Ep 126 Migraine: A Cacophony in Four Movements

more serious, like a stroke or a meningitis. Takes a lot to get me out of my bed, to drive myself to the hospital during a snowstorm, to get an IV shoved in my arm. Hopefully that gives some indication of how miserable these things are. They're not just headaches. For every day that I have actual migraine pain, there's a period afterwards of what I call the migraine hangover, where you're just completely drained and foggy, and the nausea

can be horrific. And I get really sensitive to smells, both as a trigger and in terms of getting phantom smells before a migraine hits, which is bizarre. It could be a totally debilitating thing, and it could be really hard to feel like you're being taken seriously because it's invisible. It's incredibly frustrating to have to cancel plans or call

off work because you have another migraine. But sometimes over the counters or even your prescription migraine medicine just still isn't enough to make you functional enough to go about your day.

parents knew what was going on. At the time, there weren't a lot of migraine drugs available, and especially not for young kids, so it was just over the counter painkillers, a caffeated drink, and a nap. Over the years, I also started having abdominal migraine like regular migraine, but the pain was mostly in my stomach. In high school, I occasionally had vestibular migraine, where the primary symptom is intense nausea and dizziness without much head pain, and.

trigeminal nerve to try to prevent and manage migraine. I've a hat made of ice packs to help with head pain. I see a therapist who specializes in chronic illness. I stay extremely well hydrated. I never leave home without sunglasses, and I try to be realistic when I'm feeling especially bad and take it easy, which is sometimes easier said than done.

If not, the pain starts in the top back part of my head. There was a migraine commercial a long time ago that showed lightning bolts radiating out of a spot on the woman's head, and that's what it feels like. Lights, sound, smells, and heat become painful. My cheek feels like something is pressing inward. Sometimes, if it's bad enough, my jaw and teeth start hurting and the pain begins to radiate down my back. At this point, pretty much all is lost

and I have to go lie down. Strangely, it helps to lie down on my right side and press the painful part into the pillow. It may be the cool pillow or the pressure, but if I can get to sleep, I'll generally be better the next day.

and nothing was changing. So at this point my parents were starting to feel pretty concerned. Because when you think about someone with symptoms of having one side of their body be numb, you think about someone having a stroke. So we go to the hospital and one thing I'll never forget about this day is when we got there, they needed me to sign some sort of paperwork and I couldn't do it. My hand was so numb that

I couldn't hold a pen properly. They did all of the tests that you would do for a stroke, all of which came back completely normal. After the test, doctor came in and he asked me, do you have migraines? And I said yes, And he said, I think what you're experiencing is in a typical migraine, which I had never heard of before. But he explained to me that they can come in all different shapes and sizes, but some of the more common types present as stroke symptoms.

It took about two weeks for the numbness to completely fade away, but even now, almost ten years later, I still have a small spot above my right eye that just doesn't feel quite right. But that's my atypical migraine story. Definitely one of the scarier days of my life. But I am grateful because I know what it feels like in case it happens again.

pain and to lose concentration. I was taking over the counter pain medications almost every day, and I worried about long term damage to my organs. I tried everything from diagnostics such as MRI supplements, preventive medications, and glasses that would reduce the blue light from the fluorescent lighting. And thankfully this all changed about two years ago when my

neurologists prescribed the new monocludal antibodies, the CGRP inhibitors. I have the monthly injection for prevention and an oral abhorre and this has absolutely improved the quality of my life and reduce the severity and frequency of my migraines.

I would get incredibly dizzy, nauseous, and I would have to excuse myself, go to the bathroom, throw up, and return to class because that was really the only option I had. This kind of just continued for years and years. I never really had a chance to get things checked out until god, now, fourteen years later, now that I am an adult working in the healthcare system, I have decent insurance. So over the past twelve months, I have had two MRIs that showed absolutely nothing out of the ordinary.

