406 ‒ Migraine, cluster headache, and tension headache: symptoms, causes, prevention, and treatment

1. 0:00 – 0:11

   Intro

   1. PAPeter Attia0:00

      [upbeat music] Hey, everyone. Welcome to the Drive Podcast. I'm your host, Peter Attia. [upbeat music]

2. 0:11 – 7:30

   Brian's interest in headaches and how Peter met Brian

   1. PAPeter Attia0:11

      Brian, thank you so much for, for coming, and I didn't realize until a few minutes ago that not only had you never been on a podcast, which these days is pretty unusual, especially if you're an expert in something, which you are, um, but that you've never listened to a podcast.

   2. BGBrian Grosberg0:26

      Makes me a unicorn.

   3. PAPeter Attia0:26

      Yes.

   4. BGBrian Grosberg0:27

      Yes.

   5. PAPeter Attia0:27

      So okay. Um, this is a topic that I think just affects so many people. Um, I wanna maybe understand the landscape a little bit about the field of neurology. What fraction of neurologists specialize in headache, and, and w-how did you decide that this is what you wanted to do?

   6. BGBrian Grosberg0:45

      So first of all, thank you very much for having me. I really appreciate it, Peter. Um, so I think it's important to understand that headache is one of the most common neurologic symptoms. Um, nearly at some point in, in every person's life they're gonna experience a headache. Um, surprisingly, in medical school, uh, maybe medical students and residents get a few hours a-across entire medical school of, of lectures.

   7. PAPeter Attia1:13

      I d-actually don't recall any of it. It's possible I had it-

   8. BGBrian Grosberg1:17

      Yeah

   9. PAPeter Attia1:17

      ... and I just don't recall it.

   10. BGBrian Grosberg1:17

       Yeah.

   11. PAPeter Attia1:17

       But I actually don't recall anything.

   12. BGBrian Grosberg1:19

       Yeah. And it's, um, and so that's a, a, a gap in education, and then in neurology residencies that is similar, where-

   13. PAPeter Attia1:27

       Oh, really?

   14. BGBrian Grosberg1:27

       ... people are only, neurology residents are, uh, depending on the program of course, may only get a few hours of, of headache lectures or education. And then they're experts. And so, uh, for my, um, journey, if you will, into headache medicine was actually by accident.

   15. PAPeter Attia1:44

       Hmm.

   16. BGBrian Grosberg1:44

       It's complete serendipity. Uh, my first year of a neurology residency, I took care of a litigator who was out of work for six weeks, uh, due to a prolonged migraine that had been going on for six weeks straight. And without knowing, um, the person who was caring for her turned out to be my future mentor, and so I had called this person and, um, you know, detailed her-

   17. PAPeter Attia2:06

       And you were a resident at this time?

   18. BGBrian Grosberg2:08

       I was, I was a resident.

   19. PAPeter Attia2:08

       Yeah.

   20. BGBrian Grosberg2:08

       I was probably a month into my neurology residency.

   21. PAPeter Attia2:11

       Oh, wow, okay.

   22. BGBrian Grosberg2:11

       So it was really early on.

   23. PAPeter Attia2:12

       Mm-hmm.

   24. BGBrian Grosberg2:13

       And, um, s-saw the patient, took a history, read up on it, and then detailed the history to him and he said, "Are you, um, you know, thank you so much. Are you in your last year of residency?" I said, "No, I'm a month in." He said, "Well, that was great. Um, why don't you come by my office and let's talk?" Um, and so I did that, and, um, I got very interested in seeing patients with him. He offered to s-see patients with me. Residency at that time, uh, the, uh, when you were on call, the hours weren't restricted, and so if you were in the hospital 30 or 34 hours, whatever the case was, um, I would change out of, uh, scrubs into a shirt and tie, and then I would go see patients with him in the office, even though I'd already been in the hospital for that prolonged period of time. So my training in headache medicine was very, um, expedited, if you will, during my residency. And then from there, after I finished, um, I pursued advanced training in headache medicine, and there are just a limited number of programs in the country that offer fellowship training in headache medicine.

   25. PAPeter Attia3:14

       So basically, during your residency you did a fellowship in headache medicine on your own t-time with, with w-the, the fellow who would become your mentor, and then obviously you went and did the formalized training. But going back to that first interaction with that first patient where you, y-y-you must have had some intuition about this that, that allowed you to take a history that elicited enough information that this doctor felt like, "Wow, you're a seasoned pro at this." Any idea, thinking about what it was that allowed you to have s- 'cause if, if, if I saw a patient with headaches, I don't think I could ask two intelligent questions like, uh, you know, uh, "How long has it been aching and what part of your head, and is it thro-" Like, I, I wouldn't ask a single smart, smart question.

   26. BGBrian Grosberg3:54

       I'm sure you would. [laughs] Uh, I, uh, once again, in reading up about it, um, uh, I was able to end up obtaining the features and characteristics. What really struck me, um, was the fact that she was so debilitated, and that she was coming into the hospital and receiving treatments, leaving the hospital completely headache free. Uh, that for me was, uh, an epiphany, if you will, and, um, it led me to end up thinking about something that is k- if, if you will, an invisible disease-

   27. PAPeter Attia4:25

       Mm-hmm

   28. BGBrian Grosberg4:26

       ... um, that I wasn't really getting a lot of education during, necessarily during my neurology residency up until I started pursuing it, um, uh, g- you know, led me into the field today.

   29. PAPeter Attia4:39

       So Brian, we met te- not met, but communicated over email 10 years ago, uh-

   30. BGBrian Grosberg4:45

       I can't believe it's been that long
3. 7:30 – 20:00

   Differentiating the types of headaches: primary versus secondary headache and tension versus migraine headache

   1. BGBrian Grosberg7:30

      a litany of things that can cause headache. Um, the differential diagnosis, the list of things, is probably one of the most extensive in all of medicine-

   2. PAPeter Attia7:37

      Hmm

   3. BGBrian Grosberg7:37

      ... with over three hundred different types and causes of headache. And so the, um, the International Classification of Headache Disorders, uh, kind of like the Bible of headache, but with no mention of God in it-

   4. PAPeter Attia7:48

      [chuckles]

   5. BGBrian Grosberg7:48

      ... um, breaks down primary and secondary headaches. Uh, primary headaches is a, a headache in and of itself. It's a syndrome, right? It's not attributable to some other underlying condition. Most commonly migraine or tension-type headache, cluster headache are other primary headaches. And you're right that there are, um... There really aren't biomarkers, right? There aren't substances that we can detect, if you will, that tell us this is what the diagnosis is. And so the diagnostic criteria are, um, are outlined, and, uh, they always say not attributable to another disorder. The secondary headaches are headaches that are attributable to s- to some other underlying condition, right? Um, where people will ask me, "Dr. Grosberg, do I have a, a brain tumor? Do I have an aneurysm," right? "Is there something that's life-threatening?" Um, and that's where a detailed history becomes important, um, to try to, um, not only understand all the factors, but also the person that's sitting in front of me, right? 'Cause, um, no person or presentation is identical.

   6. PAPeter Attia8:49

      So primary headaches, we'll start with those, but just to, uh, make sure I'm clear and everybody is clear, does a secondary headache always have a pathologic driver underneath? Uh, because the examples you gave of a mass, a mass effect, whether it be ultimately benign and therefore not life-threatening if removed or malignant, um, that's pathology. Aneurysm, of course, pathology. Are there any non-pathologic, uh, causes of secondary headache?

   7. BGBrian Grosberg9:20

      Yeah. So there are, there are non-life-threatening things that are causes of secondary headache. Um, so one example would be if somebody is frequently using acute pain medication. That may lead to medication overuse. It's not life-threatening, but the, the resulting increase in the frequency of headache-

   8. PAPeter Attia9:41

      Yeah. Yeah

   9. BGBrian Grosberg9:41

      ... is, is attributable to-

   10. PAPeter Attia9:42

       Got it. So caffeine withdrawal-

   11. BGBrian Grosberg9:43

       ... some underlying condition. Caffeine withdrawal

   12. PAPeter Attia9:44

       ... would be another example-

   13. BGBrian Grosberg9:45

       Right. Yeah

   14. PAPeter Attia9:45

       ... of secondary then-

   15. BGBrian Grosberg9:46

       Yeah. And so-

   16. PAPeter Attia9:46

       ... even though it's not life-threatening.

   17. BGBrian Grosberg9:47

       Right, and they have pathophysiological and mechanistic reasons for the development of those headaches, but nothing that is-

   18. PAPeter Attia9:54

       Understood

   19. BGBrian Grosberg9:54

       ... pathological.

   20. PAPeter Attia9:55

       Yep. And so I guess I just answered my second question with the example of caffeine. Not every secondary cause has a radiographic or biologic, uh, marker.

   21. BGBrian Grosberg10:04

       Correct.

   22. PAPeter Attia10:05

       So, okay. Great. So now let's go in the sort of... I think you described the big three, right? Migraine, cluster, and tension headaches. Those are three enormous categories of primaries, and then you kind of have ano- another category of the, um, the, the, the sort of others that make up that. But let's take those in any order you would like.

   23. BGBrian Grosberg10:26

       Sure. So tension-type headache is the most common headache that people experience. Uh, migraine is the leading reason why people seek care, um, either in their primary care office, um, with somebody like myself, or in an emergency room. Um, and so tension-type headache is often thought about as a headache that is, uh, affects both sides of the head or the face or the neck, um, where it's mild to moderate. It's not pulsating or throbbing. Um, there may be light sensitivity or sound sensitivity, but never both. There's no nausea, and that headache can last anywhere from thirty minutes up to a week. It's everything that migraine isn't.

   24. PAPeter Attia11:06

       Hmm.

   25. BGBrian Grosberg11:06

       So that's the most common type of headache that people experience.

   26. PAPeter Attia11:09

       So someone listening to us right now who said, "I remember having a brutal headache a couple of years ago," it, that's most likely what they had if it was a one and done and-

   27. BGBrian Grosberg11:20

       I-- Well, a brutal headache, I wouldn't, uh, say that would be tension-type headache.

   28. PAPeter Attia11:24

       I see.

   29. BGBrian Grosberg11:24

       That's something that often people can end up working through. It doesn't necessarily impact-

   30. PAPeter Attia11:28

       I see
4. 20:00 – 25:45

   The epidemiology and burden of migraine, its disproportionate affect on women, and the shortage of headache specialists

   1. PAPeter Attia20:00

      I guess we'll come to it when we talk about treatments. You've alluded to the pathophysiology of the migraine, so clearly this must have to do with, uh, I assume it has to do with ion channels, you know, calcium channels or all sorts of the usual suspects for, for excitability. Um, so maybe we'll come back to that, but obviously I want to make sure we do talk about that, uh, through the lens of treatment. Um, what else should we know? I mean, I, again, I think most people listening who themselves have not had a migraine, I'm fortunate to be in that category. By the way, what is the prevalence?

   2. BGBrian Grosberg20:32

      12%, so one, one billion worldwide.

