The Mysteries Of Migraines

IRA FLATOW: This is Science Friday. I’m Ira Flatow. A few weeks ago, I was sitting here at my desk in the radio studio reading something off a page, and all of a sudden, some of the words on the paper at the end of the sentence on the left side got a little fuzzy and gray, and the effect lasted just about five minutes and then everything went back to normal, but it got me worried, so I went to my neurologist who said he suspected what I had experienced was actually a type of migraine.

Migraine, I didn’t have any pain. How could this have been a migraine? It was only my vision that was impacted and it lasted just a few minutes. Well, it sounded a lot like what David from Anchorage called in about on our Science Friday VoxPop app.

DAVID: I have a form of migraines that does not lead to a massive headache, but to a visual aura that grows over my visual field. It appears as lines and triangles that rapidly shift between black and white.

IRA FLATOW: Mm-hmm, and that’s what my doctor called an ocular migraine, something that happens in your eye. And if you’re a migraines sufferer or a migrainer, as we are called, your experience could be totally different from mine or David’s. You may be sensitive to light or to sound. You may have a pain that’s sharp like a knife or dull and pulsating.

Migraines triggers run the gamut too, from eating too many sweets, to drinking red wine, and not getting enough sleep. Migrainers will speak of all kinds of triggers. So how can each person’s migraine be so different, and can there ever be a treatment that cures all migraines?

Well, the FDA recently approved a new drug for treating acute migraine attacks called ubrogepant. It’s one in a new class of medications that targets a critical receptor in the migraine pathway in the brain. And could it be the miracle drug migraine sufferers, well, we’ve been waiting for?

Well, we’ve got a lot of questions about migraine, and if you experience them, you probably do. If you do, we want to hear from you, 844-724-8255, or you can tweet us @scifri. Tell us what your migraine feels like. Have you had any success in treating them yourself?

We can’t really prescribe anything for you personally. That’s just unethical, and we really don’t know who you are. We will try to answer as many questions about the different symptoms of migraine, whether a universal treatment may be on the horizon. And to answer those questions are my two guests, Dr. Peter Goadsby, professor of neurology at the University of California San Francisco and King’s College London. Welcome, Dr. Goadsby.

PETER GOADSBY: Thank you for having me.

IRA FLATOW: You’re welcome. Dr. Elizabeth Loder, professor of neurology at Harvard Med and chief of the Division of Headache in the Department of Neurology at Brigham and Women’s Hospital. She’s here in our New York studios. Welcome.

ELIZABETH LODER: Thanks for having.

IRA FLATOW: Dr. Loder. Let me begin with you, Dr. Loder. The very basic question, what exactly is a migraine. There’s so many different symptoms. Is there a universal definition for them?

ELIZABETH LODER: There are widely accepted criteria for making the diagnosis of migraines and features that we look for in order to diagnose migraine. It’s a common, costly, and long-lasting illness, where people are susceptible to repeated attacks of head pain that can be severe. And some of the things we look for to make the diagnosis include head pain that is predominantly on one side of the head, pain that is moderate to severe in intensity, pain that is usually lasting four to 72 hours, makes it impossible to be physically active, and is throbbing in intensity. Not everybody has all of those features, but most people, in addition to that head pain, will also have nausea or vomiting, sensitivity to light or sound, so those are some of the things we ask about when we’re trying to make a diagnosis.

IRA FLATOW: And then there’s my kind that I had, right?

ELIZABETH LODER: There’s your kind as well. About 20% to 30% of people who have migraine also experience migraine aura. They don’t necessarily have it with every headache, and they don’t necessarily have a headache with the aura. It’s very noticeable. And so when it happens, as in your case, people typically will go to the doctor or to the emergency department and get a diagnosis.

IRA FLATOW: I’ve been told that migraine runs on the female side of families. Is that correct?

ELIZABETH LODER: I’m not so sure that’s true. It’s not entirely clear. The genetics of migraines are a focus of intense study right now. It is true that about half of people with migraine have a family member with the illness, and it’s very clearly something that is genetically influenced. Some very rare single gene types of migraine exist. But for the majority of people who have common, garden variety migraine, it’s almost certainly a polygenic disorder where there are a number of genes contributing to risk.

IRA FLATOW: And Dr. Goadsby, I mentioned in the introduction how many people talk about all the triggers that there are for migraine. Some people say they’re triggered by light, some people can be triggered by eating sweet things, not getting enough sleep. Why are these triggers, Dr. Goadsby, so different?

