WEBVTT - Ep 126 Migraine: A Cacophony in Four Movements 0:00:00.440 --> 0:00:03.640 My name is Kaylee. I've been getting migraine since I 0:00:03.760 --> 0:00:05.960 was a kid, but over the last eight years or 0:00:06.040 --> 0:00:11.360 so it's become a battle against chronic daily migraines. The 0:00:11.360 --> 0:00:14.520 singular worst pain I've ever felt in my life. I 0:00:14.560 --> 0:00:18.759 will never forget it. It was January twenty nineteen, at 0:00:18.800 --> 0:00:22.560 three am, during a blizzard. I woke up with a 0:00:22.600 --> 0:00:25.640 ten out of ten pinscale migraine, which is the kind 0:00:25.680 --> 0:00:28.080 where you worry that maybe this time it's actually something 0:00:28.120 --> 0:00:31.880 more serious, like a stroke or a meningitis. Takes a 0:00:31.880 --> 0:00:34.600 lot to get me out of my bed, to drive 0:00:34.680 --> 0:00:38.720 myself to the hospital during a snowstorm, to get an 0:00:38.760 --> 0:00:42.440 IV shoved in my arm. Hopefully that gives some indication 0:00:42.640 --> 0:00:46.080 of how miserable these things are. They're not just headaches. 0:00:46.120 --> 0:00:48.600 For every day that I have actual migraine pain, there's 0:00:48.640 --> 0:00:51.599 a period afterwards of what I call the migraine hangover, 0:00:52.280 --> 0:00:56.440 where you're just completely drained and foggy, and the nausea 0:00:56.480 --> 0:01:00.360 can be horrific. And I get really sensitive to smells, 0:01:01.440 --> 0:01:04.480 both as a trigger and in terms of getting phantom 0:01:04.520 --> 0:01:09.039 smells before a migraine hits, which is bizarre. It could 0:01:09.040 --> 0:01:12.200 be a totally debilitating thing, and it could be really 0:01:12.200 --> 0:01:17.000 hard to feel like you're being taken seriously because it's invisible. 0:01:17.240 --> 0:01:21.040 It's incredibly frustrating to have to cancel plans or call 0:01:21.080 --> 0:01:26.440 off work because you have another migraine. But sometimes over 0:01:26.480 --> 0:01:31.200 the counters or even your prescription migraine medicine just still 0:01:31.319 --> 0:01:35.679 isn't enough to make you functional enough to go about 0:01:35.760 --> 0:01:38.480 your day. 0:01:38.560 --> 0:01:41.880 I'm Katie, and I have chronic migraine. Chronic is defined 0:01:41.880 --> 0:01:44.440 as fifteen or more days a month with migraine symptoms. 0:01:44.920 --> 0:01:47.560 I average about twenty eight days a month. I've had 0:01:47.640 --> 0:01:51.000 migraine pretty much my entire life. My mom also has migraine. 0:01:51.080 --> 0:01:52.560 So when I was five or six years old and 0:01:52.560 --> 0:01:55.960 started getting excruciating headaches so bad I threw up, my 0:01:56.040 --> 0:01:58.720 parents knew what was going on. At the time, there 0:01:58.720 --> 0:02:01.360 weren't a lot of migraine drugs available, and especially not 0:02:01.440 --> 0:02:04.440 for young kids, so it was just over the counter painkillers, 0:02:04.440 --> 0:02:07.480 a caffeated drink, and a nap. Over the years, I 0:02:07.520 --> 0:02:10.840 also started having abdominal migraine like regular migraine, but the 0:02:10.840 --> 0:02:13.480 pain was mostly in my stomach. In high school, I 0:02:13.520 --> 0:02:16.720 occasionally had vestibular migraine, where the primary symptom is intense 0:02:16.800 --> 0:02:19.400 nausea and dizziness without much head pain, and. 0:02:19.440 --> 0:02:21.040 Which could last for months at a time. 0:02:21.760 --> 0:02:23.839 I carried on having a few migraine episodes a month 0:02:23.840 --> 0:02:26.440 through college, when I got sumatripton, an older. 0:02:26.160 --> 0:02:28.000 Aboard of drug, which worked for a while. 0:02:28.760 --> 0:02:30.799 Still about once a year nothing would work and I'd 0:02:30.800 --> 0:02:32.800 have to go to the er for an IV cocktail. 0:02:33.240 --> 0:02:36.239 Then in my mid twenties, the medication stopped working as well. 0:02:36.320 --> 0:02:38.960 The episodes became a lot more frequent, until they were chronic, 0:02:39.200 --> 0:02:41.920 and they'd been that way for about three years. In 0:02:41.960 --> 0:02:44.679 that time, I've tried most treatment options, some of which 0:02:44.720 --> 0:02:46.320 didn't work at all and some of which had side 0:02:46.320 --> 0:02:47.560 effects I couldn't tolerate. 0:02:47.800 --> 0:02:49.680 Right now, I've landed on one anti. 0:02:49.400 --> 0:02:52.359 Epileptic drug that helps I get an IV infusion of 0:02:52.400 --> 0:02:55.320 monoclinal antibodies once every three months, and I'd take a 0:02:55.320 --> 0:02:57.840 pill nightly and then another pill when I'm getting a migraine. 0:02:57.960 --> 0:03:00.639 Even though they don't completely treat my migraine. Drugs are 0:03:00.720 --> 0:03:03.920 huge for my quality of life, but they're also really expensive, 0:03:04.120 --> 0:03:05.680 so I spend a lot of time on the phone 0:03:05.680 --> 0:03:09.239 with insurance. I also use an neerrosimulation device and my 0:03:09.320 --> 0:03:12.400 trigeminal nerve to try to prevent and manage migraine. I've 0:03:12.440 --> 0:03:14.480 a hat made of ice packs to help with head pain. 0:03:14.800 --> 0:03:17.640 I see a therapist who specializes in chronic illness. I 0:03:17.680 --> 0:03:21.799 stay extremely well hydrated. I never leave home without sunglasses, 0:03:22.200 --> 0:03:24.400 and I try to be realistic when I'm feeling especially 0:03:24.440 --> 0:03:27.119 bad and take it easy, which is sometimes easier said 0:03:27.120 --> 0:03:27.640 than done. 0:03:29.760 --> 0:03:31.840 The first sign that a migraine is brewing is that 0:03:31.880 --> 0:03:35.400 my eyes start it's behaving. I get my migraine solely 0:03:35.440 --> 0:03:37.880 on the right side of my head, and things just 0:03:37.960 --> 0:03:41.040 look brighter out of that eye. It feels like that 0:03:41.160 --> 0:03:44.480 eye is open wider than the other, even though it isn't. 0:03:45.400 --> 0:03:48.840 I'll have flashing lights and sometimes it's hard to find words. 0:03:50.120 --> 0:03:53.400 Sometimes I can avoid getting a full on migraine if 0:03:53.560 --> 0:03:58.200 at that particular instent, I take a CGRP inhibit or 0:03:58.280 --> 0:04:03.960 rescue medication, eat a candy bar, and drink a diet soda. 0:04:04.560 --> 0:04:07.040 If not, the pain starts in the top back part 0:04:07.080 --> 0:04:09.840 of my head. There was a migraine commercial a long 0:04:09.840 --> 0:04:13.240 time ago that showed lightning bolts radiating out of a 0:04:13.280 --> 0:04:20.359 spot on the woman's head, and that's what it feels like. Lights, sound, smells, 0:04:20.400 --> 0:04:24.440 and heat become painful. My cheek feels like something is 0:04:24.480 --> 0:04:28.800 pressing inward. Sometimes, if it's bad enough, my jaw and 0:04:28.920 --> 0:04:32.799 teeth start hurting and the pain begins to radiate down 0:04:32.839 --> 0:04:36.920 my back. At this point, pretty much all is lost 0:04:36.960 --> 0:04:40.159 and I have to go lie down. Strangely, it helps 0:04:40.160 --> 0:04:42.320 to lie down on my right side and press the 0:04:42.360 --> 0:04:45.719 painful part into the pillow. It may be the cool 0:04:45.760 --> 0:04:49.040 pillow or the pressure, but if I can get to sleep, 0:04:49.160 --> 0:04:51.120 I'll generally be better the next day. 0:04:53.120 --> 0:04:57.120 My name is Darcy. I'm twenty eight, and I started 0:04:57.160 --> 0:05:00.760 having migraines when I was around ten years old. I've 0:05:00.760 --> 0:05:04.279 been diagnosed with chronic migraines, but I also have atypical 0:05:04.320 --> 0:05:08.479 migraines occasionally. So when I was nineteen, I woke up 0:05:08.560 --> 0:05:12.160 one morning and the right side of my face and 0:05:12.320 --> 0:05:15.400 my right arm felt a little tingly. The more I 0:05:15.480 --> 0:05:19.000 moved around, the worse the tingling got to the point 0:05:19.040 --> 0:05:22.200 where the right side of my body was just starting 0:05:22.200 --> 0:05:26.800 to feel numb. We let a couple hours pass, I think, 0:05:26.920 --> 0:05:30.640 and nothing was changing. So at this point my parents 0:05:30.640 --> 0:05:34.320 were starting to feel pretty concerned. Because when you think 0:05:34.360 --> 0:05:39.000 about someone with symptoms of having one side of their 0:05:39.080 --> 0:05:42.600 body be numb, you think about someone having a stroke. 0:05:43.320 --> 0:05:46.279 So we go to the hospital and one thing I'll 0:05:46.320 --> 0:05:50.200 never forget about this day is when we got there, 0:05:50.320 --> 0:05:54.040 they needed me to sign some sort of paperwork and 0:05:54.200 --> 0:05:57.720 I couldn't do it. My hand was so numb that 0:05:57.839 --> 0:06:01.560 I couldn't hold a pen properly. They did all of 0:06:01.640 --> 0:06:04.360 the tests that you would do for a stroke, all 0:06:04.400 --> 0:06:09.280 of which came back completely normal. After the test, doctor 0:06:09.360 --> 0:06:13.600 came in and he asked me, do you have migraines? 0:06:13.640 --> 0:06:16.719 And I said yes, And he said, I think what 0:06:16.800 --> 0:06:21.000 you're experiencing is in a typical migraine, which I had 0:06:21.040 --> 0:06:25.359 never heard of before. But he explained to me that 0:06:25.720 --> 0:06:28.760 they can come in all different shapes and sizes, but 0:06:29.000 --> 0:06:33.440 some of the more common types present as stroke symptoms. 0:06:34.080 --> 0:06:37.560 It took about two weeks for the numbness to completely 0:06:37.600 --> 0:06:41.320 fade away, but even now, almost ten years later, I 0:06:41.400 --> 0:06:45.200 still have a small spot above my right eye that 0:06:45.320 --> 0:06:49.839 just doesn't feel quite right. But that's my atypical migraine story. 0:06:50.080 --> 0:06:52.479 Definitely one of the scarier days of my life. But 0:06:52.760 --> 0:06:55.599 I am grateful because I know what it feels like 0:06:55.720 --> 0:06:56.920 in case it happens again. 0:06:59.200 --> 0:07:02.000 Hi, my name is I'm thirty five years old and 0:07:02.040 --> 0:07:05.880 I've been having migraines since I was about twelve. These 0:07:05.920 --> 0:07:09.840 progressed to having about fifteen to twenty headache days per month. 0:07:10.760 --> 0:07:13.720 I had a lot of anxiety around my triggers, such 0:07:13.720 --> 0:07:18.000 as flying in airplanes, weather changes, too much sun or heat, 0:07:18.360 --> 0:07:23.000 certain foods, and fluorescent lighting. I'm a veterinarian, so I 0:07:23.040 --> 0:07:25.960 went through a lot of schooling, and school could sometimes 0:07:26.000 --> 0:07:29.040 be difficult since the migraines caused me a lot of 0:07:29.080 --> 0:07:33.120 pain and to lose concentration. I was taking over the 0:07:33.160 --> 0:07:36.080 counter pain medications almost every day, and I worried about 0:07:36.120 --> 0:07:39.480 long term damage to my organs. I tried everything from 0:07:39.560 --> 0:07:45.040 diagnostics such as MRI supplements, preventive medications, and glasses that 0:07:45.080 --> 0:07:48.400 would reduce the blue light from the fluorescent lighting. And 0:07:48.440 --> 0:07:51.440 thankfully this all changed about two years ago when my 0:07:51.480 --> 0:07:56.680 neurologists prescribed the new monocludal antibodies, the CGRP inhibitors. I 0:07:56.760 --> 0:07:59.960 have the monthly injection for prevention and an oral abhorre 0:08:00.680 --> 0:08:03.360 and this has absolutely improved the quality of my life 0:08:03.520 --> 0:08:06.640 and reduce the severity and frequency of my migraines. 0:08:08.080 --> 0:08:08.200 Right. 0:08:08.320 --> 0:08:10.560 My name is Chris. I'm a twenty six year old 0:08:10.560 --> 0:08:14.320 transgender man, and I've been dealing with migraines for most 0:08:14.320 --> 0:08:19.160 of my life. It all really started rolling when I 0:08:19.240 --> 0:08:22.400 was in middle school, so around twelve years old, and 0:08:22.440 --> 0:08:27.520 I started having weekly, if not multiple times a week 0:08:27.720 --> 0:08:31.480 abouts of what I thought at the time was food poisoning. 0:08:31.720 --> 0:08:35.600 My head would hurt like there was someone blowing up 0:08:35.640 --> 0:08:39.120 a balloon inside it and there was just no space 0:08:39.240 --> 0:08:44.440 for anything to go, and the light would hurt my eyes. 0:08:45.840 --> 0:08:50.240 I would get incredibly dizzy, nauseous, and I would have 0:08:50.280 --> 0:08:53.120 to excuse myself, go to the bathroom, throw up, and 0:08:53.440 --> 0:08:56.120 return to class because that was really the only option 0:08:56.320 --> 0:09:01.360 I had. This kind of just continued for years and years. 0:09:01.840 --> 0:09:04.880 I never really had a chance to get things checked 0:09:04.920 --> 0:09:10.720 out until god, now, fourteen years later, now that I 0:09:10.760 --> 0:09:14.120 am an adult working in the healthcare system, I have 0:09:14.880 --> 0:09:18.840 decent insurance. So over the past twelve months, I have 0:09:19.000 --> 0:09:23.000 had two MRIs that showed absolutely nothing out of the ordinary. 0:09:23.480 --> 0:09:29.200 It's hard to stay hopeful in terms of treatment and possibilities, 0:09:30.000 --> 0:09:34.000 especially considering that we have no idea where this comes from. 0:09:34.080 --> 0:09:38.560 I almost was hoping that we would discover a freak 0:09:38.640 --> 0:09:42.120 brain tumor or something like that, because that would mean 0:09:42.200 --> 0:09:47.079 a real answer. It's always an interesting concept to grapple 0:09:47.120 --> 0:09:50.679 with knowing that this is something that is so incredibly 0:09:50.720 --> 0:09:55.360 common and we just have so few answers as to 0:09:55.480 --> 0:09:59.120 why so many people deal with this. But it is 0:09:59.160 --> 0:10:01.199 something that I know there is a lot of research 0:10:01.240 --> 0:10:06.920 happening with and despite having a very rocky history, I 0:10:07.400 --> 0:10:08.880 do remain hopeful. 0:10:08.920 --> 0:10:58.960 Overall, Thank you everyone who shared your story with us. 0:10:59.080 --> 0:11:01.840 We really appreciate it, We really do. 0:11:02.400 --> 0:11:04.560 Yeah, thank you for taking the time to write to 0:11:04.640 --> 0:11:07.560 us and to share your story with us and with everyone. 0:11:07.880 --> 0:11:09.440 It's yeah, thank you. 0:11:10.480 --> 0:11:14.079 Hi. I'm Aaron Welsh and I'm Aaron Allman Updyke and 0:11:14.160 --> 0:11:16.920 this is this podcast will Kill You And today we're 0:11:16.920 --> 0:11:23.559 talking migrain. Yeah. What a topic? Erin what a topic. 0:11:25.120 --> 0:11:28.080 I feel like I recently said something about, oh, this 0:11:28.160 --> 0:11:32.439 is the most requested topic, and I was wrong because 0:11:32.960 --> 0:11:35.120 it's got to be migrain, right. 0:11:35.720 --> 0:11:37.920 I think it's definitely it's up there. 0:11:38.000 --> 0:11:41.240 It's over there. Yeah, And so I really sort of 0:11:41.240 --> 0:11:43.440 feel like this has been a a long time coming. 0:11:43.520 --> 0:11:49.480 But b I still feel weirdly unprepared despite how much 0:11:49.720 --> 0:11:52.319 reading I know that we've both done on this. 0:11:52.440 --> 0:11:56.079 Same I like always feel unprepared. Yeah okay, and when 0:11:56.120 --> 0:11:58.600 it comes to brain stuff, I feel like an extra 0:11:58.720 --> 0:12:02.760 layer of unprepared. But today it's still going to be 0:12:02.760 --> 0:12:04.439 a great episode promise. 