Guest: Henrik Winther Schytz, MD, DMSc, PhD

View the recording from our Migraine Clinician Masterclass, developed in partnership with IVPN Neuropsychiatry. In this webinar, we hear from Dr. Henrik Winther Schytz, who talks about the diagnosis and management of post-traumatic headache. Please note that this video is intended for healthcare providers.

 

TRANSCRIPT

Henrik Winther Schytz, MD, DMSc, PhD: Thank you so much for inviting me. It’s really an honor to be part of this Migraine Masterclass, so thank you to IVPN and Association of Migraine Disorders for inviting me to give this talk about diagnosis and management of post-traumatic headache. I think this is a very important secondary headache that many suffer from, and it’s a difficult secondary headache to treat. It’s also an interesting secondary headache disorder because there is some overlap to migraine, which I’ll come back to in my presentation. 

So I’ll start out here with my disclosures. 

 

And first I’ll set out by showing that this is a huge problem. We see that 69 million per year actually suffer from a traumatic brain injury, so that’s actually 1% of the world’s population. And in most cases it’s a mild traumatic brain injury. If you look into the literature, we see that about one out of three of those who report acute post-traumatic headache after a trauma, they later develop persistent post-traumatic headache, so that is a staggering number. 

We of course have to be aware that the data that show these high percentages of people with persistent post-traumatic headache, that is data coming from studies where they investigate patients who are seen at emergency departments. So we don’t actually know what happens to those who hit their head and then maybe after two or three days go see their general practitioner. But probably there’s still a significant number who do not come to the emergency department who also develop persistent post-traumatic headache.

 

I work at the Danish Headache Center, in Glostrup outside of Copenhagen, in Denmark, and it’s a tertiary headache center, and we do have quite a large number of our patients, about 10 to 11% of our patients have persistent post-traumatic headache, so we have some experience in treating them. But the experience is that this is very difficult and we need new treatments for these patients. 

If you look at the large studies around the world, this is from the CENTER-TBI, but it could also be the TRACK-TBI from the US, you can see that after three months there is a quite large number of patients, here it’s about 30%, who have a headache and also of course other symptoms that you can have when you have a head trauma and have concussion. 

And what we see in so many studies across the world is that if you have symptoms after three months, then it usually continues. So it seems as if the first three months are very crucial to the prognosis of the patient. So it is probably something that we have to zoom in on, try to treat those who continue to have symptoms after maybe one month, because that’s probably those where we can really change the prognosis. So after three months it seems as if patients persist on having headache and other symptoms.

 

In this talk, I’ll talk about the diagnosis, and I’ll talk about the International Classification of Headache Disorders. I’ll talk about the presentation, what are the symptoms that these patients have and I’ll talk about treatment. And then if we have time I’ll also talk about some of the research projects that have been done at the Danish Headache Center, which is I think interesting in light of what you can call similarities between migraine pathophysiology and post-traumatic headache. 

So when I diagnose patients with a headache, I always follow the International Classification of Headache Disorders. You can go into the webpage, it’s open for everyone. Headache is not actually called post-traumatic headache, it’s called headache attributed to trauma or injury to the head, but we usually call it post-traumatic headache. And you can see that it is divided up into acute headache after a trauma and persistent headache. It starts out with an acute headache and then if you have it for more than three months, you call it persistent headache. 

It’s also further subdivided up into headache attributed to mild traumatic injury to the head and headache attributed to moderate or severe traumatic injury to the head. What we know most about and what we have experience with is those who have persistent headache attributed to mild traumatic injury to the head. So these are the typical patients that we see at the Headache Center. 

 

So if you look into acute headache attributed to mild traumatic injury, you can see the diagnostic criteria for that. So we have that it should be injury to the head fulfilling both of the following. And one, that’s actually a lot of things that you should not have been experienced. So you should not have mild traumatic injury to the head if you have been unconscious for more than 30 minutes, if your GCS score has been less than 13, if you have amnesia for more than 24 hours and so on because that will then entitle you to be defined as someone who had a moderate or severe traumatic head injury. 

