Diagnostic Considerations for New Daily Persistent Headaches and Evaluating Giant Cell Arthritis in Older Patients

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

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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.