Neurologist Morris Levin, MD, director of the UCSF Headache Center, reviews the diagnostic criteria for migraines and other headaches, followed by a breakdown of preventive and acute treatments. He explains long-standing and new options – including inhaled drugs and transdermal patches – and how to prescribe appropriately for individual patients.
on. Thanks again. So these are my disclosures? I do serve as a consultant for a few companies, but these air one time consulting, Um uh, engagements that are no longer active. I do get some royalties from things I've written, and I get some research grants. Um, What I thought I do, after thinking about the things that you probably most want to know about, is to talk about basically two big areas diagnosing migraine and ruling out other headache disorders and treating migraines both acutely. So a very bad headache, what to do in that situation and preventatively. So that's what we'll focus on A good place to start in terms of diagnosis is this classification systems called the International Classifications Headache Disorders. It was just revised in 2018, and it breaks down all headache types into primary headaches and secondary headaches. Primary headaches include migraine tension type, headache, cluster headaches and this mixed bag of headaches. That air called the other headaches. But we think of them as exertion, aligned other headaches that have some relation to each other but are in large part, very disparate, and then the other part of this classification involves secondary headaches. All of the things our patients are worried about when they come to see us with headaches, including vascular disease, intracranial masses, toxins, infections, um, causes of head pain from other organ systems. So, um, really, when you think about the diagnostic side, our job in that regard is to rule out secondary headaches. When when we see a patient who's got thes, whether they're new or old or sub acute headaches, our job is toe first. Rule out other causes, other secondary causes. Let's talk about the primary headaches first again, these breakdown into migraine tension type the cluster headaches and its relatives called the trigeminal autonomic self philologist and these other primary headache disorders. I'm gonna go through this pretty quickly because I wanna make sure this time for questions. So I'm sorry if I rushed through a lot of the slides. I'm not gonna read every word, but let's think about migraine. What makes migraine Migraine and I highlighted a couple of details here. First of all, they tend to be unilateral, although not always they tend to pulsate. They tend to throb, not always there pretty bad, pretty severe, and they're aggravated by physical activity. Um, in addition to that, there's very, very commonly nausea, and there is almost always a an aversion to bright lights. So photo phobia plus phone, a phobia aversion to loud noises. Also, asthma phobia, aversion to smells migraine with aura is, of course, fascinating. The auras can range from visual only to visual and sensory speech and language, even motor, so weakness can be an aura. There are a whole host of brain stem auras that I won't go into now, but they involve things like vertigo and the bilateral Paris thes, jys and altered consciousness and so on. And they're even auras that seemed to emanate from the retina very rare. I did my best to get pictures of what some of these orders might look like. Some patients, as you probably know, see these amazing light shows, including these jagged, colorful figures like have illustrated here. A lot of people talk about tunnel vision. They could only see the middle. They can't see the external parts of visual fields. It looks like a tunnel is the best picture I could come up with for vertigo. This is an old picture showing that there is a progression of aura that may start with a little bit of visual change and a little bit of sensory loss, maybe distantly. And then it begins to move up the arm and the visual change becomes more prominent. And like I said, they're even motor or us. The the famous Hemi politic. Migraines do occur. They're very rare, but they're very disturbing because they look like strokes, right? Chronic migraine, which I'm sure a lot of you have seen and had to deal with, refers to patients who have migraines on Mawr days than they don't have migraines. Very disturbing, very disabling. Um, what we say, what we like to say is that half of the days have to be headache days, the majority of which look like migraines. And why am I making that distinction? Turns out that when people get more and more frequent, migrants, migraine headaches don't exactly look like migraines should look. They can look more like tension headaches. They can look milder or they can be unusual. So all we really want to see is more days than not with headaches and the majority of those days looking like migraine. Um, tension type headache. What is tension type headache. Why is it different than migrant? How do we distinguish it? It's a difficult question to answer, of course, because there's certainly overlap, and you all know people who have tension type headaches may respond perfectly well to migraine treatment. But basically tension. Headache is everything. Migraine isn't its bilateral. It's not unilateral, not necessarily throbbing. People don't get so much nausea. People don't get so much photo phobia. This is this category called the trigeminal autonomic self philologist, and it includes cluster headache. And I'm sure many of you have seen cluster headaches, severe severe headaches that air generally around. And I you can see