Then you have to have at least one symptom or sign that could be transient confusion, disorientation, it can be loss of memory, but not for more than 24 hours. And then two or more of the following symptoms suggested of mild traumatic brain injury that could be nausea, vomiting, visual disturbances, dizziness, and/or vertigo. So when you look at these symptoms, if you look under number two, you can actually see that it can be actually difficult to diagnose patients because you might see them after a year after they’ve had their head trauma. And if you ask them, did you experience nausea, visual disturbances, and so on, they can of course be recalled by us.

But this is how we define it at the moment. This is probably something that we have to look more into and do more research on to try to get good criteria about mild traumatic injury to the head that leads to headache. But this is how it is.

 

It’s also very important, which is described in the criteria, that to have the diagnosis, headache should develop within the first seven days after the injury. Of course, if you have been comatose or if you had been put on sedatives and so on, right after the trauma, then you can say that it’s after that has been discontinued. But this is an important parameter, these seven days. And it’s something that has been debated. It has previously been two months, but now it is seven days within the last International Classification of Headache Disorders, version three. 

And it has been shown in the notes that this is a somewhat arbitrary time limit. And there are some who argue that you may develop a headache at a longer interval after the head injury. And they encourage researchers to do more research into this criteria. 

There are some studies who have done it. There is a study by McGeary and colleagues that was published in Cephalalgia, in 2020. That’s a retrospective study, and it’s with the US military veterans. And they found that about one out of three reported headache with an onset between eight and three months after the headache injury. 

But I think we also have to be mindful that this is a retrospective study. And this was patients who were enrolled, where they had an onset of more than one year prior to being enrolled in the study. So there might be some recall bias. This is also US military veterans. So it might not be something that can be applied to others necessarily. 

 

Then there’s a study coming out from Toronto with 300 adults who came to emergency departments. And they were actually enrolled within one week after having a head injury. And they found a different result. They found that 92% experienced headache. And that 94 of those experienced headache, they had a headache onset within 48 hours. So that’s actually encouraging in terms of the current criteria that it seems reasonable, because based on this study, most people develop headache within 48 hours. They had 6% who had headache from 48 hours to 7 days.

Of course, there are a few where we don’t know, because the study didn’t do a follow up. So we don’t know if those who did not report headache within the first seven days, if they might have developed headache later on. But based on this study, the majority develops headache within seven days.

When I look into the notes into the international classification, there is a description of the problem that you might have someone who has migraine, and who then have a head trauma. And how should you diagnose them? And you should diagnose both if the preexisting primary headache is made significantly worse, that means a twofold or greater increase in frequency and/or severity within seven days after the head trauma. And I think that that makes sense.

 

But what I have encountered in the clinic at the headache center is what if the opposite happens? Because you can have a patient, maybe a young woman 16 years old, who then after a year or so, develops a worsening of the headache, where it’s not due to medication overuse headache, it’s not due to a new head trauma. And this might be a patient where the mother and father suffer from migraine. And you could speculate, if this young woman, 16 years old, had never experienced a head trauma, could she maybe have developed migraine spontaneously because of the family disposition or just because migraine is a very frequent this disorder?

So I actually think in the new upcoming classification, we should be mindful of this dilemma. Because if you just diagnose somebody with post-traumatic headache and not give an additional migraine diagnosis that could have, at least in Denmark where I work, clinical implications, because in Denmark, it’s limited on what kind of pharmaceuticals we can offer to patients where they only have the diagnosis of post-traumatic headache. So I would suggest that you should also have the note in the classification that when a preexisting secondary headache is made significantly worse without a known cause, both a secondary and primary headache diagnosis should be considered given. 

This is just my, my own opinion. But I think this is important. And this is actually what I do now, when I see patients and I have actually experienced patients who did not respond to migraine preventives when they had post-traumatic headache. And then they later on came to me and said they had a worsening which they could not explain. And then the new headache they developed, that responded to migraine preventives. 