It's hard to stay hopeful in terms of treatment and possibilities, especially considering that we have no idea where this comes from. I almost was hoping that we would discover a freak brain tumor or something like that, because that would mean a real answer. It's always an interesting concept to grapple with knowing that this is something that is so incredibly common and we just have so few answers as to

why so many people deal with this. But it is something that I know there is a lot of research happening with and despite having a very rocky history, I do remain hopeful.

symptoms unquote. Biology section over, that's our definition. So that's the jargoned version. The way that I'm going to break down this biology section is to try and give you an idea of what migraine really is and as much as we can know about what's happening during these migraine attacks. So migraine attack can be divided into three to four main parts or kind of like sections, and then there's

intermigraine intervals, like between migraines. So first we'll go over what these parts are, what these phases of a migraine attack are, what they look like, what they feel like, which you heard a lot of in our first hand accounts. And then we'll go over what we know so far

about what's happening in our brains during these attacks. But forewarning, as will come as a surprise to no one listening to this episode if you've ever listened to TPWKY before, there's a lot that we don't know, but there is some stuff that we do know, and so I'll try to get into some of the nitty gritty of that as well. So a migraine attack generally starts with a

period of prodromal symptoms. This period is often called the premonitory symptoms period, which can start anywhere from two hours to two days prior to the actual headache that most of us associate with migraine. So these symptoms can rain from anything like fatigue or yawning or impaired concentration. You could have neck pain or stiffness, water retention, nausea, photophobia which is difficulty looking at light. You might have food cravings.

It's a really long and kind of diverse list of symptoms that someone could have for up to two days a day or two before the migraine attack itself. About eighty percent of people that get migraines have some kind of these prodrumal symptoms, and then for about thirty percent of people with migraines, the next phase is an aura. And a lot of people have probably heard of an aura, but an aura are these very bizarre, transient focal neurologic

symptoms of various kinds. Most often, like ninety percent of the time, it's these visual symptoms. The most common one is called a scatoma or a scintillating scatoma, which sounds fancy but in fact is terrifying having had these episodes. It starts as like a flickering spot, a flickering kind of light spot, either in one eye or in both eyes, and then this spot can kind of grow or move or change and keep flickering, and scatoma just means like

a blind spot. So wherever you see this flickering wave or curve of light, you can't really see anything except that light, but the vision around it usually remains the same, and this might expand, or people can see different kinds of patterns, like a crescent or a zigzag, or different shapes, and then eventually it just stops. But an aura isn't

only visual. That's one type of aura. People can also have, like paresthesias, so like feeling tingling or prickling sensations, usually just in one part of the body, or it could be like a numbness of the face or your arm.

It could even be things like difficulties with expressive language, not being able to find your words, or not being able to say words the way that you could just minutes prior, and even more rarely, an aura could be some kind of motor dysfunction, like all of a sudden not being able to use your hands or your legs. A lot of this might sound a lot like a stroke,

because some of these symptoms can really mimic that. So this aura phase usually starts anywhere from five minutes to an hour prior to the onset of the headache, and it usually lasts under an hour and is followed pretty immediately by the headache part of migraine. That's the part that people think of when they think of migraine most often. So let's get to that. What is a migraine headache itself? Aka how do we define a migraine headache versus any

other kind of headache? So, first, this is a headache that most often is unilateral. It's on one side of the head, or it at least starts off on one side of the head and then it might move to the rest of the head. It's usually described or characterized like a throbbing pain or like a pounding pain rather than a tension type pain. And in general, a migraine is classified as moderate to severe intensity, like the pain is bad enough that you can't get out of bed,

you feel like you need to just lay down. And that's also in part because the pain generally increases with activity, which essentially forces you to just lie down. So those four characteristics unilateral throbbing pain, moderate to severe intensity, and

increasing with activity. Based on the International Classification of Headache Disorders, which is like the criteria that are used to diagnose migraine, a migraine has at least two of those four criteria, Okay, And on top of that, migraine has either nausea and vomiting and or photophobia or phonophobia, so like severe light or sound sensitivity. I know your faces, it sounds.

last up to three days. Meaning you go to bed with a headache and you wake up with the same headache, and a migraine isn't even over when it's over, because the fourth phase of migraine is the post dromal phase, and this can last again another one to two days after the headache subsides. This recovery phase can have increased in tiredness or somnolence. It can have difficulties in concentration.

