The Neurology Lounge
Episode 44. Migraine with Mark Weatherall - Author of Living with Headaches
(upbeat music) - Hello, I'm Ibrahim Imaman. Welcome to this edition of the Neurology Lounge podcast. In this episode, we'll continue our exploration of migraine. And my guest today is Dr. Mark Weatherall, neurologist and a headache specialist. And we'll be talking about his book, "Living with Headaches," which was published just this year, 2024. The focus of the discussion will be his perspective of migraine, both clinical and treatment wise. Mark Weatherall is a consultant, neurologist and clinical lead for neurology at Buckinghamshire Healthcare NHS Trust. Former chair of the British Association for the study of headache and trustee of the migraine trust. He was a highly regarded historian of medicine before studying clinical medicine at Cambridge, which is an interesting background. He had gene medical jobs in Cambridge, London and Oxford, and he completed his specialist training in neurology in the northwest of England. He spent 12 months as a clinical research fellow with Professor Peter Godesby and Dr. Holger Kauber of the headache group at the Institute of Neurology in London. These are big names in the world of headache. Dr. Weatherall is a fellow of the Role College of Physicians of London and Edinburgh. His interests include the diagnosis and management of chronic migraine, facial pain, visual snow syndrome, and secondary headaches associated with systemic disorders. He's also interested, understandably, in the historical, social, and cultural aspects of headache and facial pains. Furthermore, he has made presentations on these subjects at meetings of the international headache society, the European headache federation, the migraine trust international symposium, and the association of British neurologist. Dr. Weatherall also led the development of the National Neurosciences Advisory Group's optimal clinical pathway for patients to headache and facial pain. And he actively promotes the importance of headache and facial pain disorders through social media and more traditional media platforms. And you'll add podcasting to that list today. Mark, whether you're welcome to the neurology-down podcast, and I'm most grateful that you accepted my invitation. - Thank you very much, Ian, I'm really looking forward to chatting about all things migraine and maybe a little history as well. - Yes, I'm very interested in that as well. But going back to basics, writing a book such as yours, it takes, it must take a lot of time. How did you go about writing it? And I know you're a headache specialist, but why did you write it? And it's a new book you've been in the field for quite some time. - Sure, well, I mean, obviously with my background as a historian, and even further back as a sort of student journalist, I've always been a writer and I've always enjoyed writing and found it's relatively straightforward to write. And I know that's not something that everybody is able to say, but I do find it relatively straightforward and enjoyable. And I've been intending to write something in the field of neurology for a number of years and to have various ideas and a few books, ideas that I pitched and hadn't quite come off. And then I was approached by the team at Headline to ask if I would be interested in writing a book about headaches. So they were looking to start a new series on common health problems. And obviously, as we all know in neurology, the communist problem in neurology is by far its headache. And the most common debilitating headache is my brain. And so they asked if I would do that. And it essentially gave me the task of working out what people would want to know about headaches, what people living with headaches would want to know, what people caring for, people living with headaches would want to know and what my colleagues who maybe were not headaches specialists would want to know and trying to incorporate that within the book. And so that's how the idea came about. And of course, with all of these things, it took quite a bit longer to actually get it all down on paper, but in the end, it was done and yes, published just at the beginning of this year by Headline. - Great, it's difficult pitching anything to a specialist and a general audience, which is a challenge I face with the podcast, but clearly that was the reason I picked on your book, it's this broad approach. Very early on in the book, you made the distinction between primary and secondary headaches. The difference you said was whether there is actual or potential tissue damage. What do you mean by this, this actual? - Well, this sort of goes back to the IASP definition, the international associate with the study of pain. And they have this, actually, I think really quite well thought out definition of pain has been the experience that is related to actual or potential tissue damage. Now, of course, the difference between primary and secondary headaches, primary headaches, the headaches that we experienced, just because that's the way our brains work. And of course, the common is primary headache is tension type headache for mild ache that most of us get this doesn't cause us too many problems. And of course, the most common debilitating primary headache is migraine, which I'm sure I'll talk about at length. So these are conditions where we feel as if there may be damage to tissues, people with migraines or cluster headache or other severe headache disorders, will experience or will say that they have an experience of actual damage to their brains. And people are very worried about the fact that their brains may be damaged when they have severe headaches. But there is no actual damage. It's just a network of activity that gives us the experience of pain. As opposed to secondary headaches, which are headaches where there is pain that arises from some pain sensitive structure in and around usually and around the head of the neck. So the song analysis, the jaw or the neck. And of course, in those situations, there may not be actual tissue damage, but there is stimulation of pain receptors. And again, pain receptors are stimulated either by actual damage within the tissues or by the threat of damage. Pain is a protective experience. It is supposed to elicit a response that protects us from actual tissue damage. So the fundamental dissension between primary headaches and secondary headaches is really the nature of where they come from and the potential for, you know, there to be actual damage to the tissues in situations where there is secondary pain. - Such sinister things as brain tumors, those would be secondary then obviously. - Yeah, so these are the things that people worry about. And of course, one of the, you know, one of the ironies of headache medicine is that there is this curious dichotomy between people's views of headaches has been either something that aren't trivial. You know, of note, you know, everybody gets headaches and if people complain of headaches and they just, you know, they're just making a fuss of nothing. On one side and on the other side, that they're incredibly serious and they can be the arbiters of doom from aneurysms or brain tumors or such, you know, very serious problems. And of course, the reality is that most of the time headaches are neither trivial in terms of the effect that they have on people's quality of life, nor fortunately are they sinister in that they have a serious underlying cause. Of course, in some cases they do and it can be difficult to pick those out from the types of headaches that's actually a much more benign. There are usually clues in the history, in the examination, in the nature, the pattern of what's happened to people that headaches, certain headaches may be much more worrisome than others. - So you're talking here about kind of a red flags for sinister headaches. What should one be worried about? - Well, fundamentally, most episodic headaches, most headaches that come and go and resolve completely in between times are primary headaches and they're generally benign. So, you know, recurrent dull, mild headaches, they're probably tension type headaches. Recurrent headaches are more severe and make people feel a bit sick or they don't have lights or nicest, they're probably migraines. Nasty recurrent headaches that wake you up in the middle of the night in your eye waters and you pace around the house and probably cluster headaches. Now, they're very unpleasant, but they are fundamentally benign. Headaches that start one day and don't go away are perhaps more worrying. Now, they're often benign as well. They're often chronic forms of those primary headaches that we've already mentioned. But clearly, those, that scenario of a headache that starts and just gets worse and worse and worse is something that could potentially be associated with serious underlying pathology, whether it's a tumor, whether it's systemic inflammation, new to what thinks about conditions like giant cell arthritis in the elderly and so on. So that's a sort of worrying scenario or can be a worrying scenario or at least a scenario that warrants attention. A thunder clap headache, a sudden headache that comes on, you know, within a few seconds to peak, again, that can be a worried scenario. That can indicate, you know, internal bleeding or some other serious pathology. And obviously, if people have headaches and they have focal neurological symptoms or signs, then