 

So let’s talk about the presentations, the symptoms that these patients have. Well, they have a lot of symptoms. It’s not just a headache when you have post-traumatic headache. Usually they also have symptoms of concussion. Most of them have headache, that’s the most frequent symptoms. But you can see that six out of ten have memory difficulties and concentration difficulties.

They can have a plethora of different symptoms. And I think that’s important to address. And if you actually ask them about this range of symptoms, usually you see a patient nodding his or her head, and they actually feel that they are acknowledged for the symptoms that they have, they have so many symptoms.

I usually try to sort them into cognitive symptoms, that could be concentration difficulties, mental fatigue, meaning that if they read a book for half an hour, it feels as if they’ve been reading a book for 12 hours, so they get fatigued, disproportionate to what the mental work they’re doing. They can have physical symptoms where they can have headache, nausea, light and sound sensitivity. But it’s also important to acknowledge they can have emotional symptoms. Some feel very irritable. They can have anxiety or depression symptoms. There might also be some who have PTSD-like symptoms, even after a minor head trauma.

And of course, it can vary a bit from patient to patient. And if you have cognitive symptoms, that can be a huge challenge because that can make it difficult for you to function in your work. And of course, it can also be a load for the family and the patient itself if they have anxiety and depression symptoms and they feel difficult in functioning in their social life.

 

When it comes to the post-traumatic headache phenotype, it’s of course interesting to look into some of the physical symptoms, and that is the headache and whether they have nausea and whether they are light and sound sensitive. And based on these symptoms, you can try to divide them up into those who have a migraine-like headache. It is still a post-traumatic headache, but you can divide it up into migraine-like headache and tension-type-like headache.

Of course, this can be a bit challenging because there might be some patients who have nausea every day and who are light and sound sensitive. What I do is that I ask them, well, if you have an activation of your headache, usually they have headache every day, but if you have an activation of your headache, do you then also have an activation of your nausea and light and sound sensitivity? And that’s my method of trying to divide them into these two phenotype groups. You will on rare occasion also see some who might have a post-traumatic cluster-like headache phenotype, but that’s rare.

We have looked at our patients that we had at the Headache Center, so we tried to phenotype 100 patients we had, where we interviewed them in detail. And we found out, and these were patients who’ve had headache for, on average, about four years after a head trauma. So six out of ten had a chronic migraine-like headache phenotype. The headache frequency was high. On average, it was 25 out of 30 days. And actually, most of them had it 30 out of 30 days, but there were also some who had it less frequent.

And 90% of the patients reported that most headaches were moderate or severe intensity. So that just shows us that these are so affected by the headache. It’s really a difficult headache that they struggle with every day, and it’s usually something that is life-changing for them after the head trauma in a very negative way.

We also tried to test this, whether we could actually, if we could really trust the information that they gave us. So we also gave them a one-month diary where they could fill out all the headache symptoms that would define you as having a migraine-like headache or tension-type-like headache. And we can see that it was the same.

 

So you can actually trust them when you go in and interview them. So 73, based on a one-month diary, had a chronic migraine-like headache. So actually, they might underestimate a bit whether they have a migraine-like phenotype or not. We did find that about 13% had a pure chronic tension-type-like headache, and then 13% who had a combined episodic and chronic tension-type-like headache. So that meant that they had less than 8 migraine days based on this one-month diary, because if they had 8 or more, it would be a chronic migraine-like phenotype. 

We also looked into some patient-reported outcome, the Pittsburgh Sleep Questionnaire Index, and we could see that the majority had a really poor sleep quality. We gave them the Hospital Anxiety and Depression Scale questionnaire, and we found that they seemed to be having a lot of anxiety and depression symptoms. So more than half of them had what you would call a probable-to-high risk of anxiety if it was a patient coming to, for example, the GP. And the same was also seen for depression symptoms. 

We also did the Montreal Cognitive Assessment Test, which is a short cognitive test you can do, and one out of four had signs of cognitive impairment. So again, this shows that this is a group of patients who are severely affected. 