   3. PAPeter Attia20:35

      Wow.

   4. BGBrian Grosberg20:36

      Um, rou- roughly forty-five million people in the United States impacted by migraine.

   5. PAPeter Attia20:41

      And has anyone done the exercise of quantifying the economic consequence in the United States? Because this has to be even higher than lower back pain in terms of work missed, or at least on par with it, right?

   6. BGBrian Grosberg20:56

      Yeah. So there are-- The, the economic impact is, um, at least in the workplace, is in the billions of dollars. And, and it's-

   7. PAPeter Attia21:06

      Maybe more, right? I mean-

   8. BGBrian Grosberg21:06

      It may be more

   9. PAPeter Attia21:07

      ... it could be-- Certainly hundreds of billions would be my guess.

   10. BGBrian Grosberg21:09

       Yes.

   11. PAPeter Attia21:09

       Yeah.

   12. BGBrian Grosberg21:10

       The impact is not only on presente-- uh, not only on absenteeism, but on presenteeism. By that I mean, um-

   13. PAPeter Attia21:16

       Yeah, makes sense

   14. BGBrian Grosberg21:17

       ... the, the presenteeism, you know, is somebody there, right? Are they, are they showing up to work?

   15. PAPeter Attia21:20

       Somebody there, but they're just not working at full capacity.

   16. BGBrian Grosberg21:23

       But they're not working at full capacity versus absenteeism, where they, they don't show up to work-

   17. PAPeter Attia21:27

       Yeah

   18. BGBrian Grosberg21:27

       ... due to migraine. Uh, and the, the, the heaviest burden, I would say, is on presenteeism.

   19. PAPeter Attia21:33

       Interesting, which is much harder to quantify.

   20. BGBrian Grosberg21:35

       Correct.

   21. PAPeter Attia21:36

       Yeah. Really interesting point.

   22. BGBrian Grosberg21:37

       We're actually, we're actually doing it right now, uh, through a study that we're doing.

   23. PAPeter Attia21:40

       That's interesting. So there's an enormous incentive to fix this problem, even if you personally have not experienced it. It just, society suffers as a result of it on both absenteeism and, and presenteeism. So, um, but again, for those of us that have not experienced it, we have the sort of maybe stereotypical impression of it. I'm thinking of a person who has to lay in a dark room with a towel on their head and just, you know, bear it until this thing passes, and it strikes without a warning, and it's, it's a lightning strike. And, and y- y- you know, um, how many people are kind of walking around having migraines a couple times a year and not knowing that it's a migraine? Is that a pretty rare phenomenon or?

   24. BGBrian Grosberg22:30

       I think it's actually quite common. Um, and I think the spectrum of migraine is very broad, right? And I think you, um, elicited one person, right, who is bedridden. But many people with migraine are significantly impacted and walking around, and you'd never know necessarily that they're impacted unless you're asking them or seeing their behaviors by the way they, um, dim the lights or try to end up, uh, pushing through. I think a lot of people with an invisible disease, I think back to a famous comedian, Rodney Dangerfield-

   25. PAPeter Attia23:05

       Mm-hmm

   26. BGBrian Grosberg23:05

       ... that "I don't get respect." I think that's migraine, right? Where most people think of it just as a headache without realizing it's a neurologic disease. Um, and it disproportionately affects women three times more often than men.

   27. PAPeter Attia23:17

       Oh, wow. So twelve percent is aggregate.

   28. BGBrian Grosberg23:19

       Correct.

   29. PAPeter Attia23:20

       Um, but if you do the math-

   30. BGBrian Grosberg23:22

       Eighteen percent. Yeah, eighteen percent women
5. 25:45 – 33:15

   Genetic susceptibility to migraine and the role of hormones

   1. BGBrian Grosberg25:45

      the month.

   2. PAPeter Attia25:45

      Yeah. Um, okay. Before we get into treatments, um, and other things I wanna talk about, well, we could talk about them now. Talk, tell me a little bit about genetic susceptibility. Obviously, genetics matter, given the fact that women are three times more likely than men. That always makes-- the first thing one might think is, well, is it hormonal, right? Is it, uh, how much does it relate to estrogen, progesterone? We know that there are receptors for these things in the brain. Um, does, does the frequency of this type of headache, uh, is, is it higher during the reproductive years? Is it higher during the menopausal years? That would give us a clue as to the role of hormones. And then if during the, during the reproductive years, is it higher during any part of the cycle?

   3. BGBrian Grosberg26:31

      So that's a, that's a l- a lot of information packed. I will, I will try to tease that apart. Um, and so ultimately, yes, hormones plays a role. Yes, genetics plays a role, but migraine is multifactorial in the sense that both genetic environmental factors play a role in experiencing migraine. So if somebody, uh, has a family history of migraine, they're more likely to end up experiencing migraine. Um, and, uh, through a woman's, um, reproductive cycle and across hormonal milestones, migraine can certainly have a predilection around times of puberty, uh, around times of menses, pregnancy, lactation, um, perimenopause, and menopause. And so across these hormonal milestones, m-migraines certainly will fluctuate, if you will. Um, I would say about two-thirds of women will experience, um, migraines, uh, with premenstrual attacks, where they'll note an association of migraine around their menstrual period. Um, and that association comes in two possible forms. Uh, one is women who experience pure menstrual migraine, where they experience menses, uh, and, and headaches and migraine occurring around their menses solely around their menses, but not at other times of the month. That's less common. That occurs in probably less than 10% of women who experience what's called pure menstrual migraine, where the migraine are just around the menstrual period, usually a couple days before and a couple days into.

   4. PAPeter Attia28:04

      Which, of course, is the lowest period of hormones, which suggests hormone deprivation is driving that subset.

   5. BGBrian Grosberg28:11

      Correct. And then me-menstrual-related migraine, which is present in about 50% of women, is where they experience, uh, migraine not only in temporal association with their menstrual period, but at other times of the month. And so this is, um, a very common occurrence for women. Um, the, the, um, estrogen, uh, that dates back to the 1970s studies that were looked at that kind of the natural decline in estrogen in the late luteal phase and the development of migraine. Um, if we fast-forward in time, what we know from studies is that, um, it's the, the faster rate of estrogen decline in that late luteal phase that is unique in women who experience migraine. So it's this more rapid-

   6. PAPeter Attia29:02

      That's super interesting

   7. BGBrian Grosberg29:03

      ... ma- that more rapid rate of decline in estrogen. Um, I'm very proud 'cause one of the people I was fortunate to mentor actually did th- did those studies.

   8. PAPeter Attia29:13

      I'm surprised that we don't also see that post-ovulation because you also have a very sharp decline in estradiol post-ovulation. They kind of have two.

   9. BGBrian Grosberg29:21

      Right.

   10. PAPeter Attia29:21

       Right? They're sharp after ovulation and then not as sharp, uh, at the end of the luteal phase.

   11. BGBrian Grosberg29:27

       Right.

   12. PAPeter Attia29:27

       Did they see anything, uh-

   13. BGBrian Grosberg29:29

       So-

   14. PAPeter Attia29:29

       ... mid-cycle?

   15. BGBrian Grosberg29:30

       No. So interestingly, around ovulation, there doesn't necessarily seem to be a much higher risk of developing migraine, and I think in, that's in part to this more rapid, faster rate of decline of estrogen in that late luteal phase, which is the unique part.

   16. PAPeter Attia29:47

       Yeah, interesting. It could also be the progesterone because we don't see progesterone coming-- Progesterone hasn't risen in ovulation.

   17. BGBrian Grosberg29:54

       Right.

   18. PAPeter Attia29:54

       So it's not, you know this, but just for the listener. So, so we don't see a progesterone crash at post-ovulation, whereas post-luteal, we're seeing both estrogen and progesterone come down. So is it possible that it's the combination of them or the progesterone that's causing the problem?

   19. BGBrian Grosberg30:11

       Right now, the, the belief is really the, the, the, the estrogen, that decline of estrogen, not the, not the decline per se, but the degree and rapidity of decline that is unique mostly in women who experience migraine. The other, the other couple things to end up thinking about is We know estrogen can have effects on serotonin transmission, and so serotonin is involved in migraine, right? If I go back to the, um, 1940s when serotonin was first discovered, um, in blood, um, and then fast-forward, serotonin was, was identified and, and, and noticed to be, um, lower in blood, uh, during migraine attacks and then recover- and then the recovery phase would increase. And so that was-- those studies ended up leading to the development of triptans.

   20. PAPeter Attia30:58

       Mm-hmm.

   21. BGBrian Grosberg30:58

       Um, so estrogen has a, um, a number of different roles to play in the pain pathways.

   22. PAPeter Attia31:05

       Has the experiment been done where you take susceptible women and you selectively give them estrogen during the period of time in anticipation of that? So for example, seven days post-ovulation, right, which would be peak estrogen as it's about to crash into menses, you give them physiologic estrogen replacement levels, and does that, uh, uh, mitigate any of this risk?

   23. BGBrian Grosberg31:30

       Yeah. So estrogen has been given. Those studies have, uh, been done. Um, the hard part is predicting necessarily who is going to respond. So there are some women that will get improvement in migraine. Um, there are some women who will, uh, where, um, they may not get improvement. Um, and, uh, there are some women who will take combined hormonal contraceptives, and they may get worsening of their migraine. Um, and so it's very hard to, so to speak, tease apart and know who's the individual-

   24. PAPeter Attia32:02

       Mm

   25. BGBrian Grosberg32:02

       ... that will necessarily respond. And, um, in, in caring for those patients, um, one of the things that I try to do that's unique is actually in a collaborative care model, work with a gynecologist who is a specialist on hormones. And so working together, we actually try to end up mapping out a plan for the, for individual patients.

   26. PAPeter Attia32:21

       What else do we know genetically about predispositions? Are people whose parents are sufferers of migraines more likely to be sufferers themselves?

   27. BGBrian Grosberg32:31

       Yes. Yeah. Often, uh, people ask me why they have migraine, and if their parent's in the room, I, I usually point to them and I say, "You're the cause." Um, not, not to place blame.

   28. PAPeter Attia32:40

       No, of course.

   29. BGBrian Grosberg32:41

       Yeah.

   30. PAPeter Attia32:41

       But we think it's very, very highly genetic then?
6. 33:15 – 41:31

   Migraine triggers, the impact of hormones, and the importance of a headache diary

   1. BGBrian Grosberg33:15

      is, is just, um, increased.

   2. PAPeter Attia33:18

      Maybe a silly question you haven't thought of, but, um, is there an evolutionary benefit to it? Not that this would have weighed heavily in selection, but is there an upside to the hyperexcitability? Does it manifest itself in other positive traits during the period of time when the individual's not suffering? I, I almost-- My question is through the lens of like, hey, if, if, if we're on a continuum of excitability, and when the thing goes too far, it-- you end up with, you know, the headache, and that's bad. But if you pull back just a little bit from the brink, is there some benefit to, to that state?