again, these are situations where, again, there's warrants attention. And, of course, many people with migraine will have, you know, symptoms that may raise the possibility of more worrying neurology, you know, neurological conditions such as stroke. And often, actually, these people do need to investigate. And you need to have scans just to make sure, actually, that this is, in fact, all migraine. - Well, the scenario, I think the older I get in the business, the more you get this scenario, where you've taken a good history as a neurologist or a doctor, no red flags whatsoever, but the patient is there waiting for you to fill that form for an MRI scan. How do you tell them no? I think it's-- - Well, I think it's very difficult to tell people no, because it's such a pervasive, you know, trope within literature, within, you know, in cinema, within society as a large. And it comes back to that curious dichotomy of headaches is either being totally trivial or very sinister. And, you know, when there's, you know, it's out there in films and television, you know, it's such a common thing, you know, the character starts getting headaches and then eventually it all turns out to be a tumor and it's doom and gloom. So I think it's very difficult to persuade people if people are determined that they want to scan, it's very difficult to persuade them not to have one. And I think what I often do is to say to people, you know, if I have concluded that, you know, that they probably don't need to have a scan. And most people really don't. And I would say to them, look, you know, I don't think you need to have a scan, but I would never try to persuade them out of it if they were determined upon it. But they would point out, you know, for example, that if you scan people and you expect a scan to be normal, you know, about two or three percent of the population have got odd brains. You know, they've got little cysts or little benign growths and you may want to find things that cause anxiety, cause other problems if you're actually going to expect into everything to be normal. So I think it's a difficult conversation, but I tend to find that if you explain the rationale and, you know, lots of people are relatively happy, if you can explain to them why their headaches are not serious and not an indication of tumour, then a lot of people are actually perfectly happy not to be scanned. The problem is if you don't scan people in that who are desperate to be scanned, then they're always certainly going to end up coming back, you know, either to you or to someone else until they've been down that line. The problem with that is that we know from some really nice work that was done 20, 25 years ago by Tim Steiner and colleagues that scanning people to lay anxiety only works temporarily. Unless you can actually then give them proper diagnosis and treatment plan. So you have to come back to that at the end because otherwise just scanning them and saying, you know, it'll be fine, it will all settle down. That doesn't work not in the long term. - Well, thanks for putting all that in context. We're probably honed down on migraine. You discussed 14 primary headaches, but clearly the book, you focus a lot on migraine. If indicated is one of the, is the commonest, most debilitating primary headache, why does it stand out in that regard? Why is it that common and why is it that debilitating out of 14 other headaches? - Well, so, I mean, obviously it's not the most common primary headache, it's all attention type headaches are more common, you know, virtually all of us get them at some point when they're alive. But migraine is incredibly common. 30% of women, 20% of men will get migraine at some point during their lives. And migraines by nature, by definition, are more severe, you know, they're moderate or severe headaches. And they're associated with a lot of other features. So people feel nauseous, they may find lights, and noises may be paying worse. At their worst migraines have been rendered, people completely bedbound for days at a time. And of course, you then have a quarter of people with migraine who experience, you know, trans neurological disturbances in the form of aura. And again, usually visible for sort of flashy lights and blind spots that people will experience, but those always can be more severe. People can get sensory aura, people can become dysphasic, people can become hemiplegia with auras or even pass out. So migraine is by nature a much more debilitating experience. And if you then sort of add into that fact that actually about one or 2% of the population suffer from chronic migraine, which I definition in the migraine, well, chronic is all about high frequency, so headaches more days than not, then actually there's an enormous individual and societal burden for migraine, which is why it is really the most important primary headache disorder. Now, of course, cluster headache, which is the third most common primary headache, is not that uncommon. I mean, it's got a lifetime of about 1 in 200. Most GPs will have several patients on their books with cluster headache. And of course, the other primary headache disorders are much less common and, you know, boss fascinating to headache interested neurologists like myself, you know, are very much small-print and much rare. So migraine, if people have severe debilitating recurrent headaches, then they've almost certainly got migraine. And that's really why, you know, I concentrated in this book predominantly on migraine, because actually most of the people who suffer from recurrent headaches, actually the condition they're suffering from is going to be migraine. And that's why, you know, that's why it was really the focus of the book. And it's the focus of, you know, so much of the work that want us, you know, as a headache, neurologist. - A couple of things about migraine, which you discussed, one, going back to its origin, coming from the name hemicranias, one-sided headache. And we see patients coming in and saying, they don't think it's a migraine because it's not one-sided. How did hemicrania become migraine? And how did this perception of a one-sided headache become so entrenched, which I suppose is wrong, isn't it? - Well, I think it's not wrong, but it's not the whole story. So, I mean, the kind of linguistic derivation as you rightly say comes from the original Greek word hemicrania, which just means half the head. And if you go back to the ancient literature, if you look at the kind of the primary authorities, such as Galerne or Ariteus, they talk about various types of headache. But one of the real characteristics that they mention in lots of these is these one-sided headaches that people get. And there were descriptions within those works that were written, you know, 1800 years ago now, which would be instantly familiar to anybody that kind of talks to people with headaches in the 21st century. Over time, I mean, it's the kind of the illusion from hemicrania to migraine sort of happens in old French. And that first sound is lost and hemicrania becomes migraine becomes migraine over time. And of course, the demeeming of migraine, you know, changes over the period from, you know, the Middle Ages to the 19th and 20th century. So our sort of current modern understanding of migraine sort of evolves over that sort of whole period of time. And of course, it has become, if you like, sort of more set in stone with the advent of sort of international classifications, firstly, the American had hop on in the '60s and then the international headache society various iterations since the 1980s. Now that, of course, was one of the most characteristic things about migraine was that it was often a one-sided headache, but it doesn't have to be. And many people with migraine get headaches at the front of the head or the back of the head or over the head, or even pain that predominantly is felt in the neck. And actually, some people get migraines where the pain is predominantly in their body. Migraines core powder, it's very unusual, it's very rare. And as you can imagine, it's quite tricky to diagnose. So yes, it's often one-sided. It's often a throbbing headache, but it doesn't have to be throbbing. But the characteristic of migraine is that it's a severe headache. They're bad enough to stop you doing what you want to do. And it's the other features. So if you look at the sort of overall studies of migraine and the various associated features that have the highest specificity and sensitivity of diagnosis, then the two things really that come out time and time again are nausea, so do you feel sick with your headaches? Yes, okay, they're probably going to be migraines and photophobia, does normal levels of light make your pain worse? And those two things. So actually, there are diagnostic toolkits that say actually all you've got to do is ask three people three questions. Do you get severe headaches? I do feel sick with them and do you feel sensitive to light? And if the answer to any two of those is yes, then those people have got migraine now. And there's a bit more to end up neurology than that. But actually, those are the features, those are the cardinal features in the same way that the cardinal features of Parkinson's are brainic and easy and rigidity and resting tremor, but not everybody has all of them. It's the same for migraine, the severe, we're trying to severe headaches, nausea, light sensitivity. People have got