0:12:04.360 --> 0:12:06.760 Oh yeah for sure. And I feel like listeners of 0:12:06.800 --> 0:12:11.479 the podcast have gotten used to sitting with the unknowability 0:12:11.520 --> 0:12:15.080 of certain things AKA great question, I don't know. 0:12:15.920 --> 0:12:18.400 I think that's one of my favorite parts about our podcast. 0:12:18.400 --> 0:12:24.080 On Me Too, Me Too. Another favorite part of our 0:12:24.120 --> 0:12:27.520 podcast is guess what quarantine ay time? 0:12:28.120 --> 0:12:28.240 What? 0:12:28.960 --> 0:12:33.439 Absolutely so, what are we drinking this week? This week 0:12:33.480 --> 0:12:40.400 we're drinking the hammer Head because migraines are debilitatingly painful 0:12:40.600 --> 0:12:44.120 and it feels like a hammer in your head, in 0:12:44.160 --> 0:12:45.959 your head? Ow yep. 0:12:46.400 --> 0:12:47.599 What's in the Hammerhead? 0:12:47.840 --> 0:12:53.199 In the Hammerhead is essentially like a boozy aphagatoy so good. 0:12:53.800 --> 0:12:58.160 It's got espresso, which you can do decaffeinated if you 0:12:58.200 --> 0:13:02.040 would like. It's got ice cream naturally, it's got bourbon, 0:13:02.320 --> 0:13:04.920 and it's got a little bit of amaretto yum. 0:13:05.360 --> 0:13:08.120 We'll post the full recipe for that quarantini as well 0:13:08.160 --> 0:13:11.080 as our non alcoholic plasy burrita on our website This 0:13:11.120 --> 0:13:13.839 Podcast will kill You dot com and on our social 0:13:13.880 --> 0:13:15.520 media channels of course. 0:13:16.040 --> 0:13:20.000 Of course, on our website This Podcast will kill You 0:13:20.040 --> 0:13:23.400 dot Com you can find all sorts of cool things. 0:13:23.440 --> 0:13:23.679 You know. 0:13:23.720 --> 0:13:27.679 We've got transcripts, We've got links to merch to bookshop 0:13:27.720 --> 0:13:31.079 dot org, affiliate account, to our Goodreads list, to music 0:13:31.120 --> 0:13:35.600 by Bloodmobile, to our Patreon. You can find the sources 0:13:35.640 --> 0:13:38.320 for each and every one of our episodes. There's probably 0:13:38.360 --> 0:13:41.199 more stuff. How do we not have this down by now? 0:13:41.520 --> 0:13:43.319 Oh? I thought you did a phenomenal job. 0:13:43.559 --> 0:13:46.040 Thank you, thank you. I try. 0:13:47.640 --> 0:13:51.240 Well with that. Shall we get into the biology of migraine? 0:13:51.840 --> 0:13:52.640 Yes? Please? 0:13:52.960 --> 0:13:55.600 All right, we'll take a quick break and get to it. 0:14:28.960 --> 0:14:32.920 So what even is a migraine? 0:14:33.600 --> 0:14:36.040 That sounds like a great place to start. That's where 0:14:36.160 --> 0:14:37.000 we're going to start. 0:14:39.240 --> 0:14:42.760 I'm going to start with a quoted definition which happens 0:14:42.760 --> 0:14:46.840 to be from a pretty old paper, but the definition holds, 0:14:47.160 --> 0:14:50.360 so we'll start there. This is from a New England 0:14:50.440 --> 0:14:53.479 Journal of Medicine article from like two thousand and two, 0:14:53.520 --> 0:15:00.960 which says, quote, Migraine is a common chronic in pacitating 0:15:01.560 --> 0:15:08.440 neurovascular disorder, characterized by attacks of severe headache, autonomic nervous 0:15:08.440 --> 0:15:13.360 system dysfunction, and in some patients, an aura involving neurologic 0:15:13.520 --> 0:15:23.040 symptoms unquote. Biology section over, that's our definition. So that's 0:15:23.080 --> 0:15:26.560 the jargoned version. The way that I'm going to break 0:15:26.560 --> 0:15:29.200 down this biology section is to try and give you 0:15:29.280 --> 0:15:35.440 an idea of what migraine really is and as much 0:15:35.840 --> 0:15:42.400 as we can know about what's happening during these migraine attacks. 0:15:43.760 --> 0:15:47.240 So migraine attack can be divided into three to four 0:15:47.560 --> 0:15:51.360 main parts or kind of like sections, and then there's 0:15:51.480 --> 0:15:56.840 intermigraine intervals, like between migraines. So first we'll go over 0:15:56.920 --> 0:15:59.680 what these parts are, what these phases of a migraine 0:15:59.680 --> 0:16:02.960 attack are, what they look like, what they feel like, 0:16:03.040 --> 0:16:05.440 which you heard a lot of in our first hand accounts. 0:16:06.240 --> 0:16:09.680 And then we'll go over what we know so far 0:16:10.080 --> 0:16:16.240 about what's happening in our brains during these attacks. But forewarning, 0:16:17.200 --> 0:16:20.840 as will come as a surprise to no one listening 0:16:20.880 --> 0:16:24.520 to this episode if you've ever listened to TPWKY before, 0:16:25.400 --> 0:16:30.080 there's a lot that we don't know, but there is 0:16:30.160 --> 0:16:32.120 some stuff that we do know, and so I'll try 0:16:32.120 --> 0:16:34.280 to get into some of the nitty gritty of that 0:16:34.440 --> 0:16:39.880 as well. So a migraine attack generally starts with a 0:16:39.960 --> 0:16:44.200 period of prodromal symptoms. This period is often called the 0:16:44.280 --> 0:16:50.080 premonitory symptoms period, which can start anywhere from two hours 0:16:50.280 --> 0:16:55.480 to two days prior to the actual headache that most 0:16:55.520 --> 0:16:59.920 of us associate with migraine. So these symptoms can rain 0:17:00.160 --> 0:17:06.280 from anything like fatigue or yawning or impaired concentration. You 0:17:06.320 --> 0:17:12.520 could have neck pain or stiffness, water retention, nausea, photophobia 0:17:12.560 --> 0:17:16.840 which is difficulty looking at light. You might have food cravings. 0:17:16.920 --> 0:17:20.679 It's a really long and kind of diverse list of 0:17:21.359 --> 0:17:24.280 symptoms that someone could have for up to two days 0:17:24.880 --> 0:17:29.439 a day or two before the migraine attack itself. About 0:17:29.480 --> 0:17:32.879 eighty percent of people that get migraines have some kind 0:17:32.960 --> 0:17:37.800 of these prodrumal symptoms, and then for about thirty percent 0:17:37.800 --> 0:17:41.720 of people with migraines, the next phase is an aura. 0:17:42.200 --> 0:17:44.399 And a lot of people have probably heard of an aura, 0:17:45.359 --> 0:17:51.840 but an aura are these very bizarre, transient focal neurologic 0:17:51.880 --> 0:17:56.600 symptoms of various kinds. Most often, like ninety percent of 0:17:56.640 --> 0:18:01.399 the time, it's these visual symptoms. The most common one 0:18:01.520 --> 0:18:06.479 is called a scatoma or a scintillating scatoma, which sounds 0:18:06.480 --> 0:18:10.200 fancy but in fact is terrifying having had these episodes. 0:18:11.200 --> 0:18:16.159 It starts as like a flickering spot, a flickering kind 0:18:16.200 --> 0:18:19.040 of light spot, either in one eye or in both eyes, 0:18:19.560 --> 0:18:22.760 and then this spot can kind of grow or move 0:18:23.119 --> 0:18:27.720 or change and keep flickering, and scatoma just means like 0:18:27.720 --> 0:18:31.240 a blind spot. So wherever you see this flickering wave 0:18:31.600 --> 0:18:35.200 or curve of light, you can't really see anything except 0:18:35.240 --> 0:18:38.439 that light, but the vision around it usually remains the same, 0:18:39.400 --> 0:18:43.160 and this might expand, or people can see different kinds 0:18:43.200 --> 0:18:47.080 of patterns, like a crescent or a zigzag, or different shapes, 0:18:47.800 --> 0:18:52.800 and then eventually it just stops. But an aura isn't 0:18:52.840 --> 0:18:57.080 only visual. That's one type of aura. People can also have, 0:18:57.200 --> 0:19:02.880 like paresthesias, so like feeling tingling or prickling sensations, usually 0:19:02.920 --> 0:19:05.640 just in one part of the body, or it could 0:19:05.680 --> 0:19:08.640 be like a numbness of the face or your arm. 0:19:09.960 --> 0:19:13.480 It could even be things like difficulties with expressive language, 0:19:13.520 --> 0:19:16.240 not being able to find your words, or not being 0:19:16.280 --> 0:19:18.480 able to say words the way that you could just 0:19:18.640 --> 0:19:22.960 minutes prior, and even more rarely, an aura could be 0:19:23.040 --> 0:19:25.919 some kind of motor dysfunction, like all of a sudden 0:19:25.960 --> 0:19:28.400 not being able to use your hands or your legs. 0:19:29.400 --> 0:19:31.720 A lot of this might sound a lot like a stroke, 0:19:32.280 --> 0:19:36.600 because some of these symptoms can really mimic that. So 0:19:36.720 --> 0:19:41.720 this aura phase usually starts anywhere from five minutes to 0:19:41.840 --> 0:19:45.879 an hour prior to the onset of the headache, and 0:19:45.920 --> 0:19:48.520 it usually lasts under an hour and is followed pretty 0:19:48.520 --> 0:19:52.280 immediately by the headache part of migraine. That's the part 0:19:52.359 --> 0:19:55.639 that people think of when they think of migraine most often. 0:19:56.680 --> 0:20:01.480 So let's get to that. What is a migraine headache itself? 0:20:02.000 --> 0:20:05.160 Aka how do we define a migraine headache versus any 0:20:05.200 --> 0:20:09.760 other kind of headache? So, first, this is a headache 0:20:09.800 --> 0:20:13.119 that most often is unilateral. It's on one side of 0:20:13.160 --> 0:20:16.120 the head, or it at least starts off on one 0:20:16.160 --> 0:20:18.159 side of the head and then it might move to 0:20:18.359 --> 0:20:23.040 the rest of the head. It's usually described or characterized 0:20:23.119 --> 0:20:27.040 like a throbbing pain or like a pounding pain rather 0:20:27.080 --> 0:20:32.560 than a tension type pain. And in general, a migraine 0:20:32.600 --> 0:20:37.160 is classified as moderate to severe intensity, like the pain 0:20:37.280 --> 0:20:39.800 is bad enough that you can't get out of bed, 0:20:39.880 --> 0:20:41.959 you feel like you need to just lay down. And 0:20:42.000 --> 0:20:46.320 that's also in part because the pain generally increases with activity, 0:20:46.359 --> 0:20:50.919 which essentially forces you to just lie down. So those 0:20:51.280 --> 0:20:57.560 four characteristics unilateral throbbing pain, moderate to severe intensity, and 0:20:57.720 --> 0:21:02.720 increasing with activity. Based on the International Classification of Headache Disorders, 0:21:02.760 --> 0:21:05.720 which is like the criteria that are used to diagnose migraine, 0:21:06.280 --> 0:21:10.359 a migraine has at least two of those four criteria, Okay, 0:21:10.680 --> 0:21:14.960 And on top of that, migraine has either nausea and 0:21:15.080 --> 0:21:21.040 vomiting and or photophobia or phonophobia, so like severe light 0:21:21.200 --> 0:21:25.840 or sound sensitivity. I know your faces, it sounds. 0:21:26.040 --> 0:21:31.680 I mean like I know many people that have migraines. 0:21:31.960 --> 0:21:35.800 My mom, my grandma had horrible migraines her whole life. 0:21:36.440 --> 0:21:41.280 And I think it's just when you lay out all 0:21:41.359 --> 0:21:48.720 of the things that you can experience, it's just horrific, 0:21:50.000 --> 0:21:50.639 it really is. 0:21:50.760 --> 0:21:55.040 And here's an even more horrific part. The duration. Yeah, 0:21:55.119 --> 0:21:58.640 by definition, a migraine is also a headache that's lasting 0:21:58.760 --> 0:22:04.439 between four and seventy two hours. I'm gonna say that again. 0:22:05.040 --> 0:22:10.560 This is a severe headache with nausea or photophobia, not 0:22:10.600 --> 0:22:14.919 being able to look at light that increases with activity 0:22:15.040 --> 0:22:20.560 that's throbbing in your brain for four hours at a minimum, 0:22:20.800 --> 0:22:23.480 or two hours if you're a kid, and it can 0:22:23.600 --> 0:22:27.160 last up to three days. Meaning you go to bed 0:22:27.200 --> 0:22:30.120 with a headache and you wake up with the same headache, 0:22:32.960 --> 0:22:36.920 and a migraine isn't even over when it's over, because 0:22:36.960 --> 0:22:40.720 the fourth phase of migraine is the post dromal phase, 0:22:41.160 --> 0:22:44.280 and this can last again another one to two days 0:22:44.359 --> 0:22:49.760 after the headache subsides. This recovery phase can have increased 0:22:49.800 --> 0:22:54.160 in tiredness or somnolence. It can have difficulties in concentration. 0:22:55.640 --> 0:23:00.000 A migraine altogether is a phenomenon that affects the brain 0:23:00.280 --> 0:23:03.760 on a pretty large scale, and the full duration of 0:23:03.760 --> 0:23:06.719 a migraine attack can last up to seven days if 0:23:06.760 --> 0:23:10.400 you include the premonitory and the recovery symptoms as well 0:23:10.400 --> 0:23:11.400 as the headache itself. 0:23:12.240 --> 0:23:16.680 I've heard it described as a symphony in four movements, 0:23:16.720 --> 0:23:20.679 but I feel like that's way, way too pleasant language 0:23:21.080 --> 0:23:22.640 to describe what's happening. 0:23:23.119 --> 0:23:26.919 I agree, it founds like a symphony is like nice, 0:23:27.080 --> 0:23:30.800 this is it's a cacophony in four movements. 0:23:31.480 --> 0:23:35.879 Yeah, yeah, yeah, my gosh, I know. 0:23:37.520 --> 0:23:41.280 And that's that's kind of that's just how we define 0:23:41.760 --> 0:23:46.040 the migraine. So, of course, then knowing all of this, 0:23:46.359 --> 0:23:49.840 knowing how debilitating a migraine can be, how severe it 0:23:49.880 --> 0:23:55.120 can be, the question or questions are like, why does 0:23:55.160 --> 0:23:58.199 this happen? How does this happen? Who does this happen to? 0:23:58.440 --> 0:24:01.480 How can we stop this and never have this again? 0:24:02.920 --> 0:24:05.600 As promised, I do not have. 0:24:05.480 --> 0:24:07.640 All those answers, but you have some of them. 0:24:07.680 --> 0:24:11.080 I sure do. So here is what we do know, 0:24:11.320 --> 0:24:15.600 or at least what the consensus so far is about 0:24:15.600 --> 0:24:19.359 what we think is going on in the brain with 0:24:19.440 --> 0:24:24.040 a migraine. So what we know so far is that 0:24:24.080 --> 0:24:28.440 a migraine headache depends on the activation of a pathway 0:24:28.520 --> 0:24:33.840 in our brain called the trigemino vascular pain pathway, and 0:24:34.119 --> 0:24:39.080 it very likely involves a little peptide called CGRP or 0:24:39.200 --> 0:24:43.400 calcitonin gene related peptide. This is a neuropeptide. We'll talk 0:24:43.400 --> 0:24:46.200 about it in a little bit more detail. But let's 0:24:46.280 --> 0:24:47.639 define some of these things, shall we. 0:24:48.040 --> 0:24:50.360 Yeah, So the trigeminal. 