A migraine altogether is a phenomenon that affects the brain on a pretty large scale, and the full duration of a migraine attack can last up to seven days if you include the premonitory and the recovery symptoms as well as the headache itself.

about it in a little bit more detail. But let's define some of these things, shall we.

are more efferent, sending signals for muscle contraction. Right, So, this trigeminal nerve mostly sensory, and like many nerves, most nerves,

is very interrelated with vasculature. It forms like complexes of nerves and arteries and veins, and in the case of the trigeminal nerve, its projections, especially in our brain, are very strongly associated with the vasculature in our brain and our ninges that's the covering of our brain spinal cord, both the dura mater, which is the outer layer of ourminingis, and the pia mater, which is the innermost layer of

our meaningis. So this trigeminal complex, as it's called, has these a sending nerve axons that project into a whole bunch of brain regions in our brainstem our, hypothalmus, our thalmis, our cortex. All of these regions of our brain are involved in a whole bunch of stuff that we happen to see dysregulated during a migraine. These involve our response to pain and no suception. So no susception is just the actual nerve signals of pain, like our nervous system

getting those signals is the process called no susception. Our no susceptors are pain nerve fibers. There are a bunch of other neurons that are projecting to parts of our auditory, visual, and olfactory system, part of our cortical brain, regions that are involved with movement or even concentration. All of these different brain regions that happen to correspond to a lot of the non pain symptoms of migraine as well as these no susceptive or pain related symptoms. So think things

like photophobia, nausea, vomiting, difficulty focusing, all of that. So we know that the trigeminal vascular complex is activated and involved in this process of migraine and in kind of all of the phases of it.

see released by this trigeminovascular complex during migraines. And we now know that blockade of this peptide or its receptors by various medications is effective in many cases at stopping migraine. We think that CGRP acts predominantly in the dura mater, so the outer layer of our menins, and that what it does is modulate the trafficking of these no susceptive signals.

What does that mean. It means that CGRP is involved in the sending and receiving of the pain signals that are involved in migraine, and it may also be involved in inflammation. And there's still some thought that inflammation is involved in the migraine process.

So there's a thought that like, once the pain signals have started to be sent, now our brain is acting a little bit on overdrive in response to those signals, and then yeah, you're right, that's a really hard ball to stop rolling essentially.

we don't understand the initiation of migraine pain. We don't understand why it stops eventually, why it lasts for as long as it does, why it can be so different both between individuals as well as in one individual throughout their lifetime. There is so much that we don't know it's really frustrating. It is, it is. And then there's aura.

or cortical spreading depression, depression depolarization, same thing. And so when we have an aura, the symptoms tend to start kind of small and they grow or kind of propagate rather slowly, especially compared to another rapid depolarization phenomenon that we've talked about on this podcast.

nerve is firing, like a signal is firing. But this is happening like all in this one area and then propagating along the cortex of the brain like dumb kind of yeah, And we have like MRI and PET scan studies that show additionally changes in blood flow like hyper perfusion followed by hypoperfusion, so like more blood flow and then all of a sudden less blood flow in regions of the brain that are corresponding to the symptoms of aura.

And there's evidence that this cortical spreading depression, this depolarization can then trigger or activate the trigeminovascular system, but we still don't know what the susceptibility is for this cortical spreading depolarization or depression. And we also don't know why is it then that only thirty percent of people have AURA with their migraine, et cetera. There's there's like some oh, this is involved and it activates the system, and maybe

that's the pathway to then migraine pain. But what about when you don't have an aura, Because people with migraine with aura can also still have migraines without aura, So it's complicated.

some forms of seizures or epilepsy. Yeah, so I want to go into a little bit more detail, not necessarily on this path of physiology, but on like the big picture of migraine and migraine biology. Everything that I went over and the criteria that are in the ICHD three. Those are all for migraine, like called classic migraine and migraine with aura. There is also a distinction between what's

called episodic migraine and so called chronic migraine. But the term chronic migraine is confusing and like a crappy term because like, most people who have migraines have them chronically. But what chronic migraine actually means is that people have a very high frequency of migraines. Chronic migraine is classified as at least fifteen headache days per month.

exist because they're important. There's abdominal migraine, which is much more common in kids, but can persist into adulthood. It's very similar in terms of all of the prodramal symptoms, but instead of headache pain, it's intense abdominal pain that lasts between two and seventy two hours. And it has very similar non pain symptoms nausea, vomiting, photophobia. All of this huh yeah, I have a great paper if you

want to read more details about it. But there's a huge connection between the mind and the gut, and there's association between migraine, headache, and abdominal migraine. There's a lot there. Migraine is also in relatively large part genetic, About forty to sixty percent of expression of migraine is from genetic factors. But that being said, this is nowhere close to like a one gene one disease problem. There are thirty eight different low side so far that have been identified as

increasing our susceptibility to migraines. But there are also a handful of monogenic migraine syndromes. These are a single gene mutation that also leads to migraine, and these, while they're quite rare, have become really important in terms of studying and understanding migraine because we can identify the specific changes that happened as a result of this one genetic mutation.