the picture of this man having severe pain around that I with tearing. There's often nasal congestion or nasal drainage, Andi. And it's mysterious Justus. Soon as it starts its over and about an hour, and the reason they're called cluster headaches is because they occur in these clusters of weeks to months, after which there no headaches for a while. But what you probably haven't seen are these variants that look a little bit like cluster. But the timing is different. Called paroxysmal Hemi crane, AEA short lasting, unilateral neurology form headaches and Hemi Crane E continuing all of these headaches that air related to cluster headache involved unilateral pain generally around the I generally brief. And interestingly, this is something we came up with a long time ago. The duration of the headache differentiates these headaches, and it correlates with the name length. You'll see what I mean in a second cluster headache. 15 minutes to three hours. Little shorter, longer name Paris. Islamic Rania. Less than a half hour Similar headaches, but lots more of them and their their brief, very, very brief versions are these s U N headaches. Short lasting unilateral neurology form headaches lasting up to a few minutes at the most, but usually just seconds. And then there is this variant that's much longer than cluster headaches. So I said I showed you cluster headache, which is about an hour, and these other ones that are a little shorter. Hemi Crane E continuous is basically incessant. You're probably wondering, and you have wondered, probably What's the difference when heavy Cranie continual meaning a pain and half of the head that is just persistent and migraine that are also tending to be on half of the head Well, these headaches just don't stop, and they respond to different treatments. And they, in fact, respond toe one treatment particularly well, which is in the medicine in a dose of about 25 to 75 mg three times a day. This fourth chapter in the classifications called other primary headache disorders, and there are a whole bunch of them, and I'm not gonna go through all of them. They include cough, headache and sex related headache and stabbing headaches. But I did want to show you a couple of them because they are either common or kind of interesting. So first of all, I want toe talk about this. Always get some interest whenever I talk about headaches, headaches associated with sexual activity, and these have been described for a long time in many different forms. But basically there's just one rial form of this headache, and that is an increasingly severe headache as intercourse goes on, often peaking around orgasm. These things can be very, very painful and long lasting up to a couple of days. And as you can imagine, they are really demoralizing. People don't know what to do about it. They're a little more frequent and people who have migraine. And interestingly, I won't be covering some of these headaches when we talk about treatment. So I'll tell you right now. Interestingly, they can be prevented if the person takes into methods and before intercourse. And these can occur, by the way. In Men and Women is called hip Nick Headache, also known as alarm clock headache. Which is why I put the picture of the alarm clock up their hip nick headaches Onley seem to occur in people over the age of 50. They Onley occur at night, and they wake people up almost every night when people get them almost every night at the same time of night. Very strange, disturbing headaches that people who have never had a headache in their life or very rarely have had a headache in their life now start having nightly headaches. The worst thing about them is they wake people up at night and people lose sleep. And Fascinatingly, there's one excellent treatment, and I wonder if some of you know it. It's a small dose of caffeine before going to sleep, which sounds a little paradoxical. I know because you want to not drink caffeine before asleep to get good sleep. Turns out it works like a charm for these people. New daily, Persistent Headache I'm sure you've seen some of these. These were people who may have had headaches at other times in their life. But one day they begin having this generally all over the head headache, although it can be just a part of the head, generally diffuse headaches. And from then on they have a headache. Every day they can look at a calendar and say that's when it started and from then on, daily headache. Very frustrating headaches to treat. We don't know what causes them, but we have some some theories. A lot of people have antecedent, infection, antecedent injury of some sort, and they're very frustrating. But we've made some progress. All right, let's talk about the secondary headaches, things that are patients they're worried about, like, you know, stroke masses, infections and so on. I'm not gonna go through all of these, but if you want to know more about these headaches, you can Google secondary headaches and you'll see good lists. You could go to the American Headaches Society and type and secondary headaches you can look at. I can, I can send you. Or you can go online to the International Headaches Society and look at this international classifications, headache disorders and read through it. It's not that it's not that onerous to read through it, but I'm gonna highlight a couple of secondary headaches that I think are of interest before we get there. I wanted to just sort of do a thought problem with you all, which I know you've covered before. And I know you've thought about before. When do you worry about these headaches? Are there Are there clues? Are