0:24:49.720 --> 0:24:52.760 Nerve you may have heard of, This is cranial nerve 0:24:52.840 --> 0:24:56.320 number five. So this is one of our twelve cranial 0:24:56.400 --> 0:24:59.439 nerves that is responsible for all of the sensation to 0:24:59.520 --> 0:25:03.959 our face pretty much, and also innervates muscles that are 0:25:04.000 --> 0:25:08.480 involved in chewing and biting. So this is a predominantly 0:25:08.680 --> 0:25:13.119 sensory nerve. It's mostly carrying information from the face to 0:25:13.200 --> 0:25:16.000 the brain and then from part of our brain stem 0:25:16.160 --> 0:25:20.000 into the cortex of our brain. And then there are 0:25:20.040 --> 0:25:23.800 some nerves that are also involved with muscles and so 0:25:24.040 --> 0:25:29.040 are more efferent, sending signals for muscle contraction. Right, So, 0:25:29.240 --> 0:25:36.280 this trigeminal nerve mostly sensory, and like many nerves, most nerves, 0:25:37.000 --> 0:25:41.520 is very interrelated with vasculature. It forms like complexes of 0:25:41.560 --> 0:25:44.760 nerves and arteries and veins, and in the case of 0:25:44.800 --> 0:25:52.480 the trigeminal nerve, its projections, especially in our brain, are 0:25:52.680 --> 0:25:56.080 very strongly associated with the vasculature in our brain and 0:25:56.160 --> 0:26:00.840 our ninges that's the covering of our brain spinal cord, 0:26:01.280 --> 0:26:04.920 both the dura mater, which is the outer layer of ourminingis, 0:26:05.080 --> 0:26:07.840 and the pia mater, which is the innermost layer of 0:26:07.880 --> 0:26:13.320 our meaningis. So this trigeminal complex, as it's called, has 0:26:13.359 --> 0:26:17.280 these a sending nerve axons that project into a whole 0:26:17.359 --> 0:26:21.680 bunch of brain regions in our brainstem our, hypothalmus, our thalmis, 0:26:21.680 --> 0:26:26.560 our cortex. All of these regions of our brain are 0:26:26.600 --> 0:26:29.440 involved in a whole bunch of stuff that we happen 0:26:29.520 --> 0:26:35.119 to see dysregulated during a migraine. These involve our response 0:26:35.200 --> 0:26:38.840 to pain and no suception. So no susception is just 0:26:38.880 --> 0:26:44.080 the actual nerve signals of pain, like our nervous system 0:26:44.440 --> 0:26:47.600 getting those signals is the process called no susception. Our 0:26:47.680 --> 0:26:53.080 no susceptors are pain nerve fibers. There are a bunch 0:26:53.160 --> 0:26:57.760 of other neurons that are projecting to parts of our auditory, visual, 0:26:57.840 --> 0:27:02.159 and olfactory system, part of our cortical brain, regions that 0:27:02.160 --> 0:27:06.680 are involved with movement or even concentration. All of these 0:27:06.720 --> 0:27:09.760 different brain regions that happen to correspond to a lot 0:27:09.800 --> 0:27:13.440 of the non pain symptoms of migraine as well as 0:27:13.520 --> 0:27:17.320 these no susceptive or pain related symptoms. So think things 0:27:17.400 --> 0:27:22.919 like photophobia, nausea, vomiting, difficulty focusing, all of that. So 0:27:23.040 --> 0:27:29.959 we know that the trigeminal vascular complex is activated and 0:27:30.080 --> 0:27:34.159 involved in this process of migraine and in kind of 0:27:34.240 --> 0:27:35.480 all of the phases of it. 0:27:36.560 --> 0:27:38.840 But why aarin. 0:27:42.080 --> 0:27:44.880 Have I ever answered a why question on this podcast. 0:27:44.920 --> 0:27:46.359 Actually, I'm sure that you have. 0:27:46.560 --> 0:27:50.880 Yes, I'm not going to right now. No, that's where 0:27:50.880 --> 0:27:52.760 I will get to the part where I go I 0:27:52.760 --> 0:27:54.960 don't know, but let me tell you more about what 0:27:55.000 --> 0:27:58.080 we do know, all right. So we know that it's 0:27:58.119 --> 0:28:02.320 the trigeminal vascular complex it's activated. We also know that 0:28:02.400 --> 0:28:08.120 this specific peptide, CGRP calcitonin gene related peptide is very 0:28:08.320 --> 0:28:11.600 involved in this process. This is a peptide that we 0:28:11.640 --> 0:28:17.399 see released by this trigeminovascular complex during migraines. And we 0:28:17.520 --> 0:28:21.680 now know that blockade of this peptide or its receptors 0:28:21.760 --> 0:28:27.040 by various medications is effective in many cases at stopping migraine. 0:28:28.080 --> 0:28:33.080 We think that CGRP acts predominantly in the dura mater, 0:28:33.400 --> 0:28:36.399 so the outer layer of our menins, and that what 0:28:36.440 --> 0:28:41.120 it does is modulate the trafficking of these no susceptive signals. 0:28:41.280 --> 0:28:44.600 What does that mean. It means that CGRP is involved 0:28:44.680 --> 0:28:48.040 in the sending and receiving of the pain signals that 0:28:48.080 --> 0:28:52.160 are involved in migraine, and it may also be involved 0:28:52.200 --> 0:28:55.440 in inflammation. And there's still some thought that inflammation is 0:28:55.520 --> 0:28:57.240 involved in the migraine process. 0:28:58.360 --> 0:29:03.440 So if you're blocking that or stopping that neuropeptide through 0:29:03.480 --> 0:29:07.240 whatever medication, then it's like, okay, it can't be the 0:29:07.280 --> 0:29:11.240 messenger that causes all the pain, and that also then 0:29:11.360 --> 0:29:15.880 leads to inflammation exactly. And so in terms maybe this 0:29:16.080 --> 0:29:18.440 is you know, jumping ahead a little bit, but in 0:29:18.520 --> 0:29:22.800 terms of when you say stop a migraine, is that 0:29:23.320 --> 0:29:25.840 at what point can you stop a migraine? Is there 0:29:25.960 --> 0:29:29.760 like a threshold beyond which that like the point of 0:29:29.760 --> 0:29:30.280 no return? 0:29:30.400 --> 0:29:33.400 I guess it's a really good question. In general, all 0:29:33.480 --> 0:29:36.360 the medicines that we use for migraine, especially for like 0:29:36.400 --> 0:29:41.080 acute migraine attacks, work best the earlier that they're given, 0:29:41.920 --> 0:29:45.680 And part of that is because once this process starts rolling, 0:29:45.720 --> 0:29:49.920 and especially once the pain has really started to take hold, 0:29:50.640 --> 0:29:55.200 there's an additional process we think of like central sensitization. 0:29:55.520 --> 0:29:59.480 So there's a thought that like, once the pain signals 0:29:59.520 --> 0:30:03.600 have started to be sent, now our brain is acting 0:30:04.080 --> 0:30:07.360 a little bit on overdrive in response to those signals, 0:30:07.400 --> 0:30:09.600 and then yeah, you're right, that's a really hard ball 0:30:09.640 --> 0:30:11.120 to stop rolling essentially. 0:30:11.360 --> 0:30:14.560 Okay, So it's like, ah, that old pathway, like exactly, 0:30:14.640 --> 0:30:17.040 I know it well, and then and just speed down 0:30:17.080 --> 0:30:20.800 it and then pain goes up. Yeah. And the variation 0:30:21.160 --> 0:30:24.800 in how long a migraine can last, so like, let's 0:30:24.840 --> 0:30:28.520 say that you don't stop the neuropeptide in time, or 0:30:28.880 --> 0:30:31.880 you lived in a period before there were drugs that 0:30:31.920 --> 0:30:33.920 could do that, or you don't have access to drugs. 0:30:34.000 --> 0:30:39.320 Whatever is the variability and how long that migraine will 0:30:39.480 --> 0:30:42.040 last is just sort of like the half life of 0:30:42.080 --> 0:30:43.720 the neuropeptide in your brain. 0:30:44.240 --> 0:30:49.520 I mean, maybe, no, yes, who knows? The answer is 0:30:49.560 --> 0:30:53.320 that we have no idea because everything that I just 0:30:53.360 --> 0:30:57.160 told you is a lot of information. It's a level 0:30:57.160 --> 0:31:01.360 of understanding that we did not have, say, fifteen twenty 0:31:01.680 --> 0:31:07.360 years ago, But it's also not helpful at all when 0:31:07.400 --> 0:31:12.840 it comes to understanding the why or even how this 0:31:12.960 --> 0:31:17.360 trigeminovascular system is activated in people with migraine. To begin with, 0:31:18.040 --> 0:31:22.920 we don't understand the initiation of migraine pain. We don't 0:31:23.000 --> 0:31:27.040 understand why it stops eventually, why it lasts for as 0:31:27.040 --> 0:31:29.680 long as it does, why it can be so different 0:31:29.840 --> 0:31:34.280 both between individuals as well as in one individual throughout 0:31:34.360 --> 0:31:37.760 their lifetime. There is so much that we don't know 0:31:38.720 --> 0:31:44.000 it's really frustrating. It is, it is. And then there's aura. 0:31:44.960 --> 0:31:45.920 Oh gosh. 0:31:46.480 --> 0:31:51.720 Aura is very interesting. It happens in about thirty percent 0:31:51.760 --> 0:31:54.920 of people with migraine, so it's not the most common 0:31:54.960 --> 0:31:58.440 form of migraine, migraine with aura, and it can happen 0:31:58.520 --> 0:32:01.640 in absence of a migraine headache as well, but that's 0:32:01.720 --> 0:32:06.080 even more rare. And here again we know a little 0:32:06.120 --> 0:32:11.040 bit about the mechanisms, but so much remains unknown. Aura 0:32:11.280 --> 0:32:15.000 is thought to happen from a phenomenon called spreading depolarization 0:32:15.280 --> 0:32:20.840 or cortical spreading depression, depression depolarization, same thing. And so 0:32:21.040 --> 0:32:24.880 when we have an aura, the symptoms tend to start 0:32:25.160 --> 0:32:29.000 kind of small and they grow or kind of propagate 0:32:29.160 --> 0:32:34.880 rather slowly, especially compared to another rapid depolarization phenomenon that 0:32:34.880 --> 0:32:37.040 we've talked about on this podcast. 0:32:36.880 --> 0:32:39.040 A seizure, ah okay. 0:32:39.480 --> 0:32:42.320 And so it's thought that what's happening during this time 0:32:42.480 --> 0:32:45.560 is that starting from some focal point in the brain, 0:32:46.240 --> 0:32:50.200 there's this membrane depolarization, and that's what happens whenever a 0:32:50.280 --> 0:32:52.960 nerve is firing, like a signal is firing. But this 0:32:53.120 --> 0:32:55.840 is happening like all in this one area and then 0:32:56.000 --> 0:33:01.080 propagating along the cortex of the brain like dumb kind 0:33:01.120 --> 0:33:04.840 of yeah, And we have like MRI and PET scan 0:33:05.000 --> 0:33:09.840 studies that show additionally changes in blood flow like hyper 0:33:09.960 --> 0:33:13.920 perfusion followed by hypoperfusion, so like more blood flow and 0:33:13.920 --> 0:33:16.680 then all of a sudden less blood flow in regions 0:33:16.720 --> 0:33:20.120 of the brain that are corresponding to the symptoms of aura. 0:33:21.200 --> 0:33:27.160 And there's evidence that this cortical spreading depression, this depolarization 0:33:27.880 --> 0:33:34.080 can then trigger or activate the trigeminovascular system, but we 0:33:34.200 --> 0:33:38.760 still don't know what the susceptibility is for this cortical 0:33:38.760 --> 0:33:43.200 spreading depolarization or depression. And we also don't know why 0:33:43.320 --> 0:33:46.440 is it then that only thirty percent of people have 0:33:46.600 --> 0:33:51.240 AURA with their migraine, et cetera. There's there's like some oh, 0:33:51.360 --> 0:33:54.400 this is involved and it activates the system, and maybe 0:33:54.400 --> 0:33:57.320 that's the pathway to then migraine pain. But what about 0:33:57.360 --> 0:34:01.000 when you don't have an aura, Because people with migraine 0:34:01.000 --> 0:34:04.800 with aura can also still have migraines without aura, So 0:34:05.920 --> 0:34:07.800 it's complicated. 0:34:09.400 --> 0:34:12.560 Uh So I wrote down a few questions, okay, because 0:34:14.000 --> 0:34:15.920 I knew that I was going to forget them, and 0:34:15.920 --> 0:34:20.759 I feel so overwhelmed by questions. I'm like brimming right now, overflowing. 0:34:21.200 --> 0:34:21.840 I'll try. 0:34:22.080 --> 0:34:26.960 Okay, why is the pain typically on one half of 0:34:26.960 --> 0:34:27.399 your head? 0:34:27.880 --> 0:34:30.919 Great question. So our cranial nerves are all paired, which 0:34:30.960 --> 0:34:32.879 means that you have two sets of them, and then 0:34:32.880 --> 0:34:36.240 you have two sets of those ganglia or the nerve bodies, 0:34:36.320 --> 0:34:40.360 and then two sets of those like acending axons as well. 0:34:40.640 --> 0:34:47.080 So probably you're having activation of one of your trigeminovascular complexes, 0:34:47.080 --> 0:34:50.880 like on one half of your brain at a time. Okay, 0:34:51.200 --> 0:34:54.280 but like that, that's my best guess. 0:34:54.719 --> 0:34:57.640 Why eron, I just told you I don't know her Okay, Okay, 0:34:57.680 --> 0:35:02.000 I'll try, I'll try to stay away from the ys. Okay. 0:35:02.080 --> 0:35:07.080 Another question I had was about the mechanism of aura 0:35:07.160 --> 0:35:11.920 as far as we understand, So you discussed how visual 0:35:11.960 --> 0:35:17.000 aura is the most common. Are the mechanisms the same 0:35:17.200 --> 0:35:18.800 for the other types of aura? 0:35:19.160 --> 0:35:23.000 Great question. Yes, it's thought that in general the mechanism 0:35:23.120 --> 0:35:26.080 of aura is this cortical spreading depression, and what your 0:35:26.080 --> 0:35:29.320 symptoms are will depend on where that depolarization is happening 0:35:29.360 --> 0:35:29.839 in your brain. 0:35:30.560 --> 0:35:33.560 And we don't know how aura is or is not 0:35:33.719 --> 0:35:36.560 linked to migraine pain. 0:35:37.120 --> 0:35:41.839 Mechanistically, we know from animal studies that the process of 0:35:41.880 --> 0:35:46.839 this cortical spreading depolarization can lead to activation of that 0:35:46.920 --> 0:35:52.200 trigeminovascular complex. How exactly we don't know, but we do 0:35:52.320 --> 0:35:54.320 see that correlation there. 0:35:54.680 --> 0:36:00.759 Okay, one last question. Okay, So you mentioned early when 0:36:00.760 --> 0:36:04.200 you were describing the various symptoms that can be associated 0:36:04.400 --> 0:36:10.720 during the migraine pain, like the headache part of migraine, 0:36:10.920 --> 0:36:14.120 and you commented on how similar they are to stroke. 0:36:15.600 --> 0:36:20.680 Why how? Sorry? I said, why how? 0:36:22.440 --> 0:36:24.360 I don't have a lot of hows for you either, Aaron, 0:36:25.560 --> 0:36:28.040 So that is a it's kind of a can of 0:36:28.080 --> 0:36:32.799 worms question, and in part it's because it does get 0:36:32.880 --> 0:36:39.719 into associations that exist between migraine and other neurologic and 0:36:39.800 --> 0:36:45.480 psychiatric disorders, including stroke. I don't have an easy, good 0:36:45.560 --> 0:36:50.640 answer for like why can migraine symptoms, especially aura symptoms, 0:36:51.880 --> 0:36:56.160 mimic a stroke? But they can They also can mimic 0:36:56.200 --> 0:37:00.319 some forms of seizures or epilepsy. Yeah, so I want 0:37:00.320 --> 0:37:03.000 to go into a little bit more detail, not necessarily 0:37:03.040 --> 0:37:06.920 on this path of physiology, but on like the big 0:37:07.040 --> 0:37:12.560 picture of migraine and migraine biology. Everything that I went 0:37:12.640 --> 0:37:16.640 over and the criteria that are in the ICHD three. 0:37:17.360 --> 0:37:21.319 Those are all for migraine, like called classic migraine and 0:37:21.440 --> 0:37:26.080 migraine with aura. There is also a distinction between what's 0:37:26.120 --> 0:37:31.000 called episodic migraine and so called chronic migraine. But the 0:37:31.080 --> 0:37:34.960 term chronic migraine is confusing and like a crappy term 0:37:35.040 --> 0:37:38.759 because like, most people who have migraines have them chronically. 0:37:39.520 --> 0:37:42.879 But what chronic migraine actually means is that people have 0:37:42.920 --> 0:37:47.839 a very high frequency of migraines. Chronic migraine is classified 0:37:47.960 --> 0:37:51.320 as at least fifteen headache days per month. 