We also did some sensory testing. We did the Total Tenderness Score, which is a validated score where you investigate eight different muscle groups, the trapezius muscles and the muscles at the back of the head, and also at the masseter muscle, the temporal muscle, and the frontal muscle. And you can see that compared to healthy controls, age- and sex-matched healthy controls, they were very tender. So they seem to be having probably central sensitization, which made them tender to pressure. 

 

And now we come to the difficult part, treatment. So we also asked them whether they were satisfied with the current treatment, and most of them were not. Half of them experienced lack of efficacy for triptans, and many of these patients experienced that they failed preventive medication, so they seemed to be difficult to treat.

We also did a review some years ago, where we actually looked at the literature on available studies on post-traumatic headache, and we found there were many studies. But if you are critical and go into whether these are studies where they’ve used randomized controlled trial designs, we find that there were very few, and most of these studies were open label, so we were not really able to identify studies of a good quality, so that’s a huge problem. 

 

One preventive that is used in migraine and where I actually, after this review, found that there was actually a study coming out, a randomized placebo-controlled crossover study. It was published in Military Medicine, so this was again, I believe, US military veterans, so 95% of them were males, and 80% had what is called a mild complicated TBI. So they had actually some findings on the CT of the brain, so again, probably not a group that you can translate into the usual patients that you probably see in your clinics.

They did actually find that there was an effect on, this was actually not Botox, but AbobotulinumtoxinA, so a different kind of botulinum toxin A. They found a significant difference between placebo and botulinum toxin A, but this was not an impressive study. The headache days decreased by an average of 0.14 on Botox treatment, so you could argue that this is not a clinical meaningful difference that you find when using this. But I applaud this study for doing a randomized placebo-controlled crossover study design. This is what we need when we want to treat these patients, and we definitely need more of these studies.

The overlap between the pathophysiology in migraine and post-traumatic headache is interesting. So, there are different mechanisms that you can discuss when it comes to migraine pathophysiology, and you probably also all know CGRP, calcitonin gene-related peptide, a peptide that’s found in trigeminal ganglion and in nerve fibers innervating dural vessels. And we actually did an open-label study on erenumab, Aimovig, the CGRP antibody. We wanted to start out with an open-label study to see is there any difference at all when we give this to patients. 

So, we gave it to 89 patients who had persistent post-traumatic headache, who had it for several years, and the primary outcome was the mean change in number of monthly headache days of moderate to severe intensity. And we only found that there was a drop of less than three days. We did look at the 50% reduction in mean monthly migraine days, moderate to severe intensity, and 28%. So, less than one out of three experienced something that you could say is a clinical meaningful reduction. And you have to be aware that this is an open-label study, so there’s like an extra placebo effect because everyone knows they’re getting the active drug. And when you look into the migraine clinical trials on CGRP antibodies, what you usually see on placebo is about a 25 to 30% placebo response, so this is not impressing.

There is also a study that was published as an abstract, I believe it was at the AAM. So it was fremanezumab up as a treatment for post-traumatic headache. They found a bit similar, actually a bit more impressive than us, than minus 3.6 days, reduction in moderate to severe headache days. But what they did better than us was that they had a placebo group, and in the placebo group, the drop in moderate to severe headache days was a reduction in five days. So, this shows us that even in patients who are severely affected by post-traumatic headache, you will also see a placebo response. 

And this just shows us we need to do placebo-controlled studies. It might be okay to start out with open-label studies to see if there’s even something occurring, but you will also see a placebo response, which is important to be aware of when we want to evaluate drugs that can be applied for these patients. 

 

So, when we don’t have good evidence, we can at least try to build some expert opinion on how to approach these patients. So I was part of a group that did that, and the expert opinion was to try to divide them up into these two headache phenotypes, the tension-type-like headache and migraine-like headache. And you can then try acute treatment as if it’s tension-type headache or migraine-like headache phenotype. Again, this is just expert opinion. It’s not really based on solid data, but it is what it is. 

Of course, the challenge here is medication overuse headache, because they have headache almost every day, and if you ask them to take acute analgesics every day, some of them might develop medication overuse headache. I have seen some who’ve actually gotten better after stopping acute analgesics that they have used every day.