   3. BGBrian Grosberg33:54

      Yeah. So a, um, so a colleague of mine ended up speaking about, uh, writing about this a number of years ago, where she postulated that the evolutionary benefit, uh, to women in particular may have been if they're the, uh, caregivers of their family, that they would know if there was inclement weather coming, right? Rainy storms if they had, and, uh, uh, signs of danger. Um, and so that may be one of the evolutionary benefits. The other thing is, uh, the, you know, if I, I think about the neural networks in men versus women, um, women generally have to multitask much more than men in general. And so the question is whether the neural networks, if you will, are, are, are, um, are better.

   4. PAPeter Attia34:38

      That is super interesting. So but, you know, one of those says, look, women might be more wired to be better at multitasking, and the migraine is just a manifestation of an extreme, more extreme version of that, which you're going to get if you shift the population over that way. And then the second issue is presumably through changes in barometric pressure, is that the most common weather-related triggering event?

   5. BGBrian Grosberg35:02

      So triggers are not the cause of the headache.

   6. PAPeter Attia35:05

      I see.

   7. BGBrian Grosberg35:05

      Triggers are factors that will elicit a headache in somebody who's biologically predisposed. So meaning if somebody is not biologically predisposed to having migraine, then there may be a, a, a weather storm that's coming through, and they may not experience a migraine. But in somebody who has migraine, they, uh, may have one or more triggers. Some people with migraine have no triggers. Others have multiple triggers.

   8. PAPeter Attia35:29

      I see.

   9. BGBrian Grosberg35:29

      Changes in weather, um, the letdown phenomenon after stress, um, and, and, you know, drinking or eating certain types of foods that may trigger. And it's usually a combination of two or more triggers that will precipitate an attack of migraine.

   10. PAPeter Attia35:44

       Do you have a sense of what subset of patients are indeed triggered by weather patterns and changing, uh, barometric pressure?

   11. BGBrian Grosberg35:52

       I think it's, it varies from person to person. Um, my patient population is, is one that generally suffers more, uh, because it's more so in the people who are experiencing fifteen or more days of headache per month. And so-

   12. PAPeter Attia36:05

       I see

   13. BGBrian Grosberg36:06

       ... they may, um, that reporting bias may occur. I may hear that more often than, than others may. Um-

   14. PAPeter Attia36:11

       But that kind of makes sense, right?

   15. BGBrian Grosberg36:13

       But it's pretty, but it's pretty common.

   16. PAPeter Attia36:13

       The more, the more severely impacted people would presumably have more frequent triggers, uh, or more, more diversity in their triggers as well?

   17. BGBrian Grosberg36:22

       Correct. They may, uh, but not necessarily. And that's what makes migraine, um- very nuanced, if you will. And so, uh, that's why the, the history needs to be detailed, right? So the questionnaire-

   18. PAPeter Attia36:34

       Hmm

   19. BGBrian Grosberg36:34

       ... that people are filling out for me are, you know, 15 pages. Um, it's, it's pretty extensive in trying to end up determining if I'm dealing with a primary or secondary headache, and then if it's migraine, um, how does it present? Because a headache diary is probably the most important thing that your listeners can do for not only themselves, 'cause it really empowers patients, but for, for a clinician like me to understand, because the patterns may be different from person to person.

   20. PAPeter Attia36:59

       Do you have an online version at your, on your website that patients can download?

   21. BGBrian Grosberg37:03

       Yes.

   22. PAPeter Attia37:04

       Okay. So we'll link to that in the show notes so that anybody listening to this who wants to actually have a diary and know what things to, to put in the diary, they can do it. I, I agree. You know, it's funny. There are-- You know, we live in this world where we're so obsessed with really high-tech things and sleep trackers and all these things, but honestly, like a sleep doctor, you know, if you go and see a sleep physician, they're gonna want you to do a really good pen and paper sleep diary. And, you know, we still give those to our patients who are in the biggest distress around sleep because the information it captures is so much more rich, so much more temporally related-

   23. BGBrian Grosberg37:40

       Right

   24. PAPeter Attia37:40

       ... to what's happening, and two weeks of painstakingly doing this will offer more than two years of, you know, tracker data. So sounds like very similar for you in, in, in getting a good diary. Obviously, it might take more than two weeks given the, the frequency of the headache, but-

   25. BGBrian Grosberg37:56

       Yeah, usually we're, we're looking at a, a period of several months, particularly if it's a woman who's reporting a relationship between, um, their migraine and menstrual period because ultimately, to make a diagnosis of, um, perimenstrual migraine, whether it's pure menstrual or menstrual-related migraine, um, that's usually that association is noted in at least two out of three cycles. So that's the reason why.

   26. PAPeter Attia38:22

       And obviously, thinking about the patient that first connected us 10 years ago, one of the things that stands out about me, 'cause she was a menopausal patient. This was a woman who at the time was, was in her probably late 50s, early 60s. Um, she did better on hormones, but it couldn't be too much, right? Like, there was a very, very fine line. She-- In other words, we ended up having to use estradiol and progesterone as you do in, in perimenopausal women, but less than you would normally have treated someone. In other words, we didn't-- we couldn't take her to kind of full therapeutic dose. Is that common in, in post-- in, in, in menopausal women?

   27. BGBrian Grosberg39:05

       So in, so in, um, so th-those transitions, if you will, from perimenopause to menopause, um, not only are hormonal fluctuations are occurring in perimenopause, but so is migraine. And so in a patient like that during perimenopause, um, I-- you know, there are women that will experience a significant worsening of migraine. Um, uh, probably about two-thirds of women who after they've transitioned to menopause, right?

   28. PAPeter Attia39:32

       Yeah.

   29. BGBrian Grosberg39:32

       They've finished perimenopause, that, uh, they will notice improvement in migraine. But ten to twenty percent may actually, like, either continue or get worse. Um, so s- so I, I find that there's a fallacy s- for-

   30. PAPeter Attia39:47

       Wow
7. 41:31 – 45:23

   The phases of a migraine: premonitory symptoms, aura, the headache itself, and the postdrome

   1. PAPeter Attia41:31

      Anything else about presentation and susceptibility of migraine? I want to then talk briefly about, uh, fi-- see if we have anything to finish on tension and then get to cluster.

   2. BGBrian Grosberg41:41

      Yeah. So I th- I think presentation of migraine is the, the-- I, I spoke about a couple of the phases, and not all people with migraine have all the phases of migraine. So the first phase is that premonitory phase, the kind of the calm before the storm, and a quarter to a third of people experience aura. And then it's the migraine phase, but it's not just the pain, right? It is that the, um, a co- potentially a constellation of symptoms, right? That light sensitivity, the sound sensitivity, nausea. Um, it may be autonomic symptoms. Um-

   3. PAPeter Attia42:10

      Like what?

   4. BGBrian Grosberg42:11

      So if somebody has tearing or redness of the eyes or congestion, running of the nose, um, often people think that they have, quote, "a sinus headache," but there's no such thing as a sinus headache. There's acute rhinosinusitis. There's chronic rhinosinusitis. But, uh, The based on the pathophysiology of migraine, ah, there's involvement of an aspect of the parasympathetic nervous system that can, that, uh, has a, a connection, if you will, with the nerve called the trigeminal nerve, which is the main nerve that's involved in the experience of migraine and headache. Um, and when people's parasympathetic nervous system becomes activated, people may experience tearing or redness of the eye or congestion or ringing of the nostrils, which is, uh, pretty common in people with migraine, uh, and they think they have, quote, "a sinus headache." Um, uh, and then ultimately at the end of the day, after the pain is gone, they can experience a postdrome, which is, um, the pain is gone, but I don't feel back to myself. I feel hungover. And that can last for hours up to even a couple of days. And so when I take a history of migraine, I want to understand what's the total impact?

   5. PAPeter Attia43:21

      Hmm.

   6. BGBrian Grosberg43:21

      Meaning if they experience all the phases, what is, uh, what is the duration of each of them? What is the, what is, what is the personal impact, right? Because we just focus on the pain and, but not necessarily the impact, uh, in totality. The other thing is the interictal burden. And so one of the things that you pointed out, Peter, which was, um, I really appreciated, is, um, how are people thinking about, um, their plans, their daily activities in anticipation of experiencing a migraine? Meaning I'm not experiencing a migraine now, but I don't know when it's going to come. How am I going to plan that vacation? That's what's referred to as interictal burden. And so when we think about all-

   7. PAPeter Attia44:02

      Interictal meaning between the pain bouts.

   8. BGBrian Grosberg44:04

      Between, between the pain bouts.

   9. PAPeter Attia44:05

      Yep.

   10. BGBrian Grosberg44:05

       And so that's, that's where when I'm, uh, eliciting all these pieces of history, I'm thinking about how am I, um, thinking about their acute treatment plan? How am I thinking about their preventive treatment plan if they need that? How am I thinking about non-medication approaches and then combining the picture together, um, obviously with the patient driving the decision-making once they understand the rationality of how I'm putting it together.

   11. PAPeter Attia44:34

       Can you say a little bit more about some of those postictal, uh, e-experiences? What fraction of migraine sufferers, uh, once the pain is gone, are largely able to resume activity versus those that have that postictal period where they're not back to normal for a day or more?

   12. BGBrian Grosberg44:53

       Yeah. And so there are, um, population-based studies and there are clinic-based studies that have been done. So population-based studies looking at the general population, clinic-based studies like where somebody would do an academic headache program like, like my own. Um, those numbers can range anywhere from like sixty percent to in the high eighties. So this can be-

   13. PAPeter Attia45:12

       But it's still a big number.

   14. BGBrian Grosberg45:14

       It's a big number. The same thing with the premonitory symptoms, kind of that calm before the storm.

   15. PAPeter Attia45:19

       Now, you said, by the way, for everything we're talking about here, 12% of the population,

8. 45:23 – 47:11

   Tension headaches: symptoms, causes, and prevalence

   1. PAPeter Attia45:23

      three to one women to men. Going back to tension, which we talked about very briefly, you said that's the single most common cause. It's the anti-migraine, so it's all the things that aren't migraine. What's the prevalence of that? Lifetime incidence, maybe, or lifetime, uh-

   2. BGBrian Grosberg45:36

      It's, it's pretty high.

   3. PAPeter Attia45:37

      Yeah.

   4. BGBrian Grosberg45:38

      Yeah.

   5. PAPeter Attia45:38

      A lot of people are going to experience that.

   6. BGBrian Grosberg45:40

      Yes.

   7. PAPeter Attia45:40

      Female to male difference?

   8. BGBrian Grosberg45:42

      Pretty, pretty evenly split.

   9. PAPeter Attia45:44

      What are some of the triggers, and how genetic is it?

