Sait Ashina, MD

What are these migraine-specific acute treatments that we've been mentioning? Later we'll talk about preventive treatments. Sait, maybe you can take us through what the American Headache Society Consensus statement recommendations about acute treatments are.Let’s talk about what migraine-specific acute treatments are. This is some heavy lifting I'm going to have you do, but I know you can do it. Maybe you can talk us through triptans, ergots, gepants, ditans, NSAIDs [nonsteroidal anti-inflammatory drugs], neuromodulation. Just briefly, walk us through: when do we use what? How do we decide to go to something new? When do we pull out a neuromodulation device? Our audience would love to have some guidance here about what to do and when to do it.

: Yes, Jessica. I would like to start first with the indications for treatments. And Julio [Julio R. Vieira, MD] mentioned about the correct diagnosis. The correct diagnosis is important. And for that, we do use ICHD-3 [International Classification of Headache Disorders, 3rd edition] criteria, which are developed by the International Headache Society to diagnose the migraine. After the correct diagnosis comes the correct treatment. And to find the correct treatment, what American Headache Society, for example, recommends is to use evidence-based treatments. We know that these treatments are working; they have been shown and proven to be effective in patients with migraine, and this concerns both the acute and preventative therapies. These treatment plans which I'm going to talk about are very similar for both groups of patients whether they need acute or preventative treatments or both. In my opinion or in the opinion of all my colleagues it is important to use evidence-based guidelines. Now, if you have a patient with severe nausea, as it was mentioned before, or vomiting, the other routes of administration, for example, the non-oral or device treatments, for example, could be considered in these patients. And then we also think about the tolerability and safety issues. We look at the comorbidities where certain acute medications or preventative medications may be contraindicated or not recommended, for instance, or we have some concerns about their safety. Even though there are not a lot of data, for example, for preventative drugs, we do still have some concerns, and we’re still cautious when we prescribe. Then, what we also talk about for acute treatment is availability of a soft administrative rescue medication. If you take 1 medication, if it doesn't help, do we have something else I can use as a rescue? This is very important. And 1 of another important topics, which we also mention, is avoiding the medication use or overuse of acute headache medications because we know it leads to the progression of the migraine. It leads to the so-called medication overuse headache, and it can be associated with a lot of burdens and a lot of disability, as we know. Now, for acute treatments, we do have some old medications which we have been using a lot and so-called conventional treatment. This includes simple analgesics which are not specific migraine medications but they're still proven to be effective for treatment of migraine. Among those, we have simple medications like ibuprofen, acetaminophen, but we also have ketoprofen. You have some more specific nonsteroidal anti-inflammatory drugs. And then we have the triptans which, until the last year, have been the mainstay of treatments of migraine. They've been on market since the nineties, have shown to have a proven efficacy and some tolerability. We've been using them a lot in our patients. Now, there are old so-called migraine-specific drugs like ergotamine and dihydroergotamine. They've been used less because of the adverse effect profile. However, more recently there is a new the dihydroergotamine nasal spray available which offers the better delivery options and better efficacy, and possibly more tolerability. And then more lately, we had gepants added, so-called gepants. Now we have rimegepant [Nurtec] and ubrogepant [Ubrelvy] added to our medications to help our patients. And these are CGRP [calcitonin gene-related peptide] receptor blockers, which are the newer drugs we can also offer our patients. And lastly, we also have neuromodulation devices, which are electrical simulation devices. We can also use a so-called Nerivio, which is a bigger nerve simulator to treat acute headache attacks as well. Now, for prevention, we do have old medications which have been used for many years, and these are antiseizure medications topiramate and depakote. We have also antidepressants or tricyclic antidepressants nortriptyline and amitriptyline, which we can offer the patients. And then we do have better blockers—receptor blockers—and sometimes we use also tizanidine, although the evidence for them is less than with other medications. Now, the major disadvantage with the oral medications for prevention was the so-called low adherence or patients would stop treatments because of poor tolerability and safety issues with these medications. Now, this has been overcome with the introduction of CRP [C-reactive protein] monoclonal antibodies or CRP-targeted therapies as well as oral molecule CRP antagonists for prevention of migraine, which we have been offering our patients. We have also been offering device treatments for prevention of migraine, among them a Cefaly, which can also be used for acute treatment, as well as gammaCore. Now, the Botox is indicated for patients with chronic migraine—those who have 15 or more days with headaches per month over the past 3 months.