0:37:51.760 --> 0:37:54.320 Oh my god. 0:37:54.560 --> 0:37:57.160 Yeah, that's half of a month, and at least eight 0:37:57.200 --> 0:38:00.600 of these headaches meet criteria for migraine. Some of them 0:38:00.640 --> 0:38:05.000 can be non migronists headaches. Up to five percent of 0:38:05.040 --> 0:38:09.040 people with migraine meet criteria for chronic migraine at some 0:38:09.440 --> 0:38:14.120 point in their like migraine lifespan, because migraines can also 0:38:14.400 --> 0:38:18.840 change over time. But there are other types of migraine 0:38:18.880 --> 0:38:21.040 as well that I'm not going to really get into 0:38:21.080 --> 0:38:23.279 detail on, but I just want to mention that they 0:38:23.440 --> 0:38:29.839 exist because they're important. There's abdominal migraine, which is much 0:38:29.880 --> 0:38:34.000 more common in kids, but can persist into adulthood. It's 0:38:34.160 --> 0:38:37.640 very similar in terms of all of the prodramal symptoms, 0:38:37.960 --> 0:38:42.359 but instead of headache pain, it's intense abdominal pain that 0:38:42.440 --> 0:38:45.600 lasts between two and seventy two hours. And it has 0:38:45.960 --> 0:38:50.400 very similar non pain symptoms nausea, vomiting, photophobia. All of 0:38:50.440 --> 0:38:53.440 this huh yeah, I have a great paper if you 0:38:53.480 --> 0:38:56.640 want to read more details about it. But there's a 0:38:56.760 --> 0:38:59.399 huge connection between the mind and the gut, and there's 0:38:59.400 --> 0:39:03.439 association between migraine, headache, and abdominal migraine. There's a lot there. 0:39:05.120 --> 0:39:10.120 Migraine is also in relatively large part genetic, About forty 0:39:10.200 --> 0:39:14.920 to sixty percent of expression of migraine is from genetic factors. 0:39:15.880 --> 0:39:18.960 But that being said, this is nowhere close to like 0:39:19.000 --> 0:39:23.399 a one gene one disease problem. There are thirty eight 0:39:23.440 --> 0:39:27.440 different low side so far that have been identified as 0:39:27.680 --> 0:39:32.239 increasing our susceptibility to migraines. But there are also a 0:39:32.280 --> 0:39:38.120 handful of monogenic migraine syndromes. These are a single gene 0:39:38.239 --> 0:39:44.120 mutation that also leads to migraine, and these, while they're 0:39:44.200 --> 0:39:47.960 quite rare, have become really important in terms of studying 0:39:48.000 --> 0:39:53.000 and understanding migraine because we can identify the specific changes 0:39:53.480 --> 0:39:56.320 that happened as a result of this one genetic mutation. 0:39:57.640 --> 0:39:59.480 One of those that I just want to shout out 0:39:59.600 --> 0:40:05.320 is called familial hemiplegic migraine, and this is characterized by migraines. 0:40:05.360 --> 0:40:09.560 They're hereditary and in addition to having all the features 0:40:09.600 --> 0:40:13.440 I just talked about of migraine and aura, they also 0:40:13.560 --> 0:40:18.520 cause a temporary hemiparesis, which means a one sided muscle 0:40:18.560 --> 0:40:21.720 weakness really like looks like a stroke. 0:40:22.040 --> 0:40:23.400 Yeah. 0:40:23.440 --> 0:40:27.880 And there are four different subtypes of this particular monogenic 0:40:27.960 --> 0:40:33.040 migraine syndrome, and they're caused by missense mutation in genes 0:40:33.239 --> 0:40:37.560 that are involved in neurotransmitter function, specifically in these vaulted 0:40:37.600 --> 0:40:40.279 gated ion channels. And I know that that's a lot 0:40:40.280 --> 0:40:46.680 of like BIOCHEMI words, but the point is that it's 0:40:46.719 --> 0:40:51.280 these specific like ion channels that are responsible for passing 0:40:51.400 --> 0:40:54.799 information in our brain that are involved at least at 0:40:54.880 --> 0:40:58.560 this level of migraine. So it gives us a lot 0:40:58.600 --> 0:41:02.560 of idea on potent targets for migraine treatment, both for 0:41:02.640 --> 0:41:07.120 people with these gene disorders as well as migraines. In general. 0:41:07.480 --> 0:41:08.920 That's that's really interesting. 0:41:09.200 --> 0:41:12.120 Yeah. So there's a lot of work on, like mice 0:41:12.160 --> 0:41:15.120 model studies and things like that with these type of 0:41:15.160 --> 0:41:18.840 migraine disorders. But I'm not done. 0:41:19.360 --> 0:41:21.680 Okay, Can I ask a question before we go off? 0:41:21.840 --> 0:41:22.240 Yeah? 0:41:22.440 --> 0:41:26.800 Okay, So it was when you mentioned abdominal migraines and 0:41:27.160 --> 0:41:31.160 I remembered I wanted to ask about, like why the 0:41:31.440 --> 0:41:34.440 nausea and vomiting and how, at least I read in 0:41:34.480 --> 0:41:37.799 some historical accounts people felt better after vomiting and then 0:41:37.840 --> 0:41:40.759 everything was fine, which, like I'm sure is not a 0:41:40.920 --> 0:41:44.920 universal truth. But is it just that, like there are 0:41:45.000 --> 0:41:46.520 pathways that are connected. 0:41:47.400 --> 0:41:54.400 So yes, In part, it's because these trigeminovascular complex afferent nerves, 0:41:54.400 --> 0:41:56.560 the ones that are going from parts of our brain 0:41:56.640 --> 0:41:59.000 to other parts of our brain and carrying signals with them, 0:41:59.200 --> 0:42:01.000 are going to parts of our brain that might be 0:42:01.080 --> 0:42:05.200 involved with causing nausea, like involved with maybe our vestibular 0:42:05.239 --> 0:42:11.200 system or something. But it's also because the spinal trigeminal 0:42:11.280 --> 0:42:16.160 nucleus in our brain stem, in addition to receiving information 0:42:16.320 --> 0:42:20.000 from our trigeminal nerve, it also gets information from a 0:42:20.000 --> 0:42:23.520 bunch of other nerves like our facial nerve, our glossophringal nerve, 0:42:23.880 --> 0:42:28.640 and our vagus nerve, which is our main parasympathetic nerve. 0:42:28.719 --> 0:42:31.000 And so whenever you have a mess up in our 0:42:31.080 --> 0:42:35.279 parasympathetic system, you can have a lot of very generalized symptoms. 0:42:35.680 --> 0:42:38.640 Right now, why would people feel better after they barf? 0:42:39.040 --> 0:42:44.600 I don't, I don't know, correct, But yeah, that's so, 0:42:44.640 --> 0:42:49.319 it's it's all complicated, it's all involved. But if all 0:42:49.320 --> 0:42:53.560 of that wasn't enough, as I kind of briefly mentioned 0:42:53.600 --> 0:42:58.520 when you brought up stroke, Aaron, there are also associations 0:42:58.560 --> 0:43:03.920 that are not well understood mechanistically but definitely seem to 0:43:03.960 --> 0:43:09.480 exist epidemiologically between migraine and a bunch of neurologic and 0:43:09.560 --> 0:43:16.040 psychiatric disorders. This includes epilepsy, it includes stroke, depression, anxiety, 0:43:16.120 --> 0:43:19.520 and probably more that I'm not mentioning. And one of 0:43:19.560 --> 0:43:21.880 the things that kept coming up in everything that I 0:43:21.960 --> 0:43:26.080 read that was so interesting about these relationships is that 0:43:26.120 --> 0:43:32.120 they're often described as bidirectional. For example, having an episode 0:43:32.200 --> 0:43:36.120 of major depressive disorder puts one at higher risk of 0:43:36.160 --> 0:43:40.600 having migraine, and having migraine puts one at higher risk 0:43:40.680 --> 0:43:44.120 of having major depressive disorder. At least based on some 0:43:44.360 --> 0:43:47.719 epidemiological studies, like in both directions. 0:43:47.520 --> 0:43:50.120 That sounds like a horribly vicious cycle. How do you 0:43:50.120 --> 0:43:53.440 do exactly break out of that? Can you? Right? 0:43:53.560 --> 0:43:56.839 And the same is true for epilepsy. Migraine and epilepsy 0:43:56.880 --> 0:44:00.520 are these comorbid conditions that seem to similarly have this 0:44:00.840 --> 0:44:06.799 bidirectional relationship, which maybe suggests some underlying similarity in the 0:44:06.840 --> 0:44:11.600 path of physiology, but we don't know. And it's also 0:44:11.680 --> 0:44:15.040 associated with an increased risk of stroke, especially in the 0:44:15.080 --> 0:44:19.360 case of migraine with aura, and specifically in the highest 0:44:19.440 --> 0:44:23.320 risk in people assigned female at birth under age fifty. 0:44:24.320 --> 0:44:34.880 And then there's triggers. Yeah, when it comes to migraine triggers, 0:44:36.080 --> 0:44:39.759 there's not really one thing that is true for all 0:44:39.800 --> 0:44:46.120 individuals with migraine, and we don't know because we know 0:44:46.200 --> 0:44:50.840 so little about the mechanisms of migraine initiation. We don't 0:44:50.880 --> 0:44:55.080 know how triggers that people may have identified in themselves 0:44:55.960 --> 0:45:00.200 trigger a migraine in them or in anyone else. But 0:45:00.360 --> 0:45:04.160 there are some things that seem to be relatively common 0:45:04.239 --> 0:45:07.560 triggers for most people that experience migraines, and these are 0:45:07.600 --> 0:45:11.480 things like stress, which could be emotional or physical stress, 0:45:12.239 --> 0:45:16.800 lack of sleep or poor sleep quality including jet lag, 0:45:17.600 --> 0:45:24.440 and hormonal fluctuations, in particular estrogen or a withdrawal of 0:45:24.680 --> 0:45:28.160 estrogen compared to where you were at previously. This is 0:45:28.200 --> 0:45:32.719 often a huge precipitate or trigger, especially for people who menstrate. 0:45:33.800 --> 0:45:37.440 We have very significant hormone fluctuations on a cyclic basis, 0:45:37.560 --> 0:45:41.319 So for some people that means increases in migraines with periods. 0:45:42.400 --> 0:45:45.840 For some people, pregnancy and breastfeeding causes a decrease in 0:45:45.920 --> 0:45:51.000 migraine symptoms, and then menopause causes an increase in migraines, 0:45:51.360 --> 0:45:56.160 whereas postmenopause might be a decrease or an elimination entirely 0:45:56.480 --> 0:45:57.279 of migraines. 0:45:58.840 --> 0:46:05.680 It's like, it's just not complicated at all, so straightforward. Yeah, 0:46:05.719 --> 0:46:10.120 and I'm sure consistent for every person I know. 0:46:10.280 --> 0:46:11.160 Yeah, totally. 0:46:11.280 --> 0:46:15.759 You can predict it, right, Yeah, totally. And how are 0:46:16.600 --> 0:46:21.440 hormones thought to be related? Don't now? 0:46:23.480 --> 0:46:28.600 Okay, oh, Aaron, not a clue. I mean we think 0:46:28.640 --> 0:46:31.200 that it's estrogen. What is estrogen doing or what is 0:46:31.200 --> 0:46:34.600 the withdrawal of estrogen doing, like the sudden decrease in estrogen. 0:46:35.840 --> 0:46:38.440 Don't know, don't know, no idea, and it's not like 0:46:38.480 --> 0:46:41.960 it's universal. Right, Not only that not everyone who mens 0:46:41.960 --> 0:46:44.920 streets has a migraine, but even people who do menstraight 0:46:45.120 --> 0:46:48.279 who get migraines may or may not have any association 0:46:48.480 --> 0:46:53.200 with their mensies. So it's it's not even close to universal. 0:46:53.480 --> 0:46:55.320 We have no idea what's happening? 0:46:57.760 --> 0:47:00.480 Yeah, and I mean and yet we know so much 0:47:00.520 --> 0:47:02.000 more Like it used to be thought that it was 0:47:02.040 --> 0:47:06.520 all about vasodilation and it was all vascular and it's not. 0:47:08.080 --> 0:47:10.640 So we know a lot more than we did, and 0:47:10.760 --> 0:47:15.560 you're right, we still know so little. The good news 0:47:15.840 --> 0:47:19.520 is that what we do know has led to the 0:47:19.600 --> 0:47:24.440 creation of a lot more effective medicines for treatment of migraines. 0:47:24.680 --> 0:47:26.520 So despite the fact that there's a lot that we 0:47:26.560 --> 0:47:29.319 don't know, there is good news to be had, and 0:47:29.320 --> 0:47:33.879 that is that migraines for many people are treatable. There's 0:47:33.880 --> 0:47:37.000 a number of different medicines. Some of them, like the 0:47:37.080 --> 0:47:40.960 trip dands work at the five HT or the serotonin 0:47:41.000 --> 0:47:47.200 receptors which cause vasoconstriction and inhibit the release of a 0:47:47.239 --> 0:47:52.879 whole bunch of neurotransmitters, including CGRP and others, and then 0:47:53.000 --> 0:47:56.839 there's newer medications that you've probably seen commercials for if 0:47:56.880 --> 0:48:01.400 you don't pay for premium Hulu like me, Like ubrel 0:48:01.520 --> 0:48:06.520 V and ner Tech. These medicines are specifically inhibitors of 0:48:06.560 --> 0:48:11.439 that CGRP peptide that we talked about. And then we'll 0:48:11.440 --> 0:48:15.040 talk in the current events section about other modalities that 0:48:15.080 --> 0:48:19.719 have come up and how much research is being done. Yeah, 0:48:19.960 --> 0:48:22.279 none of these treatments are perfect, but there are a 0:48:22.320 --> 0:48:28.200 lot of options. So, Aaron, tell me, how did we 0:48:28.280 --> 0:48:31.640 get here? How do I even ask that question? 0:48:31.920 --> 0:48:32.360 Yeah? 0:48:32.440 --> 0:48:35.160 How do I even answer it? I guess we'll find 0:48:35.200 --> 0:49:06.360 out after the break. Okay, migraines, What are they, what 0:49:06.560 --> 0:49:11.239 causes them, who gets them, how to retreat them? So 0:49:11.360 --> 0:49:13.400 Ori Aer, and I'm not going to ask you to 0:49:13.480 --> 0:49:16.359 redo the entire biology section. You're like, wait, I thought 0:49:16.400 --> 0:49:17.279 that always done? 0:49:17.360 --> 0:49:20.640 Like I answered some of those Yeah, yeah. 0:49:20.440 --> 0:49:24.239 So you already gave us the answers to what we 0:49:24.440 --> 0:49:28.040 know or what we think we know about migraines today. 0:49:28.880 --> 0:49:32.240 But the answers to all of those questions like whether 0:49:32.400 --> 0:49:35.239 or not aura has to be present for something to 0:49:35.280 --> 0:49:39.279 be considered a migraine, or whether migraines are caused by 0:49:39.360 --> 0:49:43.960 vascular or neurological changes, or if they have a physiological 0:49:44.000 --> 0:49:47.440 basis at all, those are not going to be the 0:49:47.480 --> 0:49:52.400 same throughout the history of migraine and how those answers 0:49:52.480 --> 0:49:55.719 evolve can tell us more about what was going on 0:49:55.880 --> 0:49:59.200 in the medical field or even society more broadly than 0:49:59.200 --> 0:50:02.400 it can tell us about the path of physiology of migraines. 0:50:02.440 --> 0:50:05.359 To be honest, it can tell us about what new 0:50:05.400 --> 0:50:09.480 ideas were popular at certain times or what new discoveries 0:50:09.520 --> 0:50:13.640 were made. Like for instance, when allergies or allergens were 0:50:13.680 --> 0:50:18.480 first identified as a concept, many physicians thought, hey, maybe 0:50:18.520 --> 0:50:22.960 migraines are caused by allergens, and they tried desensitization as 0:50:23.000 --> 0:50:28.080 a result, like allergy shots, or when hysteria was a 0:50:28.120 --> 0:50:33.280 popular diagnosis, it was you bring this on yourself, and 0:50:33.640 --> 0:50:36.600 you know, the advice was just don't be so stressed out, 0:50:36.680 --> 0:50:39.680 don't be so overworked if you want to prevent migraines, 0:50:39.800 --> 0:50:43.840 like just just don't work so hard, chill out, just 0:50:43.840 --> 0:50:48.080 just chill out. Yeah. Or when you're finding earthworms crop 0:50:48.160 --> 0:50:51.800 up as an ingredient for migraine treatment, that's a sign 0:50:51.920 --> 0:50:56.000 you're probably in the medieval period in Europe, we'll get there. 