few weeks), they are suicidal during those weeks. And when the headaches go away, much less risk of suicide. So, during the cycle, I try to get my patients in as fast as possible, get the medications in as fast as possible, but basically just be there to let them know that we have options, and so that they consider me as their first option, rather than something darker.

Dr Smith: How successful is first-line therapy in these patients and what's your success rate with your initial attempt at treatment?

Dr Burish: On the acute side, the as-needed medicines (sumatriptan, oxygen) - if you give an injection (not the oral; that takes too long) - incredibly effective; for most patients, one or both of those will work. We usually prescribe both because the injections - usually you can't get that many (they can be quite expensive, realistically speaking). But also, just practically speaking, patients can have headaches up to eight times a day and you're not really supposed to be taking sumatriptan eight times a day, so we also give oxygen (but then again, oxygen is not very portable, so that's where the sumatriptan comes in). On the preventive side - not great. There's been some studies suggest maybe fifty percent is as good as any preventive is going to work for you, and that's not considering side effects and other things that patients might stop them. So, we do need to have a few different preventive options and you may have to go through a few different things. Chronic cluster headache (which is the more rare version, where patients have them year-round) is anecdotally much more refractory to treatment.

Dr Smith: Can you talk a little bit about bridge therapy? You differentiate bridge from prophylactic therapy in your article.

Dr Burish: Yeah. When you're approaching one of these patients - let's say they're completely naive to any medications - usually we will give them a couple of as-needed, acute medications (sumatriptan injections and oxygen). We’ll give them a preventive like verapamil, but the verapamil takes a few weeks to kick in. So, the obvious question is, “What am I supposed to do in the meantime, while you're ramping it up and it's kicking in?” So, we use these short-term preventives, which we call bridge therapies or transitional therapies. These are short-acting preventives; they kick in quick, but you can't take them for very long. The most common by far is prednisone. Or an occipital nerve block with some sort of steroid (so, steroids in some sort of fashion). We will usually give them right at the beginning of a cycle (right at the beginning of a flare for chronic cluster headache patients) while we are uptitrating something like verapamil.

Dr Smith: This may be a really silly question, but the next time I see one of these folks and I want to start oxygen, how do I do it? What are the logistics of giving someone oxygen for this, and how do patients navigate that, right? If you're having eight attacks a day during a cluster and you work as a nurse in the headache clinic, you probably have oxygen there. But you get where I'm going, right? - it's logistically challenging. How do you order it, and do you have words of wisdom to make it easier for patients to use?

Dr Burish: There's a whole kind of system of oxygen, durable medical equipment - stuff that I've had to learn. To boil it down, there are basically two types of oxygen. There's a concentrator - kind of just a machine that takes room air and turns it into about ten percent oxygen - that is sometimes effective for patients. But sometimes ten liters per minute (which is the highest that can give) is not enough and you need fifteen liters per minute. In that case, you need an oxygen tank (the big metal cylinders that you see with a extra device on top called a regulator, that can crank it up to fifteen liters a minute. For both of these - fifteen liters a minute - you're going to need a mask. The nasal canula is just - it doesn't get up to fifteen; it's not going to be enough, so we give you this bag mask (the non-rebreather mask, or the bag hanging out below it). You really need high dose, pure oxygen for these things to work, so you have to write orders that say, “fifteen liters a minute, with regulator and non-rebreather mask.”

Dr Smith: I'll refer our listeners to your Continuum article. I know a lot of our listeners use Continuum at point of care. And, of course, you can access it electronically, so there's really great pearls there. Another question for you: CGRP agents have really transformed migraine; what role do they play, if any, in management of these headaches (cluster, SUNCT, and SUNA)?

Dr Burish: I think this is a fascinating emerging area of cluster headache research. One of the studies in the last three years came out that it was successful for episodic cluster headache, called galcanezumab, and it did not work for chronic cluster headache. Meanwhile, a couple other CGRP companies have tried them and they were unsuccessful, at least according to the data on ClinicalTrials.gov. And some other CGRP studies are still emerging. We know that both migraine and cluster headache work on the trigeminal system (I mean, this is a trigeminal autonomic cephalalgia - it's in the name) and CGRP is involved in the trigeminal system. That's probably where the commonality between migraine and cluster headache come from - they both work on the same pain system. But why all of them seem to work for migraine and only some of them – you know, some of these medicines work for cluster headache - is a fascinating thing. Does that mean that we don't have the dose right? Does that mean that we don't have the timing of these clinical trials right? Does that mean it's just not as effective? And there's other things that are involved in cluster headache - it's an interesting mechanism that we can start to explore.