   10. BGBrian Grosberg45:47

       Yeah. So I, I think that the, the name is maybe a little bit, um, le-lends people to think necessarily that it's just tension or stress that causes the headache, and that's not necessarily the case. That's why it's referred to as tension type headache. And so that's the experience of where people have that, um, no light or sound sensitivity, mild to moderate pain that can be around the head, uh, the muscles around the head, the muscles in the neck. Um, and the nerves that are involved, uh, in the anatomy and physiology, there's overlapping, if you will, uh, because the, the, the, the nerves that supply sensation to the face and the head and the neck are similar to what's involved in migraine. Um, there are genetic factors that are responsible. There are environmental factors, and then there's pe-pericranial or around the head muscle nerve tenderness, if you will. That's a contributing factor as well.

   11. PAPeter Attia46:46

       If a person has a tension headache and they take a thousand milligrams of Tylenol and they get better, do they have a tension headache? Or in other words, could it respond to something as, as simple and, you know, over-the-counter as that?

   12. BGBrian Grosberg46:59

       Yes.

   13. PAPeter Attia46:59

       Okay.

   14. BGBrian Grosberg47:00

       Yeah. I mean, once again, as, as long as we know that that's what it is, that it's a tension-type headache, because making any diagnosis not only meets criteria, but also that it's not attributable to something else.

   15. PAPeter Attia47:10

       Okay.

9. 47:11 – 56:46

   Cluster headaches: extreme pain, distinctive symptoms, and frequent misdiagnosis as a sinus infection or allergies

   1. PAPeter Attia47:11

      And obviously, we're going to come and talk about these, the, the, the, um, the, the potential treatments for these things. Um, so let's round it out with cluster then. So what, what's a cluster headache?

   2. BGBrian Grosberg47:21

      So cluster headache is, is relatively uncommon, right? Pretty rare relative to migraine and tension-type headache, but it's one of the most painful disorders, um, known, known in the world. Um, I've, I have a, a, a woman patient who's likened it to giving birth to a hundred babies at the same time without an epidural. I mean, that's the exquisite nature of the pain. And so it's pretty distinctive in its presentation. Um, it disproportionately affects men more often than women, so that ratio that is now about three to four to one. It's, um, it has a very, um, uh, it's got characteristics where people may have a circannual periodicity or circadian periodicity. By that, I mean that the, at the longest and shortest days of the year, uh, January and February and July and August, people can experience cluster periods where they may have daily or near-daily attacks, sometimes multiple attacks per day. Um, and this pain, it often is conceptualized as in and around or behind one eye. It's, it's usually almost exclusively side-locked, so just on one side of the head or the face. The rapidity of onset is very quick. Unlike migraine, which generally will gradually build up, cluster headaches peak, uh, within about five to 15 minutes. The attacks generally last anywhere from 15 minutes up to three hours, and, uh, it can be characterized as stabbing, boring, exquisite in nature, um, and, uh, and then as soon as it came can often be as soon as it goes. And with the pain, people can end up getting very characteristic features. About 97% of patients can experience a droop of the eyelid on that side, a tearing or redness of the eye on that side, congestion or running of the nostril. And so not only can you see the experience o- of, on the person's face, but you could actually see the visual symptoms often. And about 90% of people with cluster headache can experience a sense of restlessness with the attacks where they can't sit still. They, they're, they need to move about. That's in contrast to migraine, where the vast majority prefer to be still or lie down in a dark, quiet room. And so the, the presentations are very, very distinctive. Um, and where cluster headache is, it's, it's also been nicknamed suicide headache, not only because of the intensity of the pain, but the frequency of which these attacks occur. So on average, people can experience up, you know, three attacks per day. The criteria allow people to have either one attack every other day, up to eight attacks per day, and these cluster periods could be, depending on the person, weeks to months, sometimes longer. So depending on if somebody has episodic cluster headache, where they get this cluster period and then a break in time, or chronic cluster headache, where they have no break at all, they're just having multiple attacks per day.

   3. PAPeter Attia50:28

      And does the term suicide headache stem from the fact that people will take their life if it's extreme enough?

   4. BGBrian Grosberg50:34

      Yes.

   5. PAPeter Attia50:36

      Um, yeah, that's, uh, terrifying. Um, does that suggest that, that the drive to move provides some relief?

   6. BGBrian Grosberg50:49

      I don't know if the drive to move, uh, provides relief as much as the areas in the brain that are involved during the attack of cluster headache are, can cause manifestation of symptoms, and one of those manifestation of symptoms is a sense of restlessness or agitation.

   7. PAPeter Attia51:08

      Mm-hmm. What el- what else do we know about these things? How genetic are these?

   8. BGBrian Grosberg51:10

      So we know that there are genetics that play into cluster headache as well, um, and so, uh, first-degree relatives may be at higher risk. Um, like I said, it's not, not common, but these are, um, very highly motivated patients, just like migraine, but maybe even more so because of the exquisite nature, um, because, um, they also, like migraine, often go under-diagnosed or misdiagnosed because of the presentation of pain. Um, because there, there can be a predilection for attacks to occur January and February, so people may come into their doctor at that period of time, say that I have pain, I have nasal congestion, they're, and they may be told, "Oh, you have a, a sinus infection," then receive an antibiotic. And July and August, they may come to their doctor and say, "I have pain, tearing or redness of the eye," and they may be told, "You have allergies. You need allergy shots." Some people will have pain that's, uh, around the teeth or the face, and they, uh, have had teeth pulled or major dental surgery or sinus surgery without realizing, um, that the presentation is actually cluster headache.

   9. PAPeter Attia52:21

      Part of, um, the log that people can download from your site that allows them to take an accurate history, is that something they could take into their primary care physician if they're having a headache? And, and does it, does it highlight enough for the doctor the, the flag that says, "Hey, this might actually be a cluster headache, and this, this might be one of the times when even though it's hard to get to headache specialists 'cause of the frequency or the, the low, uh, number of them, uh, it's worth, it's worth taking the time to get the, to get the right clinician on board before we make a mistake and treat you for something you don't have"?

   10. BGBrian Grosberg52:59

       Yes. Uh, I, I think that becomes very important. I, I think about my primary care colleagues and the number of things that they have to address in a relatively short period of time. Um, and headache-

   11. PAPeter Attia53:10

       Yeah, they can't, they can't take this history

   12. BGBrian Grosberg53:12

       ... and headache may be just one of them.

   13. PAPeter Attia53:12

       Yeah, yeah.

   14. BGBrian Grosberg53:12

       And I think that's the, that's the hard part, right?

   15. PAPeter Attia53:15

       So we wanna kind of, uh, um, arm patients with a ton of data so that when they meet their PCP, um, they can do the lifting for them, that they, you know-

   16. BGBrian Grosberg53:27

       Correct

   17. PAPeter Attia53:27

       ... in the, in the 10 minutes that that primary care doc has, they're not gonna be able to do the detailed history you would do. But if they can walk in with it, hopefully the doctor is receptive and says, "Oh, gosh, yeah, I didn't, I d- I wouldn't have had the time to elicit this," or wouldn't have even had the knowledge base to elicit this.

   18. BGBrian Grosberg53:41

       I was about to say, it's, it's not only receptive, it's, and the time, it's also having the knowledge and education experience to make the diagnosis and then offer the appropriate treatments. So I, uh, uh, all the stars need to align, if you will. Most people with, um, with headache will, if th- they're coming in, they're not coming to me for the first time. Sometimes they do, uh, but they're often going to their primary care. So that's the gateway, if you will. The, the hard part becomes is kind of navigating afterwards the gateway, um, particularly if they don't have a diagnosis or they're misdiagnosed.

   19. PAPeter Attia54:15

       And patients come and see you from all over the place. Obviously they're-

   20. BGBrian Grosberg54:18

       All over the world.

   21. PAPeter Attia54:18

       Yeah, yeah. Um, uh, so I mean, that's a, that means that obviously a lot of them can't see you when they're in the throes of suffering. Does that matter?

   22. BGBrian Grosberg54:28

       So for patients with cluster headache, um, that's kind of the, the password, if you will, in my office [laughs] um, in the sense that if somebody who's in a, uh, either an established patient or somebody who's trying to get in, um, they will say that they have cluster headache. And if, if in fact they at least, uh, on the basis that a questionnaire seemed to check off um, information that alludes to that possibility, then yes, they're seen, um, quicker in general just because It's been nicknamed suicide headache. So the-

   23. PAPeter Attia54:57

       Is there a benefit to you seeing them while suffering-

   24. BGBrian Grosberg55:00

       Correct. Yes

   25. PAPeter Attia55:00

       ... to make a diagnostic or treatment decision?

   26. BGBrian Grosberg55:02

       Yes. Yes. And the reason why is often, uh, the patients with cluster headache require multiple treatments, and so, uh, one could be acute treatment, meaning when they experience the attack, they're using a treatment to rapidly abort the pain. The other is a preventive treatment, so they're taking something, one or more things, to prevent attacks because often these patients with cluster headache are experiencing frequent attacks a day over a period of potentially weeks to months, and then transitional treatment. The preventive treatments often take weeks to months to build up, even for migraine, and so what is being done in the transitional period to offer relief-

   27. PAPeter Attia55:44

       And sorry, just to be short.

   28. BGBrian Grosberg55:45

       Yeah.

   29. PAPeter Attia55:45

       And sorry to interrupt, Brian.

   30. BGBrian Grosberg55:46

       No, go ahead.
10. 56:46 – 1:12:00

    Lifestyle interventions to prevent headaches

    1. PAPeter Attia56:46

       are the modifiable lifestyle interventions that you would keep in your playbook for these patients? And, um, are they the same across all the headaches? Is, is, if, you know, does everything you just said, for example, around correcting sleep apnea, minimizing alcohol, avoiding naps during the day, would you give that advice to any, uh, person suffering from headache or are you really narrowing that on the cluster patient, whereas the migraine patient you have a different playbook?

    2. BGBrian Grosberg57:15

       Migraine itself has, um, certain identified risk factors, um, and even the subtypes of migraine may have their own, um, identified risk factors. Um, so if we know from studies that were done, uh, that if somebody's experiencing at least one migraine a week, uh, more than that may put them at greater risk for more frequent attacks of migraine. So the higher the frequency of attacks at baseline, uh, maybe, uh, lead to chronification or transformation of more frequent migraine. Somebody who has stressful life events, right? We all do, but that's a risk factor as well. Sleep disturbance, that may be insomnia. That may end up being, um, sleep apnea, so once again, modifiable. A person's mood, depression, anxiety are comorbid with migraine, right? They coexist at a higher than expected by chance, and there's a bidirectional relationship between mood disorders and migraine. And so addressing those, that's why I try to explain to patients that, um, all the stars kind of need to align, right? It's not just taking care of your pain, but we need to end up addressing these risk factors. Um, people frequently using acute pain medications. So there are some classes of pain medications where if they're used two or more days per week on a regular basis over an extended period of time, that can actually create more frequent headaches. It doesn't happen for everybody.

    3. PAPeter Attia58:38

       That could be NSAIDs and acetaminophen or opioids.