that triad that they've almost certainly got migraine. And the concept of the migraine is touching in the neck. It's, oh, oh, how do you... So the neck is, you know, the neck is so controversial. And I, you know, I jokingly say in the book that if you find yourself at a party sort of pornoed by two headache specialists and you know, what sort of party is that? But if you did, then, and he wanted to make you a quick guess-away, which of course you would, then the best thing to do is just mention the neck and then they'll start arguing and you can put a slip away while they do that. I think, you know, there are many people in, there are many people in, you know, who are interested in headaches who believe that, you know, the neck is the kind of, the font of all headache disorders and pretty much all headaches come from the neck. I think that's manifestly not the case. There are other people on the other side and, you know, my old boss, Peter Goatsby, you know, was one of those who said, look, you know, actually nearly all the neck pain that you get associated migraines is actually caused by migraine, it's a consequence of migraine. Now, I think, you know, I think the truth has always lies between those two extremes. The neck is very important because sensory information from the neck, you know, C2, C3, C4 feeds into the bit of the brain that is activated and starts to generate pain experiences in migraines. It's the bit of the brain called the trigeminal survival complex and normally processes sensory information from the trigeminal nerves that survive the front of the head in the face and these, the highest survival nerve roots. And I think, you know, there's an idea that from an evolutionary point of view, it makes sense that there will be more parts of the brain that would deal with sensory inputs coming from the whole of the head and the neck area because, again, as a protective instinct, if you are being threatened anywhere in the head and neck area, then you need to respond very quickly and actually doesn't really matter too much whether it's coming from the front or the back. So that is a single area that takes input from all of these places and, you know, this is an image in a lot of the lecture physiological studies clearly demonstrate that one of the initiating features in migraine attacks is activation in that area. So in a lot of cases, you have a scenario where people have a propensity to migraine, you know, you sit down with somebody, you know, you say, well, you know, it's right, but in the family with headaches and you get often the family history of a parent or two parents or grandparents or aunts or uncles with headaches with migraines. And you may get a personal history of some of the things that happen earlier in life. So, you know, abdominal, you know, repeated, you know, abdominal pains or vomiting is in childhood, which, again, we know our childhood pretty her system on your brain. And then, you know, then you get this with maybe a history of kind of quite classic to the migraine with all of us in their teens or twenties. And then as people get older, we all get wear and tear and not neck. And for most people, that just causes a bit of pain in the neck. But if people have that migraine biology, abnormal sensory inputs from the neck, potentially can feed into that bit of the brain and can drive migraines. Of course, then you get this vicious cycle because you get more migraines. The migraines cause more necks, stiffness and neck discomfort, the neck gets stiffer, it gets sore, that drives more migraines. So very often, very often, when you see people who have chronic migraine, they also have longstanding issues with the neck. And one of the keys is to recognize that and identify that and try and find ways of actually improving the neck, but say, because even though that's not the fundamental cause of their headaches, it's really an important part of what keeps that whole cycle going. - That explains why some of my patients ask for an MRI of their neck as well. - Yes, of course, you know, I mean, it's a bit like doing an MRI of the brain. You know, if you know what, you're gonna find. You're gonna find wear and tear, 'cause we all have wear and tear. And, you know, most of the time, the issue is not something that really comes up on an MRI, but it's mostly to do with the kind of soft issues that's mostly to do with the muscles ligaments. And, you know, a common scenario is entrapment of the occipital nerves, the nerves that survive the scalp, that feed backwards, curve around the base of the skull. And they're very, you know, they're quite vulnerable there. At that point, they can become entrapped and inflamed as they go through those muscle layers. It's sort of like a parpal tunnel syndrome over the head. And, but again, you know, that could be a, you know, very important thing to recognize and to treat when you're trying to sort of calm down a system that's very overactive and this sort of kind of gets engaged into these vicious cycles that keep headaches and migraines going. - My agreement has a tendency to pull in very different directions. I'll try and focus on something you've mentioned twice now, which is central to migraine, which is the aura, an interesting phenomenon you'd explored extensively. And then you yourself have personal experience of migraine aura. Do you tell us what yours are like? - Yeah. So, I mean, I mean, I'm in minor, minor pretty sort of classic visual auras. And I mean, my first experience of this was, as I sort of described in the book was at the back of the age of 14, I don't know if, you know, playing cricket in the garden and chased after a ball and suddenly realized I couldn't see a little bit of my vision. And what I developed then and what I have continued to have on and off ever since then is sort of, you know, basically the classic sort of small shimmering dot that then starts to expand into a sort of present with a kind of shimmering, slightly zigzaggy outer edge. And just a sort of, for me, a sort of fairly narrow, sort of skitoma just behind it and clearing from the centre and that sort of goes out. And in my case, as it sort of goes into my peripheries, it becomes kind of more extensive and actually a little bit more uncomfortable. There's almost like a sort of strobe effect, which is a little bit uncomfortable, just in terms of visual, you know, stress. And then it just sort of clears out the vision completely. I mean, in my case, it typically takes about 15 or 20 minutes. When I was young, you know, as a teenager, I would then get a severe sick headache afterwards. And I remember a particular event and this shows both my age and what sort of teenager I was. I went to a cinema showing of all three star wars films in order. And I got a migraine halfway through star wars, completely missed Empire Strikes Back and kind of came to halfway through Return of the Jedi, which was a real shame because I missed the best film in the trilogy. And, but I, you know, it was that sort of, that was the sort of thing that I would have. And then I get, interestingly, I stopped having those when I was about 20. I didn't have another migraine or until I was in my late 30s. And I had a single isolated one. And then about 10 years ago, I had a six week spell one summer where I had 12 or 13 episodes within a short period of time. And even I was starting to get a little bit, I'm sure it's going on here. Maybe I should have myself scanned. And then it all settled down completely. And I've had a couple since then. So it's migraine or it's quite nutritious. You know, we talk about triggers. We talk about lifestyle things. And, you know, these are really important for a lot of people with migraine. But in a lot of cases, that goes more for people who get migraine without all. You know, or has a bit of a life of its own. It comes and goes. And, you know, want to see a lot of people who get these flowings of recurrent episodes of all over a short period of time. And, you know, usually, you know, 99 times I've got 100 when you investigate those people because you often end up doing that. You just never really find anything. And it is just migraine doing what migraine does. So war, you know, I spent a lot of time talking about war in the book. And I think, you know, this is one of these things that people who write about migraine do this. I mean, all of a sax is, you know, sort of seminal, you know, book on migraine that, you know, he wrote back in the late 60s, early 70s. You know, he concentrates a lot on all. And I think as neurologists, you know, we get very sort of fascinated by all the extraordinary things that war can do. But I think it is really useful to actually put that down on paper because a lot of people experience these things and do get very worried about what these experiences actually mean. And, you know, people do worry that they're having, you know, mini strokes or that they've got, you know, MS or some other condition because, you know, they've got these visual services or these, you know, these odd tingles that sort of spread up and down one side of the body. Or, you know, even in the sort of more extreme cases, you know, people that end up going into hospital thinking they're out of stroke because they just want to read down one side. So, actually, you know, putting people's experiences down on paper and say, look, these are the sort of things that migraine can do. And, yes, of course, sometimes