0:50:58.440 --> 0:51:02.200 Humans have always tried to explain diseases or other phenomena 0:51:02.320 --> 0:51:06.719 within the bounds of whatever knowledge we currently have, and 0:51:07.000 --> 0:51:10.799 the way we treat those diseases is heavily influenced by 0:51:10.880 --> 0:51:15.480 popular ideas about what their causes are. We still do that, 0:51:16.040 --> 0:51:18.600 and it's easy to lose sight of that that our 0:51:18.719 --> 0:51:22.680 current perception of migraine is only the latest in a 0:51:22.840 --> 0:51:27.760 long line and is subject to change and likely will change, 0:51:28.160 --> 0:51:32.400 hopefully for the better. But before you can tell us 0:51:32.400 --> 0:51:35.319 about what those positive changes might be, let's first go 0:51:35.440 --> 0:51:38.080 back to the early history of migraines so we can 0:51:38.160 --> 0:51:41.680 see just how far we've come, at least in some ways. 0:51:43.200 --> 0:51:45.360 And I want to give a huge shout out to 0:51:45.400 --> 0:51:48.360 the book that I used as my primary source for 0:51:48.440 --> 0:51:52.359 this history section, and that is Migraine, a History by 0:51:52.440 --> 0:51:56.000 Catherine Foxhall. It's a great read, and I'll definitely be 0:51:56.080 --> 0:52:01.440 quoting from it. It shouldn't surprise you even just how 0:52:01.480 --> 0:52:05.480 incredibly prevalent they are to learn that migraines have been 0:52:05.560 --> 0:52:11.120 known about, written about, experienced, treated for thousands of years. 0:52:11.880 --> 0:52:15.520 You can find mentions of migraines in basically any ancient 0:52:15.640 --> 0:52:19.400 medical text from any part of the world. The Ebers 0:52:19.440 --> 0:52:24.759 Papyrus from around fifteen fifty BCE describes extreme pain in 0:52:24.920 --> 0:52:28.520 one half of the skull that should be treated by 0:52:28.560 --> 0:52:31.680 anointing the head with the skull of catfish fried in 0:52:31.719 --> 0:52:34.600 oil or fat for four days. Of course, I don't 0:52:34.640 --> 0:52:37.520 know if that meant fried for four days or just 0:52:37.560 --> 0:52:40.160 like anointed. I'm guessing anointed for four days. 0:52:40.320 --> 0:52:42.759 I would have guessed fried for four days. So that's fascinating. 0:52:42.800 --> 0:52:50.040 Oh okay. In ancient China, migraines were treated with acupuncture. 0:52:50.400 --> 0:52:54.480 In ancient Greece bloodletting. And while it has been often 0:52:54.520 --> 0:52:58.719 suggested that tripanning was done throughout the ancient world to 0:52:58.760 --> 0:53:02.279 relieve the pain during a migraine, specifically so trepanning like 0:53:02.400 --> 0:53:06.160 drilling a hole, cutting a hole into your skull, there 0:53:06.320 --> 0:53:09.840 isn't really much in terms of evidence supporting that that 0:53:09.880 --> 0:53:11.640 it was specifically for migraines. 0:53:12.040 --> 0:53:15.800 It's for dust. Everything I know about trapani is from 0:53:16.560 --> 0:53:17.480 the Capital. 0:53:17.280 --> 0:53:22.839 Compass, and trepanning was definitely done, but whether or not 0:53:22.960 --> 0:53:26.920 it was for migraines probably will never know. If anything, 0:53:27.200 --> 0:53:31.719 tripanning was used specifically for migraine. More in the twentieth century, 0:53:31.880 --> 0:53:35.800 than in ancient times, at least as far as we know. Yeah, okay, okay, 0:53:36.239 --> 0:53:39.120 of course I can't leave the Hippocratic texts out of this. 0:53:39.880 --> 0:53:43.360 And it's in these texts from the fifth century BCE 0:53:43.760 --> 0:53:47.000 that we find our first clear description of migraine with 0:53:47.160 --> 0:53:53.240 aura a young man phoenix with quote flashes like lightning 0:53:53.280 --> 0:53:56.560 in his eye, usually the right And when he had 0:53:56.600 --> 0:54:00.240 suffered that a short time, a terrible pain developed towards 0:54:00.280 --> 0:54:03.600 his right temple, then in the whole head, and then 0:54:03.640 --> 0:54:05.480 into the part of the neck where the head is 0:54:05.520 --> 0:54:09.800 attached behind the vertebra, and there was stretching and hardness 0:54:09.840 --> 0:54:13.279 around the teeth. He kept trying to open them, straining 0:54:14.040 --> 0:54:17.520 vomits whenever they occurred, averted the pains I have described 0:54:17.600 --> 0:54:23.839 and made them more gentle. Phlebotomy helped, okay. About five 0:54:23.960 --> 0:54:28.440 hundred years after this description, Galen originated the term hemicrania 0:54:28.640 --> 0:54:33.040 to describe a condition a syndrome really wasn't like considered 0:54:33.080 --> 0:54:35.560 a disease. It was more of a syndrome, I guess, 0:54:36.200 --> 0:54:39.120 where half of your head was in pain and sometimes 0:54:39.120 --> 0:54:45.680 associated with stomach disturbance. Hemicrania turned into emigrania in Latin 0:54:45.840 --> 0:54:49.800 and Middle English, and then to migran in medieval Welsh, 0:54:50.280 --> 0:54:52.720 and then to magrime, and then we see all sorts 0:54:52.719 --> 0:54:58.920 of variations like migrim, migrime, migrime, like the spellings. 0:54:58.480 --> 0:55:00.720 Are all all over the place, slonky. 0:55:01.120 --> 0:55:05.640 Yeah, And the French word migraine began to be used 0:55:05.760 --> 0:55:09.640 more widely in medical literature starting around the eighteen seventies. 0:55:10.800 --> 0:55:16.880 So yeah, and the widespread use of these names for migraine, 0:55:17.000 --> 0:55:19.680 and all of the variations of these names, I think 0:55:19.719 --> 0:55:23.320 it clearly shows that migraine was not some obscure condition. 0:55:23.880 --> 0:55:29.600 It was highly recognizable and extremely common. But what was it? 0:55:29.719 --> 0:55:33.719 What did people think caused it? Aaron, I'm sure you 0:55:33.760 --> 0:55:36.520 can guess with the leading hypothesis for the cause of 0:55:36.560 --> 0:55:39.760 migraines from like ancient times until I don't know, seventeen 0:55:39.840 --> 0:55:40.560 hundreds or. 0:55:40.520 --> 0:55:44.839 So, something like humors being off. 0:55:45.160 --> 0:55:48.400 Yes, so I knew that all my talk of the 0:55:48.520 --> 0:55:52.200 humoral theory of disease has paid off so much. I 0:55:52.200 --> 0:55:58.400 feel like this season especially Yeah, basically an imbalance in humors. 0:55:59.120 --> 0:56:01.440 In the case of my it was attributed to an 0:56:01.520 --> 0:56:05.440 excess of bilious humors yellow bile and youth and black 0:56:05.480 --> 0:56:09.480 bile in adulthood, and so it follows then that treatment 0:56:09.600 --> 0:56:14.560 involved getting the humors back into balance. For example, consider 0:56:14.640 --> 0:56:19.680 this somewhat complicated treatment, aren't they always from an old 0:56:19.719 --> 0:56:22.920 English medical text called Bald's Leech Book from nine to 0:56:23.000 --> 0:56:25.759 fifty CE. I know, I want a copy of this 0:56:25.960 --> 0:56:31.080 me too. Quote for ache of half the head, take 0:56:31.120 --> 0:56:34.600 the red nettle of one stalk, bruise it, mingle with 0:56:34.719 --> 0:56:37.600 vinegar and the white of an egg. Put all together, 0:56:38.080 --> 0:56:42.320 anoint therewith. For a half head's ache, bruise and vinegar 0:56:42.440 --> 0:56:45.719 with oil the clusters of the loris. Smear the cheek 0:56:45.760 --> 0:56:48.560 with that. For the same take juice of rue ring 0:56:48.600 --> 0:56:51.239 on the nostril, which is on the sore side. For 0:56:51.320 --> 0:56:53.960 a half head's ache, take dust of the clusters of 0:56:54.040 --> 0:56:57.960 laurel and mustard, Mingle them together, Pour vinegar upon them, 0:56:58.160 --> 0:57:01.520 smear that with the sore side, or mix with wine 0:57:01.520 --> 0:57:04.560 the clusters of laurel, or rub fine in vinegar the 0:57:04.640 --> 0:57:07.759 seed of rue. Put equal quantities of both. Rub the 0:57:07.840 --> 0:57:08.920 back of the neck with that. 0:57:10.480 --> 0:57:14.680 Are those for like all just different options? Yeah you 0:57:14.760 --> 0:57:19.760 have available to you? Wow, okay, right, yeah. 0:57:19.160 --> 0:57:22.760 And okay, So first of all, there is actually a 0:57:22.880 --> 0:57:27.440 logic behind these ingredients because in general, with the humoral 0:57:27.480 --> 0:57:30.080 theory of disease, you were supposed to treat a condition 0:57:30.240 --> 0:57:34.280 with ingredients that had the opposite qualities of that disease. 0:57:35.040 --> 0:57:37.760 If migrain was thought to be a cold, moist condition, 0:57:38.000 --> 0:57:43.160 you would prescribe dry, hot ingredients like nettles and mustard seed. Okay, 0:57:43.880 --> 0:57:48.400 why so very many options. Again, there's a reason for it. 0:57:49.200 --> 0:57:53.600 Not all plant or animal ingredients would have been available 0:57:53.680 --> 0:57:56.840 year round. If a recipe calls for a fresh nettle 0:57:56.920 --> 0:57:59.160 and you're in the middle of winter, like, where are 0:57:59.200 --> 0:58:01.600 you going to get that? Or even if you just 0:58:01.720 --> 0:58:05.480 run out right. Yeah, And the availability of ingredients would 0:58:05.480 --> 0:58:09.560 have also changed as trade became more widespread and more 0:58:09.560 --> 0:58:12.600 herbs and spices were introduced, which I think is so 0:58:12.720 --> 0:58:14.800 interesting to think about, Like you can sort of track 0:58:14.960 --> 0:58:20.680 how trade influenced home remedies for certain conditions over time. 0:58:20.800 --> 0:58:26.480 Yeah, that's super interesting. Yeah, and the seasonality part too. Yeah. 0:58:26.800 --> 0:58:29.560 So let's see what kind of created solutions people came 0:58:29.640 --> 0:58:34.640 up with. So one from thirteenth century Whales is to quote, 0:58:34.760 --> 0:58:40.080 eat a baked or roasted hare's brain stuffed with rosemary flowers, 0:58:40.240 --> 0:58:42.360 followed by sleep end the quote. 0:58:42.840 --> 0:58:46.360 I uh uh, I mean don't do that. I still 0:58:46.440 --> 0:58:49.680 feel like from our preance episode, like just don't eat brains. 0:58:49.920 --> 0:58:55.000 Don't eat brains. That's a pretty good rule. Yeah. Yeah, 0:58:55.240 --> 0:58:58.720 yet another remedy. Not sure where it's from. Quote we 0:58:58.760 --> 0:59:02.400 anoint the temples, not nostrils, and pulsating veins with rose 0:59:02.440 --> 0:59:05.480 water together with the milk of a woman who is 0:59:05.560 --> 0:59:09.560 nursing a male child, and we induce sleep. End quote. 0:59:10.640 --> 0:59:12.760 Oh yi okay, uh huh. 0:59:12.720 --> 0:59:18.720 Uh huh yep, yep, how about that. Gargling with all 0:59:18.760 --> 0:59:21.880 sorts of mixtures of things and blood letting were also 0:59:22.040 --> 0:59:25.240 really common treatments. And which side of the body you 0:59:25.360 --> 0:59:27.680 bled from and how much, and what time of day, 0:59:27.760 --> 0:59:30.080 what time of year. All of these things could be 0:59:30.120 --> 0:59:34.520 adjusted to treat migraines specifically, which I think is interesting 0:59:34.560 --> 0:59:35.120 to think about. 0:59:35.360 --> 0:59:38.480 It's really interesting. I also kind of wonder with blood letting, 0:59:38.800 --> 0:59:41.959 like how much blood I've wondered this for a while, 0:59:42.000 --> 0:59:45.520 like how much blood would they let number one? And 0:59:45.560 --> 0:59:49.000 I actually wonder if there would be any benefit if 0:59:49.840 --> 0:59:54.760 you let out enough that then you had vasoconstriction. That 0:59:54.800 --> 0:59:59.120 seems like a bad I plan. Yeah, I just kind 0:59:59.160 --> 0:59:59.560 of wonder. 1:00:00.560 --> 1:00:05.200 So I can't remember. I have come across actual quantities, 1:00:05.240 --> 1:00:07.439 but I don't remember anything at this point in time, 1:00:07.800 --> 1:00:09.160 and I think it was pretty variable. 1:00:09.560 --> 1:00:09.760 Yeah. 1:00:09.760 --> 1:00:11.400 It just feels like you would have to do a 1:00:11.440 --> 1:00:13.560 lot for it to have any kind of effect. 1:00:13.840 --> 1:00:17.200 Yeah, and then you're just, you know, inviting a whole 1:00:17.200 --> 1:00:18.960 host of other problems. 1:00:18.640 --> 1:00:20.520 Yeah, into your life, et cetera. 1:00:20.920 --> 1:00:28.280 Yeah, yep, okay, Okay. But besides bloodletting, which was actually 1:00:28.320 --> 1:00:35.240 really common, another oddly common ingredient was what I mentioned earlier, earthworms. 1:00:35.920 --> 1:00:37.040 Yeah, what okay? 1:00:37.400 --> 1:00:41.160 Quote, take six spoonfuls of the gall of an ox 1:00:41.280 --> 1:00:45.040 or cow. Put there too, two spoonfuls of the powder 1:00:45.160 --> 1:00:48.480 of the long worms of the earth, and the powder 1:00:48.560 --> 1:00:52.520 of half a nutmeg grated. Boil all these together upon 1:00:52.560 --> 1:00:55.800 a chafing dish of coals until it be so thick 1:00:56.120 --> 1:00:59.160 as you may spread it upon a cloth. Then take 1:00:59.240 --> 1:01:02.600 a double linen cloth and cut it fit for your forehead, 1:01:02.880 --> 1:01:06.720 and as it may cover the temples, spread this upon 1:01:06.760 --> 1:01:09.720 it and lay it to your forehead, lukewarm, and let 1:01:09.760 --> 1:01:16.040 it lie until it do fall off itself. So in 1:01:16.080 --> 1:01:20.360 case you missed it, ground up earthworms, the long worms 1:01:20.400 --> 1:01:24.400 of the earth made into a paste that you put on. 1:01:24.280 --> 1:01:29.560 Your forehead with some like goat cow parts of cowcall stuff. Yeah. 1:01:29.680 --> 1:01:30.920 Why why? 1:01:31.360 --> 1:01:35.560 Why you can find earthworms in all kinds of remedies 1:01:35.600 --> 1:01:40.120 for things like constipation, jaundice, fevers, or other diseases of 1:01:40.160 --> 1:01:44.560 the head and brain, like throughout the medieval period again 1:01:45.400 --> 1:01:49.280 why Yeah? And I feel like we've come across so 1:01:49.440 --> 1:01:53.919 many of these, you know, a very strange to us 1:01:54.040 --> 1:01:57.720 combination of ingredients, and we're just like, haha, how weird. 1:01:57.880 --> 1:02:00.640 Moving on. But in this book was the first time 1:02:00.960 --> 1:02:07.120 that I've actually come across an explanation for why earthworms, 1:02:07.440 --> 1:02:11.440 for example, Okay, there is a reason, and honestly I 1:02:11.920 --> 1:02:13.480 kind of like it. I think it's very I think 1:02:13.480 --> 1:02:17.640 it's very interesting. Earthworms, because they lived in the dirt 1:02:18.000 --> 1:02:23.120 feeding on rotten matter, were believed to also eat or 1:02:23.240 --> 1:02:26.760 consume the rotting matter in your body that caused whatever 1:02:26.800 --> 1:02:27.640 disease you had. 1:02:28.120 --> 1:02:28.920 Huh. 1:02:28.960 --> 1:02:32.800 And so if migrains were caused by like rotting or 1:02:32.920 --> 1:02:37.680 toxic or putrefied stuff in your head, then that earthworm 1:02:37.720 --> 1:02:41.160 paste in theory would have eaten up the putrefying matter. 