You did a great job covering all our different categories of treatments. I did want to just add 1 neuromodulation device that recently has been FDA cleared. It's such a long name. It's an electrical stimulation device that stimulates both the occipital nerve and the supraorbital nerve and it’s used for acute treatment of migraine. And just again, to make clear, Botox is onabotulinumtoxinA as its generic name. We do have an arsenal of treatment options. Now, how do we know which ones to use when? We look at whether the patient has episodes of migraine, or episodic migraine, or do they have chronic migraine? Sometimes that help helps with prevention for acute treatment. It doesn't really matter if you have episodic or chronic migraine.

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Sait Ashina, MD, reviews current AHS (American Headache Society) treatment recommendations for the acute and preventive treatment of migraine.

Acute and Preventive Treatment Options for Migraine

: Julio, you mentioned acute and mentioned preventive. What are the differences? This gets everybody a little confused. What do we mean when we say acute treatment? What do we mean when we're talking about preventive treatment? We talked about why you'd want prevention— because we want to reduce frequency of attacks—but why would you take an acute treatment? When is the right time? And we talked about goals. What do these things mean?

: Definitely. Whenever you have a migraine attack, you should have the availability of an appropriate treatment and try to take it right away to try to minimize your disability, to achieve pain improvement. And nowadays, we've been talking about pain freedom. And at the end of the day, patients are only mostly interested in, when am I going to be able to return to my function, to my life, to my event, to work—to whatever they were doing before? And the earlier that you were able to onboard your medication, the better. Despite us having a lot of medications which are migraine-specific available to us for such a long time, most patients do not have access to that. There's epidemiological data showing that approximately 92% of patients with episodic migraine use acute therapies. Only 36% of those were having migraine acute therapy, and that's not even the migraine-specific therapy. Only 18% of those were taking migraine-specific medications at the time, which were triptans. About 12% of them were taking opioids, which, unfortunately, remains very common in patients overall, and 6% of those were taking barbiturates. Out of them, 16% of participants were migraine. They were currently taking opioids, and 14% were prior users of opioids. Even those who can discontinue, yet it's still prevalent among different providers. And the goals of acute and preventive therapy—they're very different. There are 3 steps for successful access to migraine-specific medications, and they seem very simple, but unfortunately, sometimes it's not very easy to get to it. Number 1 would be appropriate medical consultation. Get into a provider, get into a headache specialist, get into a general neurologist who can make that diagnosis, which is the next 1: having an accurate diagnosis like we're talking about. Sometimes patients come to see us, and they have not just 1 type of headache, but they have multiples. And sometimes if they go see another provider and they're like their headache specialist is crazy. And suddenly, we have all these diagnoses. And sometimes people can have more than 1 headache at the same time. And then also to develop an effective treatment regimen, which most of the time must be individualized. Like Jessica was saying, why don't all your patients all have the same medication, right? And with all of those, with the epidemiological data, the AMPP [American Migraine Prevalence and Prevention] study shows that only 26% of participants have passed those 3 steps, which means that we as clinicians, overall, we're not doing a good job to get patients to do this. Of course, specialists are a good breed, but unfortunately, a rare breed. There are only approximately 500 of us in the country. We should try to educate our other colleagues, general neurologists, and primary care providers as well. Looking at the goals of acute therapy is for patients to achieve pain improvement, pain freedom, and also the complete absence of most bothersome symptoms, which he touched base on—the photophobia, phonophobia, nausea. And at the end of the day, the most important question, the million-dollar question that the patients want to know is, when can I return to my life? And in terms of prevention therapy, the goal for that will be to decrease the number of attacks that patients have or trying to eliminate them altogether to minimize the impact of migraine headache–related disability and those health-related quality-of-life issues; that a migraine is not just a headache like many people think. It also causes such a huge burden of disability. It is the second most debilitating condition in the entire world.

: Those are all really great key facts about acute and preventive therapy and how every patient needs acute therapy. Some of our patients, especially when they have a disability that's high, need prevention.