PETER GOADSBY: Well, one of the things we’re learning about trig– firstly, they’re variable, because humans are variable, and migraine manifest– migraines manifestations, while there is a very clear core that Dr. Loder just pointed out, there is considerable variability in the individual manifestation of the disorder. The same thing applies to the triggers. An important thing we’ve found out– I think we’ve understood better in perhaps the last decade is that not all triggers are triggers.

And what I mean by that is that there’s a phase of the attack before the pain comes, the so-called premonitory phase, when someone might start to feel a brain fog, concentration problems, some mood change, they feel sleepy, tired, they might yawn, oddly, they might pass more urine, or they might crave sweet or savory things, and this may go on for hours or days before their pain starts. It’s clear that some of the– some of the things that are being attributed to triggers are actually the premonitory phase or the attack starting. So for example, if you’re sensitive to light in the premonitory phase, and that happens hundreds of times, you might come to the conclusion that after light exposure, because you’re sensitive and you notice it, then your headache develops.

Actually, what’s going on biologically is the attack already started and that’s why you’re sensitive to light. So some of these triggers aren’t triggers at all. They’re an invitation to understand the disorder better.

IRA FLATOW: You know, when I was talking about this on Twitter– I was tweeting about this– the number of reactions you get, you don’t realize how many people have migraines until you start talking about it. And people will come up with all different things that they’ve tried, that they’ve done. A lot of people said that once– they’ve had migraines their whole lives, once they got menopause, they went away. Dr. Loder.

ELIZABETH LODER: Well, we hear all kinds of things, and no one thing seems to be true for absolutely everybody. We tend to hear about it when people have sudden remission of their attacks, and if it happens in association with something that’s very noticeable, like menopause, it often is attributed to that. Whether that’s true in any individual case is somewhat difficult to tell.

You’re absolutely right, though, about the number of people who have migraine, and it’s interesting that you got so many reactions on Twitter. You should try being a headache specialist and going to a party or any sort of gathering. We hear a lot about it.

And the reason is it’s so incredibly common. It is, by conservative estimates, something that affects 38 million people in the United States. It’s long-lasting, and the majority of people who have it have onset before the age of 35. You might be an exception.

IRA FLATOW: That’s amazing. Dr. Goadsby, do we know what is happening in the brain that causes– or when a migraine takes over?

PETER GOADSBY: We know quite a bit about it. It is a brain disease, as you’ve said. It’s what you’d call a network brain disease. So there are areas in the brain that are interacting with each other, and they start to interact in a pattern that’s abnormal or dysfunctional.

Much of it starts from a deep part of the brain, a part called the hypothalamus that’s involved in very primitive– driving very primitive things, our wanting to eat, wanting to sleep, wanting to pass urine, for example. These areas dysfunction, and the pattern with which they dysfunction determines much about the manifestation of the disease. Brain imaging’s helped us a lot in nailing down– beginning to nail down some of the important biology and dispelling any myth that migraine is anything other than a serious and biologically-determined problem

IRA FLATOW: Dr. Goadsby, let’s talk about this new class of FDA-approved drugs that have been coming out. Tell us what they are, and how are they different from earlier generations of migraine drugs?

PETER GOADSBY: Yeah, the new class you’re referring to are called gepants or gepants, it depends which side of the Atlantic you probably want to sit on. Any pronunciation at the moment’s fine. They’re called CGRP, as you said, calcitonin gene-related peptide to it’s closer friends. Receptor antagonist, they block that receptor, as you said. They’ve been developed because CGRP is involved importantly in parts of the signaling process, the network abnormality that’s going on in migraine, and they stop the effect of CGRP.

IRA FLATOW: Can they be used both for treatment and prevention?

PETER GOADSBY: Well, you– yeah, you specifically asked about ubrogepant, which has been developed and has a product label– a label in the– an FDA label for acute treatment. It has a cousin called atogepant that is being developed for prevention. One of the probably most disruptive things that’s happening in our thinking is that as one understands the biology better, you can manipulate the medicine, you might say, to suit the patient needs rather than trying to squeeze a patient into the boxes that we have for them so far. Let’s be clear that ubrogepant is not a preventive, but the concept’s being evolved that way.

IRA FLATOW: Dr. Loder. Is it working? I mean, I’ve heard miraculous stories about these drugs.

ELIZABETH LODER: Well, I haven’t used ubrogepant. It’s been recently approved by the FDA, so I haven’t had a chance to use it yet, but in the clinical trials– I think you link on your website to an article that reports on some of the clinical trials, and if you look at how many people who take the medicine have improvement of their pain at two hours, 49% of people who took placebo had improvement compared with 61% of the drug. So clearly, it’s more effective than placebo.