One of those that I just want to shout out is called familial hemiplegic migraine, and this is characterized by migraines. They're hereditary and in addition to having all the features I just talked about of migraine and aura, they also cause a temporary hemiparesis, which means a one sided muscle weakness really like looks like a stroke.

this level of migraine. So it gives us a lot of idea on potent targets for migraine treatment, both for people with these gene disorders as well as migraines. In general.

system or something. But it's also because the spinal trigeminal nucleus in our brain stem, in addition to receiving information from our trigeminal nerve, it also gets information from a bunch of other nerves like our facial nerve, our glossophringal nerve, and our vagus nerve, which is our main parasympathetic nerve. And so whenever you have a mess up in our parasympathetic system, you can have a lot of very generalized symptoms. Right now, why would people feel better after they barf?

I don't, I don't know, correct, But yeah, that's so, it's it's all complicated, it's all involved. But if all of that wasn't enough, as I kind of briefly mentioned when you brought up stroke, Aaron, there are also associations that are not well understood mechanistically but definitely seem to exist epidemiologically between migraine and a bunch of neurologic and psychiatric disorders. This includes epilepsy, it includes stroke, depression, anxiety,

and probably more that I'm not mentioning. And one of the things that kept coming up in everything that I read that was so interesting about these relationships is that they're often described as bidirectional. For example, having an episode of major depressive disorder puts one at higher risk of having migraine, and having migraine puts one at higher risk of having major depressive disorder. At least based on some epidemiological studies, like in both directions.

And then there's triggers. Yeah, when it comes to migraine triggers, there's not really one thing that is true for all individuals with migraine, and we don't know because we know so little about the mechanisms of migraine initiation. We don't know how triggers that people may have identified in themselves

trigger a migraine in them or in anyone else. But there are some things that seem to be relatively common triggers for most people that experience migraines, and these are things like stress, which could be emotional or physical stress, lack of sleep or poor sleep quality including jet lag, and hormonal fluctuations, in particular estrogen or a withdrawal of estrogen compared to where you were at previously. This is often a huge precipitate or trigger, especially for people who menstrate.

We have very significant hormone fluctuations on a cyclic basis, So for some people that means increases in migraines with periods. For some people, pregnancy and breastfeeding causes a decrease in migraine symptoms, and then menopause causes an increase in migraines, whereas postmenopause might be a decrease or an elimination entirely of migraines.

that is that migraines for many people are treatable. There's a number of different medicines. Some of them, like the trip dands work at the five HT or the serotonin receptors which cause vasoconstriction and inhibit the release of a whole bunch of neurotransmitters, including CGRP and others, and then there's newer medications that you've probably seen commercials for if you don't pay for premium Hulu like me, Like ubrel V and ner Tech. These medicines are specifically inhibitors of

that CGRP peptide that we talked about. And then we'll talk in the current events section about other modalities that have come up and how much research is being done. Yeah, none of these treatments are perfect, but there are a lot of options. So, Aaron, tell me, how did we get here? How do I even ask that question?

But the answers to all of those questions like whether or not aura has to be present for something to be considered a migraine, or whether migraines are caused by vascular or neurological changes, or if they have a physiological basis at all, those are not going to be the same throughout the history of migraine and how those answers evolve can tell us more about what was going on in the medical field or even society more broadly than it can tell us about the path of physiology of migraines.