    4. BGBrian Grosberg58:41

       It could be nonsteroidal anti-inflammatories, simple analgesics. It could even be triptans, migraine-specific medications. It could be barbiturate-containing combination analgesics, medications like Fioricet or Fiorinal. So, um, opioids. So-

    5. PAPeter Attia58:54

       Hmm

    6. BGBrian Grosberg58:54

       ... um, and then, um, if, uh, s- somebody has other pain disorders, obesity is a risk factor for more frequent migraine, and the greater the degree of obesity, the greater the risk for chronification.

    7. PAPeter Attia59:05

       And do you think that's inflammatory? Do you think it's insulin related?

    8. BGBrian Grosberg59:10

       So it's, it's probably multifactorial as well. Um, and, um, you know, uh, so I, I think the migraine itself has a pro-inflammatory component to its pathophysiology.

    9. PAPeter Attia59:21

       Hmm.

    10. BGBrian Grosberg59:21

        And so there may be shared mechanisms that underlie that.

    11. PAPeter Attia59:25

        And is this modifiable if a person is-- So first of all, do you know what the hazard ratio is or the increase in relative risk with obesity versus not with respect to the headaches?

    12. BGBrian Grosberg59:33

        Yeah. So people who are morbidly obese are at fi- five times higher risk for more frequent migraine.

    13. PAPeter Attia59:37

        Oh, so it's not subtle.

    14. BGBrian Grosberg59:38

        It's not subtle.

    15. PAPeter Attia59:38

        This is dramatic.

    16. BGBrian Grosberg59:40

        Dramatic. And there are studies, um, with weight loss, um, surgical and non-surgical, showing improvement in migraine, not uniformly across the board for every individual, but certainly showing improvement. And so modifying that, uh, risk factor is very helpful as well.

    17. PAPeter Attia1:00:00

        A- again, some of these numbers are shocking. The, the women being three to one is not shocking with my lived experience because when I stop to think about it, almost all of the people I've encountered with migraines, or most of them, are, are women, so that, I get that. Um, the obesity is five X. That is surprising. That's-

    18. BGBrian Grosberg1:00:20

        More, morbidly obese.

    19. PAPeter Attia1:00:21

        Okay.

    20. BGBrian Grosberg1:00:21

        More p- Yeah, morbidly obese.

    21. PAPeter Attia1:00:22

        So morbid meaning 35 BMI?

    22. BGBrian Grosberg1:00:23

        Yeah. Yeah.

    23. PAPeter Attia1:00:24

        Yeah. Okay, so-

    24. BGBrian Grosberg1:00:24

        But once again, um-

    25. PAPeter Attia1:00:25

        But what about obese? What about-

    26. BGBrian Grosberg1:00:26

        Right. Obese

    27. PAPeter Attia1:00:26

        ... 30 to 35?

    28. BGBrian Grosberg1:00:28

        Greater risk.

    29. PAPeter Attia1:00:28

        How much? Two X?

    30. BGBrian Grosberg1:00:29

        Two X.
11. 1:12:00 – 1:23:12

    Pharmacological treatments to prevent headaches

    1. PAPeter Attia1:12:00

       Um, so let's now talk a little bit about pharma through both lenses, the prophylactic lens, uh, the things that you would have somebody take all the time to reduce the probability or severity of an attack, and then we'll-- after that, we'll talk about the treatments that you would use acutely as a rescue medication.

    2. BGBrian Grosberg1:12:21

       Sure. So, uh, from the-

    3. PAPeter Attia1:12:23

       Wanna do it by class of drug? Uh-

    4. BGBrian Grosberg1:12:24

       I could, I could certainly-

    5. PAPeter Attia1:12:25

       And then we can, we can talk about it by class. We can also then talk about it by pros and cons of each drug, success rate, or, you know, things like that.

    6. BGBrian Grosberg1:12:32

       Yeah. I, I, I think, I think I would start off first by saying what are the goals of preventive therapy? Um, because I think that's important for your listeners to know. Um, the idea of using prophylaxis or prevention is not to cure headache, is not to cure migraine, but to ultimately reduce the frequency, intensity, or duration of attacks. Um, it also helps improve potentially responsiveness to acute treatments. It can-- By using prevention, you can reduce disease burden. Right? You can end up reducing progression of migraine, right? So as I said, people who experience more frequent migraine are at greater risk for developing even more frequent migraine attacks. Um, it could end up improving, um, other comorbidities. So some prevention may be helpful with sleep. Some prevention may lead to, uh, potential for weight loss. And so you may be able to leverage some of those benefits as well. The, the other thing is it improves functionality and quality of life, um, which is obvious. Um, but it also ends up helping reduce interictal burden. And so that was one of the things-

    7. PAPeter Attia1:13:38

       Yeah

    8. BGBrian Grosberg1:13:38

       ... I was talking about where people have this almost anticipatory anxiety. So there are multiple goals for using prevention. The indications for using a preventive medication are is if somebody's experiencing frequent attacks or attacks that are very disabling, even despite acute treatment, um, if somebody has, uh, rare types of migraine or headaches that, um, may limit their ability to use certain acute treatments, or if acute treatments are either contraindicated, poorly tolerated, or ineffective. And so that's where some of the indications for preventive therapy. The preventive therapy, um, come into a number of classes which you're alluding to.

    9. PAPeter Attia1:14:19

       Before we do that, Brian, just to close the loop-

    10. BGBrian Grosberg1:14:20

        Sure, sure

    11. PAPeter Attia1:14:21

        ... on that point. Overall, all comers of people who suffer from, um, migraine, what percentage do you think do not meet criteria to justify the drug burden of a preventive drug?

    12. BGBrian Grosberg1:14:35

        So I would say probably about forty percent or so of people with migraine may be eligible for prevention, but like a s- much smaller percentage-

    13. PAPeter Attia1:14:45

        But eligibility is not-- I don't just mean-

    14. BGBrian Grosberg1:14:48

        Yeah

    15. PAPeter Attia1:14:48

        ... through the lens of reimpers- reimbursement-

    16. BGBrian Grosberg1:14:50

        Sure

    17. PAPeter Attia1:14:50

        ... on insurance, but, um, in your mind, medically justified.

    18. BGBrian Grosberg1:14:53

        Yeah.

    19. PAPeter Attia1:14:53

        Forty percent, yes.

    20. BGBrian Grosberg1:14:54

        Forty perc-

    21. PAPeter Attia1:14:55

        Sixty percent, we-- they don't have it enough or it's not severe enough to justify, and we can do enough good with an acute medication.

    22. BGBrian Grosberg1:15:01

        Once again, it, it-- looking at population-based studies, right? The, I, I-

    23. PAPeter Attia1:15:04

        Yeah, your population is gonna be probably-

    24. BGBrian Grosberg1:15:05

        My population-

    25. PAPeter Attia1:15:06

        ... the vast majority

    26. BGBrian Grosberg1:15:06

        ... the vast majority, right.

    27. PAPeter Attia1:15:07

        Yeah.

    28. BGBrian Grosberg1:15:07

        So, um, but the, the hard part is the, the, kind of the, the discrepancy or the gap, if you will, where forty percent of people may be eligible based on indications for migraine prevention, but only like sixteen or seventeen percent are actually receiving preventive therapy.

    29. PAPeter Attia1:15:23

        And how much of that is economic, where their insurance companies don't cover? These are-- these drugs can be pretty expensive, some of them, right?

    30. BGBrian Grosberg1:15:29

        Yeah. So I think it's varied. I think it may end up being that it's not recognized by the treating clinician.
12. 1:23:12 – 1:29:12

    What's known about the pathophysiology of migraines: neurovascular changes, release of neuropeptides, and inflammatory response

    1. PAPeter Attia1:23:12

       The class of drug that I remember when it came about were these monoclonal antibodies. In fact, the patient that we keep referring to, um, I remember being one of the first patients on it because you got her into a clinical trial. Um, and it was a resounding success. Can you say a little bit more about these drugs and their utility today?

    2. BGBrian Grosberg1:23:33

       Sure. So the class of what are called CGRP or calcitonin gene-related peptides, um, so, uh, I, I think in order to be able to speak about the class, I'd probably have to give a little bit of background on the pathophysiology of migraine.

    3. PAPeter Attia1:23:47

       Absolutely.

    4. BGBrian Grosberg1:23:47

       Okay.

    5. PAPeter Attia1:23:48

       And this is a podcast where we don't shy away from depth, so treat this as though, uh, you're giving a lecture.

    6. BGBrian Grosberg1:23:55

       Okay. Um, always trying to understand my audience. I, um, I'll speak a little medicalese and, and speak English at the same time.

    7. PAPeter Attia1:24:04

       We're twenty-five percent physician by audience-

    8. BGBrian Grosberg1:24:06

       I love it

    9. PAPeter Attia1:24:06

       ... by the way. It's crazy.

    10. BGBrian Grosberg1:24:07

        I love it. Um, so the brain sens- the brain itself is insensate. It's not pain sensitive, but the coverings around the brain, um, like the meninges or specifically the dura and the blood vessels that are both within the dura and in the brain have, uh, pain-sensitive nerve terminals, nerve endings. And the main nerve that's involved in migraine is the trigeminal nerve. If we go back in time to probably the nineteen-forties, the thought of migraine is there was a vascular hypothesis where the thought about migraine is it was purely a vascular phenomenon. There was dilation of blood vessels that occurred during the pain phase, and then a constriction that occurred during the, so to speak, recovery phase, if you will. Um, with the advent of, uh, increasing research, particularly over the past, I would say fifty years, um, we know that that model is just too simplistic. So now we know that it's a neurovascular phenomenon, and so that there's involvement of not only the nervous system, but the s- uh, cranial blood vessels as well. And so what ends up happening is that these, uh, nociceptive or pain-sensitive information is conveyed from these pain-sensitive structures, so the dura mater, that covering around the brain, and the dural and intracranial blood vessels, and then it, it- relayed back centrally along a nerve called the trigeminal nerve that has three branches primarily along the, the first division, the ophthalmic division of the trigeminal nerve passes through an area called the trigeminal ganglion, and then synapses or connects in an area of the brainstem called the trigeminal nucleus caudalis. And so, uh, that pain sense of information is c-carried back there. At the same time, nerves that supply sensation to the back of the head, the neck, and the shoulders from the upper cervical roots in the neck, so C1, C2, C3, carries information back, primarily C2 and C3, into the same area of the brainstem, which is why people with migraine often will have associated neck pain, or people with tension-type headache will have associated neck pain, where they may not realize that it's a referral pain pattern because of this convergence of information. Now, when the, those nerves become stimulated, people can experience peripheral sensitization, where if they're turning their head or bending down, they can get a throbbing type of feeling that occurs, that can occur early into a migraine. And when pain-sensitive information goes back to the brainstem, the-- if there's sustained firing of nerve cells, people can get central sensitization. And one clinical marker for that, that presentation, is the phenomenon of allodynia, that uncomfortable sensation to things that normally aren't uncomfortable. That's the putting the hair back in a tight ponytail and brushing hair. That generally will kick in about thirty to sixty minutes or so into a migraine headache, and then, um, using triptans during that time may be less effective. So that's the reason why knowing if somebody experiences that with their migraine becomes important when you're advising them when to treat. When-

    11. PAPeter Attia1:27:13

        We'll come back to the triptans-

    12. BGBrian Grosberg1:27:14

        Yeah, yep, yep

    13. PAPeter Attia1:27:14

        ... when we talk about acute treatments, yeah.