It doesn’t work for everybody, but nothing we have does. It’s wonderful to have medicines that work in new ways because every new treatment provides an additional option that we can offer to patients. And some of them have important attributes, like fewer side effects, and so on and so forth.

IRA FLATOW: Our number, 844-724-8255. When we left, we were talking about two medications, especially one new for– one new form that was being okayed by the FDA to come out, but there are some ones that are still out there. That was an orally administered one, and Dr. Loder, you were talking to me about one that’s injectable.

ELIZABETH LODER: Yes, we have other treatments that also work on calcitonin gene-related peptide. These are antibody treatments, biological treatments, so technically, not really drugs at all. And three of them are currently available and in use, and one is about to become available.

So these are injections. They’re intended to reduce the number of attacks that people have. They’re taken on a regular schedule. And the first was approved in mid 2018, the others later in 2018. So we have a fairly good amount of experience with these treatments now, and it’s nice to have, as I said earlier, additional things to offer patients.

Many people like the convenience of a once a month injection. For many people, these have relatively few side effects, although nothing is side effect-free, and some serious side effects have emerged, and there have been some updates to the safety labeling. But overall, it’s wonderful to have new options.

IRA FLATOW: Can people go and ask their doctors for these things?

ELIZABETH LODER: They certainly can. Now, preventive treatment, treatment aimed at reducing attacks isn’t necessarily the right approach for everyone. Some people have relatively few attacks and they do better just treating the attacks when they come. It’s also the case that often, less expensive other medications that, for many people, work equivalently well to these new treatments should be tried first.

IRA FLATOW: And of course, I can tell you from my phone board lighting up here, everybody has their own little method of getting rid of their migraine. Some work, some better than others.

ELIZABETH LODER: Yes, that’s right. And of course, people who have many attacks and have migraine for a long period of time become experts on their own illness, as you might expect, and we hear a lot of interesting things in the clinic. Almost every day I hear something I’ve never heard before.

IRA FLATOW: Well, let’s see if we can give you one you haven’t heard from Lynn in North Carolina. Hi, welcome to Science Friday.

LYNN: Yes hi, Ira. Hello, doctors. I suffered with migraines three days to four days out of every single week for about 10 years.

And as a surgeon, I was volunteering the few good days that I had at a community surgery project, and it changed everything, because I quickly found out when I started pairing when I got the migraines to what I was doing that I was super sensitive to cornstarch. When I used powdered gloves, I got the migraine, when I stopped the powdered gloves and I avoided– I started avoided all sorts of starches in my diet, I couldn’t lick stamps, I couldn’t lick envelopes, I mean, corn starch, and tapioca starch, and rice starches, and everything. But when I seriously looked into it and I started avoiding it, now I may have one migraine once a month.

IRA FLATOW: Wow. Dr. Loder, there’s something new for you, right?

ELIZABETH LODER: That’s exactly right. And first of all, I’m really glad that your headaches are better. I mean, your situation illustrates how disabling they can be. People who have that many attacks every month are in a category called chronic migraines, 15 or more headache days a month. And I’m glad that in your particular case, you were able to identify something and able to avoid it. That is a new one for me.

IRA FLATOW: Let’s see if we can get one from Karen in Gainesville, Florida. Hi, Karen.

KAREN: Hi, how are you guys?

IRA FLATOW: Fine. Go ahead.

KAREN: Yeah, so I’m 40, and I’ve been getting migraines since I was 17, and I was curious about if anything is known about hormonal effects during pregnancy. I typically only get about four a year. They’re very classic, visual aura, nausea, vomiting, needing to be in a quiet space, they last four to seven hours. But when I was pregnant with my two children, during the first trimester, I was getting them maybe every other day. And of course, I didn’t want to take anything, because I didn’t want to harm the baby, so I just sort of suffered through them. But I was curious about pregnancy and migraines.

IRA FLATOW: Dr. Goadsby, can you advise what’s going on? Is anything you can do? Obviously, you can’t take drugs when you’re pregnant.

PETER GOADSBY: I’m happy to advise. You have one of the recognized experts in the world sitting next to you. I’ll give my simple view. Starting in– starting in late adolescence, and problem still at 40, hormonal effects in pregnancy.