Dr Smith: I wanted to learn more about the circadian aspects of this - I found that really interesting, and you commented that you're interested in that in a research perspective. Can you describe that phenomena a little bit and just tell us what your thoughts are?

Dr Burish: The interesting thing about cluster headaches, specifically, is that the headaches happen, for most patients, the exact same time every day – so, within an hour each day. So, my patient usually will say, “They're at two AM.” Across different time zones, every study that’s been done - well, not every study, but many studies have been done - two AM is the most common time of day. But if you ask an individual patient, patient number one will say, “They happen every day at two AM; patient number two will say, “They happen every day at three in the afternoon.” I had a patient who was, I think, kind of getting fed up with all the questions I was asking about his headaches, and he said, “Dr Burish, it's three o’clock; if you want to wait until three fifteen, I'm going to get a headache - you can see what it's like.” That's how sure he was about when the headaches were going to happen. And other than maybe hypnic headache, there are a few other headaches that have that level of circadian predictability. So, it's just an odd, curious, unique thing to these headaches and we don't quite understand why yet.

Dr Smith: So, I'm curious if the time of day patients get their headaches is in any way correlated with other aspects of sleep phenotype, right? There's broad variability in your sleep phase - the length of it, when it starts and ends. Is there any relationship, in your experience, between the time of day (two AM, ten PM) and other aspects of their sleep?

Dr Burish: We haven't seen that, to my knowledge. People have looked, for example, at sleep studies while patients are having attacks. These attacks occur out of REM sleep, non-REM sleep - it doesn't seem to matter. Anecdotally, patients will say, “My cycle last year - I had headaches every day at two AM. But my cycle this year - I have headaches every day at five in the afternoon.” So, even a same patient who, theoretically, is not having big sleep changes over different years, has different timing of attacks.

Dr Smith: Mark, what's the latest thing? What's most exciting in the field that you can tell our listeners about?

Dr Burish: There are a lot of new treatments for cluster headache. There's the galcanezumab, which we discussed a little bit. There is a new dose for prednisone. We weren't sure how effective it was; now we're using kind of neuroimmunology-level doses of prednisone (100 milligrams daily; kind of titrating down from there). And then there's an occipital nerve stimulator for the chronic cluster headache patients. Since the last Continuum review on this topic, these three trials have been successful, and I think what gets lost is how impressive each one of these is in different ways. The prednisone study is impressive because you had to study that medicine (which we thought worked but didn't have a good clinical trial), and it's really hard to enroll patients in a placebo-controlled study where you already think it works. Another was done by a large pharmaceutical company. This is not an advertisement for or against, but these companies have rarely ventured into studying cluster headache until recently. The third study, the stimulator study, was a ten-year, multisite study involving surgeons and neurologists - just a monumental effort. It's because of these impressive studies that we now have data on how to treat the patient.

Dr Smith: Just so interesting. I tell you what - I mean, if you told me twenty years ago I would be this interested in headache, I would have said, “You're crazy.” But now I see why our residents are so interested in it and why you are. This is fascinating. I could keep going for another hour or two asking you questions, Mark, but maybe we can pivot back to where we began. You told us your story about enriching your resident clinic - and for those residents listening, those are words of wisdom right there, my friend. But here's my question for you: we've already talked about access to care and how you manage access for these patients, but we have a huge access issue in neurology broadly and we desperately need more neurologists. As you're probably aware, there are some of our colleagues that don't think pain is neurology (I'm not one of them, but I know some of them and respect them otherwise). If there's an access issue for neurology, there's a access crisis for pain neurologists. And you don't just see headache, as I understand it; you see other patients with pain. So, I want to give you the last few minutes of our Continuum Audio episode to do your pitch, right? What do you have to say to the residents that are listening to us (or students) about why you find managing pain so rewarding and why they should consider this as a field?