there red flags? So here are my red flag list for headaches that probably should be looked into. So new or change in pattern of headaches later on. Set in life, effort induced or positional, meaning that they are much worse in certain positions. There's a fever or a systemic illness or hints that there is a systemic illness. There's been a change in personality or thinking neurological symptoms, neurological findings. And once you have these kinds of symptoms, e think it bears looking into with M r. I scan, maybe even LP. But fortunately, most headaches will ever see really in clinic our primary headaches and therefore benign. So what are the secondary headaches that we see a lot off post traumatic headaches? And we're seeing so many of these and soldiers who've returned from combat in athletes and we don't understand them that will they sometimes resemble migrant, and when they do, they seem to respond to migraine treatment. But they sometimes don't, and they sometimes respond to no treatment. I think of them as part of the post concussive syndrome. What you know is being divided into different, um, subtypes. But all of those subtypes of the post concussive syndrome include headache. It exploded. Vascular disorders. There are abundant causes of headaches in the vascular world. But what we're really worrying about right now is, uh, when we see a patient, for example, with an acute headache or sub acute headache is hemorrhage inflammation of arteries, arthritis, um, cerebral venous thrombosis, Um, or impending, um, rupture of aneurysm or actual rupture of aneurysm. This is one that you've all wrestled with. I think our most of you have wrestled with patients who develop more and more headaches as a result of taking too many acute headache medications. When I first learned about this, I was in my residency and I almost didn't believe it. You know, if it wasn't withdrawal and if it wasn't toxicity from the medication, how could that cause a recurring headache? You know, what was the mechanism? We still don't know many, many years later. We still don't know the mechanism, but the way it's defined and the way that it works in practice is that these air people who may have migraine, pre existing or other headaches, tension, headache and they end up taking more and more medications. And as they take more and more medications, they feel, you know they feel some relief. But once they cross a particular barrier, the taking of the acute meant seems to call it more and more headaches. And a rule of thumb that makes a lot of sense is if you could get patients to use fewer than acute medicines on fewer than two days, three days a week, so two days, a week or less of acute medication used, they probably won't get into this medication. Overuse, headache. Cervical genetic is becoming more and more interesting to me as I see more and more cases. What's hard about cervical genic headache is that, you know many, many people have neck problems. Many, many people have have chronic arthritic changes have had ruptured. Discs have had mild, fashionable injuries in the neck. Do they all get headaches? No. But a lot of people with upper cervical pathology will get headaches because of the way pain is referred from the upper neck. A lot of people with even mid cervical problems because of splitting of the neck and because of again the referral pattern of pain may get headaches. And it's important to rule those out because they must be treated by treating the cervical genic paying generator. You know, this is a picture that you've seen all ah, lot. I mean, lots of people have next. It looked like this a little bit of straightening a little bit of disk bulging. Is that enough to cause cervical genic headache? Maybe it is in a few people mostly know, most of the time you need something more profound. Patients with rheumatoid arthritis patient with cervical disks. But it's something toe look into. I like the Sperling test. I like putting a little bit of strain on the head and neck just to see if I can duplicate headache from doing things to the cervical spot. What I'd like to talk about now is, uh, treating migraines will focus on migraine. I have lots to tell you about cluster headache and other headaches, but we're gonna focus on migraine because it's just so common. I thought I'd do first is talk about acute treatment. So what? What do patients do when they have a very severe migraine? And they just wanted to stop. So we have three. Um uh, non specific areas by non specific. I mean, these things work for any pain. And that includes NSAIDs, Dopamine agonist. Excuse me? Antagonist. Like, uh, like composing Thorazine and opioids here. They all are. I've given you some samples. I'm not gonna linger on this slide. But you you all know these things. The problem is that I'll take non steroidals first. They have a lot of side effects, of course. And if people take enough to help their headaches, they're ending up taking a high dose and opioids. Of course, we know they're problematic. It's so easy. As we've all learned for patients to become habituated toe opioids. So we avoid those now the neuroleptics, anti medics, the neuroleptics like Finnegan composition Thorazine. They're very useful. But the problem with them is there also sedating, and they have some side effects. And really, I reserve them for er use. So in the ER, urgent care, they're they're very useful intravenously. We have to pre treat with Benadryl, of course, and the side effects of of dystonia and apathy, Asia or riel. And we have to be careful. Then there are the specific migraine acute meds and these involved trip towns er, gots and