To be honest, it can tell us about what new ideas were popular at certain times or what new discoveries

were made. Like for instance, when allergies or allergens were first identified as a concept, many physicians thought, hey, maybe migraines are caused by allergens, and they tried desensitization as a result, like allergy shots, or when hysteria was a popular diagnosis, it was you bring this on yourself, and you know, the advice was just don't be so stressed out, don't be so overworked if you want to prevent migraines, like just just don't work so hard, chill out, just

just chill out. Yeah. Or when you're finding earthworms crop up as an ingredient for migraine treatment, that's a sign you're probably in the medieval period in Europe, we'll get there. Humans have always tried to explain diseases or other phenomena within the bounds of whatever knowledge we currently have, and the way we treat those diseases is heavily influenced by

popular ideas about what their causes are. We still do that, and it's easy to lose sight of that that our current perception of migraine is only the latest in a long line and is subject to change and likely will change, hopefully for the better. But before you can tell us about what those positive changes might be, let's first go back to the early history of migraines so we can see just how far we've come, at least in some ways.

And I want to give a huge shout out to the book that I used as my primary source for this history section, and that is Migraine, a History by Catherine Foxhall. It's a great read, and I'll definitely be quoting from it. It shouldn't surprise you even just how incredibly prevalent they are to learn that migraines have been known about, written about, experienced, treated for thousands of years. You can find mentions of migraines in basically any ancient

medical text from any part of the world. The Ebers Papyrus from around fifteen fifty BCE describes extreme pain in one half of the skull that should be treated by anointing the head with the skull of catfish fried in oil or fat for four days. Of course, I don't know if that meant fried for four days or just like anointed. I'm guessing anointed for four days.

And it's in these texts from the fifth century BCE that we find our first clear description of migraine with aura a young man phoenix with quote flashes like lightning in his eye, usually the right And when he had suffered that a short time, a terrible pain developed towards his right temple, then in the whole head, and then into the part of the neck where the head is attached behind the vertebra, and there was stretching and hardness

around the teeth. He kept trying to open them, straining vomits whenever they occurred, averted the pains I have described and made them more gentle. Phlebotomy helped, okay. About five hundred years after this description, Galen originated the term hemicrania to describe a condition a syndrome really wasn't like considered a disease. It was more of a syndrome, I guess, where half of your head was in pain and sometimes

associated with stomach disturbance. Hemicrania turned into emigrania in Latin and Middle English, and then to migran in medieval Welsh, and then to magrime, and then we see all sorts of variations like migrim, migrime, migrime, like the spellings.

What did people think caused it? Aaron, I'm sure you can guess with the leading hypothesis for the cause of migraines from like ancient times until I don't know, seventeen hundreds or.

involved getting the humors back into balance. For example, consider this somewhat complicated treatment, aren't they always from an old English medical text called Bald's Leech Book from nine to fifty CE. I know, I want a copy of this me too. Quote for ache of half the head, take the red nettle of one stalk, bruise it, mingle with vinegar and the white of an egg. Put all together, anoint therewith. For a half head's ache, bruise and vinegar with oil the clusters of the loris. Smear the cheek

with that. For the same take juice of rue ring on the nostril, which is on the sore side. For a half head's ache, take dust of the clusters of laurel and mustard, Mingle them together, Pour vinegar upon them, smear that with the sore side, or mix with wine the clusters of laurel, or rub fine in vinegar the seed of rue. Put equal quantities of both. Rub the back of the neck with that.

year round. If a recipe calls for a fresh nettle and you're in the middle of winter, like, where are you going to get that? Or even if you just run out right. Yeah, And the availability of ingredients would have also changed as trade became more widespread and more herbs and spices were introduced, which I think is so interesting to think about, Like you can sort of track how trade influenced home remedies for certain conditions over time.

it lie until it do fall off itself. So in case you missed it, ground up earthworms, the long worms of the earth made into a paste that you put on.

Moving on. But in this book was the first time that I've actually come across an explanation for why earthworms, for example, Okay, there is a reason, and honestly I kind of like it. I think it's very I think it's very interesting. Earthworms, because they lived in the dirt feeding on rotten matter, were believed to also eat or consume the rotting matter in your body that caused whatever disease you had.

ingredients that you could find relatively easily. And that's evidenced by the fact that migraine treatments found their way into many home remedy books during the fifteen hundreds and sixteen hundreds, also showing once again how common migraines were. In one there was even a diagnostic tool where you were supposed to be able to like I didn't quite understand it, but it was like, how much I think of your hand or your thumb you can fit into your mouth?