Dr Julio R. Vieira defines acute versus preventive treatment for migraine and highlights the differences in goals of therapy for each.

Acute Versus Preventative Treatment of Migraine

We're going to be talking about the management of migraine, probably one of the most interesting and exciting parts of our field. Not only do we get to diagnose and be there with our patients through their lifespan, but we get to engage in conversations with them about all the different therapeutic options that we have to offer them to improve the quality of their life. We are going to start this conversation by talking about how we can individualize plans for the patient that's sitting in front of us, and I thought, Sait, maybe you can talk to us about why it is so important for the migraine patient to have an individualized plan.

: I want to go back to what we already said about the burden and the impact the migraine has in an individual. And that brings us to this level that we need to help patients; we need to treat them. And unfortunately, the reason ethological data show that migraine patients remain undertreated and underdiagnosed, but undertreated as well, despite availability of effective treatments. Why do we need to treat the patients? Why do we need to help them? One of the major reasons is to give them pain relief. Are they able to go back to their lives, to their families, to have the ability to function in every day life. And those are the main factors that we looked at. But in addition, we want to prevent patients to progress to have more chronic headaches, which again, in turn, can cause the burden. Now the goals of acute treatment would be to give the rapid and consistent freedom from pain and associated symptoms to relieve the most bothersome symptoms. For example, photophobia in some patients is a very bothersome symptom; in some people, it could be nausea, prevent a recurrence of the migraine attacks with the acute treatment, the ability to function, restore movement of that, and then we're thinking of the minimal or less severe adverse events. When we choose, with our choices are based on the drugs that can help the patient but at the same time, they don't cause adverse effects. And another important thing is the financial considerations, the cost of the medications. For the preventive treatments, the goal is to decrease the headache frequency by at least 50% or more. Again, improve the ability to function as well as prevent patients from having another attack. And here we also talk about, for example, there are certain subgroups of migraine such as hemiplegic migraine or frequent auras for those preventative treatments are needed for those patients. The risk of acute analgesic overuse with the patients are at risk of that. Then there is also indications for preventative treatment.

: What I hear you saying is that we have to look at the characteristics of the type of migraine the patient is having. Do they have aura? Which can come with high burden for some patients? Do they have nausea? Are they really disabled? Perhaps they need prevention. If they have a lot of associated symptoms like nausea, perhaps they need a non-oral acute treatment. Really focusing in on patient-specific symptoms to try to individualize the treatment plan. And not everybody gets the same treatment. This is extremely frustrating to patients. I know in my waiting room; the patients will talk to each other. And then they'll come to the back and say, "Dr Ailani, why is your other patient on this treatment, and I'm on this treatment? How come we're not on the same thing?". And I always tell them, "Did you want me to treat all of you like you're the same person?". And this always gets them, they're like, "No". You are all individuals. "Yes". And all your migraines are different. "Yes, yes". And that usually settles them right down. But it's extremely important that our patients also understand that we are talking about treatment options. We're finally in a generation period where we have so many options to offer them that we can start individualizing treatment plans.

Sait Ashina, MD, and Jessica Ailani, MD, comment on the importance of individualized treatment regimens for the management of migraine.

Approaching the Treatment of Migraine

These are all excellent points. Another way we can utilize tools to help us make diagnoses are headache diaries and sometimes other types of forms we can have patients complete to help us understand their disability. I wanted to ask both of you—and maybe, Julio, you can tell us first—how often are you having patients use headache diaries? And how often are you using any kind of patient-reported outcome measures in your clinic, like the MIDAS [migraine disability assessment] scale or the HIT-6 [Headache Impact Test], having them fill these things out? Or are there any other tools that help you not only understand the impact of the disease, make the diagnosis, but follow the patient through time to see how they're doing?

: Yes. There was a review paper a few years ago that showed that they analyzed 30 different tools. I didn't even know we have that many tools. And every time things start to get complicated, it's also harder for us to include those tools into our daily clinical life, and especially in our peers that we try to educate as well—general neurologists and primary care who are not used to using these different tools. Going back to what we were talking about before, I still believe that the ID-Migraine questionnaire is one of the best tools that can be spread out there, which shows the disability, nausea, and photophobia. Or sometimes people use the mnemonic “PIN”. P-I-N stands for “photophobia” “inability to function” “ad nauseam”. And that's an easy tool to be used.