Well, if that’s not effective, and it usually is not, then you can try amitriptyline, mirtazapine, and venlafaxine which have been shown to be effective in tension-type headache. You can try that in those who have a tension-type-like headache phenotype, and you can then try antihypertensives and antidepressants in those who have migraine. We discussed whether we should suggest antiepileptics, like topiramate and so on, but the problem with these drugs is that they have a lot of side effects. And some of the side effects can be concentration difficulties and fatigue, and that’s something that the patients have already as part of their post-traumatic headache, so usually you’ll just aggravate those unpleasant symptoms that they have.

 

We need more knowledge about Botox, CGRP antibodies, and so on, and I hope there’ll be some more studies in the future investigating this in post-traumatic headache. In Denmark, we cannot offer this to patients with post-traumatic headache, so we don’t have a lot of experience on it. We’re not allowed to as long as there is no solid data from RCT showing that there is an effect. So that’s how it is from my perspective.

 

Be aware of medication overuse headache. That’s actually something that you can do something about it, in my experience. 

 

What we are doing right now at the headache center when we have these patients is using a multidisciplinary approach. So we have a 12-month program where they’re met by a doctor who prescribes candesartan or amitriptyline based on the headache phenotype. They go to a nurse school where they learn about their symptoms and the diagnosis. 

They’re seen by a physiotherapist, and the physiotherapists are trying to get them into living the life they’ve had before. So we encourage them to try to be physically active, but of course, it should not just be a jump back to how they were before, so they should gradually increase the level of physical activity. They also give them exercises in how to have less tense muscles and also to build muscle strength at the neck muscles, which might stabilize the head in a way that will help them have less symptoms.

We also have psychologists who see them as a group three times, and they can also be seen on an individual basis before and after. We try as the last option to try to treat them with gabapentin, and right now we are gathering data to see can we actually change these patients that we see who have persistent post-traumatic headaches. So that’s data we’ll present later on. 

 

I think I have a little time to talk about research before we go to questions. There are two studies I’ll talk about. One is not a group from us, but that’s from Huang and colleagues, but they did an interesting study of 111 patients with mild TBI where they had concussion symptoms, and they did a very excellent study where they had 111 healthy controls. So they looked at microbleeds, and they could see that it seems as if there were more who actually had microbleeds after even a mild head trauma compared to healthy controls. 

We did a similar study, and we found something else. We had almost the same number of patients and also healthy controls. We found that only 3% had microbleeds, which was totally the same as healthy controls, so we couldn’t find any signs of microbleeds in these patients. 

So why was there a huge difference between these two studies? Well, the study by Huang and colleagues, that was patients who were scanned 25 days after the head trauma, and in our study, it was 37 months after the head trauma.

So you could speculate that there might be some who have in the beginning some microbleeds, but they disappear. And in my opinion, this is something that is good to tell the patient that it’s actually not needed to do an MRI if there are no red flags in the story. So it’s not needed if they have had a head trauma for several years, because that’s something that I encounter on a frequent basis. On a frequent basis that patients want and demand an MR scan of the head because they have so much headache. 

We also, in our study, looked at white matter lesions, and we could not find a difference between post-traumatic headache patients and healthy control. So it doesn’t seem to affect the white matter when you just have a mild TBI.

 

An interesting study that my colleagues at Hammel Neurocenter, in West Denmark did, that was a study where they measured CGRP. CGRP has been measured in some studies, and in migraine, shown to be elevated during attacks. So they had a study where they had patients coming in with concussion, and then they did serum samples after 4 months and 11 months. And what they could see is that there was actually, in comparison to healthy controls, an elevation of serum CGRP.  This was something that was driven by elevated CGRP in females, which was the majority of patients, but overall, that seemed to be an increase, and that was after 4 months. 

And then they investigated what happens after 11 months, and then it seemed to have normalized, so there was a drop in CGRP. So the conclusion of this study is that within the first year, there seemed to be CGRP that is raised initially. That’s, of course, interesting also when we discuss treatment, so you could speculate, well, if there is an increase in CGRP, well, maybe it makes sense to try to treat them at an early stage with CGRP antibodies or receptor antagonists.