What during a migraine? Because if you can't fit however many knuckles in, then you had a migraine.

people to purchase and doctors to patent and prescribe. Then, as hospitals were increasingly built and high population densities and cities meant that doctors could see really orders of magnitude more patients in a year than in past times, they started to observe more about migraines, how frequently they occur, how long they last, what age they usually first happen, the range of symptoms. And armed with these new observations, they began to draw conclusions about who was getting migraines

and why. Were migraines just a cost of social progress in temperance, sedentary lifestyles, lack of restraint, urban living. All of these things the negative side of social progress, were thought to contribute to the rise of quote unquote nervous conditions, something that we've absolutely talked about on the podcast in terms of at least gout and asthma. Essentially, the view was that as society grew more corrupted, so did our bodies. Was it a wandering uterus?

later on a personal failing. And part of this was, ironically, because physicians were paying more attention to this condition and taking note of other symptoms like gipset or dizziness as pain as the primary feature took a back seat. The delegitimization of migraines in the late seventeen hundred and throughout much of the eighteen hundreds shifted who was responsible for managing this condition. It was no longer the doctor that had to figure out the correct course of treatment. It

was now on the person themselves. If only they didn't overeat, if only they ate at more normal times, if only they didn't drink as much, didn't lays around as much, didn't work so hard, exercised more, exercise less, studied more studied, less, slept more. We're less ambitious, we're less sensitive, less feminine, stronger. Then maybe, just maybe they wouldn't bring this on themselves. Oh Okay, I.

nerves themselves were more under a person's control. But those things, what things affected nerves, of course, depended on the person. And with this increased attention on migraines, physicians began to split them up into different types, often gendered. For example, so called anemic migraines affected quote mothers in the lower classes of life end quote, whose bodies were quote hourly

drained by lactation end quote. But don't worry. If you were a woman in a higher class, you could still get migraine just called neuralgic headache, which were quote undoubtedly hysterical end quote in origin.

towns end quote. But for men of a somewhat higher social grade, it was generally using your brain too much, like reading too much, writing too much, working in legal chambers or the counting house, too much competition, the excitement of the university and professional life, the anxiety that came from too much ambition and so on. It could be literally anything, but it's always the person's fault, and the remedies for all these different types of migrain were fairly straightforward.

A break from the stressors, which could include maybe a more nutritious diet, not working or studying as much, or for an overworked mother, a forced absence from the home. Yeah, that happened, okay, And they're just like, you're afraid to delegate. There's tons of people that can help out with your kids, like just leave them. And whether or not any of these things were practical, Like let's say that you are

working in one of these factories. It's not like you could just be like, oh yeah, let me just take some days off work, No problem, I'll take a vacation to the countryside where the fresh air, the fresh sea air will do me good.

to changes in lifestyle. The rise of hospitals and other medical institutions like asylums provided ample opportunities for physicians to test out experimental treatments just the latest and greatest, including opium, potassium bromide, arsenic quinine, and cannabis, which was actually a favorite among many doctors and patients, but nothing reliably worked,

as I'm sure you could guess. And contributing to this lack of meaningful progress in migraine research, at least in terms of treatment through the late nineteen and into the

twentieth century was the lack of certainty in diagnosis. As a quote unquote invisible illness, people with migraine could appear healthy even in the midst of a horrific attack, which made it easier for physicians to dismiss their pain or not take it seriously, with some physicians saying that, oh, someone who is in that much pain can't be relied upon to recount their experiences accurately. Okay, not sick enough to be considered chronically ill, but not well often enough

to be healthy. Something like that. It was just like middle ground pain as a subjective experience couldn't be trusted by these physicians as the sole diagnostic criterion for migraine,

and so they turned to aura. Visual disturbances had long been associated with migraine, but hadn't really been studied in a systematic way until the mid to late eighteen hundreds, when two scholarly men, British mathematician, astronomer and chemist Sir John Herschel and physician Hubert Airy, presented their experiences of quote unquote ocular spectra at a couple of scientific meetings.