Going back to the headache diary, I recommend every time. It's always useful. The only time which is sometimes hard to recommend is for those patients who have either daily headache or constant headache, which becomes very boring. And after a while, they're like, "Nah, forget it. I have headaches every day. Why would I even do this?" And then we try to flip the table and generate the diary in a way that's a reward. And we tell the patients to record good days and they're like, "Yay. I have a good day today" instead of recording every single day, which becomes boring. When studies were done about with diary, patients thought that they knew how many headaches they have without documenting and having a true diary. But study after study show that once you start recording, it's a whole different story. And most of the time they have more headaches than they thought. Going back to the other tools that you were mentioning, like the MIDAS or HIT-6, the headache specialists always try to utilize those tools, which are used for us to measure disability. But I don't think it's very common within the general neurologists and other providers.

I agree with your assessment of headache diaries. They can be very useful, especially in the beginning, but very difficult in someone who has daily or continuous headache. I often find they can be very demoralizing for those patients. We'll often use them when we're changing treatments or making adjustments just to ensure the patient has some response to treatment, or when they're using a frequently used acute medication just to see how things are going. But I also agree with the reward process of "Look, you're having headache-free days; just mark those down". And then, the patient-reported outcome tools can be very difficult. When a patient is very disabled, on the same point, even episodic migraine, many of the patients in a headache clinic are on the high disability side. It's very hard to measure changes in high disability; there is no change if your MIDAS levels are already at highly impacted, and you’re improved, but you're still highly impacted. It's very hard to say that that's making great strides of improvement, even though the patient can tell you they're much better and they're functional. Sometimes you come up with other creative ways to measure improvement: changes in emergency room visits, going back to work, how many hours are they working, missed social life functions. And there are other creative ways to evaluate how your patient is doing if you try to keep it consistent in the same patient.

What about you, Brad? Do you find headache diaries to be useful? Any tricks to offer our audience on ways to measure how a patient is doing over time?

: I agree with your approach, Jessica, that the best use of headache diaries is early in the therapeutic relationship, and specifically, where I find it to be most useful is when we're having that discussion about possible triggers. And I'll give the example of when I describe tyramine. No, I don't necessarily advocate that patients cut out all things tyramine. But I do say, when you're keeping that diary, if you take a close look at those foods that are rich in tyramine, consider those suspects. And if you see them appearing often in your diary, then you know it may be a good idea to cut that out. But I agree. As time goes on and the therapeutic relationship continues, and we've been working together for a while, that utility does go down quite a bit. In our practice, we utilize the HIT-6 tests with every patient on every visit, and what we’ve found in our practice is that it's given us robust data. If we've decided we're interested in a certain topic—for example, in telemedicine—we were able to look at HIT-6 scores with our telemedicine patients, and it can give us rich information.

 If you want to do research in your center, I agree with Brad. Also part of what Julio was saying is, in keeping those calendars, it becomes really important. It is very difficult to do even retrospective data when you're relying on methods like I have, which is, How are you feeling?, that doesn't really fly in any kind of retrospective data analysis at all.

: And it helps you to put symptoms in perspective to record certain triggers like menses, for example. And also, to set up a perspective on what the patient expects in their treatment and their relationship with you, because many times if the patients are not keeping a diary, they come in and they say, I still have headaches. But then you'll say, Let's keep a diary. The next visit, they come in, they kept a diary, and they're doing better, but still have that expectation. We need to differentiate between having tons of headaches or having headaches or migraines or not having any. One of the things that I try to tell my patients is, I think I can make you better. I'm not sure exactly by how much but there's got to be a relationship 1 day at a time. I will take it from there.

 Setting expectations, goal setting, again, are very important points and something that has to be revisited, not necessarily every visit but frequently through the relationship of the health care provider.

Experts in neurology, Drs Julio R. Vieira, Jessica Ailani, and Bradley Torphy review diagnostic tools available for migraine, including patient use of headache diaries.