We did a study. This was measured in plasma levels. That was our assay. And this was the patients who had it for several years, for about an average of 4 years, and we actually found that CGRP seemed to be lower after 1 year. And these were also patients who didn’t really respond that much to CGRP antibodies. So this is an interesting finding. This is the opposite of our hypothesis. We believed that if they had so much headache, they would have elevated CGRP, but we found the opposite. So that’s how it is.

 

This is actually something that my colleagues in the cluster research group have also found for chronic cluster headache patients, that CGRP is lower, so probably it’s complex when it comes to CGRP. 

 

We also did some human headache models where we investigated CGRP infusion, and even though they have lower CGRP levels, they seem to be sensitive to CGRP infusion. So they do develop a headache after CGRP infusion. And my colleagues have also investigated this for PACAP38, which is a signaling molecule also found in nerve fibers around the dural vessels, and they found that 95% develop headache worsening with migraine-like features after PACAP38, and that is significant compared to placebo. It actually seems to be more than what we see in migraine patients, where it’s usually about 66% who experience migraine attacks after PACAP38.

The last drug that has been investigated is a potassium-channel opener, levcromakalim, and in migraine patients, it’s 100% who experience migraine after this drug is given. But in this trial, in post-traumatic headache, it’s almost just half of the patients who develop headache worsening, so this was a bit surprising. So even though there is some sort of overlap to migraine pathophysiology, in my opinion, this shows that headache after head trauma is not necessarily the exact same as having migraine. I think that’s an important point.

 

So that sums up my lecture. So diagnostic criteria for post-traumatic headache, I think it’s important, and it’s based on this seven days interval. The phenotype is most often migraine-like headache phenotypes. They have other symptoms. There’s no yet solid evidence for acute or preventive treatment of post-traumatic headache, and it should be based on an individual basis, based on headache phenotype, other symptoms, and of course also comorbidities. 

 

So thank you so much for listening. This is a picture of the headache center.

 

Heba Bani Hani, BSc Pharm, RPh, MBA: Thank you very much. I do have a few questions, starting with the phenotype and how you are treating based on the phenotype of the headache. Having said this, you said it could be tension-type headache, and it could be migraine-like, and you said mostly they are chronic. Am I getting this right? So mostly post-traumatic headache is chronic in nature, so it’s more than 15 days usually? 

 

Schytz: Yes. So just to everyone that when Heba and I talk about chronic, that means that it’s for three months or more, then that’s at least 15 days where they experience headache, 15 days out of a month of 30 days. So yes, we see that. We don’t very often see those who have less than 15 days. So yes, that’s a predominant phenotype. 

 

Bani Hani: So is that because this is a tertiary headache center? Is it because you see the most difficult cases, or do we know how often people who do have post-traumatic headache, how many of them actually have chronic versus how many of them have episodic and transient that does get better? Do we have that kind of data? 

 

Schytz: We don’t have that much data on it yet. I think that’s data that we need more studies on, because the TRACT-TBI and CENTER-TBI, it’s more like, do you have a headache or not? So we don’t know that much yet, but I believe that there are some studies coming out that also support our findings that it seems to be chronic. But we do need some more data on this exact phenotype and frequency of headache after head trauma. 

 

Bani Hani: And more are migraine-like headaches? So 61% are migraine-like headaches versus tension-type headache. Are there predictors of, is there family history is more in this group? Are they people who had headache before and now it becomes worse with the trauma? How does it progress? 

 

Schytz: Actually, in the study where I presented this 61%, this was a study where we actually only investigated patients who did not experience migraine before and did not have a first-degree relative with migraine. So even with that criteria, it seems as if there are more who have a migraine-like phenotype.

Migraine has been shown as a factor that make patients more prone to develop a persistent headache. So it seemed to be a risk factor based on the large census studies. So migraine is a risk factor for developing persistent post-traumatic headache. And if you’ve had head trauma before, and also if you are young and if you’re female. So that’s also something that has been shown to be risk factors for developing persistent post-traumatic headache. That probably also show that there must be some sort of overlap between the pathophysiology in migraine and post-traumatic headache.