the new category called G Pants. We now have a lot of trip hands here. They all are. I don't really have a preference, a couple of trip hands or different than others. Let me point out those first of all, assume a trip hands symmetry Pence's Onley one available in injectable form, and it's really effective. It's one of the most effective agents for anything I've ever seen. However, it's a little bit of a hassle for patients, and there are a few side effects to injectable symmetry pretend that are not dangerous at all. But some patients don't like them. Robert tripped and is a pill, but a very, very long acting pill. It's about got a half life of about 26 hours. And so people who have these long lasting headaches are recurring headaches after they've taken something like sumatriptan and Orel. Provo tripped and is a really good choice, but the other ones are very good. Um, a lot of us use, Uh, right is a trip, Dan quite a lot l A trip then I think most of them are now generic, so they're affordable. Er, God's I'm not going to spend too much time on those of you who are older will remember things like half forgot or gotta mean tar trade. It's a very strong medication, works very well for migraine, but it's highly vase or constrictive. And so if there's any degree of peripheral or central arterial pithy, you can't use it, and I just don't use it much at all anymore, except with one exception. Intravenous dye, hydro or God, I mean we used in the hospital. I'll mention that later. Now this new category, the G pants have to family members who grow Japan, also known as a gravy and remain. Japan Nortek Very effective. They don't help everybody, but they seem to not have any vezo active properties. They are C G R P um, antagonistic. I'm going to skip through that slide. I just wanted to mention the trip hand side effects just so that you know, when patients tell you these things, it's quite common. Some tingling warmth flushing in the in the upper thorax chest neck. Um, sometimes they do get some chest pain with. We're almost certain that's just due to intercostal muscles and other muscles. They get jaw pain. Sometimes you'll know that this is a trip hand side effect. If it passes within 20 minutes. If it last then needs to be looked into, um, dizziness. Sometimes people get sleepiness. Sometimes people get they're supposed contra indications to trip tens, and they include Hemi Plea GIC migraine, meaning there is a motor aura, um, uncontrolled hypertension. Nobody uses M A O inhibitors anymore, so that's not much of an issue on day shouldn't be used with their gods and their pregnancy categories. See, however, there is so much information now about specifically sumatriptan in women who inadvertently took it when they were pregnant. with zero. Just literally zero congenital problems. Um, that is considered safe and pregnancy by most of us. So I wanted to, um, talk a little bit. I'm gonna skip through this slide. But I wanted toe talk a little bit about some of the newer things that you might be seeing in in ads and so on. They're they're actually re re treads of older things, but three are kind of interesting. One is this nasal spray. That's a powder called on Xetra. Very useful. Another one is inhaled. Die hydro or gotta me is gonna be a pretty useful met, I think. And, uh, this needle micro array gonna move my screen because it looks like I'm getting some light on you. I'm sorry about that. Okay? There's finally a new class of acute medication, and these are the serotonin. One event, uh, agonist less middleton being one of them. Uh, there will be more, and I won't say much more about it, but it's on the markets called revel. Let's talk about migraine prevention. You know, the typical list of preventive meds that have been used for years, including anticonvulsants, beta blockers, anti depressants, calcium channel blockers, Now we have angiotensin receptor blockers. They've been used as well. Um, ace inhibitors I haven't had as much luck with and I have had a little luck with the anti spasmodic. So we have a long list. I'm sure you've gone through a lot of these with a lot of your patients, But now we have a new, um, category of migrant prophylactics and those air the C g r p monoclonal antibodies. So I'm going thio first, just show you some typical doses of the traditional Orel prophylactic agents. So pyramid, 200 mg a day is about where most people get a lot of benefit propranolol in the 1 60 mg a day cycling antidepressant. My favorite happens to be nor tripling because it seems to be less fraught with side effects. Ravenal is not bad. It's not the most useful in can dishearten can help some patients. The c g r P story started a few years ago when it became clear that C g R p calcitonin gene related peptide, uh, was elevated in people with migraine during migrant attacks and also believe it or not between migrant attacks. So I won't I'll spare you all the details, but it became a target. C G R P became a target of therapy, and the initial CTRP antagonists turned out to be a little hip pad of toxic. These were small molecule antagonist, and so monoclonal antibodies were developed. Let's get through this, and there are four of them and you've heard the names aim a big age. Oh, vm Galati. And this new one, Epstein is a mob. The first three rent a mob. Galligan is a mob and feminism mob are available in subcutaneous injectables. Patients inject themselves. I'm gonna show you some pictures in a minute of each one of them. The newest is Epstein is a mob, which is an intravenous preparation. The response to these has been really good, not universal. Some patients do not respond, but