Using Diagnostic Tools to Assess Migraine

 Part of the challenge of making a diagnosis of migraine is that it’s not just 1 type of headache. People can have different types of headache. Even if you have migraine, you can have migraine with aura, migraine without aura, tension-type headache, or other types of headache disorders. A person who comes in might describe 1 type of headache and then, on a follow-up, another type of headache. Even as a headache specialist, I’ll struggle with the diagnosis because it turns out the patient has 4 or 5 headache disorders. This will delay or impact treatment options for the patient because I’m treating migraine, but they have cluster and tension type, and they’re trying to treat everything with 1 type of medication. Sometimes have to peel through different types of criteria, which can take a lot of time.

I often tell my colleagues, “It’s OK to understand that this is a relationship you’re starting, so take your time during the visits. If you don’t have the time to set up multiple visits, try to get the history a few times over to ensure nothing new is coming up.” Repeatedly, our epidemiology studies suggest the same thing: those who are most disabled are going into sick care. But the care we’re providing isn’t always the best care. Patients who need help aren’t always getting preventive treatment. This is where all of us are failing, and it can be problematic.

When we’re trying to teach our patients about different headache disorders, Brad, what are some key tips to differentiate migraine? We learned about how to differentiate migraine with different auras and without aura, but what about migraine vs tension-type headache or migraine vs cluster? These are the 2 most common things our health care colleagues wonder about but also patients. How do you differentiate these 2 types of headaches from each other?

This is such an important point. One thing I’ve learned is not to necessarily listen to the diagnosis that the patient has brought into the office because patients will often say they have cluster headache or tension headache. Obviously, we want to listen to our patients, but we have to look at this methodically. When we speak with residents and medical students about this, impact on activity can play a huge role, and what activity does to the headache. With tension headache, activity can sometimes improve the headache in some cases. With migraine, routine activity will typically worsen the symptoms. That’s 1 key way to differentiate.

We all know that tension headache is more common than migraine. But by the time a person comes to speak to a health care provider, if it’s not a secondary headache, it’s overwhelmingly likely to be migraine. When we’re making our diagnosis, we want to make sure we’re looking through that lens as well. With cluster headache, how do we make the distinction? These are top-line approaches. What’s the activity of the patient when they’re having their attacks? Patients with cluster headache are typically going to be the folks who are pacing—they’re restless, they’re doing distracting activities. Patients with migraine are going to tend to lie down in a dark room. A cluster patient can’t sit still. Those are some top-level approaches. Of course, if we think about characteristics typical of cluster patients, they’re more likely to be met. Migraine in adult patients is 3:1 more common in women. Certainly, we’ve all seen cluster patients who are women and men. But as we continue to think about those factors, that helps us make the diagnosis.

Jessica Ailani, MD, and Bradley Torphy, MD, discern the signs of migraine and comment on the importance of ensuring accurate diagnosis for patients.

Differentiating Migraine From Other Headache Disorders

 In this segment, we’re going to be talking about migraine diagnosis, a challenge that many of us still face in clinic. The challenge is to be able to take an excellent history. Sometimes it involves getting our patients to tell us their story. That sounds relatively easy. Unfortunately, patients are often told it’s not a big deal. That’s to such a great extent that by the time they come to see us in clinic about headaches, they’ve been having, they focus on 1 or 2 key aspects and aren’t used to telling their entire story from start to finish. It’s important that we focus on a couple of key items and allow the patient space to tell us their history from the start, so we can pick up on key elements of the diagnosis. Hopefully, this segment will get you to understand those key segments you need to hear from the patient to make the appropriate diagnosis of migraine.

Brad, I thought we’d start with you. What are the essential parts of making the diagnosis of migraine? Is this something we’re pulling out of air, or are there criteria involved in making the diagnosis?

It’s such a good question. One challenge in making that diagnosis of migraine is that patients are not used to telling their stories. If we think about it, migraine is most often in primary care. Primary care providers may have dealt with diabetes and hypertension, and when their hands are on the doorknob and they’re ready to leave, the patient finally gets a chance to talk about her headaches. Patients aren’t used to going in depth with the provider and sharing information that could be helpful. In our practice, we start by saying, “Tell me about your headache. Tell me what you think I need to know.” I know that can be challenging. We’re all on the clock. We have a lot of time to see our patients. If we spend a little time up front letting the patient share her story, then afterward we can focus on specific questions we have.