    14. BGBrian Grosberg1:27:17

        And then that no- that pain sense of information then travels from the brainstem to the thalamus, which is the kind of the sensory processing area of the brain. Um, so there's some nuclei like ventroposteromedial thalamic nuclei that are involved, and then from there, nociceptive information then goes to the sensory cortex of the brain and then other pain matrix areas of the brain. Now, while this is all occurring, there's a cascade of events that occurs. So that trigeminal nerve, um, uh, information has a reflex with that parasympathetic information in the brainstem, which is why people can experience s- those autonomic symptoms, the tearing, the redness of the eye, the congestion or running of the nostril. At the same time, parasympathetic innervation is relayed to the cranial blood vessels, the blood vessels within that dura mater, with that covering around the brain and the intracranial blood vessels, and people can experience dilation of blood vessels and the release of chemical messengers or neurotransmitters, so things like substance P, neurokinin, CGRP-

    15. PAPeter Attia1:28:22

        God, I haven't heard the word, I haven't heard substance P in years.

    16. BGBrian Grosberg1:28:25

        [laughs] I'm, I'm happy to bring it back. I'm happy to bring it.

    17. PAPeter Attia1:28:27

        I love it.

    18. BGBrian Grosberg1:28:28

        Um, and then calcitonin gene-related peptide, or what's known as CGRP. And so, and then at the same time, there's a pro-inflammatory response that occurs, so a neur-- what's called neurogenic inflammation, um, and then a release of, uh, histamine, mast cells, nitric oxide. Once again, a, a, a full cascade of events. This becomes important because, um, through studies that have been done over the years, there have, the studies that looked at jugular venous blood, um, noted elevations of CGRP during migraine. And so that really, that calcitonin gene-related peptide, that, w- those studies led to the possibility that this may be a target for migraine treatments.

13. 1:29:12 – 1:38:52

    CGRP antagonists for the treatment of migraines: large monoclonal antibodies and gepants

    1. BGBrian Grosberg1:29:12

       And, and then when sumatriptan or Imitrex came on the market, there were studies that looked at patients who were treated with it, um, and what happened to their CGRP or calcitonin gene-related peptide levels, and, um, and they normalized, so meaning they were increased during migraine and then, uh, the use of sumatriptan would end up normalizing levels. And so there was like that aha moment, and that's what led to the class of what are known as CGRP antagonists. And the CGRP antagonists are, um, are kind of broken down into, uh, two, two buckets. One are the, what are called, uh, l- large monoclonal antibodies, which is the, the medication that our patient is, uh, was placed on, and then, uh, small molecules, what are known as gepants. So that's the kind of the history that led into the formulation of that class of medication.

    2. PAPeter Attia1:30:11

       And these are drugs that are administered intravenously? At what frequency?

    3. BGBrian Grosberg1:30:18

       Yeah. So, um, so the CGRP antagonists, um, the large monoclonal antibodies, three of them are self-injection medications. They're like Epi, almost like EpiPens.

    4. PAPeter Attia1:30:30

       Yep.

    5. BGBrian Grosberg1:30:31

       And those medications have a long half-life, so roughly about twenty-eight days.

    6. PAPeter Attia1:30:36

       Mm-hmm.

    7. BGBrian Grosberg1:30:36

       And so they're administered in a monthly fashion, um, or every twenty-eight days. Um, and, uh, that's the three of them. There's one that's actually given quarterly as an infusion every three months. So that-

    8. PAPeter Attia1:30:53

       Any difference in efficacy?

    9. BGBrian Grosberg1:30:55

       Once again, it varies from person to person. There are no, there are no large head-to-head studies of these medications, and so that's the challenge with being able to end up using data to end up answering that question.

    10. PAPeter Attia1:31:07

        Yeah.

    11. BGBrian Grosberg1:31:08

        Yeah.

    12. PAPeter Attia1:31:08

        So basically, you might start with the home-use pen 'cause it's easier. I assume it's cheaper. And if it's, if they're failing those things, you would have to just go with the quarterly infusion.

    13. BGBrian Grosberg1:31:20

        Right. So that's, that's one reason. The other reason is, is what the insurance will dictate in terms of what they will allow me, the clinician to prescribe.

    14. PAPeter Attia1:31:27

        Yeah, what your PBM formulary says.

    15. BGBrian Grosberg1:31:28

        Right, right. Yeah.

    16. PAPeter Attia1:31:28

        Got it.

    17. BGBrian Grosberg1:31:29

        Um, oh, go ahead.

    18. PAPeter Attia1:31:30

        These have changed the game though, right? Is this-- am I-- Obviously, I'm biased perhaps by my small, small sample set of the patients I know that have, have had a significant improvement with these. But across your clinic, which is very high risk, but obviously very diverse-

    19. BGBrian Grosberg1:31:46

        Right

    20. PAPeter Attia1:31:46

        ... how much have these been, uh, an improvement in, in, uh, mitigating onset and severity?

    21. BGBrian Grosberg1:31:53

        Significant improvement. I mean-

    22. PAPeter Attia1:31:54

        The biggest change you've seen in your clinical practice?

    23. BGBrian Grosberg1:31:57

        Yes.

    24. PAPeter Attia1:31:58

        Wow.

    25. BGBrian Grosberg1:32:00

        It doesn't mean that they work for everyone, and like-

    26. PAPeter Attia1:32:04

        For what fraction of patients do they not work?

    27. BGBrian Grosberg1:32:06

        So they probably work for up to 60% or so of patients with migraine, right? And so that's why I say sometimes there is trial and error. Um, the other thing is there are some people that will be, um, much quicker responders than others. So some people, uh, will get benefit within the first month with these medications. Other people may take up to three to four months.

    28. PAPeter Attia1:32:28

        And when you say 60% success, does that mean 60% of patients who take this drug regularly will no longer suffer migraines?

    29. BGBrian Grosberg1:32:35

        No. There's a spectrum.

    30. PAPeter Attia1:32:37

        Uh-huh.
14. 1:38:52 – 1:43:35

    Use of calcium channel blockers and Botox to treat cluster headache and migraine

    1. PAPeter Attia1:38:52

       Rounding out this list, calcium channel blockers and Botox, correct?

    2. BGBrian Grosberg1:38:57

       Yeah.

    3. PAPeter Attia1:38:57

       Yeah, let's talk a little bit about those two.

    4. BGBrian Grosberg1:38:59

       So calcium channel blockers, uh, doesn't have as much data for prevention of migraine. More classically, it's used for prevention of, uh, a headache like cluster headache. Um, but still, people may end up using calcium channel blockers, which is a blood pressure medication for prevention of migraine.

    5. PAPeter Attia1:39:19

       And they're doing this at a lower dose, I'm assuming, as well?

    6. BGBrian Grosberg1:39:22

       A lower dose, but sometimes the doses are increased, particularly in patients with cluster headache.

    7. PAPeter Attia1:39:26

       So what do you do if you have a normotensive person with cluster headaches? How do you treat them with verapamil?

    8. BGBrian Grosberg1:39:31

       Right. And so there are some patients that I have where the-- usually in collaboration with a cardiologist. Um, there's one patient I'm thinking of that I just recently saw where, um, this person was on, at one point, over a thousand milligrams of verapamil. And for your audience to know, that is an exceedingly high dose. Um, so once again, EKGs need to be checked, blood pressure, pulse needs to be checked, tolerability needs to be checked. Um, but that, that, that was the dose that was needed, and that person tolerated it amazingly.

    9. PAPeter Attia1:40:03

       And obviously it reduced-

    10. BGBrian Grosberg1:40:05

        Yes

    11. PAPeter Attia1:40:05

        ... significantly the frequency of cluster headaches.

    12. BGBrian Grosberg1:40:08

        Correct.

    13. PAPeter Attia1:40:09

        So this is the trade-off in pharmacology, right?

    14. BGBrian Grosberg1:40:11

        Right.

    15. PAPeter Attia1:40:11

        It's nothing comes without a side effect, but the side effect can often be well worth it.

    16. BGBrian Grosberg1:40:16

        Right.

    17. PAPeter Attia1:40:17

        Um-

    18. BGBrian Grosberg1:40:18

        And then you mentioned Botox.

    19. PAPeter Attia1:40:19

        Botox. Okay, when I think about Botox, I think about tension headaches, but does it also play a role in migraines and clusters?

    20. BGBrian Grosberg1:40:25

        Surprisingly, Botox doesn't work well for tension-type headache.

    21. PAPeter Attia1:40:28

        Okay.

    22. BGBrian Grosberg1:40:29

        Yeah. Um-

    23. PAPeter Attia1:40:29

        Shows how-- It's a good thing I'm not a neurologist.

    24. BGBrian Grosberg1:40:31

        [laughs] It's okay. You have me on set, so I'm-

    25. PAPeter Attia1:40:32

        [laughs]

    26. BGBrian Grosberg1:40:33

        I'm more than happy to help. Um, so, uh, serendipitous finding that Botox, uh, was helpful for migraine. There was, um, um, a plastic surgeon, uh, Bill Binder in, um, in, uh, in California, who was, uh, giving it to patients cosmetically and then was told by patients that, uh, "You know, my, my headaches are getting better. My migraines are getting better." And that's actually what led to Botox or onabotulinum toxin, uh, being studied for prevention of migraine, specifically chronic migraine. So that's where, whereby people experiencing fifteen or more days of headache per month, that's where Botox has mostly been studied and where it has the current FDA approval for that. Um, and so it's not by cosmetic effects that it works, but actually it interferes with the release, um, of, uh, certain, uh, snare and snap proteins, certain proteins, and also involvement in CGRP, calcitonin gene-related peptide. Once again, we come back to this.

    27. PAPeter Attia1:41:37

        Because of systemic delivery?

    28. BGBrian Grosberg1:41:40

        So it has effects on pain pathways where-

    29. PAPeter Attia1:41:43

        Again, pardon my ignorance.

    30. BGBrian Grosberg1:41:45

        No, no.
15. 1:43:35 – 1:52:13

    Drugs for the acute treatment of migraines

    1. BGBrian Grosberg1:43:35

       of chronic migraine.

    2. PAPeter Attia1:43:36

       Okay. So let's talk about the rescue drugs. So you've, you've, you're now in the throes of a headache.

    3. BGBrian Grosberg1:43:42

       Yes.

    4. PAPeter Attia1:43:43

       What can you do?

    5. BGBrian Grosberg1:43:44

       So there are many classes that we end up using. Um, there are non-migraine specific classes, and then there are migraine-

    6. PAPeter Attia1:43:50

       NSAIDs

    7. BGBrian Grosberg1:43:50

       ... specific classes. So mi- non-migraine specific, um, so analgesics like acetaminophen, nonsteroidal anti-inflammatory drugs like NSAIDs. Um, and then-

    8. PAPeter Attia1:44:02

       Do opioids play any role here?