 

Bani Hani: And I thought the most interesting part for me was the CGRP, where in principle, if it’s migraine-like, it’s a headache, I would expect that there would be more CGRP circulating, but you said it’s exactly the opposite. They have lower than just the general population in terms of circulating CGRPs. Did I understand this right? 

 

Schytz: Yes, that’s correct. That’s what we found in the study. And it’s really difficult to interpret this. Have they actually had a surge of CGRP released? So there’s kind of a depletion of CGRP because of chronic activation of nociceptive nerves. We don’t fully know. Probably CGRP, it is probably also just a difficult biomarker to measure in plasma and serum. So it doesn’t seem to be a very helpful biomarker for predicting who has migraine or not. But it is interesting. 

 

Bani Hani: I have a lot of questions in the Q&A. So I’m just reminding everybody that this is where we’re going through these questions for this presentation, and then we will move to the next one and then at the end of it. So if you have any question for Dr. Schytz, please put it in the question and answer. 

So I have a few that I think are all very interesting. The first one was what medications, you’ve talked about managing headache, what the options are, but do you also address cognitive impairment or cognitive decline or symptoms in people living with post-traumatic headache? Is this something that at your center you do address these as part of the condition? 

 

Schytz: I think that’s a very good question. I don’t believe that we use medication, that we say we use it to improve their cognitive abilities because we don’t. I’m not aware of any that would be helpful for that. Of course, patients have to eat healthy and so on, but we don’t have any specific drugs for that. 

I also think that because that’s my experience for patients who have chronic migraine, if you have chronic migraine, usually your cognition can also be affected by that because it is difficult to function on a high level if you very often have migraine. So we do try to treat the headache as best possible with medication and we then also sometimes see that that can then also help on their cognition. 

 

Bani Hani: It’s the same with chronic migraine, you’re absolutely right. If you treat the underlying cause, possibly there will be an improvement in the symptoms, not only the cognition, right? 

 

Schytz: That also goes for the psychiatric symptoms. That has been shown that the anxiety and depression symptoms can also decline if you treat migraine in a proper way. 

 

Bani Hani: I’m not sure if this is available as an answer or the question, if there is an answer to it. Do we know the percentage of patients with post-traumatic headache that do develop cluster headache? You said that in your presentation, but we didn’t see a number. Do we have a percentage? 

 

Schytz: No, I think it has only been presented in case reports. I have seen one or two with headache after head trauma and I think, I mean, we had about 1,000 patients at the Danish Headache Center over the years where I’ve been there, so it is rare. And that, I mean, of course, if they develop, I said that you usually don’t have to scan and I would scan someone who had a head trauma and has developed a cluster-like phenotype. 

 

Bani Hani: And we didn’t talk about this, any role, so this is one question that is specific about one supplement. Any role for supplements in post-traumatic headaches? Do you try anything? 

 

Schytz: No, we take general blood tests when they come in at the Headache Center. And of course, if they have low, if their thyroid function is out of balance and so on, then we treat them, but we don’t give them any supplements. And I don’t think there’s evidence for that. But of course, if they have low blood percentage, it might end up that they have a lack of B12 vitamin. 

 

Bani Hani: So the question was very specific on B12. So you do first screen for it if there is depletion, but you don’t give it empirically. You don’t give it for people empirically. 

I have a very specialized question that is, do you have any systematic approach to decide who needs screening for secondary headache in particular intracranial potential cerebrospinal leak? Because this is a doctor in the concussion clinic. I know the doctor, this is Dr. Cortel-LeBlanc from Ottawa. So he’s asking, would you screen for other secondary headaches post-traumatic? 

 

Schytz: I think that’s an excellent question. I’m happy it’s asked. Thank you for that. We screen via the clinical interview. So we do ask them if there are red flags in the patient’s history. If they say that, okay, I have a worsening of headache when standing up, and it’s better when I lie down, or if they have positive tinnitus, are overweight, and have visual symptoms, then we’ll go on and investigate them with imaging and ophthalmological examination and so on. So, we do look for red flags that would point to secondary headaches.