After the patient has had an opportunity to share her story, what she thinks might be important—we probably are going to get most of the information from that part of the history—we focus on a few key things: migraine light sensitivity, phonophobia, photophobia, nausea. Those are key features of migraine. For a lot of providers, if they’re not specifically focused on migraine and headache, looking at the ICHD-3 [International Classification of Headache Disorders, third edition] classification, it can be daunting. But Richard Lipton’s ID Migraine is a very valuable tool, not only in the neurology setting but also in primary care. Is there photophobia and phonophobia with your migraine? Is there impact—are you missing work or school? Is there nausea? If patients answer yes to 2 of 3, there’s a positive predictive value of over 90% that the patient has migraines. Listening to the patients can be challenging, but we can garner a lot of information.

 This is a great tip. ID Migraine is something I encourage my residents and fellows to use to pick up those key elements when a patient is telling you their history.

Julio, we talked about the challenges of making the migraine diagnosis. What are some of the factors we see in the literature that suggest problems with underdiagnosis of migraine? Does anything in the literature suggest this is an underdiagnosed disease?

 That’s interesting. Unfortunately, we have a very suboptimal diagnosis of migraine. We’re a rare breed as headache specialists. We’re used to dealing with migraine, but a lot of clinicians—neurologists but also primary care—have a lot of difficulty diagnosing migraine. There are numbers that show us the consultation patterns and suboptimal migraine diagnosis and care. There are certain data showing that the United States had consortium therapies and migraine-specific pharmacology therapies. They usually require prescriptions for the migraine-specific medications. Looking at those data, two-thirds of patients have consulted a health care professional in the past year before having a diagnosis of migraine. Patients usually end up seeing either their primary care provider or general neurologist. Unfortunately, we’re not having those diagnoses.

There are also data from epidemiological studies, like the American Migraine study, showing similar data. Also, 68% of women and 57% of men who have migraine express that they have seen a health care professional in a previous year. Unfortunately, they didn’t have a diagnosis of migraine at that time. Similarly, the AMPP study, the American Migraine Prevalence and Prevention study, showed 45.5% of patients with episodic migraine—those who have migraine frequency on the low side. However, those who have headache-related disability have seen a physician in the previous year.

A few issues were identified in those epidemiological studies. Predictors for potential migraine consultation include—it seems obvious—having health insurance. A lot of people lack health insurance and do not seek a provider. Others include a higher level of headache-related disabilities—the worse they are, the more likely they are to seek help—and a greater report of headache pain intensity that usually helps patients seek care.

Other studies, like the CaMEO study, show that among subjects with migraine, about 40% who have chronic migraine end up seeing a physician at the time of enrollment. They were able to identify several predictors that were likely to have brought the patients to seek care. Health insurance was the biggest, with 4.6 times higher odds of a person seeking care. Also, higher BMI [body mass index] was a common factor, with those overweight and especially obese more likely to seek care. Other factors are older age, those with greater migraine-related disability, and those with greater-severity migraine symptoms—the ones who are not doing as well. Only 4.5% of participants who end up seeking care have appropriate treatment for chronic migraine.

They also identified 3 obstacles for care: having a consultative health care professional for migraine, having received an accurate diagnosis, and having been prescribed minimum acute and preventive pharmacological treatments. For headache specialists, it seems to be so obvious and easy for us to recommend patients. But as clinicians, including general neurologists and primary care, we’re not doing a good job with that.

As our colleagues were saying, the first thing is to obtain a very good history and identify those features. Most of the time, when we’re collecting our data, we use the ICHD-3 criteria to ask all the questions that our questionnaires usually collect. But I agree with Dr Torphy that the ID Migraine is such a great tool that we can propose it to clinicians—general neurologists and primary care as well. Going back to what Dr Andrew Charles was talking about, for patients who have aura, sometimes it’s not easy to identify, particularly the sensory aura. Sometimes it gives you tingling on the fingertips. Sometimes it gives you changing tastes, like metallic taste. Sometimes, when I ask my patients, they’re like, “What are you talking about? Yes, I have that.”

Drs Bradley Torphy and Julio R. Vieira share insight on approaching the diagnosis of migraine as well as current challenges in diagnosis.