In the generality of things, pregnancy, certainly in the second and third trimester, is more likely to reduce migraine. It’s probably the most effective preventive that one could have, although it’s obviously not something one can practice on too regular a basis. The first trimester can be worse and can be quite troublesome, can be quite difficult to manage. Our best understanding of the changes in pregnancy are the changes in female hormones that occur, particularly estrogen, which becomes– which elevates and then becomes quite stable in the second and the third tri– in the second and third trimester.

IRA FLATOW: And we go to the world expert, Dr. Loder.

ELIZABETH LODER: Well, the situation that this particular person is describing is not all that uncommon. The good news is that for the majority of women, though not all, migraine does eventually improve during pregnancy, when, as Dr. Goadsby says, the estrogen levels become high and stable, but the first trimester can be a problem, perhaps partly because people are not sleeping terribly well. Many women are quite sick to their stomach, and those sorts of things can make migraine worse.

We do try very hard to minimize the use of medication during the first trimester and throughout pregnancy, but there are some medications, which in conjunction with your doctor, probably would be reasonable to use. We also, when we know that pregnancy is likely, and in it is wise to plan your pregnancies if you have migraine, we like to get measures in place such as training people in biofeedback or other measures, or helping them cut back on work or home responsibilities that can minimize attacks too.

IRA FLATOW: Well, related to the [INAUDIBLE] tweets, can you speak to migraines and birth control? It seems there is limited options for women. Dr. Loder?

ELIZABETH LODER: Well, it’s a very complicated subject. It is the case that women who have migraine with aura, who have that visual aura, about 20% to 30% of people have it, are usually advised against using hormonal contraception that contains estrogen. There are other forms of contraception, hormonal and nonhormonal, that are reasonable for them, and there are individual situations where it still might be reasonable to consider that. As a general rule, though, we recommend that women who have migraine with aura should avoid estrogen-containing contraceptives. And then depending on which group is making the recommendations, sometimes there also is a recommendation to avoid estrogen-containing contraceptives in women over a certain age.

IRA FLATOW: Only a couple of minutes left. Dr. Goadsby, what is the frontier of research in combating migraines? I mean, are we happy with what we have? Where do we go next?

PETER GOADSBY: Oh, we’re not happy. For all the medicines that we have, there’ll still be millions of people who are not doing well, who are disabled, but reversibly disabled is the important thing. If we get it right, we can improve them.

The frontiers are in understanding the inherited component of it, the genetically determined part so we understand how it starts, understanding in detail the parts of the brain that are involved so we can understand the chemicals, the transmitters that are involved, so eventually, we can– we can make bespoke– we can make our treatments more bespoke, better suited to the circumstance of the patient. I think the frontier is biology. Understand the disorder and we’ll be able to fix it much better.

IRA FLATOW: How close is it genetically related or a gene? Can you look for a single gene that causes migraine?

PETER GOADSBY: As Dr. Loder mentioned earlier on, there are some very rare inherited what are called weakness down one side of the body hemiplegic migraines where the genes have been identified, but that’s a very, very small group. We generally think it’s a polygenetic problem where there’s a number of genes that are involved, not one. So yes, it is something that almost invariably runs in families. And with enough investment in migraine– and there isn’t enough investment in migraine research, I’ll say that– we can understand this and we can really bring new hope to the millions of people who have this very troublesome problem.

IRA FLATOW: Why do you think there’s not enough investment in migraine, Dr. Loder?

ELIZABETH LODER: I think there are many reasons. First of all, it’s a pain disorder. Pain is subjective, and historically, hasn’t been paid as much attention to as other maybe more compelling illnesses, such as cancer.

It’s also a disorder that principally affects women, and I think that until women moved into the workplace, the disability associated with migraine was largely hidden. It was easier for people to rearrange their days and less noticeable when people were disabled by the illness, so many reasons.

IRA FLATOW: There’s reason to be hopeful then. Now that women are out there, they’re going to be paid attention to a little more.

ELIZABETH LODER: Oh, absolutely. And we have groups like the Alliance for Headache Disorders Advocacy that every year, run Headache on the Hill, where they go lobby Congress to spend more money on research and do other things that will be helpful to people with migraine.

IRA FLATOW: OK, hope we have moved the ball a little bit toward the goal line. Dr. Peter Goadsby is professor of neurology at the University of California San Francisco and King’s College London. Elizabeth Loder, professor of neurology at Harvard Med, chief of the Division of Headache, Department of Neurology at Brigham and Women’s Hospital. Thank you both.

ELIZABETH LODER: You’re welcome. Thanks for having me.

IRA FLATOW: For enlightening us today.

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