1:02:41.720 --> 1:02:41.959 Huh. 1:02:42.240 --> 1:02:46.000 Yeah. And earthworms weren't alone in this like other creatures 1:02:46.040 --> 1:02:50.600 that were quote unquote bread of putrefaction, like earwigs and snails, 1:02:50.760 --> 1:02:54.800 were also often used in remedies to like get the 1:02:54.840 --> 1:03:00.560 toxins out of you, how putrefaction? Yeah, okay. Up through 1:03:00.640 --> 1:03:03.040 the late seventeen hundreds or so, it seems like the 1:03:03.160 --> 1:03:06.960 vast majority of these migraine treatments, with the exception of bleeding, 1:03:07.280 --> 1:03:10.520 consisted of recipes that you could make at home with 1:03:10.800 --> 1:03:15.920 ingredients that you could find relatively easily. And that's evidenced 1:03:15.960 --> 1:03:19.040 by the fact that migraine treatments found their way into 1:03:19.200 --> 1:03:23.640 many home remedy books during the fifteen hundreds and sixteen hundreds, 1:03:24.200 --> 1:03:29.200 also showing once again how common migraines were. In one 1:03:29.440 --> 1:03:32.800 there was even a diagnostic tool where you were supposed 1:03:32.840 --> 1:03:36.040 to be able to like I didn't quite understand it, 1:03:36.120 --> 1:03:38.160 but it was like, how much I think of your 1:03:38.200 --> 1:03:41.960 hand or your thumb you can fit into your mouth? 1:03:42.400 --> 1:03:46.040 What during a migraine? Because if you can't fit however 1:03:46.040 --> 1:03:49.040 many knuckles in, then you had a migraine. 1:03:49.080 --> 1:03:51.680 Because you couldn't like open your mouth, could open your mouth? 1:03:51.760 --> 1:03:52.240 Yeah. 1:03:52.280 --> 1:03:52.800 Interesting. 1:03:53.040 --> 1:03:57.160 Yeah. The author of Migraine a History pointed out another 1:03:57.240 --> 1:04:00.640 interesting aspect of migraine treatments from the Mead, Evil and 1:04:00.680 --> 1:04:04.320 beyond times, which is that while the diversity of treatments, 1:04:04.720 --> 1:04:08.680 both in terms of methods and ingredients for migraines seems 1:04:09.040 --> 1:04:13.600 completely never ending, they all share one feature. There are 1:04:13.600 --> 1:04:18.560 no magical or religious elements in them. Migraines had a 1:04:18.600 --> 1:04:21.520 physical basis and were treated as such. 1:04:22.320 --> 1:04:23.480 That's fascinating. 1:04:23.800 --> 1:04:28.959 Yes, it is because it didn't stay that way. 1:04:29.400 --> 1:04:34.080 Yeah, I can imagine, because I feel like migrain has 1:04:34.120 --> 1:04:36.760 so much similarity to things that we've covered in the 1:04:36.800 --> 1:04:41.680 past that absolutely did not have the consideration of a 1:04:41.720 --> 1:04:42.880 real physical basis. 1:04:43.120 --> 1:04:47.160 Uh huh. It's so amazing to me given the stigma 1:04:47.240 --> 1:04:51.919 and the shame and the bias surrounding migraines today, even 1:04:51.960 --> 1:04:55.160 though we know that there is physical basis for them, 1:04:55.960 --> 1:04:59.840 how much disregard how much dismissal there is when for 1:04:59.840 --> 1:05:03.080 the the vast majority of its history from ancient times 1:05:03.160 --> 1:05:06.440 through the early to mid seventeen hundreds or so, the 1:05:06.520 --> 1:05:11.480 prevailing medical beliefs around migraines didn't change all that much. 1:05:11.960 --> 1:05:15.280 It had a physical basis. It came down to humors. 1:05:15.960 --> 1:05:16.400 Wow. 1:05:17.200 --> 1:05:22.640 Yeah, But like we've seen with many other diseases, especially 1:05:22.720 --> 1:05:26.280 chronic diseases that we've covered on the podcast like asthma 1:05:26.320 --> 1:05:30.919 and epilepsy, come to mind. Once medicine became more centralized 1:05:30.960 --> 1:05:34.360 and commercialized as people moved into cities in the late 1:05:34.400 --> 1:05:39.080 seventeen hundreds and into the eighteen hundreds, perceptions of migraine 1:05:39.360 --> 1:05:43.600 began to shift. It started with patent medicines taking the 1:05:43.640 --> 1:05:47.720 home out of home remedy and making concoctions available for 1:05:47.840 --> 1:05:52.919 people to purchase and doctors to patent and prescribe. Then, 1:05:53.200 --> 1:05:57.240 as hospitals were increasingly built and high population densities and 1:05:57.280 --> 1:06:01.200 cities meant that doctors could see really orders of magnitude 1:06:01.480 --> 1:06:04.600 more patients in a year than in past times, they 1:06:04.600 --> 1:06:08.720 started to observe more about migraines, how frequently they occur, 1:06:09.200 --> 1:06:12.440 how long they last, what age they usually first happen, 1:06:13.040 --> 1:06:18.480 the range of symptoms. And armed with these new observations, 1:06:18.840 --> 1:06:22.800 they began to draw conclusions about who was getting migraines 1:06:23.160 --> 1:06:28.800 and why. Were migraines just a cost of social progress 1:06:29.040 --> 1:06:34.560 in temperance, sedentary lifestyles, lack of restraint, urban living. All 1:06:34.640 --> 1:06:38.040 of these things the negative side of social progress, were 1:06:38.080 --> 1:06:42.480 thought to contribute to the rise of quote unquote nervous conditions, 1:06:42.520 --> 1:06:45.240 something that we've absolutely talked about on the podcast in 1:06:45.320 --> 1:06:50.080 terms of at least gout and asthma. Essentially, the view 1:06:50.200 --> 1:06:53.640 was that as society grew more corrupted, so did our bodies. 1:06:54.960 --> 1:06:56.480 Was it a wandering uterus? 1:06:56.880 --> 1:06:57.440 Perhaps? 1:06:57.920 --> 1:07:03.480 Probably? Was it being to creative? Could be what? Yeah, 1:07:04.040 --> 1:07:06.840 not getting a break from the kids, or being afraid 1:07:06.920 --> 1:07:10.920 to delegate household yours? Oh god, sure, I know right 1:07:11.000 --> 1:07:17.520 it is I I boil, I know yep. The perception 1:07:17.640 --> 1:07:21.480 of migraine, at least among the people writing about them 1:07:22.040 --> 1:07:27.680 male physicians, of course, shifted from a legitimate medical condition 1:07:28.040 --> 1:07:32.280 with a real physiological basis, even if it was thought 1:07:32.280 --> 1:07:36.640 to be humoral imbalance, to first a social and then 1:07:37.040 --> 1:07:41.720 later on a personal failing. And part of this was, ironically, 1:07:42.040 --> 1:07:46.320 because physicians were paying more attention to this condition and 1:07:46.400 --> 1:07:51.080 taking note of other symptoms like gipset or dizziness as 1:07:51.400 --> 1:07:56.000 pain as the primary feature took a back seat. The 1:07:56.040 --> 1:08:00.880 delegitimization of migraines in the late seventeen hundred and throughout 1:08:01.000 --> 1:08:04.920 much of the eighteen hundreds shifted who was responsible for 1:08:05.160 --> 1:08:09.000 managing this condition. It was no longer the doctor that 1:08:09.120 --> 1:08:12.000 had to figure out the correct course of treatment. It 1:08:12.080 --> 1:08:17.160 was now on the person themselves. If only they didn't overeat, 1:08:17.520 --> 1:08:20.519 if only they ate at more normal times, if only 1:08:20.600 --> 1:08:23.400 they didn't drink as much, didn't lays around as much, 1:08:23.560 --> 1:08:29.320 didn't work so hard, exercised more, exercise less, studied more studied, less, 1:08:29.439 --> 1:08:34.400 slept more. We're less ambitious, we're less sensitive, less feminine, stronger. 1:08:35.160 --> 1:08:38.600 Then maybe, just maybe they wouldn't bring this on themselves. 1:08:40.960 --> 1:08:42.519 Oh Okay, I. 1:08:42.439 --> 1:08:47.439 Know, I know, I'm not surprised by it, but it's 1:08:47.479 --> 1:08:48.520 still upsetting. 1:08:49.439 --> 1:08:53.800 Is a very upsetting. I know what had once been 1:08:54.120 --> 1:08:58.000 a humoral imbalance was now a nervous disease. And I'm 1:08:58.000 --> 1:09:01.479 not talking about like a neurologic disease that we think 1:09:01.520 --> 1:09:04.920 of today. I'm talking about the nineteenth century idea of 1:09:04.960 --> 1:09:08.160 a nervous disease, of which there were many different types, 1:09:08.720 --> 1:09:12.200 and nerves could be affected by any number of things, 1:09:12.280 --> 1:09:16.439 according to these physicians, and these things, and thus the 1:09:16.479 --> 1:09:22.439 nerves themselves were more under a person's control. But those things, 1:09:23.200 --> 1:09:27.200 what things affected nerves, of course, depended on the person. 1:09:28.439 --> 1:09:32.720 And with this increased attention on migraines, physicians began to 1:09:32.760 --> 1:09:38.160 split them up into different types, often gendered. For example, 1:09:38.680 --> 1:09:42.920 so called anemic migraines affected quote mothers in the lower 1:09:42.960 --> 1:09:48.200 classes of life end quote, whose bodies were quote hourly 1:09:48.360 --> 1:09:52.800 drained by lactation end quote. But don't worry. If you 1:09:52.840 --> 1:09:55.280 were a woman in a higher class, you could still 1:09:55.280 --> 1:10:01.760 get migraine just called neuralgic headache, which were quote undoubtedly 1:10:01.840 --> 1:10:04.480 hysterical end quote in origin. 1:10:04.560 --> 1:10:06.320 Ai yeay yay yi. 1:10:07.000 --> 1:10:10.559 But also it was just the domestic life in general 1:10:10.800 --> 1:10:16.840 that gave women so many migraines. Quote, the anxious forecasting 1:10:16.920 --> 1:10:21.160 and much serving, which slowly undermined the nervous energies of 1:10:21.360 --> 1:10:27.240 many wives and mothers end quote. Working class and mothers. 1:10:28.840 --> 1:10:33.120 Working class men got migraines after being exhausted from quote 1:10:33.160 --> 1:10:37.759 unquote excessive hours of labor or working in the quote 1:10:38.080 --> 1:10:42.200 unwholesome and ill ventilated workshops and dwellings of our crowded 1:10:42.240 --> 1:10:47.280 towns end quote. But for men of a somewhat higher 1:10:47.320 --> 1:10:51.320 social grade, it was generally using your brain too much, 1:10:51.800 --> 1:10:55.360 like reading too much, writing too much, working in legal 1:10:55.439 --> 1:10:59.920 chambers or the counting house, too much competition, the excitement 1:11:00.080 --> 1:11:04.000 of the university and professional life, the anxiety that came 1:11:04.040 --> 1:11:08.280 from too much ambition and so on. It could be 1:11:08.320 --> 1:11:14.320 literally anything, but it's always the person's fault, and the 1:11:14.320 --> 1:11:18.720 remedies for all these different types of migrain were fairly straightforward. 1:11:19.200 --> 1:11:23.000 A break from the stressors, which could include maybe a 1:11:23.040 --> 1:11:27.360 more nutritious diet, not working or studying as much, or 1:11:27.400 --> 1:11:32.800 for an overworked mother, a forced absence from the home. Yeah, 1:11:32.800 --> 1:11:36.599 that happened, okay, And they're just like, you're afraid to delegate. 1:11:36.680 --> 1:11:39.320 There's tons of people that can help out with your kids, 1:11:39.520 --> 1:11:45.800 like just leave them. And whether or not any of 1:11:45.840 --> 1:11:48.680 these things were practical, Like let's say that you are 1:11:49.160 --> 1:11:52.519 working in one of these factories. It's not like you 1:11:52.520 --> 1:11:54.240 could just be like, oh yeah, let me just take 1:11:54.320 --> 1:11:57.599 some days off work, No problem, I'll take a vacation 1:11:57.840 --> 1:12:01.559 to the countryside where the fresh air, the fresh sea 1:12:01.600 --> 1:12:02.599 air will do me good. 1:12:02.880 --> 1:12:04.680 It's not like they were able to use this for 1:12:04.800 --> 1:12:07.920 like unionizing efforts and actually getting better working conditions. 1:12:08.040 --> 1:12:15.000 I absolutely not. Yeah, yeah, but that didn't These like 1:12:15.120 --> 1:12:19.439 practical things didn't matter to the physician prescribing them, right, 1:12:20.320 --> 1:12:24.120 And the physicians prescriptions, by the way, were not limited 1:12:24.160 --> 1:12:27.760 to changes in lifestyle. The rise of hospitals and other 1:12:27.800 --> 1:12:32.360 medical institutions like asylums provided ample opportunities for physicians to 1:12:32.439 --> 1:12:37.560 test out experimental treatments just the latest and greatest, including opium, 1:12:38.000 --> 1:12:42.840 potassium bromide, arsenic quinine, and cannabis, which was actually a 1:12:42.960 --> 1:12:47.880 favorite among many doctors and patients, but nothing reliably worked, 1:12:48.160 --> 1:12:53.000 as I'm sure you could guess. And contributing to this 1:12:53.520 --> 1:12:57.320 lack of meaningful progress in migraine research, at least in 1:12:57.400 --> 1:13:00.960 terms of treatment through the late nineteen and into the 1:13:00.960 --> 1:13:06.439 twentieth century was the lack of certainty in diagnosis. As 1:13:06.720 --> 1:13:12.080 a quote unquote invisible illness, people with migraine could appear 1:13:12.280 --> 1:13:15.920 healthy even in the midst of a horrific attack, which 1:13:15.960 --> 1:13:19.400 made it easier for physicians to dismiss their pain or 1:13:19.439 --> 1:13:23.080 not take it seriously, with some physicians saying that, oh, 1:13:23.200 --> 1:13:26.080 someone who is in that much pain can't be relied 1:13:26.160 --> 1:13:33.160 upon to recount their experiences accurately. Okay, not sick enough 1:13:33.200 --> 1:13:37.920 to be considered chronically ill, but not well often enough 1:13:37.920 --> 1:13:40.280 to be healthy. Something like that. It was just like 1:13:40.479 --> 1:13:45.960 middle ground pain as a subjective experience couldn't be trusted 1:13:46.560 --> 1:13:51.120 by these physicians as the sole diagnostic criterion for migraine, 1:13:51.840 --> 1:13:56.200 and so they turned to aura. Visual disturbances had long 1:13:56.240 --> 1:13:59.240 been associated with migraine, but hadn't really been studied in 1:13:59.280 --> 1:14:02.680 a systematic way until the mid to late eighteen hundreds, 1:14:03.080 --> 1:14:08.040 when two scholarly men, British mathematician, astronomer and chemist Sir 1:14:08.160 --> 1:14:13.479 John Herschel and physician Hubert Airy, presented their experiences of 1:14:13.680 --> 1:14:17.919 quote unquote ocular spectra at a couple of scientific meetings. 