Challenges of Migraine Diagnosis

 Andy, what is episodic migraine? What is chronic migraine? When is a patient episodic or chronic, what’s the magic behind 15 days? Talk about how the disease could progress between episodic vs chronic and how that’s taken in the clinical practice.

 As you alluded to, the definitions are evolving. There’s some push to change the definition of episodic vs chronic migraine. The key point there is that the cutoff is 15 headache days per month. There’s some push to make that more nuanced because 15 days is an arbitrary cutoff. To your point about disability, your migraine has a spectrum of severity, clinical symptoms, and disability associated with it. At the very mildest end, people may have 1 attack every month or every few months that they’re able to manage. But in our practice, it’s much more common for people to be profoundly disabled by migraine. That disability includes inability to function socially with family and friends.

Of course, there’s a tremendous associated inefficiency and lack of productivity at work associated with migraine attacks. As Dr Ashina mentioned, it’s not just the headache that can create this disability for some. It’s the fatigue, the cognitive dysfunction, the inability to function normally. That’s important in terms of producing, either home or work, disability. On the positive side, what’s striking with some of our newer therapies when we achieve success is that people had no idea how much the migraine was affecting their life until they have some attack-free days. They’re in wonder because they haven’t experienced this sense of wellness for such a long time.

I find it interesting when someone you think is well controlled gets on a therapy that’s effective for them. Suddenly, it’s not just about migraine pain. All their associated symptoms start to get better. They tell you that they’re feeling, for the first time, really clear of mind. It’s this sense of well-being and feeling normal…that makes you realize that burden of disease is so high. It’s more than pain. Interictal symptoms, as Sait was mentioning, that in-between fear of attack, but the cognitive slowing, the burden of the postdrome that patients will often have can disable the patient.

Sait, we’re talking a lot about episodes of migraine attacks, interictal burden, and developing disease that’s frequent. How would you suggest patients try to reduce this risk of chronification? Do you try to prevent this disease burden from becoming high? What things do you suggest to patients?

This is an important and great question. Thank you for asking. Just to add to Andy’s explanation about the burden, we have a study showing that patients with even 4-plus migraine days per month are as disabled as patients with so-called chronic migraine, which is 15 or more days per month. In our practice we tell patients to keep a diary with all the information about the headaches to visualize this, to see how many days they experience per month. It gives them an opportunity to see not only the number of days but also the triggers—for example, what triggers their migraine attacks, what’s it associated with? In this way, the patients can find out about their triggers and go back and try to control them.

Among the top 10 triggers for migraine are dehydration, lack of sleep, stress, etc. They’re all associated with progression of migraine. In a given year, 2.5% of people with migraine can progress from episodic to chronic. How can we prevent that? There are some risk factors, and some of them are modifiable. Some of them are nonmodifiable. For example, nonmodifiable is the female sex. We know that migrane is more common in women than in men. That’s another burden. Younger age is also a risk factor. Then we the modifiable risk factors—for example, anxiety, depression, or allodynia, which is increased sensitivity to touch on the head or face experienced during an attack. If we try to control these risk factors and explain them to patients, we may be able to prevent progression from episodic to chronic state.

These are great points. Nowadays female sex might be a modifiable risk factor. I’m not saying that as a joke. There are some new studies, very few, about people transitioning gender. Unfortunately, for male-to-female transition, they pick up the risk of female gender when it comes to migraine. It seems you can change your risk factor, but it’s unclear if you transition from a woman to a man. We don’t have enough data to know if you can reverse your risk. I’m not saying that’s a good reason to transition genders. That’s a personal choice.

I agree with you. With my transgender patients, I see estrogen as a trigger, which is challenging. Of course, we try to overcome it with prevention, aggressive treatment of migraine. It’s an interesting area to investigate in the future studies.

This is something we need to learn much more about, and there are some young investigators looking into this. It’s an exciting area.

Andrew C. Charles, MD; Jessica Ailani, MD; and Sait Ashina, MD, discuss the impact of migraine on a patient’s quality of life and share strategies for reducing the clinical burden of disease.