They described disruptions in visions that could be induced by the shining of a strong light and a quote singular shadowy appearance end quote that sat at the corner of vision and then came into full view with kaleidoscopic, colorful

geometric patterns. Airy also shared a drawing of his visual disturbance, which he called hemiopsy, and his drawing, which was jagged swirling lines on a black background, became one of the most famous and recognizable illustrations of migraine aura, which had become front and center in migraine diagnosis and research as debates continued about whether the condition had a vascular or neurological basis, and effective treatments were of course still nowhere

to be found, and that's how things remained for the first decades of the twentieth century. The pain from migraines took a backseat to aura, which had become romanticized, especially with people claiming all sorts of historical and religious figures must have had aura and migraine because their religious visions or drawings resembled aura. Hildegarde of Bingen, if that's how you say it, hopefully, a saint who lived in Germany in the twelfth century, was foremost among these and has

been called the patron saint of migraines. And really her retrospective diagnosis kicked off a whole bunch more, including Moses Ezekiel, Daniel, Saint John, the Divine, Charles Darwin, Pablo Picasso, Rudyard Kipling, Virginia Wolf, etc. And I don't know the details of what went into each of these retrospective diagnoses, like what symptoms did they use. I think for Picasso they just looked at his drawings and they were like, yeah, sure,

Like did he ever write about pain anyway? And of course it is possible that several or even all of these people had migraines. Migraines are incredibly prevalent after all.

But the problem with these retrospective diagnoses was how they were used by some people to push this message, which was that a visual aura was the defining feature of migraines and that b people who had the most extreme visual disturbances with migraine were the quote clever, intellectual people endowed with the creative type of mind and quote yeah, and it furthered this idea of there being a quote unquote migraine personality, which had evolved from the gender and

class stereotypes of the late nineteenth century Prepare yourself, my dear. According to the American physician Walter Alvarez from the mid twentieth century or so, the typical migraine patient was female, quote tense, perfectionist, hypersensitive, easily fatigued, and often depressed or disconnected end quote. They also had bad periods and quote unquote defective and poorly functioning pelvic organs. What but don't worry. She was also quote decidedly feminine and sexually attractive quote

but with a masculine vibe. That quote causes her to act independently and to think dispassionately, much as does an able businessman.

They were impatient and resentful, cold, and aloof been brought on migraines by not adapting well to situations like going on vacation. Just like relax. You can't relax on vacation. You're going to get a migraine. You're going to give yourself a migraine.

the prodromal phase of a migraine itself. So like, so it's really even more frustrating to hear like these, oh, you're you're causing yourself stress, Like it could genuinely be that people's brains are increasing certain stress responses or something in a way that's entirely outside of your control, and then a migraine follows.

going to feel comfortable asking for help? It's so frustrating because, like I said, for the vast majority of human written history, migraines were handled as real medical problems with a physical basis, only to have that undermined by physicians who were probably projecting their own insecurities over not being able to effectively treat migraines or define them. And I have no doubt that contributing to this was the gender distribution in migraines,

with women much more likely to experience them. This dismissive attitude towards migraines, the idea of a migraine personality or a taking center stage as a symptom. We're still feeling all of the effects from this today. And there's a book that I didn't get a chance to read for this episode, but I really want to read, called Not Tonight, Migraine and the Politics of Gender and Health by Joanna Kempner that goes into this in much more depth, and

I'll link to it on our website. But this downplaying of migraines as just really bad headaches and sort of the casting off of pain, like dismissing pain as the feature for most migraines has contributed to the gap in research funds for migraine treatments and the lack of general awareness around the cause and especially the impact of migraines.

They can be debilitating, incapacitating, excruciating, even with stress control, whatever that means, even with sufficient sleep, even with taking a break from the kids, even with medication, even with doing whatever else a doctor tells you not to do, so that you don't bring this on yourself. You can't. I'm just so frustrated, and I can't help but feel that doctors in the late nineteenth century in early twentieth century they took one look at migraine and thought, I

don't know what this is. I can't treat this. Therefore it must not be real, or at the very least, it must not be as bad as they say, or it's probably a personal failing on their part, because I'm a trained medical professional and I can't admit that I don't know something or can't treat something. Let me read you one final quote from a physician, and then I'll get us off this rage train. Maybe. In nineteen o two, J. M. Aiken wrote in jama that quote, of all the common

and much dreaded nervous diseases we recognize. None are less perfectly understood than migraine. Nor is there any other nervous disorder which is so disastrous to the physician's ability for treatment. It is easy to say what migraine is not, but difficult to define what it is end quote.

a lot of progress in how to treat it, first with the introduction of ergotamine and then like migral tablets, which was a combination of ergotamine, caffeine, and cyclazine introduced in the nineteen fifties. And then also another treatment that you mentioned, which was introduced in the nineteen eighties was

the trip dans, with the first one being sumatriptan. And so we've come a long way in our understanding and prevention slash management of migraine, but we clearly have so far to go still, not just in treatments and making those treatments accessible for everyone who needs them, but also in reducing stigma, shame, and blame surrounding migraines, like believing people what a concept? Why is it so hard? Why is pain the most dismissed thing?