you need to look at this carefully and make sure that it really isn't anything else. But, actually, is that outside the envelope of what a migraine experience can be? And that's a really useful thing, I think, to reassure people to be able to say, look, you know, I've heard that before, you know, people have told me that before. I've seen people with that particular experience and, actually, yes, it can or will just be migraine. And you talked about the different types of migraine, visual aura, kaleidoscope, broken vision, blind spots. Why does the aura come in so many different forms if it's all visual? Well, I think it's because of the differences in the kind of, in the areas of the visual cortex that are affected. So, the aura process is, I think, now universally understood to be a cortical spreading depression. So, this is a physiological process, first discovered by the Canadian Physiologists out in the 1940s. And what you get is a wave that crosses the cortex at about 3 millimetres a minute. And what you get is you get a peak of over-excitability. So, you've got over-activity in your neurons for a period of time. You've then got a period of silence and neuronal silence. And then you've got a resolution. And if you recall that experimentally, you know, with a series of EEG, you know, dipoles going forward, you see that process spreading forward. And Liao himself sort of suggesting, well, you know, this mind fit for migraine. And, again, the Canadian neuropsychologist Milner, Peter Milner, in the 1950s, again, kind of raised this as a possibility. But I think it really wasn't until the 1980s when the mountain lionson, yet also the Danish group, kind of showed spreading oligemia that crossed the boundaries of different kind of areas of blood supply. So, therefore, kind of debunking the model that Ora was due to somehow to, you know, to the constriction of the major blood vessels. Just, I mean, never really made sense, but they absolutely proved that it wasn't. And then more recently, you know, in models, you've seen those sort of Ora, you know, of course, because of any depression processes occurring. So, that's the physiological substrate of this. That's what's happening, you know, at a sort of cellular level. What our experience of that is depends on where abouts in our core grain, in our cortex, that starts and how that affects those bits of the grain. So, you know, the fundamentally, you know, clinically, what you're looking for with migraine or is a combination of positive and negative features, you know, the flashy spots, but also the term of also the blind spot. If people get sensory or then, you know, you're looking for kind of tingling, but also numbness, and again, that sort of sense that things are spreading steadily over a sort of minute. And what exactly happens depends really, you know, exactly where abouts in the brain, those processes occur. And so, there is a pre-delection for the occipitalosis, the visual parts of the brain, for reasons that I don't think anybody really still understands why the visual, you know, cortices are particularly prone to this. But if that process, you know, keeps on going or it starts a bit further forward, then, you know, you hit sensory cortex or language areas of the brain or even motor areas. So, you know, or as an experience is protein and it can do so many different things, but I think, you know, physiologically, the reason is it's the same process, but what we experience depends exactly where it is in the brain. And I think, I mean, there's been some, I mean, there've been, you know, there've been one or two beautiful kind of studies, one of the American victims of a fantastic, you know, study where they were kind of, you know, recording people's, you know, they had a particular patient who recorded that really carefully and they could actually map what that patient was drawing to, you know, specific cortical areas. And of course, you know, a lot of our thoughts actually is relatively silent in terms of our experience. So, again, it's not surprising that, you know, that sometimes or is fragmentary, sometimes there is, you know, both visual and sensory disturbance, you know, it's a complex, you know, it's not a sort of straightforward thing, you can't straightforwardly map the visual world out there onto, you know, the cortex in here, like a pinhole camera, it's, you know, it's much more complicated than that. And that's one of the reasons why Aura is such a varied experience for different people and also for individual people within their own kind of mind, brain, life. We can have the whole podcast on the Aura, but I still have a couple of questions based on it. One, does it mean an individual has can only manifest one type of visual aura or can you have the different visual auras in one person? I think, I think, generally speaking, people, I mean, you know, we often, when we sort of think about epilepsy, we often, you know, often looking for people to have very stereotyped episodes and, you know, that's something that makes us think, yes, no, okay, this is, this is a specific focus and this is, my great is often, you know, yes, I mean, for a lot of people their experience is very sort of standard. So, you know, if they have an aura, it's likely to be the kind of same sort of thing. But for example, many people will have, you know, that sort of expanding, you know, the fortification spectra that expanding crescentic kaleidoscope type picture. And 95% of the time it will happen, you know, in their right visual fields originating from the left hemisphere. Just that one time in 20, depending on the other side. Sometimes, you know, that process, you know, that, again, for reasons for the melanoma, that process usually peters out within the occipital cortex, but if it keeps on going, you know, sometimes people may have, you know, their typical visual aura and then get a sense of sweetest zones and then become this phasing. So, you know, most people who experience aura over the course of a lifetime, it's often a kind of, there's often an evolution, but it often has kind of themes and people would normally recognize their organs. But you do have a situation where some people suddenly get something very different. And of course, that, you know, again, that can be, you know, that can be very disconcerting and that can bring people to make a potential and they suddenly have something different. So, people can certainly have different types of auras that's perfectly common. But often, there is a sort of theme to it and often people have, you know, relatively similar experiences over the course of a lifetime. And of course, one of the most common patterns is that when people are young, they will have aura, and then they will have afterwards a very severe ciche. And then as they get older, they will continue to have episodes of aura, but headaches will often kind of settle away. And, you know, in old age, you know, people often continue to get all a well-entilated life, but actually don't get much of a headache with it. That's my point for you. One last thing on the aura, which you explored in the context of the Alice in Wonderland syndrome. I know that migraine is not the only thing that gives this, but what is the Alice in Wonderland syndrome? Is it a manifestation of the migraine aura or something different? Well, I think, as you say, you know, migraine aura is one of the potential underlying causes of that experience. So Alice in Wonderland syndrome was a term that was coined for experiences of distortion of body image. So that feeling that part of one's body is either much larger than it should be, or much smaller than it should be. Now, of course, the name was given because Alice in Wonderland in Lewis Cowell in Charles Dodgison book. Alice has these experiences where, you know, she becomes much bigger and much smaller by, you know, drinking the potions and eating the cake. And the speculation is that we know that Charles Dodgison, who's Cowell, had migraine. We know that he did because he writes about it in his diaries, and we know that, for example, he read Peter Latham's lectures on migraine that were delivered and unboxing Cambridge in the 1870s, because he writes about that in his diaries. And so people have sort of speculated that maybe some of these kind of slightly psychedelic experiences that he put in the book may have related to his own experiences or just some sort of body image with migraine. I mean, actually, I think the most bizarre kind of Lewis Cowell's speculation is that the Cheshire cat, and you remember that the Cheshire cat sits on a branch and then starts to fade away and eventually all you can see is the brim, which is the smile before that goes. And some people think that's a kind of skitoma that's may have been pushing it a bit far. So this is that's how that's how the syndrome, but it's named. Now, of course, you know, this, this, the presumption is that within a migraine scenario, what's happening is it is, you know, there is that that process that cortical process is affecting those bits of the parietal of the kind of kind of give us our, our sort of sense of self and that there is a, there is a temporary kind of derangement of that. And of course, you know, that has been, you know, people have, you know, there are other pathological processes epilepsy stroke and neurodegenerative disorders that have been reported to kind of create the same sort of thing. Obviously, migraine