Reducing Clinical Burden of Migraine

 titled “Optimal Management of Acute and Preventive Migraine.” I’m Dr Jessica Ailani, the director of the MedStar Georgetown Headache Center and a professor in the department of neurology at MedStar Georgetown University Hospital in Washington, DC. Joining me are my friends and colleagues Dr Bradley Torphy, the medical director of the Headache Centers of America and the managing director of the Chicago Headache Center and Research Institute in Chicago, Illinois; Dr Sait Ashina, an assistant professor of neurology at the Beth Israel Deaconess Medical Center in Brookline, Massachusetts; Dr Andrew Charles a professor of neurology at the UCLA School of Medicine in Los Angeles, California; and Dr Julio Vieira, a headache specialist and an epidemiologist at Nuvance Health in Kingston, New York, and an assistant professor of neurology at Albert Einstein College of Medicine in the Bronx, New York. Welcome, friends. I’m excited that you guys are joining me. Let’s get started talking about migraine.

Our first topic is going to go through an overview of migraine. We’re going to get into the pathophysiology of migraine and how it pertains to clinical practice. I thought we’d start by asking Dr Charles about the biological pathways that underline the symptoms associated with migraine. Dr Charles, can you walk us through some of the pathophysiology of migraine and how we might think about that clinically when we’re seeing our patients?

We have to start with the concept that a migraine attack is much more than just a headache. It’s a wide idea of symptoms that can evolve over hours to days. Broadly speaking, the phases of a migraine attack can be described as the prodromal, or premonitory, phase; the aura phase; the headache phase; the postdrome phase; and the interictal phase. The symptoms that happen during the premonitory phase can be wide-ranging and variable. They include neck pain, mood change, fatigue, change, appetite, light sensitivity, and a host of others. The aura phase typically comprises visual aura symptoms but may also be sensory or language or rarely motor or brain stem symptoms. Those typically last 15 minutes to an hour…. A lot of premonitory and sometimes even aura phase symptoms can persist into the headache phase of the attack. In the postdrome phase are the residual symptoms that persist after headache, including some of the same ones that were in the premonitory phase: neck pain, fatigue, mood change, change in appetite. Finally, the interictal phase is the time between attacks.

Some people, especially with those with chronic migraine, may even have persistent symptoms between attacks. In terms of pathophysiology, it’s a very complex cascade of events. One thing that’s important is that with functional imaging studies, fMRI [functional MRI], and PET [positron emission tomography], you can see changes in brain activity in different brain regions that correlate with this variety of symptoms. For example, changes in the cortex corresponding with visual symptoms, and changes in sensory cortex or thalamus corresponding with sensory symptoms. We’re beginning to get a picture of the different brain regions that are activated or inactivated during these phases of a migraine attack.

Sait, how do you bring this to your patients in clinic? Andy talked to us about the different phases. I’m sure that in clinic, patients talk to you about their migraines. How do we refocus and get the broad picture, asking them about prodrome and postdrome? What do they tell you? What kinds of questions do you ask to get to the bottom of this? How long do these phases usually last? What do patients usually tell you?

My first question about those symptoms starts with my headache intake form, which I give my patients at their initial visits. In that form, there are questions about the phases, which Dr Charles mentioned: premonitory phases or symptoms and the headache symptoms, as well as the postdrome symptoms, which I ask about. More recently, I started to ask the patients about the time between their attacks. What happens to them between their attacks? How do they feel? There are studies showing that the patients are disabled between their attacks because they sometimes may experience symptoms. I usually ask them what happens before your headache starts, hours or even days before. What symptoms they experience. I even give them some examples, so they can go over these examples and check the boxes if I have difficulty remembering. It may be difficult for patients to express about their premonitory symptoms because they never think about them. As I said, the intake forms help them do that and help receive this information. Migraine is not just a headache. It also includes symptoms before the headache. Then there’s a headache phase. There may be some aura symptoms, and then there is so-called resolution phase, or postdrome phase, where the patients can experience some of the symptoms. This could be as debilitating as the headaches themselves.

You talked about the interictal period, the time between attacks. That’s relevant to patients with migraine, whether they have what we call episodic or chronic migraine.

Andrew C. Charles, MD, and Sait Ashina, MD, provide an overview of the pathophysiology of migraine and discuss its 5 clinical phases.