many, many migraine patients respond beautifully, and they respond quickly and in and in a sustained way. So here's a move big. It's an auto injector. The doses of 7140. It's a monthly injection. There's latex in the needle cover. Eso We were a little concerned, but we haven't seen one single reaction even in patients who were latex sensitive. Um, when we prescribed the 70 mg. Some patients don't see a benefit, and we might go up to the 1 40. It's in every 28 day injection, so once a month, very easy for patients to use. And again, the side effects are just almost non existent. Once in a while, people get constipation, and that's a serious issue for them. And, uh, we deal with it by either stopping it and using a different one or, um uh using, uh, meds to counter act constipation. This is a job, e. It's and it's also an auto injector. The auto injector just came out, I said, Not an auto injector, but it just came out. Mm Galati! And finally, the Upton is a mob showing a patient getting an intravenous infusion. We were wondering at first about the CTRP antagonists. What the downside to blocking C G R P might be, and C g R P, if you know, is found in many, many different organ systems, particularly gastrointestinal tract and blood vessels. So we have been wondering if there is a downside and we have seen virtually no problems. However, if patients have significant G I illness, particularly if there's reduced motility. If patients have really risk real solid risk for cardio or cerebrovascular disease, generally that they've had an M I or had a stroke if they have inflammatory disease, recent surgery, obviously pregnancy and it hasn't been shown to be safe. And Children these none of these monoclonal antibodies, then we hold off generally. Are there other choices of prophylaxis and migraine? Yeah, there are. And you know, when patients are frustrated by side effects toe oral agents, we will offer some of these non medicinal, non pharmacological options. Sorry, I wanted to just spend a moment addressing something that you all see, which is chronic migraine. So again, this is thes air people who have a migraine on more days than they don't. The pyramid is useful. Botox can be very useful. The gripe monocle antibodies can be very useful. Nerve blocks have been helpful for a lot of patients, and we have ah program here at UCSF called the Headache Inpatient Headache Unit, where we use inpatient infusion therapies that I'll tell you more about is ah, diagram showing where we inject Botox for chronic migraine. The nerve blocks we generally use include occipital regular temporal and super orbital. We do these for various um, conditions. What about medication? Overuse? Headache way touched on it a little bit. It's very difficult, um, not the least reason of which is that when you tell patients there headaches or due to taking too many medications, you know what they hear. They hear us saying, the one thing that has helped you now you can't take it anymore. So very frustrating for patients. But what usually happens is after a little bit of education and stopping that medication using a bridge therapy and there a number of bridge therapies that I'll show you in this next slide. Steroids can help for a week or so, using benzodiazepines for maybe a week, quantity and sometimes sometimes longer acting barbiturates when the short acting barbiturate is the offending medicine, Um, caffeine, when we've withdrawn them from an agent like etcetera or fior. A set that has caffeine in it sometimes are infusions, including E G and sometimes and sets. I know that many of you have referred patients to the UCSF Headache Center, and, uh, we have a checklist because we're so inundated that we've tried to figure out how toe reduce the the overflow. And so here it is. I wanted to just go through this with you, and I'm happy to answer questions about that later, too. We need our patients toe, have a PCP that's not usually a problem. We need to have a modicum of records patients that we do best with our patients who have had longstanding headaches not on daily opioids or barbiturates and not in the midst of, ah, neurological work up. So let's talk about in patients. We do have an inpatient program that I'll be happy to tell you more about if we have time. Um, and it's designed for patients who failed outpatient therapy are in the midst of medication overuse. Um, they generally do not do well in our program if they're, uh, in the midst of an addictive issue. Although someday we hope toe have dual diagnosis, resource is, and we need for patients to be medically neurologically and psychiatrically stable. Um, the choices that we have include Die hydro gotta mean similar action to the trip hands. This is our dhe protocol. We have patients admitted on a Monday. We start in ivy and we administer it three times a day for four days and leave on the last day. The fifth day on board. There are some adverse effects is which is why we have to do it in the hospital. But we control those, and we had really good results. Most patients who go through this, uh, seemed to improve dramatically to the point where our numbers look like about 75% success rate. Do control nausea. There's a list, the other two meds. We use our chlorpromazine and develop pro X, both intravenous, some of the pitfalls we encounter in the inpatient program or that they do have some side effects, but we handle it all. It's right now. I I don't know how many of you have had patients that we've admitted. It's at the ST Mary's Hospital again. These are the three men's we use, and I wanted to break their to take questions about migraine treatment