can do so, but in a temporary reversal, so it's a fascinating thing. And I mean, one of the interesting things about as the Wonderland syndrome is it does seem to be more common in children than in adults. And it is the sort of thing that when you talk to people who have had a lifelong experience in migraine with aura, you know, not infrequently, if you kind of delve into their experiences, they will say, well, when I was a child, you know, I used to feel like this. And then it seems to become much less of a thing as people get older, which I don't, I don't think anybody's really kind of explained why that is, but it's, it's a sort of, you know, it's one of these sort of, again, it's many sort of interesting observations and sidelines that you get, you know, from talking to people with, with migraine. Fascinating, as you said, but coming down to my brain with aura is not the commonest form of migraine, is that a point we should make its most. Yes, no, I mean, but only about the course of people with migraine gets older, and I think this is, you know, there's a number of reasons why people get a misdiagnosis. And I think one of the, you know, one of those reasons is that there is still, in some courses, you know, an idea that it can't, unless people get older, it can't be migraine. And so, you know, yes, it's very important to point out that, you know, three points of people who, you know, experience migraine do not get over, they get, you know, severe and current headaches associated with nausea, and it's typically to lie as noise is movement, so on. So, yes, the presence of aura is helpful in a diagnostic manner, but it is, yes, it's by far, well, it's not by far, but it's much less common for people to experience all of it is not. And then, for the phobia, light sensitivity being more common, you mentioned the, on the line pathology being some connections between the retina and the phalamus, how does that kind of play with bringing this light sensitivity. So I think this is, I think this is one of the most interesting pieces of research that's been done in the last 25 years, that migraine, and this was done by Ramy Burstein, who's a migraine scientist, who's based over at Harvard, who works with teams at Mass General. And what they've, what they were doing is that they were talking to people with migraine that had been born sighted, but then had become blind. And those people still experienced photophobia, in other words, that is worsening of their migraine pain by exposure to normal levels of light. And so, they were trying to understand how this could be when they were blind. And what they showed was that there are direct connections between the retina and the thalamus, so there are direct retinothalamic connections which they demonstrated in, in suitable animal models. And then kind of demonstrated in so far as it was possible to do so that these connections are likely to be present to humans. And they're postulated that these direct retinothalamic connections are actually part of the defense mechanism. So essentially, again, you know, if one is exposed to very bright light, this is what people experience pain. There's a pain sensation, and again, that's a protective sensation in the same way that if you put your hand on a, you know, on a hot stove, or, you know, there's a sensation of pain, and that's supposed to protect you from tissue damage. It's the same thing, exposure to over-bright light can damage the retina so that creates a pain response, and that's thought to be modulated through these retinothalamic pathways. In migraine, what's happened in migraine, we talked to, mentioned earlier on about this, trying to demonstrate the cycle complex, which is kind of deep down within the brainstem. And, you know, that's normally very active because our body's a constantly getting sense of information from the head and the neck and shoulders and so on. Most of the output from that area is kind of just kept under control by descending pathways from higher up in the system. In migraine, that whole system kind of starts to run hot and actually override those control pathways, and it may be the fact that, you know, fundamentally, the genetic basis of migraine is the fact that those control mechanisms don't work as much as it should do. A single start to come up, and, you know, the relay centers from taking sensory information from, you know, deep bits of the brain, which are kind of working in the background and we're not aware of, to, you know, our cortex and the bit of the brain that tells us all you're in pain, that relay station is the thalamus. And so, again, the idea is that all of these sensitivities that people aren't in migraine, sensitivity to normal levels of light, normal levels of sound and touch, these are almost certainly modulated through connections that happen in the thalamus. And so, you know, this normal input from this circuit is enough just to kind of give those migraine signals that kind of, you know, a kind of shove on their way up to your cortex and just wind everything up. So it's a really interesting piece of science starting off from, again, starting off from a clinical observation that these patients who became blind could still experience photophobia, and then working out why that might be. And then coming back and saying, okay, this is probably how it works with migraine. But in that further, do we see a thalamic deep brain stimulation as a treatment then for, or migraine is that in the cards. I mean, I mean, people, I mean, you know, people have, obviously, you know, newer stimulation has been an area of interest in primary headache disorders. Well, actually also secondary headache disorder is a new allergy in particular, for, you know, for about 30 years. And, you know, when I trained with with Peter and Holker back that's, you know, at the Institute, you know, 20 or years ago now, you know, my very good friend and colleague, who was doing his work on, you know, simple nurse stimulation in foster headache. And if this was a kind of big area. DBS has been used for primary headache disorders and there are various sort of targets that have been, you know, used and postulated. The problem with DBS, of course, is that, you know, it's an invasive procedure. And so it's always has been regarded as very much the sort of last resort. Now, of course, 20 years ago, we didn't have the options that we have today. So, you know, this is in an area before people were using Botox, the chronic migraine. This is well before the modern CGRP, modulating drugs, the monoclonal antibodies and the G-Pans. And so, you know, there was, you know, there was a patient population back at that time that, you know, had been through dozens of kind of drugs for, you know, amateurly and beta blockers through to kind of, you know, long shots that worked, you know, in a little case series from a random, you know, American headache center in the middle of, you know, in the middle of nowhere. So, you know, there was a real interest at that stage. There is an ongoing, there is still an ongoing interest in invasive neuro stimulation as a headache treatment, but I think it's much smaller scale now. What the has continued to be is an interest in non-invasive neuro stimulation. So, the idea that changing input from those nerves that feed into that central processing system could be helpful is something that, you know, is still actively being worked on. And there are, you know, there are devices, you know, there's, you know, there's, you know, lots of sort of toys and, you know, devices that come out, but, you know, you look at things like super orbital nerve stimulation, typical nerve stimulation, visual nerve stimulation, the neck or the ear, transcranial magnetic stimulation at the cortex, and even remote electrical stimulation, you know, the devices that's licensed in the states, which give you a bit of a buzz and a bit of a pain in your arm to distract your brain from your migraine pain. And all of these things, you know, can sort of work in some cases, and again, you know, this, they're all based to a greater or less extent on the sort of the old theories of gating and pain. So, I think, you know, deep brain stimulation will continue to kind of sort of be there in the background. People are always interested in, you know, neurosurgeons love to kind of, you know, put around inside the skull and do things and, you know, sometimes they can work with useful things like that. But I think it's always going to be relatively small scale and, obviously, the advent of the treatments that have come through in the last 10 years, I think has made it perhaps a little bit less necessary across the board to have those sort of, you know, very much last resort in basic treatments. Well, appropriate time to go into those treatments. And you established, I mean, the background was this WHO step ladder approach to the treatment of migraine. Does this suggest that the approach is rigid or is that you can kind of jump in and pick and choose. Well, so, so the point really I was making with the WHO stepwise ladder. So that's really the, I mean, that's, that's the WHO ladder for pain generally. And of course, for those of those people who don't know, you know, basically, it starts off with sort of simple, you know, analgesic, so, you know, how set them all non-stories anti-inflammatories. And then it goes up to weak opiates, like codeine, then it goes up to strong opiates like