1:14:18.400 --> 1:14:22.160 They described disruptions in visions that could be induced by 1:14:22.160 --> 1:14:25.760 the shining of a strong light and a quote singular 1:14:25.880 --> 1:14:29.640 shadowy appearance end quote that sat at the corner of 1:14:29.800 --> 1:14:35.600 vision and then came into full view with kaleidoscopic, colorful 1:14:35.720 --> 1:14:41.360 geometric patterns. Airy also shared a drawing of his visual disturbance, 1:14:41.400 --> 1:14:45.400 which he called hemiopsy, and his drawing, which was jagged 1:14:45.680 --> 1:14:49.680 swirling lines on a black background, became one of the 1:14:49.720 --> 1:14:55.880 most famous and recognizable illustrations of migraine aura, which had 1:14:55.880 --> 1:14:59.519 become front and center in migraine diagnosis and research as 1:14:59.520 --> 1:15:02.640 debates continued about whether the condition had a vascular or 1:15:02.760 --> 1:15:07.280 neurological basis, and effective treatments were of course still nowhere 1:15:07.320 --> 1:15:11.280 to be found, and that's how things remained for the 1:15:11.320 --> 1:15:15.480 first decades of the twentieth century. The pain from migraines 1:15:15.520 --> 1:15:20.280 took a backseat to aura, which had become romanticized, especially 1:15:20.320 --> 1:15:24.000 with people claiming all sorts of historical and religious figures 1:15:24.360 --> 1:15:28.200 must have had aura and migraine because their religious visions 1:15:28.280 --> 1:15:33.800 or drawings resembled aura. Hildegarde of Bingen, if that's how 1:15:33.840 --> 1:15:37.200 you say it, hopefully, a saint who lived in Germany 1:15:37.240 --> 1:15:41.240 in the twelfth century, was foremost among these and has 1:15:41.280 --> 1:15:44.840 been called the patron saint of migraines. And really her 1:15:44.960 --> 1:15:51.400 retrospective diagnosis kicked off a whole bunch more, including Moses Ezekiel, Daniel, 1:15:51.600 --> 1:15:55.400 Saint John, the Divine, Charles Darwin, Pablo Picasso, Rudyard Kipling, 1:15:55.479 --> 1:15:58.920 Virginia Wolf, etc. And I don't know the details of 1:15:58.920 --> 1:16:02.960 what went into each of these retrospective diagnoses, like what 1:16:03.160 --> 1:16:05.960 symptoms did they use. I think for Picasso they just 1:16:06.040 --> 1:16:08.599 looked at his drawings and they were like, yeah, sure, 1:16:09.640 --> 1:16:16.559 Like did he ever write about pain anyway? And of 1:16:16.600 --> 1:16:19.840 course it is possible that several or even all of 1:16:19.880 --> 1:16:23.639 these people had migraines. Migraines are incredibly prevalent after all. 1:16:24.280 --> 1:16:28.479 But the problem with these retrospective diagnoses was how they 1:16:28.520 --> 1:16:33.160 were used by some people to push this message, which 1:16:33.280 --> 1:16:37.760 was that a visual aura was the defining feature of 1:16:37.840 --> 1:16:42.160 migraines and that b people who had the most extreme 1:16:42.360 --> 1:16:47.799 visual disturbances with migraine were the quote clever, intellectual people 1:16:48.000 --> 1:16:53.439 endowed with the creative type of mind and quote yeah, 1:16:53.520 --> 1:16:57.280 and it furthered this idea of there being a quote 1:16:57.360 --> 1:17:01.720 unquote migraine personality, which had evolved from the gender and 1:17:01.800 --> 1:17:07.200 class stereotypes of the late nineteenth century Prepare yourself, my dear. 1:17:07.800 --> 1:17:12.280 According to the American physician Walter Alvarez from the mid 1:17:12.439 --> 1:17:17.000 twentieth century or so, the typical migraine patient was female, 1:17:17.600 --> 1:17:24.400 quote tense, perfectionist, hypersensitive, easily fatigued, and often depressed or 1:17:24.439 --> 1:17:29.000 disconnected end quote. They also had bad periods and quote 1:17:29.080 --> 1:17:35.679 unquote defective and poorly functioning pelvic organs. What but don't worry. 1:17:36.560 --> 1:17:43.560 She was also quote decidedly feminine and sexually attractive quote 1:17:44.720 --> 1:17:49.000 but with a masculine vibe. That quote causes her to 1:17:49.080 --> 1:17:53.360 act independently and to think dispassionately, much as does an 1:17:53.439 --> 1:17:54.440 able businessman. 1:17:55.280 --> 1:17:56.960 I can not. 1:17:58.040 --> 1:18:01.000 I know, I know, I hate it so much. 1:18:02.840 --> 1:18:04.040 Oh my god. 1:18:07.360 --> 1:18:10.840 Alvarez went so far as to claim that he could 1:18:10.920 --> 1:18:14.360 spot a migraine patient without even talking to them. 1:18:14.880 --> 1:18:19.240 I don't like this guy, and he was known in 1:18:19.400 --> 1:18:20.240 his ideas. 1:18:20.439 --> 1:18:24.360 There's many people as you can dislike. In the nineteen 1:18:24.439 --> 1:18:28.520 forty eight book Headache and Other head Pain, author neurologist 1:18:28.520 --> 1:18:32.959 Harold Wolfe wrote that his migraine patients had as children 1:18:33.080 --> 1:18:38.040 been quote delicate, shy, withdrawn, and obedient to their parents 1:18:38.280 --> 1:18:42.439 end quote, but also stubborn, and as adults they were 1:18:42.560 --> 1:18:49.160 quote unusually ambitious and preoccupied with achievement and success end quote. 1:18:49.640 --> 1:18:55.280 Unusually ambitious, unusually ambitious, They had a hard time delegating. 1:18:55.439 --> 1:19:00.559 They were impatient and resentful, cold, and aloof been brought 1:19:00.600 --> 1:19:04.759 on migraines by not adapting well to situations like going 1:19:04.760 --> 1:19:08.200 on vacation. Just like relax. You can't relax on vacation. 1:19:08.560 --> 1:19:10.439 You're going to get a migraine. You're going to give 1:19:10.479 --> 1:19:11.360 yourself a migraine. 1:19:12.560 --> 1:19:17.519 I want to highlight that, you said a book from 1:19:17.680 --> 1:19:24.000 nineteen forty eight. Uh huh, that was not long ago? No, yeah, okay. 1:19:24.960 --> 1:19:28.400 Another physician from around this time wrote that people with 1:19:28.600 --> 1:19:33.919 migraines had quote a personality that seeks and creates stress 1:19:34.120 --> 1:19:37.799 and a physiology that handles it poorly end quote. 1:19:40.880 --> 1:19:45.760 So yeah, it's really interesting because there's evidence now that 1:19:45.920 --> 1:19:49.519 some of the things that people have historically or even 1:19:49.560 --> 1:19:53.040 maybe personally identified as like potential triggers or things like 1:19:53.320 --> 1:19:57.640 quote unquote stress, et cetera, may actually be part of 1:19:57.800 --> 1:20:04.640 the prodromal phase of a migraine itself. So like, so 1:20:04.680 --> 1:20:09.160 it's really even more frustrating to hear like these, oh, 1:20:09.240 --> 1:20:12.640 you're you're causing yourself stress, Like it could genuinely be 1:20:13.000 --> 1:20:20.200 that people's brains are increasing certain stress responses or something 1:20:20.240 --> 1:20:23.960 in a way that's entirely outside of your control, and 1:20:23.960 --> 1:20:25.280 then a migraine follows. 1:20:25.320 --> 1:20:28.800 Like it's just yeah, as though, like all of these 1:20:28.840 --> 1:20:33.879 things are under someone's control anyway, right, Like be less stressed, 1:20:34.200 --> 1:20:39.360 try not to worry so much, just like, don't worry. 1:20:38.360 --> 1:20:40.920 That advice has helped no one ever. 1:20:41.760 --> 1:20:47.800 No, And so when you're met with this kind of 1:20:47.920 --> 1:20:51.840 dismissal and blame from someone who is supposed to be 1:20:51.880 --> 1:20:55.760 giving you health care, whom you are paying for health care, 1:20:55.800 --> 1:21:00.000 whom you look to as an expert how are you 1:21:00.240 --> 1:21:05.479 going to feel comfortable asking for help? It's so frustrating because, 1:21:05.520 --> 1:21:09.280 like I said, for the vast majority of human written history, 1:21:09.520 --> 1:21:14.600 migraines were handled as real medical problems with a physical basis, 1:21:15.200 --> 1:21:19.520 only to have that undermined by physicians who were probably 1:21:19.600 --> 1:21:24.080 projecting their own insecurities over not being able to effectively 1:21:24.120 --> 1:21:28.599 treat migraines or define them. And I have no doubt 1:21:28.840 --> 1:21:32.760 that contributing to this was the gender distribution in migraines, 1:21:33.360 --> 1:21:38.680 with women much more likely to experience them. This dismissive 1:21:38.720 --> 1:21:44.600 attitude towards migraines, the idea of a migraine personality or 1:21:44.680 --> 1:21:48.320 a taking center stage as a symptom. We're still feeling 1:21:48.560 --> 1:21:52.320 all of the effects from this today. And there's a 1:21:52.360 --> 1:21:54.360 book that I didn't get a chance to read for 1:21:54.400 --> 1:21:57.879 this episode, but I really want to read, called Not Tonight, 1:21:58.280 --> 1:22:01.639 Migraine and the Politics of Gender and Health by Joanna 1:22:01.720 --> 1:22:04.720 Kempner that goes into this in much more depth, and 1:22:04.760 --> 1:22:08.120 I'll link to it on our website. But this downplaying 1:22:08.160 --> 1:22:12.720 of migraines as just really bad headaches and sort of 1:22:12.760 --> 1:22:17.400 the casting off of pain, like dismissing pain as the 1:22:17.720 --> 1:22:22.680 feature for most migraines has contributed to the gap in 1:22:22.760 --> 1:22:26.839 research funds for migraine treatments and the lack of general 1:22:26.880 --> 1:22:31.400 awareness around the cause and especially the impact of migraines. 1:22:32.720 --> 1:22:40.480 They can be debilitating, incapacitating, excruciating, even with stress control, 1:22:40.720 --> 1:22:44.040 whatever that means, even with sufficient sleep, even with taking 1:22:44.120 --> 1:22:47.360 a break from the kids, even with medication, even with 1:22:47.479 --> 1:22:51.479 doing whatever else a doctor tells you not to do, 1:22:52.040 --> 1:22:55.639 so that you don't bring this on yourself. You can't. 1:22:56.320 --> 1:23:02.519 I'm just so frustrated, and I can't help but feel 1:23:02.680 --> 1:23:06.679 that doctors in the late nineteenth century in early twentieth 1:23:06.760 --> 1:23:10.320 century they took one look at migraine and thought, I 1:23:10.360 --> 1:23:14.040 don't know what this is. I can't treat this. Therefore 1:23:14.360 --> 1:23:17.519 it must not be real, or at the very least, 1:23:17.520 --> 1:23:20.320 it must not be as bad as they say, or 1:23:20.920 --> 1:23:24.320 it's probably a personal failing on their part, because I'm 1:23:24.360 --> 1:23:27.280 a trained medical professional and I can't admit that I 1:23:27.280 --> 1:23:31.880 don't know something or can't treat something. Let me read 1:23:31.920 --> 1:23:35.280 you one final quote from a physician, and then I'll 1:23:35.400 --> 1:23:42.080 get us off this rage train. Maybe. In nineteen o two, J. M. 1:23:42.160 --> 1:23:47.240 Aiken wrote in jama that quote, of all the common 1:23:47.360 --> 1:23:51.719 and much dreaded nervous diseases we recognize. None are less 1:23:51.760 --> 1:23:56.120 perfectly understood than migraine. Nor is there any other nervous 1:23:56.120 --> 1:24:00.559 disorder which is so disastrous to the physician's ability for treatment. 1:24:01.600 --> 1:24:04.600 It is easy to say what migraine is not, but 1:24:04.720 --> 1:24:07.960 difficult to define what it is end quote. 1:24:09.040 --> 1:24:11.160 I mean even just the framing of that as like 1:24:11.880 --> 1:24:13.520 this is hard for doctors. 1:24:13.800 --> 1:24:16.479 Oh yeah, And I didn't even get into like some 1:24:16.680 --> 1:24:20.240 of the gendered advertisements from the mid twentieth century for 1:24:20.640 --> 1:24:24.680 migraine treatment, where it's like geared towards doctors that are like, 1:24:25.240 --> 1:24:28.200 it's not just a problem for your female migraine patient, 1:24:28.280 --> 1:24:31.040 it's also a problem for you, kind of implying like 1:24:31.120 --> 1:24:34.120 she's complaining to you and she keeps seeking help, so 1:24:34.520 --> 1:24:35.320 prescribe her this. 1:24:36.360 --> 1:24:37.120 Wow. 1:24:38.520 --> 1:24:45.120 Oh wow, it's good stuff. Yeah. In the second half 1:24:45.200 --> 1:24:49.720 of the twentieth century, we did make substantial progress in 1:24:49.880 --> 1:24:54.920 understanding what migraine was, especially with the introduction of the 1:24:54.960 --> 1:25:00.639 International Classification of headache disorders in nineteen eighty eight, progress 1:25:00.680 --> 1:25:04.439 in what caused it, with the neurological framework sort of 1:25:04.520 --> 1:25:08.240 overtaking the vascular one and then kind of being integrated 1:25:08.280 --> 1:25:14.600 with this new neuro vascular framework, and we also made progress, 1:25:14.760 --> 1:25:17.599 a lot of progress in how to treat it, first 1:25:17.600 --> 1:25:22.400 with the introduction of ergotamine and then like migral tablets, 1:25:22.880 --> 1:25:27.839 which was a combination of ergotamine, caffeine, and cyclazine introduced 1:25:27.840 --> 1:25:32.640 in the nineteen fifties. And then also another treatment that 1:25:32.720 --> 1:25:36.240 you mentioned, which was introduced in the nineteen eighties was 1:25:36.640 --> 1:25:41.240 the trip dans, with the first one being sumatriptan. And 1:25:41.280 --> 1:25:45.439 so we've come a long way in our understanding and 1:25:45.600 --> 1:25:51.559 prevention slash management of migraine, but we clearly have so 1:25:51.880 --> 1:25:55.960 far to go still, not just in treatments and making 1:25:56.000 --> 1:25:59.719 those treatments accessible for everyone who needs them, but also 1:25:59.800 --> 1:26:06.120 in reducing stigma, shame, and blame surrounding migraines, like believing 1:26:06.240 --> 1:26:11.080 people what a concept? Why is it so hard? Why 1:26:11.160 --> 1:26:14.320 is pain the most dismissed thing? 1:26:15.240 --> 1:26:17.880 I feel like we talked about this in our Endometrios 1:26:17.920 --> 1:26:20.639 this episode a lot as well. 1:26:20.920 --> 1:26:26.560 Yeah, Yeah, also hugely gendered aspect there, likely. 1:26:28.120 --> 1:26:32.920 Because you can't see pain, like when we talk about 1:26:33.080 --> 1:26:36.240 being able to measure something right, right, but. 1:26:36.240 --> 1:26:42.480 We also can't see aura. Yeah that's true, Or like nausea. 1:26:42.560 --> 1:26:45.120 But but you can see vomiting. 1:26:44.840 --> 1:26:46.240 You can see vomiting. Yeah. 1:26:46.360 --> 1:26:46.839 Yeah. 1:26:47.240 --> 1:26:50.080 I think that I spent so much time sort of 1:26:50.439 --> 1:26:54.840 in the earlier history of migraines because I really did 1:26:54.880 --> 1:26:58.800 want to get across the point that we used to 1:26:59.160 --> 1:27:02.720 be better are at this. I mean, yes, it was 1:27:02.720 --> 1:27:05.120 the humoral theory of disease, but it was like, oh, 1:27:05.160 --> 1:27:08.439 here's this real thing. Here are some real treatments for it. 1:27:08.920 --> 1:27:09.400 Yeah. 1:27:09.520 --> 1:27:12.600 Oh, but maybe it's not real. Maybe it's all in 1:27:12.640 --> 1:27:17.200 your head, and it's just it's so many diseases are 1:27:17.280 --> 1:27:18.839 like this that we've covered on the podcast. 1:27:18.880 --> 1:27:19.040 You know. 1:27:19.040 --> 1:27:21.880 We've talked about asthma, We've talked about lupus, we've talked 1:27:21.880 --> 1:27:25.720 about epilepsy, we've talked about, of course, endometriosis. That have 1:27:25.920 --> 1:27:30.400 undergone this shift that I think coincides with when medical 1:27:30.439 --> 1:27:34.320 knowledge was increasing overall but not necessarily shedding any light 1:27:34.400 --> 1:27:38.479 on those conditions, and so rather than saying maybe it's 1:27:38.479 --> 1:27:41.960 something that we don't know about yet, it had to 1:27:41.960 --> 1:27:44.439 be put in this box of maybe it's in your head. 1:27:45.479 --> 1:27:47.920 I'm sure that we'll look back on this period of 1:27:47.960 --> 1:27:53.120 time with similar diseases that right now are classified as 1:27:53.920 --> 1:27:58.479 psychosomatic or whatever it is, you know, Like anyway, I'm 1:27:58.520 --> 1:28:01.400 at the very end of this gone on this rant, 1:28:01.720 --> 1:28:04.439 and now I should just stop myself and turn it 1:28:04.680 --> 1:28:05.719 over to you, Aaron. 1:28:05.880 --> 1:28:10.040 So but I love it, Aaron, I mean I hate it? Yeah? 1:28:10.120 --> 1:28:13.160 Oh yes, So where do we go from here? Oh? 1:28:13.400 --> 1:28:17.559 Okay, okay, let's take a break, take a breath, and 1:28:17.640 --> 1:28:56.360 we'll find out. Migrain is estimated to affect one billion 1:28:56.920 --> 1:29:03.160 people worldwide, depending on the paper that you read and 1:29:03.200 --> 1:29:07.720 what data you use, meaning if you consider definite and 1:29:08.200 --> 1:29:15.120 probable migraines based on those ICHD criteria, that's between fifteen 1:29:15.439 --> 1:29:20.879 percent of the global population or as high as thirty 1:29:21.040 --> 1:29:26.479 five percent of the general population having migraines each year. 1:29:27.560 --> 1:29:31.680 Thirty five percent arin if you include probable migraine. 