My colleagues and I actually right now, and I hope we can soon present the data on that, we are actually investigating whether patients with post-traumatic headache, if they have sign of low intracranial pressure, spontaneous intracranial or traumatic intracranial hypotension. So we are looking into that if they have signs on that, because we have investigated a lot of them with MR. So that’s something I can present later on. 

 

Bani Hani: During your presentation, you talked about botulinum toxin and the reduction in number of days. But then you said that when it was placebo controlled, it showed that it’s possible that there is not as much, or did I misunderstand that bit? Does anybody look at severity and return to function in these studies? That number of days might not be really significant, but do they look at return to function? Are they able to at least go back to work or if there’s a reduction in disability? 

 

Schytz: Not to my knowledge. On the study I presented, that was published in Military Medicine on US military veterans. But I do think that we need a study on that, investigating patients with post-traumatic headache, that we should maybe try to investigate botulinum toxin A, but do it in a placebo-controlled fashion. 

So I’m not allowed to treat it, but I have had patients who then go to private clinics and get Botox and who then come back and say they actually feel that there’s a relief in the headache severity, that it’s less. So it is something that is interesting to look into. And it doesn’t give them cognitive side effects like antiepileptics would do, for example. 

 

Bani Hani: And this is what we hear from patients that if something is not approved, so it doesn’t get reimbursed, which means they have to pay out of pocket and they do get it out of pocket. They get the prescription, pay out of pocket and then come back and say, well, it works enough for me to actually also one of the things that we need is for their abortive to work better. That is an end point. And they say that, yes. And when I do have a headache, it goes away. While before, even if I took my abortive medication, it didn’t go away. So this is something that might be interesting to see in practice. 

 

Schytz: And to that, I can just say there is a guideline coming out from the International Headache Society on how to do clinical trials in patients with post-traumatic headaches. So that’s a much needed guideline. And that’s something that we can then as researcher and clinicians try to follow when we do clinical trials. So I hope that that can then encourage more clinical trials on that. 

 

Bani Hani: One of the questions is around medication overuse headache. If they’re chronic and they take the medication, is there medication overuse without headache like or but if you withdraw, it doesn’t affect how much they get. So medication overuse headache and post-traumatic headache. Does it happen more often or is it less than the general chronic headache population? Any idea about the link? 

 

Schytz: Yeah, it’s a good question. My own clinical experiences that there are some who actually get better if they stop taking acute analgesics every day. But that’s just my own experience. We need some clinical data on this. So it’s really difficult to know. But it could be speculated that those who are encouraged to take acute analgesics right after the head trauma, do they actually then develop into medication overuse headache that that’s actually the cause of the persistent headache. I think that that’s a possibility. 

So I think it’s important when they go to the emergency department, they should then be told, well, you can take acute analgesics, but don’t turn it into a habit of taking it every day because it might just lead you into having persistent headache. But there are more research to come on that field, I hope.

 

Bani Hani: And strategically speaking or in terms of strategy, do you ask them to go cold turkey or do you start a preventive first and then they will not need it as often? How do you deal with medication overuse? 

 

Schytz: I think my experience is that they actually usually they don’t really experience that much effect from it. So it’s actually not that difficult for them to go cold turkey, but I usually recommend them to take a preventive at the same time, because that’s what we also do for patients with migraine and medication overuse headache. And if they cannot go cold turkey, then ask them to take it two days per week. And that’s usually a recommendation that they’re okay following. 

 

Bani Hani: Thank you very much. Again, I’m biased. You’re my professor. I’ve heard you speak and I think you’re one of the best people to speak about this subject. And it was an honor and a great opportunity for us to listen to you on our 16th Migraine Masterclass. And we’re hoping to be able to hear from you also on other subjects that you’re an expert on. And thank you very much for accepting our invite tonight. 

 

Schytz: Thank you. My pleasure.