morphine. So there's a kind of stepwise thing. The point I was making really is that from migraine and before head pain generally, this is not the appropriate thing to be using because opiates, in particular, are not good treatments for head pain disorders. So, you know, there's actually very little evidence behind using opiates, codeine, tramadole morphine for migraine or any head pain disorders. And of course, the problem that comes with them, well, there's several problems. Firstly, opiates make people constipated, which is generally unhelpful when people are having migraines because we hear a lot of gastroparesis and gut alterations anyway. Secondly, they often don't work particularly well. And thirdly, the potential for overuse evopiates to cause worsening of headaches, to cause medication overuse headache, is extremely high, whereas, for example, that risk with non-steroidal anti-conductions is very, very low. Now, of course, you know, you say, well, that's fine. So don't use opiates. What do we use? And for the last 30 years, what we used is trip tans. So the trip tans were first discovered by a charcoal pet, Humphrey, who worked at Gladstone in the 1980s, but Humphrey was looking for a sort of better, cleaner drug for migraine. And at the time, the main leading theory was that migraine was modulated through serotonin metabolism within brain. And so Humphrey used a model, the Los Sefinas Bay, model to try and find drugs that would stimulate serotonin subtype receptors. And he found this drug called GR13075, which we're all much more familiar with as summer trip tans, which seemed to do what he wanted to do in his model. And then once it was given to volunteers seemed to be extremely good, and actually stopping people from having migraine. So summer trip tans was first released and marked it in 1990, almost instantly incredibly successful, because it really did work very well and was much cleaner and better tolerated than the earcalls. And of course, almost immediately out of that came the work that Peter Gold's Peter Lars Edmondson did that showed that, whilst, yes, the trip tans stimulate serotonin subtype receptors, the consequence of that is the presanaptic blockage of the release of CGRP acetone and gene-related peptide. And it was the rise and fall of that peptide that seemed to most grossly applaud with the rise and fall of pain in migraine. And it was blocking that peptide and not other candidates like substance P and VIP and lots of other sort of neuro transmitters that people were interested in the time, drugs that blocked those did not block migraine, drugs that blocked CGRP did. And that's really been the basis of a lot of the migraine science of the last 30 years. It's been trying to kind of work out the whole CGRP story where it is, what it does, how it works, and we're still still kind of doing that and still trying to work out how this all kind of comes about. And then obviously pharmaceutical companies recently quickly kind of looked at the success of the trip tans and said, right, well, you know, maybe we should be looking at other drugs or create other drugs that block CGRP. So the first generation of the new CGRP drugs were the first generation G-Pats. These were drugs that were direct CGRP antagonists. The idea was that, you know, the trip tans are generally very, very safe drugs indeed, but because they stimulate serotonin receptors, they can cause a very small amount of vasoconstriction. Now, under law circumstances in healthy individuals, that really doesn't cause any problems, but obviously it does make them advisable in people that are known to have had heart disease, heart disease, strokes, and so on. So there was an interest, even from the very beginning, in finding drugs that would modulate CGRP in what direction. And the first generation G-Pats never made it to market. Some of them were financially commercially unviable. The one Tejapant that made it all the way to Phase 3 trials, unfortunately, was subsequently discovered to, of course, liver problems in some people and it was withdrawn. So that first generation of those CGRP drugs never made it to market. I mean, when I was appointed as a consultant back in 2007, I remember talking at my interview. And I was saying, oh, we've got these fantastic new drugs, you know, the trials are out, you know, because they're going to be out next year and it's all very exciting. And they just never came because they were all withdrawn. The CGRP story didn't go away, and it was really the sort of monoclonal antibodies that were created, originally as lab tools, to kind of locate CGRP in, you know, brain specimens. But a bright spark sort of decided that if you had something that was specifically by CGRP, then maybe that you produced that as a treatment and showed so it proved. And so the monoclonal antibodies, you know, all the trials came through in the kind of about, you know, 10 years ago, and they were all through for use in the States and in Europe back in 2018, obviously on the NHS in the UK, between 2020 and 2022. And those have been, you know, enormously successful drugs because their efficacy is very good. You know, at least 50% of people who go on them have a 50% or more reduction in their headache and migraine days, which, you know, is a big deal for people who are that, you know, that severely trouble by the condition. And they're very well tolerated, you know, the side of their profiles are very benign by comparison with a lot of the old drugs that were used to use before. Now, of course, there are all sorts of logistic issues that, you know, they're relatively expensive. So we have to think about that as a societal burden in terms of the past, logistically, you know, being provided by headaches specialists and we don't have enough headaches specialists. So there's all sorts of issues that come around that. But it's fantastic to have modern migraine specific effective drugs that we can use. And then, of course, in the last couple of years, you've got the second generation jeep hands, so the oral treatments that, you know, still that same idea that, you know, they target CGP more specifically. And these drugs are very interesting because, again, they were originally developed to be huge treatments like trip plans. But it's been shown that some of them, at least, the more people took them, the fewer migraines they had, and actually two of the jeep hands were measured back to the togepan are licensed as preventive treatments. And so we have this interesting scenario that, you know, people like me for the last 20 years have been telling people not to take any painkillers because it's going to make their headaches worse, whereas with the jeep hands, that doesn't seem to be an issue. And there's lots of interesting kind of mechanistic questions about why that might be true for them. But not true for the trip plans, not true for opiates, and maybe less true for anti advantage. So, a lot to uncover them in the CGP world. Yeah, which conventional preventatives will you use before you think about going to the CGP drugs. So, it's becoming increasingly difficult, actually, because the standard ones that we use have used for 40 or 50 years and still we use today are, you know, to tricyclic. So, I'm a trip to Lee, you know, obviously a much lower doses than people used to use for depression, but they can still be really effective drugs for people. And then you block B2 blockers, you know, most of the kind of commonly used B2 blockers, the Pranolol, the Tenorol by Sokololol, they all have a great action. And again, they can be, they can work really very well. The problem with those drugs is tolerability, lots of people don't get on with them for various reasons. And of course, there are people that can't take B2 blockers because they have asthma, peripheral vasculosies and so on. The other drug that's really sort of coming to quite widespread usage in the last 10 years has been Candace Martin. So, obviously, that group are anti-tensin blockers. And actually, there's also a trial that shows the telmosatin, where nobody's ever done trials at the other sartons. But Candace Martin, I mean, again, interesting story, a chance observation by Lars Stolfner's group in Norway, a couple of their patients 25 years ago that were put in for blood pressure and came and told them that their migraines were better. And I suspect that most of us would have come from, oh, that's a really interesting, I'm really pleased for you. And they're not really taking it on very further. But Lars's group, you know, kind of really ran with that and have done, did two really well-conducted, well-run trials that showed that, you know, it really was an effective migraine medication. The other interesting side by the hand of SARS-AN is that, obviously, COVID, the SARS-CoV-2 virus, was discovered to bind to, you know, the AIDS receptor. And one of the pieces of information that came out as part of the research that was being done into potentially how COVID might cause pain or what the neurological symptoms was that that was found that that receptor was actually expressed in the tridemic organics, which is part of the relay system that's activated in migraine. And so you suddenly have that really sort of interesting link that just comes in and you suddenly go, oh, maybe that's where Candace SARS-AN is working. Because we know that the gang, tridemical gang, or at least part of it sits outside the blood-bain