1:29:31.320 --> 1:29:34.520 And that's every year. That's not lifetime. 1:29:34.960 --> 1:29:39.960 So this is yeah, annual prevalence. It's not incidents. We 1:29:40.120 --> 1:29:47.479 don't have great data on incidents, but that's annual prevalence. Now, 1:29:47.560 --> 1:29:54.080 across all age groups, prevalence of migraine is significantly higher, 1:29:54.160 --> 1:29:57.240 usually two to three times higher depending on age, in 1:29:57.320 --> 1:29:59.960 people who are assigned female at birth compared to peer 1:30:00.000 --> 1:30:06.920 people assigned mail and prevalence tends to peak usually in 1:30:06.960 --> 1:30:12.360 the thirties, but really age twenty five to forty, so 1:30:12.439 --> 1:30:19.240 this is young people being very significantly affected. Among people 1:30:19.320 --> 1:30:24.840 with active migraine, the median monthly attack frequency, so how 1:30:24.880 --> 1:30:28.639 many episodes of migraine per month is one point five 1:30:29.920 --> 1:30:34.720 but a quarter of people have weekly attacks. And remember 1:30:35.120 --> 1:30:38.519 that the total duration of a migraine attack can last 1:30:39.040 --> 1:30:43.120 up to a week. Oh my gosh, right, And up 1:30:43.200 --> 1:30:47.880 to five percent have chronic migraine, which again means fifteen 1:30:47.920 --> 1:30:53.519 headache days a month, eight of which meet criteria for migraine. 1:30:54.479 --> 1:30:57.599 So with all of that being said, it should come 1:30:57.640 --> 1:31:01.800 as no surprise, though this was shocking to me. The 1:31:01.840 --> 1:31:07.120 World Health Organization ranks migraine as the most prevalent disabling 1:31:07.439 --> 1:31:13.320 long term neurologic condition period and it's not necessarily because 1:31:13.320 --> 1:31:17.960 it's the most common. Even in terms of headaches, tension 1:31:18.000 --> 1:31:22.320 type headaches are far more common than migraine, but migraine 1:31:22.680 --> 1:31:28.840 is so disabling that, as an example, while tension type 1:31:28.840 --> 1:31:33.559 headache affects almost a billion more people worldwide, like eight 1:31:33.680 --> 1:31:39.840 hundred million more people than migraine, migraine causes six times 1:31:39.960 --> 1:31:44.080 as many estimated disability adjusted life years or years lived 1:31:44.080 --> 1:31:44.880 with disability. 1:31:45.200 --> 1:31:45.439 Whow. 1:31:46.960 --> 1:31:52.200 Migraine in twenty eighteen caused an estimated forty five million 1:31:52.479 --> 1:31:56.040 years lost to disability, compared to seven point two million 1:31:56.200 --> 1:31:59.360 for tension type headache. Oh my gosh, and the data 1:31:59.400 --> 1:32:03.479 hasn't changed changed much over the years. That estimate was 1:32:03.479 --> 1:32:07.000 from a twenty eighteen paper based on twenty sixteen data. 1:32:07.040 --> 1:32:10.240 Based on twenty nineteen data, it's an estimated forty two 1:32:10.280 --> 1:32:18.920 point one million years lost to disability. That's it's obscene, Yeah, 1:32:19.520 --> 1:32:24.879 especially because we have treatments. Migraine is the leading cause 1:32:24.960 --> 1:32:30.040 of disability worldwide for people younger than fifty years, especially 1:32:30.439 --> 1:32:34.479 for women. And I don't want to just go based 1:32:34.479 --> 1:32:38.240 on disability adjusted life years or years lost to disability, 1:32:38.280 --> 1:32:42.160 because we know that that's an imperfect metric. But I 1:32:42.200 --> 1:32:45.439 also have read that in studies that have looked based 1:32:45.479 --> 1:32:50.200 on survey data from the US at least on people's 1:32:50.280 --> 1:32:55.400 reported effect on their lives, that up to thirty percent 1:32:55.400 --> 1:32:57.880 of people who live with migraines say that it affects 1:32:57.960 --> 1:33:01.720 their careers in some way, thirty percent say that it 1:33:01.760 --> 1:33:06.120 affects their parenting in some way, and nearly fifty percent 1:33:06.200 --> 1:33:11.040 feel that it affects their relationships. Yeah, that's huge, and 1:33:11.360 --> 1:33:14.640 caveat that those numbers are based on US data, so 1:33:15.080 --> 1:33:20.639 we don't know the universality of that. But it's I mean, 1:33:20.680 --> 1:33:24.320 this is not a minor disorder. 1:33:24.080 --> 1:33:27.720 To live with, right, and like just living with that 1:33:28.600 --> 1:33:34.479 uncertainty and that unpredictability. Yeah, and planning. How can you 1:33:34.560 --> 1:33:37.240 plan around a migraine when you don't know if you're 1:33:37.280 --> 1:33:38.080 going to have one? 1:33:38.560 --> 1:33:43.679 Yep, exactly, Oh my gosh. If you're more interested in 1:33:44.040 --> 1:33:50.000 money and cost, In Europe, financial costs that are attributed 1:33:50.080 --> 1:33:54.799 to migraine are estimated at between fifty and one hundred 1:33:54.880 --> 1:33:59.679 and eleven billion dollars, and that was like fifteen years ago. 1:34:01.040 --> 1:34:04.440 And what's interesting is that in Europe the vast majority 1:34:04.479 --> 1:34:08.040 of that cost is estimated to be indirect cost, meaning 1:34:08.280 --> 1:34:12.799 not healthcare dollars, but dollars lost in other ways because 1:34:12.800 --> 1:34:17.280 of lost productivity at work, et cetera. Whereas in the US, 1:34:17.960 --> 1:34:23.280 direct costs are estimated at eleven billion dollars annually and 1:34:23.560 --> 1:34:29.000 indirect cost twelve billion dollars annually. Wow, So there's a 1:34:29.000 --> 1:34:31.479 lot of discrepancy there. I'm sure there's a whole podcast 1:34:31.479 --> 1:34:39.679 about that. So migraine is a massive issue, and most 1:34:39.720 --> 1:34:42.880 of the data that we have on migraine come from 1:34:43.040 --> 1:34:48.160 Europe and the US and high income countries, but migraine 1:34:48.240 --> 1:34:53.800 is a global phenomenon that affects people across the entire world, 1:34:54.360 --> 1:34:57.400 and in low and middle income countries. Not only do 1:34:57.439 --> 1:35:00.439 people tend to lack access to a lot of treatment 1:35:00.640 --> 1:35:05.160 or even diagnosis options, people are far less likely to 1:35:05.200 --> 1:35:09.120 be diagnosed accurately with migraine in low and middle income countries. 1:35:09.920 --> 1:35:14.200 We also have much less data to guide policy and 1:35:14.240 --> 1:35:17.880 to guide programs, and part of this is because the 1:35:17.920 --> 1:35:20.679 focus tends to be in low and middle income countries 1:35:20.720 --> 1:35:25.120 on other additionally pressing health issues, things things like TB 1:35:25.240 --> 1:35:27.519 and HIV, which are more common in low and middle 1:35:27.560 --> 1:35:31.800 income countries. But that's despite the fact that migraine is 1:35:31.840 --> 1:35:37.040 also causing massive amounts of disability in these countries as well. 1:35:37.160 --> 1:35:39.400 Right, And there's. 1:35:39.360 --> 1:35:43.360 Estimates from a whole bunch of different countries that indirect 1:35:43.360 --> 1:35:47.800 costs alone can be as much as two percent of 1:35:47.880 --> 1:35:56.080 gross domestic product annually WHOA because of migrain. Yeah, So 1:35:56.280 --> 1:36:00.600 when it comes to current research, it's a little hard for 1:36:00.640 --> 1:36:02.080 me to even know where to begin. 1:36:02.680 --> 1:36:03.599 Is that a good thing? 1:36:04.600 --> 1:36:05.000 I don't. 1:36:05.160 --> 1:36:06.559 I don't know, Okay. 1:36:06.720 --> 1:36:10.679 Sometimes in this section I'm able to say, like, here's 1:36:10.680 --> 1:36:14.000 this one new great thing that just happened or is 1:36:14.040 --> 1:36:17.800 on the horizon it's about to happen. I don't have 1:36:18.040 --> 1:36:23.240 that one great thing for migraine, Okay. But that's not 1:36:23.400 --> 1:36:28.000 because there haven't been great strides made in migraine research. 1:36:28.640 --> 1:36:32.320 There have been a number of really new drugs in 1:36:32.360 --> 1:36:35.400 the last year, really this year, in twenty twenty three, 1:36:35.720 --> 1:36:37.800 and in the last couple of years that have come 1:36:37.840 --> 1:36:42.200 down the pipeline. There have been new monoclonal antibodies that 1:36:42.280 --> 1:36:47.280 specifically target this CGRP pathway, and many of which are 1:36:47.320 --> 1:36:51.360 intended to be used as preventative treatment, so especially for 1:36:51.439 --> 1:36:54.879 people who have chronic migraine or just a high burden 1:36:54.960 --> 1:36:57.639 of migraine, you know, each week or each month, even 1:36:57.680 --> 1:37:01.920 if they don't meet criteria for chronic migraine preventative rather 1:37:02.000 --> 1:37:05.080 than just what are called abortive treatments or treatments made 1:37:05.120 --> 1:37:09.880 to be used when a migraine happens. Right, And there 1:37:09.880 --> 1:37:13.840 have also been other oral medications that includes that whole 1:37:13.960 --> 1:37:18.120 class called the jeptins, which are the ones that have 1:37:18.160 --> 1:37:24.639 commercials right now, like Ubrelv and Nurtec. I probably shouldn't 1:37:24.680 --> 1:37:27.799 use brand names, but whatever. These are things that also 1:37:27.960 --> 1:37:32.439 target that CGRP peptide. There's also a brand new nasal 1:37:32.479 --> 1:37:35.000 spray that targets the same peptide. 1:37:35.040 --> 1:37:36.800 Oh fascinating, I know. 1:37:37.200 --> 1:37:40.320 And there's a relatively new I think in twenty nineteen 1:37:40.439 --> 1:37:43.479 was when it was approved by the FDA, was a 1:37:43.479 --> 1:37:46.920 medicine in a class called ade tan, which are very 1:37:46.920 --> 1:37:52.000 similar to triptans, but they have less vasoconstrictive effects, which 1:37:52.040 --> 1:37:55.519 means less cardiac risk and therefore more people can probably 1:37:55.600 --> 1:38:00.240 use it. Cool, and then there are really creative things 1:38:00.320 --> 1:38:08.000 like botox injections, trigger point injections, neuromodulatory mechanisms, and probably 1:38:08.040 --> 1:38:10.880 a bunch more drugs coming down the pipeline as well. 1:38:12.000 --> 1:38:16.400 But there isn't like a silver bullet, and a lot 1:38:16.400 --> 1:38:18.800 of that is because there's still just so much that 1:38:18.880 --> 1:38:20.959 we don't know when it comes to migraine. 1:38:21.720 --> 1:38:21.920 Yeah. 1:38:22.439 --> 1:38:25.160 So some of the other big areas of research besides 1:38:25.240 --> 1:38:31.840 just therapeutics are things like identifying biomarkers, either blood biomarkers 1:38:32.000 --> 1:38:35.280 or imaging biomarkers. Things that we can identify on an 1:38:35.400 --> 1:38:39.559 MRI that can either predict the risk of migraine or 1:38:39.800 --> 1:38:43.479 predict treatment targets so that we can develop even other 1:38:43.760 --> 1:38:45.040 types of therapeutics. 1:38:45.920 --> 1:38:47.440 But in general, there's. 1:38:47.240 --> 1:38:50.439 A lot of mixed results when it comes to a 1:38:50.439 --> 1:38:53.320 lot of things with migraine research, but especially with this 1:38:53.520 --> 1:38:58.360 attempt at identifying various biomarkers. I think the thing that 1:38:58.439 --> 1:39:02.280 gives me hope is I will say that when I 1:39:02.439 --> 1:39:07.439 was researching for this episode, I found more very recent 1:39:07.520 --> 1:39:13.840 papers in like well regarded journals about migraine research than 1:39:13.880 --> 1:39:17.839 I have found for any of our recent episodes. Oh wow, Okay, 1:39:18.720 --> 1:39:21.360 like a lot. There's a whole series that came out 1:39:21.400 --> 1:39:24.840 in the Lancet three paper series that came out in 1:39:24.880 --> 1:39:29.320 twenty twenty one. There's Nature papers and New England Journal papers, 1:39:29.360 --> 1:39:32.960 like a lot of kind of high profile research that's 1:39:33.040 --> 1:39:35.960 really really recent when it comes to migraine. So that 1:39:36.439 --> 1:39:39.320 gives me hope that it's getting a lot more attention 1:39:39.600 --> 1:39:44.000 because we're recognizing what a massive issue it really is, 1:39:47.040 --> 1:39:48.000 that's migrain. 1:39:49.640 --> 1:39:52.960 Gosh, I hope we did it justice. 1:39:53.160 --> 1:39:53.360 Yeah? 1:39:53.479 --> 1:39:54.639 Is that enough? 1:39:55.040 --> 1:39:55.479 I don't know. 1:39:56.120 --> 1:39:59.360 I don't think so, tell Us, could it ever be enough? 1:39:59.600 --> 1:39:59.760 No? 1:40:01.160 --> 1:40:04.240 Luckily there's more reading. 1:40:04.720 --> 1:40:07.400 There's so much more. Let us tell you about it. 1:40:08.760 --> 1:40:11.639 I'm going to shout out again Migrain a History by 1:40:11.720 --> 1:40:15.080 Catherine Foxhall, and a'll link to it on the website. 1:40:15.360 --> 1:40:18.680 I have a lot of sources for this episode. A 1:40:18.760 --> 1:40:23.679 few that I loved were Migrain a Primer from Nature 1:40:23.760 --> 1:40:28.040 Reviews Disease Primers in twenty twenty two. There was also 1:40:28.200 --> 1:40:32.840 a paper titled Migraine and the Trigeminovascular System forty years 1:40:32.840 --> 1:40:37.160 in counting from the Lancet Neurology in twenty nineteen. Also 1:40:37.240 --> 1:40:40.360 I mentioned already, but there's a great series. It's three 1:40:40.520 --> 1:40:45.800 different papers about different aspects of migrain, from the epidemiology 1:40:46.080 --> 1:40:53.000 to disease characterization like biomarker research and approaches to management 1:40:53.000 --> 1:40:55.599 and emerging treatments that all came out in the Lancet 1:40:55.640 --> 1:40:59.120 twenty twenty one. We'll have a list of this and 1:40:59.320 --> 1:41:02.880 all of our sources from this episode and all of 1:41:02.920 --> 1:41:05.120 our episodes on our website This podcast will kill You 1:41:05.200 --> 1:41:07.360 dot Com under the episodes tab. 1:41:07.760 --> 1:41:14.040 We certainly will a big, huge, tremendous, incredible thank you 1:41:14.400 --> 1:41:19.400 to everyone who shared their experience, their story with migrain. 1:41:19.479 --> 1:41:20.759 We really can't thank you enough. 1:41:21.160 --> 1:41:24.559 Yeah, thank you. Thank you also to Bloodmobile for providing 1:41:24.600 --> 1:41:28.080 the music for this episode and every one of our episodes. 1:41:27.840 --> 1:41:31.400 And thank you to Leana Squalacci for the amazing audio mixing. 1:41:32.080 --> 1:41:34.760 Thank you to the Exactly Right Network, and thank you 1:41:34.840 --> 1:41:38.320 to you listeners. We hope that you, I don't know 1:41:38.720 --> 1:41:41.280 got something out of this episode learned something. 1:41:41.360 --> 1:41:43.880 I hope so know, let us know. 1:41:44.400 --> 1:41:45.160 We appreciate you. 1:41:45.720 --> 1:41:48.280 And a special shout out as always to our patrons. 1:41:48.320 --> 1:41:51.840 Thank you so much for your continued support. We really 1:41:51.880 --> 1:41:52.559 appreciate it. 1:41:52.720 --> 1:41:59.240 Yeah, thank you. Well. Until next time, wash your hands. 1:41:59.080 --> 1:42:00.280 You filthy animal elf. 1:42:02.040 --> 1:42:09.679 M um um. 1:42:13.040 --> 1:42:16.840 Um um 1:42:20.600 --> 1:42:20.640 U