I'm sure that we'll look back on this period of time with similar diseases that right now are classified as psychosomatic or whatever it is, you know, Like anyway, I'm at the very end of this gone on this rant, and now I should just stop myself and turn it over to you, Aaron.

this is young people being very significantly affected. Among people with active migraine, the median monthly attack frequency, so how many episodes of migraine per month is one point five but a quarter of people have weekly attacks. And remember that the total duration of a migraine attack can last up to a week. Oh my gosh, right, And up to five percent have chronic migraine, which again means fifteen headache days a month, eight of which meet criteria for migraine.

So with all of that being said, it should come as no surprise, though this was shocking to me. The World Health Organization ranks migraine as the most prevalent disabling long term neurologic condition period and it's not necessarily because

it's the most common. Even in terms of headaches, tension type headaches are far more common than migraine, but migraine is so disabling that, as an example, while tension type headache affects almost a billion more people worldwide, like eight hundred million more people than migraine, migraine causes six times as many estimated disability adjusted life years or years lived with disability.

especially because we have treatments. Migraine is the leading cause of disability worldwide for people younger than fifty years, especially for women. And I don't want to just go based on disability adjusted life years or years lost to disability,

because we know that that's an imperfect metric. But I also have read that in studies that have looked based on survey data from the US at least on people's reported effect on their lives, that up to thirty percent of people who live with migraines say that it affects their careers in some way, thirty percent say that it affects their parenting in some way, and nearly fifty percent feel that it affects their relationships. Yeah, that's huge, and caveat that those numbers are based on US data, so

we don't know the universality of that. But it's I mean, this is not a minor disorder.

of lost productivity at work, et cetera. Whereas in the US, direct costs are estimated at eleven billion dollars annually and indirect cost twelve billion dollars annually. Wow, So there's a lot of discrepancy there. I'm sure there's a whole podcast about that. So migraine is a massive issue, and most of the data that we have on migraine come from Europe and the US and high income countries, but migraine is a global phenomenon that affects people across the entire world,

and in low and middle income countries. Not only do people tend to lack access to a lot of treatment or even diagnosis options, people are far less likely to be diagnosed accurately with migraine in low and middle income countries. We also have much less data to guide policy and to guide programs, and part of this is because the focus tends to be in low and middle income countries on other additionally pressing health issues, things things like TB and HIV, which are more common in low and middle

income countries. But that's despite the fact that migraine is also causing massive amounts of disability in these countries as well.

down the pipeline. There have been new monoclonal antibodies that specifically target this CGRP pathway, and many of which are intended to be used as preventative treatment, so especially for people who have chronic migraine or just a high burden of migraine, you know, each week or each month, even if they don't meet criteria for chronic migraine preventative rather than just what are called abortive treatments or treatments made

to be used when a migraine happens. Right, And there have also been other oral medications that includes that whole class called the jeptins, which are the ones that have commercials right now, like Ubrelv and Nurtec. I probably shouldn't use brand names, but whatever. These are things that also target that CGRP peptide. There's also a brand new nasal spray that targets the same peptide.

But there isn't like a silver bullet, and a lot of that is because there's still just so much that we don't know when it comes to migraine.

twenty twenty one. There's Nature papers and New England Journal papers, like a lot of kind of high profile research that's really really recent when it comes to migraine. So that gives me hope that it's getting a lot more attention because we're recognizing what a massive issue it really is, that's migrain.

I mentioned already, but there's a great series. It's three different papers about different aspects of migrain, from the epidemiology to disease characterization like biomarker research and approaches to management and emerging treatments that all came out in the Lancet twenty twenty one. We'll have a list of this and all of our sources from this episode and all of our episodes on our website This podcast will kill You dot Com under the episodes tab.