barrier. So, again, we don't, I mean, if we're absolutely honest with ourselves and anybody else, we don't know specifically how really any of these drugs work in great detail as prevented. But those are still in widespread use. Now, of course, when I started, you know, in headache back in, you know, 25 years ago, we would then go on to use epilepsy drugs. But we do so far less frequently now. So, and the reason for that is that the drugs that have the best efficacy behind them are sodium evaporated to pyramid. And of course, our biggest population is women, because more women might be in the men, of child-bearing age. So we just don't use those drugs anymore. And obviously, sodium evaporate, first of all, and now more easily, to pyramid, you know, very clear evidence that these are not good drugs to be given to, you know, women, or even in the case of evaporate, probably men, you know, actually child-bearing age. So, you know, those have really fallen out of favor. Other epilepsy drugs that we used to use, like Gavapentin and Pre-Gavapentin, I think are pretty conclusively been demonstrated actually really don't work very well for my drug. I'm very used for neuropathic pain, but not really for money. Then you've got old-fashioned drugs, really old-fashioned drugs. There's also a thing that is still around, but obviously, again, can cause a lot of side effects. So this is a bit of a problem now, because, as many people know, on the NHS, if we want to move on and use Botox injections for a migraine, or if we want to use the cheap hands, or if we want to use a lot of how that's about these. You know, theoretically, we have to have tried, and people have done at least three previous preventive medications. Now, those, you know, it must be said, there is no evidence that suggests that, as we've done it, so that was a kind of automatic decision that was made back when Botox was being approved for use on the NHS, you know, 15 years ago. But, you know, that's what came out of that, and we were kind of stuck with that now as a concept, but that's what we should be doing. But it's quite difficult to do that, because, you know, 10 years ago, we would have given pretty much everybody to pyramid, and we've got lots of people to operate, whereas really these days, you know, we hardly do. And so most people now maybe have actually might be to block them if they can have a beach block and kind of start them. But, you know, after that, where do you go? It's, we don't have it, you know, as many options as we used to, actually, for very good reasons. And I think the reality is that, over time, what will happen is particularly the new oral CGRP antagonist, the G-Pans, will start to become used earlier in early. And I think the future is likely to be that those drugs will find a much earlier place, and they will probably actually be used quite a lot within general practice, even before people get referred on to people like me for other sort of treatments. And actually, I think, personally, I think that's a very good thing. It would be a very good thing for my main sufferers, because they're very effective, well-tolerated drugs. But, of course, you know, on an NHS side, there were also implications in terms of the cost of that and so on and so forth. But, yeah, you know, these things evolve, and, you know, with my historians' hands on, you know, you look back 50 years, and the drugs that were regarded as kind of standard treatments, you know, simple-heptidine, comedy, you know, methyserge-ide, which was a really good drug that just died, you know, about 15 years ago. You know, we don't use any of those anymore, and probably for good reasons, in most cases. So, it might be the headache world might borrow from the epilepsy world, where you define drug-resistant migraine as the failure of two drugs, rather than... Yes, I mean, I think that may happen. And, of course, you know, one of the main differences between the weight that we manage things in the headache world and the weight that, you know... Well, that's going to say my colleagues manage epilepsy, but I manage it for that speed in my general biology life, is that we very rarely use combination therapies. So, you know, we do tend to move on from one drug to another and stick with monotherapy. I mean, there is probably no... I mean, there's no good reason why that is the case, that is just the way things have generally been done, whereas, of course, in epilepsy, it's very different. You might try a couple of drugs with monotherapy, but if you're not winning, then you'll almost immediately move on to, you know, to combination therapies. So, yes, I think... Yes, I do think probably that is going to... I think that will change over time. And, you know, to peer rates, I mean, to peer rates is still, you know, as we speak today, it's still recommended as the first line in the nice guidance for, you know, management. But again, that's just not going to be tenable as a pregnancy prevention program comes in. You know, these things will have to change because, you know, practice changes over time. So many questions to ask, but I think we'll probably take... I've taken a lot of your time already. One last thing, which from reading your book seems to be emerging, which is this pituitary adenal cycle is prudent. Is it a cup or pack up? Pack up. Pack up. You said CJIP is not the only game in town. What is pack up? What is it promising the treatment of migraine? Yes, pituitary adenal cycle is a pack up for sure, so it's much easier to say pack up. So basically, I mean, we know that firstly, we know that not everybody responds to CJIP or to let you drugs. And of course, part of that is, you know, a nonspecific effect of poor absorption or recommend metabolism. That's lots of reasons why people may not want to drug. But there are clearly people in whom CJIP pathways, which are so important for so many people with migraine and also cluster headache, are not actually as important as they offer other people. And so that has been an interest, has been an ongoing interest in looking, you know, at relevant brain areas. So, particularly areas like the triteminal ganglion, some of the brainstem areas that modulate, you know, that sort of have that descending control of the, you know, triteminal cycle complex and so on. And looking to see, you know, are there other neurochemicals that are expressed in these areas that might be relevant? And pack up has been the one that really has shown some performance. So we know that pack up is involved in triteminal signaling in the same way that if you give people migraine an infusion of CJIP, it will induce migraine attacks in a significant portion of those people. You do the same with pack up and you get the same result. So again, it seems, you know, very likely that it is, you know, involved in those pathways in a significant proportion of people. So there have been drugs that target that pathway. And they're now in late stage, you know, pays free clinical trials, pays true trials work. Repositive, you know, showed, you know, promising results looking very similar to the tryptans and the G-pans in terms of response rates and tolerability. So these drugs will, I think, you know, I think they're going to be the next sort of thing that comes through from the science into clinical practice. I think, you know, sometime within the next three to five years, I think we will probably have the first of these drugs coming through. And I think it will be very interesting because, as I say, there are people that, even under the best circumstances, do not respond to CJIP modulating drugs. And for those people, you know, will these be good options? Well, we'll see. It will be very interesting to see, but they may well be. And again, it's, you know, it's useful across the board to have, you know, from my point of view, you know, it's very useful to have as many options as we can. And it's also, you know, really important to that, you know, we keep, you know, we don't sort of think that the story's over with CJIP because it really isn't. And I think the other area, you know, I think is going to be very interesting. It's 10 years to 15 years, maybe, is the whole question of the end of the category system. And, you know, how that may, you know, that may also be an issue. So there's some interesting early proof of concept studies for drugs that modulate end of category receptors and tone as potential migraine options. And so I think that's going to be, you know, that's going to be the story. You know, the story of the last 30 years, which we've seen today, and that's kind of, it's still playing itself out. But the next 30 years, I think there's going to be other things that we're going to be interested in. And those historians of 2050 might look back at the 2020s and 30s and say, yeah, that happens the year of, you know, X or Y. And then they might kind of look at us a little bit, critically, and go, oh, she was still, still sticking box of line of toxin in people. How are you doing that that way? Well, that's high brow. Coming in low brow, things that could probably not change. What three lifestyle changes do you recommend to your patient with migraine? Yeah. So, I mean, most of the time, I don't have to recommend lifestyle changes. My patients, my patients, my patients, because people with migraine are usually pretty good at recognizing what is a good thing to do and what is not a good thing to do. I think the main things, if