    9. BGBrian Grosberg1:44:05

       So opioids-

    10. PAPeter Attia1:44:06

        Not withstanding the loaded nature-

    11. BGBrian Grosberg1:44:07

        Yeah. Yeah

    12. PAPeter Attia1:44:07

        ... of addiction and things like that or dependency.

    13. BGBrian Grosberg1:44:10

        Yeah. So, uh, we go back to the risk factors for migraine, uh, chronification, and one of the risk factors is medication overuse. And the two largest culprits for the possibility of medication overuse are opiates and barbiturate-containing combination analgesics like Fioricet or Fiorinal, which is even banned in, in some countries in the world. And so opioids or these, this class of medications, the barbiturate-containing combination analgesics, even used a handful of times per month, even if it's not for migraine, right? The nervous system, once again, uh, may not like that, and they have a particularly high risk for medication overuse. And so that's the challenge with opioids.

    14. PAPeter Attia1:44:52

        And is the issue that? In other words, is the issue that if we give patients these drugs, the probability of excessive use becomes high enough, which is itself a trigger?

    15. BGBrian Grosberg1:45:04

        Yes.

    16. PAPeter Attia1:45:04

        Okay. Um-

    17. BGBrian Grosberg1:45:05

        Or a potentiating mechanism.

    18. PAPeter Attia1:45:07

        I see. Okay. So in other words, you would not prescribe these in your practice. We have-- you have enough other tools that you're-

    19. BGBrian Grosberg1:45:13

        Yes

    20. PAPeter Attia1:45:13

        ... not gonna do that.

    21. BGBrian Grosberg1:45:14

        Yeah, I, once again, opioids, uh, for me, are a, a last line, right? Like, um, after people have explored everything, if you will. Um-

    22. PAPeter Attia1:45:26

        Yeah

    23. BGBrian Grosberg1:45:26

        ... and so, you know, even in the emergency room, we're, we really try to end up, um, staying away from opioids just because of the, this potential. Um, in terms of migraine-specific medications, uh, triptans were the first class that was, uh, specifically designed for the acute treatment of migraine. What predated that were the ergotamines, which are still used. And so these are medications that come from a particular type of fungus, um, that have effects on serotonin, which is heavily involved in migraine. And so, um, they're, uh, they don't-- they work on not only serotonin receptors, but they work on other receptors as well. Whereas triptans work specifically on certain subtypes of migraine receptors, namely what's called 5-HT1B/1D receptors. And the 1B receptors have different effects. Those are, um, on smooth muscle cells, and so they are involved, um, uh, on that, on, on that aspect. And the 5-HT1D are involved in, in some of the chemicals that are neurotransmitters that are released. And so triptans, uh, the advent of them really ended up was a game changer for migraine. And, and even now-

    24. PAPeter Attia1:46:42

        Twenty, what? Thirty years ago?

    25. BGBrian Grosberg1:46:44

        So we're probably going back to the, the, the nineteen nineties. Um, yeah.

    26. PAPeter Attia1:46:49

        Yeah, mid-nineties maybe.

    27. BGBrian Grosberg1:46:49

        Yeah.

    28. PAPeter Attia1:46:50

        Yeah, that's right.

    29. BGBrian Grosberg1:46:50

        And so, um, and, and so ultimately sumatriptan was the first one that was in tablet and injection form. It's also available in nasal spray. And then since that time, there are six more that came along. So there are seven triptans in total.

    30. PAPeter Attia1:47:05

        And are these drugs like statins or GLP-1 agonists where each new version gets more effective and has fewer side effects?
16. 1:52:13 – 1:57:03

    Treatment of migraines with electrical stimulation devices

    1. PAPeter Attia1:52:13

       Outside of these treatments, what about any sort of electrical stimulation, you know, TENS? Have any of these other things shown any benefit?

    2. BGBrian Grosberg1:52:21

       Yeah. So you're, you're referring to the class of-

    3. PAPeter Attia1:52:23

       Or TMS. I'm sorry.

    4. BGBrian Grosberg1:52:24

       Yeah.

    5. PAPeter Attia1:52:24

       I said TENS, but what I meant was TMS. Yeah.

    6. BGBrian Grosberg1:52:26

       Of, of neuromodulation devices.

    7. PAPeter Attia1:52:28

       Yeah, yeah.

    8. BGBrian Grosberg1:52:28

       Right? So the, the idea of neuromodulation is to-- that a, a stimulus is being used, um, and that stimulus may be in various forms. It may be magnetic stimulation, it may be electrical stimulation, um, that, uh, targets, uh, some, uh, system, if you will. In this case, the nervous system. And there are different forms of neuromodulation that have postulated mechanisms that work on different targets based on the pathophysiology or the anatomy of migraine. So, uh, one example would be a device that delivers stimulation to the nerves, um, the superficial branches of the trigeminal nerve over the eyebrow. So there's a device that will do that, and, um, they all-- Well, I shouldn't say they all, but, um, that works by, so to speak, uh, kind of, uh, suppressing pain transmission, if you will, superficially to end up having effects centrally, right, uh, within the nervous system. There are devices that will, uh, stimulate electrically the vagus nerve.

    9. PAPeter Attia1:53:34

       Mm-hmm.

    10. BGBrian Grosberg1:53:35

        Um, and so, uh, that, uh, can also be helpful for prevention and acute treatment of migraine, right? These are all-- what I'm talking about are external devices. These are devices that can be applied or held, not necessarily implanted. I think that becomes an import- important point of distinction. And then a device like remote electrical neuromodulation, which is an armband device-

    11. PAPeter Attia1:53:59

        Hmm

    12. BGBrian Grosberg1:53:59

        ... um, called Nerivio that is worn on the arm and that delivers, um, that's operated by an, an app on the phone that delivers a level of stimulation to a nerve in the arm that relays messages to the brain that uses the brain's own natural mechanisms to down-regulate pain.

    13. PAPeter Attia1:54:15

        And that's used as a prevention or a treatment?

    14. BGBrian Grosberg1:54:18

        So, uh, that particular device, uh, has an indication for prevention and acute treatment of headache.

    15. PAPeter Attia1:54:25

        How successful is it in each domain?

    16. BGBrian Grosberg1:54:27

        Across neuromodulation, there are, uh, varying successes. There are no head-to-head studies of these devices. Um, where medications have to be FDA-approved, devices get FDA-cleared. Um, and so w- uh, uh, our headache center was actually the lead site in the world that led to that FDA clearance for that armband device. Um, and so once again, depending on the study, um, the, the, the benefits are, are pretty significant depending on the patient and the, the attack profiles, if you will.

    17. PAPeter Attia1:54:58

        Are these devices expensive?

    18. BGBrian Grosberg1:55:00

        They can be, depending on the devices. So some of them are bought, uh, like the device that's worn on the head that delivers stimulation. Um, the device that applies vagal nerve stimulation is actually l- uh, kinda like rented or leased, and so there's a monthly payment for that. The armband device has a certain number of treatments, uh, within a month, and so that's, uh, purchased or, um- get some reimbursement through insurance, and then there's another device that delivers stimulation to both to the nerves in the front of the head as well as the nerves in the back of the head. And so that can be purchased or, or quote, quote, rented or leased as well.

    19. PAPeter Attia1:55:37

        And are you under the impression that a lot of patients who are suffering from headaches don't even know these advices- these devices exist, and therefore they're missing out on another therapeutic opportunity?

    20. BGBrian Grosberg1:55:49

        So yes, uh, the devices themselves may be used, um, either as first-line or in conjunction or as rescue, depending on the person and their attack profiles. I think the hard part becomes is some people are coming in, uh, th- waiting for a prescription in the form of the medication. Um, as some people, uh, because of the cost prohibition, may not want to end up looking at devices. Um, but there may be other people that have preferences, right? I prefer not to be on a prescription medication to the extent possible. Can we try nutraceuticals or supplements? Um, could we end up trying neuromodulation devices? Uh, if it's somebody who may be looking to get pregnant-

    21. PAPeter Attia1:56:34

        Yep

    22. BGBrian Grosberg1:56:34

        ... um, then we may, for that, aside from patient preference, but if we're looking for people who are in that period of time, and during that time, even though the devices have not necessarily been studied during pregnancy, one of them has, uh, for acute treatment, but the knowing their mechanisms of action, they're not associated with medication, it's presumed that their safety and tolerability would be okay during that period of time.

    23. PAPeter Attia1:57:02

        Do we know

17. 1:57:03 – 1:59:04

    Use of THC or cannabis to treat headaches

    1. PAPeter Attia1:57:03

       anything about, uh, THC or cannabis directly?

    2. BGBrian Grosberg1:57:07

       Uh, it's interesting that you ask that.

    3. PAPeter Attia1:57:08

       I hear, I hear mixed things, right?

    4. BGBrian Grosberg1:57:09

       Yeah. Yeah. So, uh, we actually, uh, ended up doing one of the largest studies looking at use, uh, in our patient population in academic headache program of people using cannabinoids. And what we found, which was, uh, was about a third of our patient population are using cannabinoids. Um, and so, uh, the hard part becomes is, uh, it's not, um, it's not everybody's using-

    5. PAPeter Attia1:57:35

       And you standardized-

    6. BGBrian Grosberg1:57:36

       Right

    7. PAPeter Attia1:57:36

       ... and, and in the study, did you standardize the vehicle?

    8. BGBrian Grosberg1:57:39

       Right. And so-

    9. PAPeter Attia1:57:40

       Or was it an outpatient just-

    10. BGBrian Grosberg1:57:41

        Out-outpatient survey study, it's, it's next to impossible because, um-

    11. PAPeter Attia1:57:45

        We have no idea what they're using

    12. BGBrian Grosberg1:57:46

        ... routes, formulations, combinations, right? It's, it, it's very hard. The other challenge becomes is even those people who say that they may get benefit, the question becomes is-

    13. PAPeter Attia1:57:56

        What else are they doing?

    14. BGBrian Grosberg1:57:56

        Right. What else are they doing? Is it direct benefit for headache? Is it indirect benefit by helping with sleep or anxiety that may be comorbid with, with, with migraine? So I think that's the hard part to, to tease apart. The other challenge is, is sometimes it's hard to advise patients because we don't know about the potential drug-drug interactions.

    15. PAPeter Attia1:58:14

        So no one's done or is doing an RCT where you're using a pharmacologic consistent grade of THC and trying to identify the actual effect of the active agent delivered in a standardized way.

    16. BGBrian Grosberg1:58:29

        There is a study, um, that was done that looked at it for acute treatment of an attack using one formulation.

    17. PAPeter Attia1:58:36

        Yep.

    18. BGBrian Grosberg1:58:36

        And so these are, um, because of regulatory concerns, these are really hard studies to implement. There's a company right now that is also looking at doing larger studies in the future on this. So I, I think those studies will come, but they're gonna be very slow.