Dr Burish: Yes - I also did a fellowship in pain medicine, in addition to my headache research, so I see a little bit of both. For me, the patients are very appreciative because you are talking with them about what they are interested in. They are not interested in the change in the MRI between last time - I mean, they are interested in it, but not as much as, “I hurt today.” So, patients are more than happy - they're very grateful that you are addressing their primary concern, the thing that they're going home with that day that they're worried about. For me, seeing these patients has been very rewarding. From the research side. I think it's fascinating that there's just not enough research in this area - you can create your own niche; you can look into your own mechanisms - there's just not a lot of people in this field. And then, I think from a clinical side, other than the rewarding nature of it, there's a lot of options that we have. There's all of these neuropathic medications; there's all these different headache medications. If you want to wade into the procedural side of things (which I did with pain management), you can get into fluoro-guided procedures and spinal cord stimulators and all these different options that we have for these patients that help them, in addition to whatever they're going through. I have patients that then come back and say, “Well, by the way, I have these seizures; do you mind helping me kind of just go through my antiepileptics.” And they're generally well controlled and they consider me kind of a general neurologist for them. So, I’ve found it extremely rewarding and I wouldn't do anything different.

Dr Smith: Well, that's really great information and I hope our resident listeners will take that to heart. Your article is truly amazing, Mark. I can't tell you how much I was impressed with it, and for our listeners - you gotta check it out. I've got a list of ten other things on my piece of paper here I could ask Mark about, but I think we're probably at time. So, Mark, thank you so much. Congratulations on an amazing article and really fascinating and exciting area of neurology.

Dr Burish: Thank you. Thank you very much for having me.

Dr Smith: Again, today we've been interviewing Dr Mark Burish whose article on cluster headache - appears in the most recent issue of Continuum, which is on headache. Be sure to check out Continuum audio podcasts from this and other issues, and thank you very much to our listeners for joining us today.

Dr. Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practice. Right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024 or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members: go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.

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: Acute Treatment of Migraine

Subscribe to Continuum: continpub.com/Spring2024

Earn CME (available only to AAN members): continpub.com/AudioCME

Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud

More about the American Academy of Neurology: aan.com

Social Media

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@ContinuumAAN

Host: @headacheMD

Guest: @RebeccaCBurch

Full Transcript Available

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 was not the case when I wrote the final draft of this article. So, new formulations of medications are coming out and that's just really exciting. I think different patients prefer different things, and so I kind of like having different options to give them. I'm really interested in a couple of different things. There's been a lot of research coming out recently about the migraine prodrome - this sensation or symptom constellation that some patients get before what we think of as the more typical migraine – so, before the pain, maybe even before the more typical sensory hypersensitivity. Some patients know that an attack is coming, and there has been some research very recently coming out showing that, with gepants, taking the gepant before the attack actually happens in the prodromal phase can stave off an attack. I think that's cutting edge. I haven't really started talking to patients about it, but I'm interested to see what happens when that research is fully published and we kind of start test driving it. I'm also interested in the way that gepants don't seem to cause medication overuse headache in the same way that triptans or frequent use of NSAIDs do. I'm kind of thinking that the line between acute treatment and preventive treatment may start to get blurred a little bit with gepants.

Dr Monteith: It's already blurred.

Dr Burch: It's already blurred! It’s pretty blurred, right?

Dr Monteith: I agree. And it'd be cool to see an update on this article. It might need to be just a whole - imagine a whole kind of issue on its own, on just acute treatments.

Dr Burch: Yes, for sure.

Dr Monteith: Great. Thank you so much for being here.

Dr Burch: Thanks. It's always a pleasure to talk to you, and I'm really excited for this article to make it out into the wild in the real world and for people to get a chance to take a look at it.

Dr Monteith: Yeah, I know our listeners are going to love this article - they're going to get a lot out of it. And most importantly, their patients are going to get a lot out of it.

Dr Burch: That's my goal.

Dr Monteith: Again, today we've been interviewing Dr Rebecca Burch, whose article on acute treatment of migraine appears in the most recent issue of Continuum, on headache. Be sure to check out Continuum audio podcasts from this and other issues. And thank you to our listeners for joining me today.

Dr. Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practice. Right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024, or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members: go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.