you can achieve them, firstly, you know, simple things like hydration. So, you know, we all drink too much coffee and not enough water. And I think we should all be, you know, most of us, not all of us, but most of us could do with hydrating ourselves better. Migraine definitely thrives on dehydration and actually quite caffeine whilst it can be helpful. There's a few treatments. Again, overexposed caffeine can make people more headachey. So, that's a simple thing. You know, no more than a couple of caffeine experience a day and try and drink, you know, 2.5 to 3.5 liters of fluids, depending on how active you are. Number one. Number two, migraine likes people to be a bit boring, implies people to eat regularly, to sleep regularly. So, if you can keep to a routine and particularly with sleep, then that's good. Now, of course, these are not necessarily straightforward things to do. You know, modern life does not necessarily leave itself to keeping strict hours. And what you don't want is you don't want people to kind of go overboard and try and kind of live, you know, too strict a life. And you do see this and, you know, in many, in some ways, it's almost as bad as, you know, the opposite where people kind of, you know, let my brains run right. So, yeah, if you can keep to a sort of sensible routine, you know, making sure that you don't miss meals, try and have a kind of reasonably stable and set sleep hygiene routine. That's all, that's also helpful. So, that's number two. Number three is most of us spend a large portion of our lives doing what you and I are doing just now, which is sitting in front of computer screens. I saw that coming. Yeah, and this is all about posture and this comes back to almost blurry started, really, which is talking about neck. It's really important that, you know, the neck is not being run under the headache in any, any shape or form, but it is a really important component to think. And we do spend a lot of our lives these days with our head kind of bent over phones or laptops. And it's very important to try and make sure that actually you, particularly if you are a headache person, someone who gets why it means that you reduce the impact of that as much as possible. And so, it's, you know, very helpful to make sure it's a simple thing to make sure that your screens are raised, making sure that you have, you build in breaks, you know, five minutes and a half hours, five minutes in the app, together, stretch out, retry, and then go again. And of course, there's lots of good evidence that if you do that, then it makes you more productive anyway. But it's those long periods of immobility, which are just not good for us and migraines, you know, we'll thrive on that. So, that's the third one. Those three will do for starters. I will tell my next guest that we're going to take a break after 30 minutes. Miss the boot with you. Are you writing any book at the moment or any big project? So, I've got a, so I've got a couple of possibilities that we're considering. So, I'm very interested. Well, I've got one that's kind of sort of serious, and then one that's a bit right. So, the serious one is that one of the other things that I have done over the last five years is I have worked for a medicinal cannabis clinic. And I'm really interested in writing about that and trying to write a sort of honest and straightforward book about what, you know, what that can and can't do because I think, you know, it's becoming a very big business in the UK. There's a lot of hype about it. It's a lot of misunderstanding about what, you know, what it is. So, I think that's an area that I'd really like to try and explore. And I think probably, you know, there's a, you know, there would be a need for something that's kind of balanced and straightforward. So, that's the sort of serious, well, the light hearted one is last year, or early this year, Donna Davidson, who now ex-tory. MP, very brave woman who came out and signed from that job as a minister because of her quality money grant, and has now left Parliament. Donna actually managed to investigate a debate in the House of Parliament on my grade and headache disorders, which was the first one since the early 1960s. And I was lucky enough to attend, and it was very good, and there were some quite fond people that came and spoke very well. As a historian, I thought, interested to look back and see, you know, what they were talking about back in the previous debates in the 1960s. And what I discovered is that one of the things they were talking about was an entity called the Putney Migraine Clinic. Now, I never heard of the Putney Migraine Clinic. I never heard that such a thing had existed. And I started to look into it, and there's an extraordinary story that is begging to be told about this clinic, because it was essentially set up in Putney, as the name suggests, by a philanthropist who was working in a health centre. And she got in a kind of Harley Street specialist to come and see patients with migraine, free of charge, and sort of try and treat them. Now, the Harley Street specialist was a sort of slightly, you know, slightly left of centre guy who had some very odd ideas about migraine and clearly thought that he had discovered the secret for migraine and was going to end up picking up his Nobel Prize in Stockholm, not Scotland. And nevertheless, of course, it never quite worked out by that. But so that's the other project that in the back of my mind, I think the history of the Putney Migraine Centre would make, you know, it would make an entertaining read and, you know, quite a good film as well. So maybe that will be my other project on the side for the next 12 months or so. Okay, we might bring you back to hear about. Last question, what three books would you recommend on migraine or about the brain generally for listeners? Well, for migraine, there is really only one book that has stood at the test of time, you know, as a sort of popular read, as opposed to kind of, you know, wolf's headache. And that's one of a saxes book on migraine. It's an extraordinary book. And actually, if you, if you, I mean, it's an extraordinary character, it was an extraordinary character. If you read his autobiography, the second bit of it in the book on the move, it describes the whole circumstances around the writing of that book, which are extraordinary and contain a lot of descriptions of the effects of survival. And the effects of presumably narcissism and vitamins, which he was experimenting with at the time. Out of this, he produces an extraordinary book, which has a wealth of clinical detail and observations. And whilst, sax doesn't really get the best press in the sort of, in the formal headache world, you know, a bit jealous of it, really. But it's a beautiful read. And again, it encompasses so much of the experience of people with migraine. And, you know, as I say in my own book, that really, you know, what I wanted to do is to try and produce something, you know, similar for the 21st century and, you know, the pretend to be a writer of his quality. But that's, you know, it's a beautiful book on migraine. I think the other, you know, I mean, if you're thinking more generally about neurology and brain issues, I think the dining bell and the butterfly, the French journalist's extraordinary account of his experience of locked in syndrome is something that I think all, well, I could get everybody should read it. But I think all neurologists should certainly read it, just to sort of get in just that smallest insight into what it is like to live within a sort of completely alien world that some of our patients inhabit. So that is, that's number two. And then I think the third set of books that I would recommend to anybody is, are those by, I think, somebody that you've, I think you've just interviewed for this podcast series, which is Andrew Leeds. I think his books are beautiful, brain spotting, you know, the eventually the madman and his kind of his little collection of neurological tweets that he's just published. I think they are extraordinary books and, and the neurological birds song, you know, as a historian, I kind of, I delve in and out of that book and I'm instantly reminded of the Hippocratic aphorisms. You know, I think they're the same sort of the same approach to the world and the same sort of timeless qualities to them. So I would, you know, I would definitely recommend sacks, the diving bell and the butterfly and anything by Andrew Leeds, as fantastic reads, and incredibly wonderful book that he's all I concur totally with number three. I do have a podcast on locked in coming in the future. So I'm sure the diving bell, the butterfly will feature there. Okay, I'm up whether I'll thank you very much for participating in this episode of the Neurology Lounge podcast. I'm most grateful. And for listeners or viewers of this podcast, if you found it interesting, you want to check Mark's book. And after that, then you can check my book surfing the brain. And for things more academic, have a website called the, and called neuro checklist. And to make sure you don't miss the next episode of the podcast, why not subscribe to the iTunes, YouTube or Spotify channels. Until then, thank you very much. And Mark, thank you very much for your time. I really appreciate it. And I've learned quite a lot today. But that's the pleasure of it. It's been fantastic to talk to you. Thank you. [Music] [BLANK_AUDIO]