    19. PAPeter Attia1:58:51

        But these have to be done as almost, um... You have a-- I think you almost have to have the patients come in to be administered the drug because it's Schedule I.

    20. BGBrian Grosberg1:58:59

        Correct.

    21. PAPeter Attia1:58:59

        Which is, again, kind of-

    22. BGBrian Grosberg1:59:00

        It's, it, it's-- Yeah, the feasibility is not so easy.

    23. PAPeter Attia1:59:03

        Brian,

18. 1:59:04 – 2:03:03

    What Brian wants people to know about headaches

    1. PAPeter Attia1:59:04

       is there anything we haven't talked about as far as headaches that people should know from a primary perspective?

    2. BGBrian Grosberg1:59:13

       So I think from a primary perspective, what I would end up saying is people should have hope, um, in the sense that it's very important to be as empowered as possible by keeping a log of information, by, um, uh, providing their clinicians or the treating physicians or providers with, uh, the details of their headache, um, and recognizing the importance of those lifestyle factors, which can't be overstated. Um, uh, I often think about an equation of e-expectations over reality, E over R. What are their-- what is their reality, right? What are their expectations? And so how do I try to match it as long as the expectations aren't necessarily exceeding reality? Um, I think it's important for people to, um, take ownership, which is not so easy. Some people will say, you know, "You're the doctor, you tell me what to do." And I have to say, "Well, you know, you're, you're, you're-- we're partnering together," right? "This is a partnership." Um, recognizing that preventive medications may take weeks to months, right? Uh, I, I often say that this is not Amazon Prime, right? I know we live in Amazon Prime society.

    3. PAPeter Attia2:00:23

       [laughs]

    4. BGBrian Grosberg2:00:23

       You know, everybody's used to next day delivery, but often good things come to those who wait. We're building on incremental gains, and so I'm, uh, sometimes cheerleading people, if you will. Um, then, uh, in thinking about the, um, the overall frequency of attacks, letting-- knowing that preventive options, sometimes people need one or more preventive medications, right? Uh, it's not one size that fits all, so it really is a very tailored approach. Um, for acute treatment, it's also knowing and, and, and for clinicians to know that not everybody is necessarily gonna respond to one acute treatment. They may need a backup. They may need a rescue treatment. Um, so I think that's important. Uh, for patients who are, uh, very debilitated, there are also intravenous medications that can sometimes be used to try to, um, suppress a prolonged attack that may be known as status migrainosus, where a migraine is occurring for-

    5. PAPeter Attia2:01:19

       Oof. That sounds awful

    6. BGBrian Grosberg2:01:20

       ... longer than three days, like that first patient I was telling you about who was in-- had a prolonged migraine for six weeks. Um, uh, you know, it's, it's, um... And then And then recognizing that ultimately at the end of the day, it's a, it's a marathon, not a sprint.

    7. PAPeter Attia2:01:35

       I just want to spend a minute on-

    8. BGBrian Grosberg2:01:37

       Sure

    9. PAPeter Attia2:01:37

       ... secondary causes-

    10. BGBrian Grosberg2:01:38

        Yeah

    11. PAPeter Attia2:01:38

        ... because I want to make sure that people understand that if you're having a headache for the first time or a headache that's not well-characterized and documented as one of the ones we've spent the last couple hours on, um, you're not missing something medically. So when a person experiences a headache, um, what are the-- Not to create fear 'cause I'm guessing most of the time, ninety-nine times out of a hundred, it is not going to be a mass effect or a vascular lesion or something. But, but, you know, I'll give you an example of something that, that has now come across my radar twice, meaning I've known two people in the last year who have had CSF leaks. One was traumatic, so they fell skiing, and then over the ensuing months, they just kept getting these headaches, and it took months-

    12. BGBrian Grosberg2:02:25

        Yeah

    13. PAPeter Attia2:02:25

        ... to figure out, oh my God, you have a leak of the CSF, and we're gonna go down the path of fixing it. In the other case, it was an individual who had a spontaneous CSF leak, and you can imagine how long it took to figure that out, um, which says nothing of how difficult it was to treat that. So, uh, I don't know. Do you want to say anything about CSF leaks? [chuckles] A-again, my bi- my bias is like, oh my God, these are occurring all the time, but they're clearly not. But they're debilitating, and they're easy to miss.

    14. BGBrian Grosberg2:02:57

        Right. So I, I think maybe if I could, um, provide

19. 2:03:03 – 2:09:10

    Brian's advice on when to see a doctor about headaches and how to prepare for that visit

    1. BGBrian Grosberg2:03:03

       some pieces through the mnemonic that, uh, people should be aware of, um, that may raise concern. So if, if somebody is having, uh, new onset headaches, um, or a change in the headache pattern, that may be something that they want to speak to their doctor about. Um, if they're having a-associated fevers, rashes, um, a, a headache that's, uh, they can't necessarily-- it's painful to t- uh, flex their head and touch their chin to their chest, that may be signs of something that's concerning. Um, if somebody is having unintended weight loss, um, that may be a reason too. So those systemic symptoms. If, if somebody is having new types of headaches or change in a headache pattern, um, during pregnancy, once again, migraine can occur during pregnancy. But as a general rule, um, migraine without aura improves during pregnancy. And so probably about forty-seven percent people notice-- women notice improvement in the first trimester and then eighty to eighty-seven percent or so in the second and third trimester. So, um-

    2. PAPeter Attia2:04:11

       Do you think that's estrogen related, presumably?

    3. BGBrian Grosberg2:04:13

       Yeah.

    4. PAPeter Attia2:04:13

       Yeah.

    5. BGBrian Grosberg2:04:13

       Yeah. Yeah. And so once again, if it's worsening, there are people who can have new onset migraine, um, and where migraine may not improve. But i-if that's the case, that would be something that I would, uh, look at a little bit more closely. If people are on medications that suppress their immune system and they're starting to have headaches or, uh, experiencing more frequent headaches, I have to look at that. Uh, if somebody's having neurologic symptoms with the headache, right? So, um, you know, uh, weakness, numbness, uh, problems with speech or language, double vision, loss of vision, problems with balance. Uh, if somebody is, um, you know, older than the age of fifty with a new type of headache or a change in the pattern, we, we have to think about secondary conditions, one of them being temporal arteritis. Um, most people, uh, who experience this are, are, um, older. Um, uh, but sometimes the, the, the, the misconception is that the pain is just in the temple 'cause it's called temporal arteritis, but the pain of that headache could be anywhere in the head or face. Um, and then is the headache thunderclap? Does the pain peak at maximal intensity within seconds to a minute? That can be what's referred to as a thunderclap presentation. W- sometimes a CSF leak can actually present as that if it's a spontaneous leak, not always. And then we get to the other factors, like is the headache specifically provoked by cough, exertion-

    6. PAPeter Attia2:05:36

       Mm

    7. BGBrian Grosberg2:05:36

       ... sexual activity or sleep, or if there's a positional component. Often people with a CSF or cerebrospinal fluid leak may have a positional component to their headache, such that if they sit up or stand either right away or a, quote, "second half of the day syndrome," meaning as the day goes on, they start developing a headache. Um, that can be issues. Uh, sometimes people with a CSF leak can have interscapular pain, so pain that develops in between the scapula. Um, there are a myriad, uh, of manifestations which makes it so difficult to diagnose and treat, right? So it's, it's people like myself ultimately and others, other colleagues of mine that may be seeing, uh, patients like this. Um, that's why Duke, um, uh, has a, a CSF program, right? That's one of the programs that's dedicated specifically for patients like that.

    8. PAPeter Attia2:06:28

       Well, Brian, this was, this was really interesting. Um, incredibly grateful for the work you're doing with patients, but also just g- really grateful for you taking the time to, to come out here and be away from those patients for a couple of days to, to have this discussion 'cause I think a lot of people are going to benefit from this. Um, I'm sure a number of them are gonna want to come and see you. Uh, do you-- Is your d-- What is the wait list like for people to come and see you? Obviously, when there's only-- when there's so few doctors doing what you're doing, I know how difficult it is to get in to see you.

    9. BGBrian Grosberg2:06:58

       So me personally, when I, I, I moved to Connecticut about ten years ago from New York, um, I would say probably the vast majority of those patients I was seeing in New York who were driving or flying, um, are now just coming to Connecticut, um, which is humbling and flattering. Uh, the hard part becomes is, you know, I want to care, take care of everybody, but it's, it's hard. So my personal wait list is actually quite long, but there is a link that people can go on. Um, often if people live out of the state or out of the country, I'll, I'll ask them just to have like a local physician that can help with prescribing medications and, and be able to h- kind of help implement the p-plans. Uh, but I have-- thankfully, I have other great colleagues as well, and so-

    10. PAPeter Attia2:07:37

        In, in your practice you have partners?

    11. BGBrian Grosberg2:07:38

        In my practice, yeah.

    12. PAPeter Attia2:07:39

        Okay. Great.

    13. BGBrian Grosberg2:07:39

        Yeah, we're, we're probably one of the largest headache programs in the country.

    14. PAPeter Attia2:07:42

        Got it. Okay. So, so people can get in the door into your practice, and if it's anything like my practice, seeing one of my colleagues is no different than seeing me.

    15. BGBrian Grosberg2:07:50

        Right.

    16. PAPeter Attia2:07:50

        And is it the same with you?

    17. BGBrian Grosberg2:07:52

        So y- I have great colleagues who have the same philosophy. I would say I, I, I was very fortunate to have great mentors, and so un- un- um-

    18. PAPeter Attia2:07:59

        But can they curbside you?

    19. BGBrian Grosberg2:08:00

        Yes, they can curbside me.

    20. PAPeter Attia2:08:01

        Yeah, yeah. That, that's sort of what I mean.

    21. BGBrian Grosberg2:08:02

        Yeah, yeah, yeah.

    22. PAPeter Attia2:08:02

        Like it's, it's a, it's an open system.

    23. BGBrian Grosberg2:08:04

        It's an open system.

    24. PAPeter Attia2:08:04

        It's a collaborative system.

    25. BGBrian Grosberg2:08:05

        It's a collaborative system.

    26. PAPeter Attia2:08:06

        Yeah, yeah.

    27. BGBrian Grosberg2:08:06

        Yeah.

    28. PAPeter Attia2:08:06

        Awesome. Um, and then again, I think encouraging people to go to the site. We'll link to your, um, your headache journal so that anybody, whether they're going to see their local doctor or ultimately coming to see you, should really, really, as you said, put in the time, the effort, the ten to fifteen minutes, twenty minutes a day that it would take to really accurately log this for a month because you're gonna get better treatment.

    29. BGBrian Grosberg2:08:31

        Absolutely.

    30. PAPeter Attia2:08:31

        At the end of the day, it's just gonna improve the quality of your care and your, your outcomes. So, um, Brian, thank you again. This was really exciting.

Episode duration: 2:09:10