S3:Ep2 – Individualizing Migraine Treatment with Functional Medicine

Topic Recap:

1. Neurology Anatomy 1:10-3:15
2. Brain State Theory 3:15-7:20
3. Comparing Normal Neurons to Migraine Neurons 7:20 – 11:40
4. Identifying impacted areas and receptor based therapies to use 11:40-22:30
5. Examination and treatment process 22:30-25:20

TRANSCRIPT

Voice-over: Welcome to Spotlight on Migraine, hosted by the Association of Migraine Disorders. Join us for fresh perspectives by medical experts and advocates as we explore the spectrum of migraine and dig deeper into this complex disease. This episode is brought to you by our generous sponsor, Lundbeck.

Dr. Adam Harcourt of Imagine X Functional Neurology explains the migraine brain and discusses the importance of personalized assessments for identifying neuronal dysfunctions to help choose appropriate non-medicinal treatments.

Lundbeck is a global pharmaceutical company that is committed to improving the lives of people living with brain diseases. Lundbeck is pleased to offer a treatment option for migraine prevention. To learn more, visit LundbeckUS.com.

Adam Harcourt: Hi, I’m Dr. Harcourt. Thank you so much for being here with me today, even if it is virtually, for the Association of Migraine Disorders Migraine Symposium. I was really looking forward to this in person, but this will be second best. The good news is you get to enjoy this from the comfort of your own home.

So today, I’m going to be talking to you about the receptor-based applications for the treatment of migraine, which is a different paradigm as to how we look at migraine, treating migraine, different therapies that may or may not work. And we’re going to kind of explore why that is, what things could be helpful, and then, more importantly, when they could be helpful, right?

So, again, before I get started, I just want to thank everybody at the Association of Migraine Disorders. This is a big honor. There’s a lot of great speakers today. You guys are in luck. There’s some wonderful, wonderful researchers you get to enjoy, so I hope you enjoy them as much as I have been so far.

So we’re going to get started with some very basic neurology relating to how migraine works. I promise it’s only two slides, and then we’ll move on, all right? So the first thing we need to get a handle on is what an ion channel is and how it relates to migraine. So again, before you glaze over and get bored early on with the science-y stuff, this is actually extremely important to how we use what we call receptor-based applications when it comes to migraine. All right?

So think of a neuron, right, like a person, right? It has all these different parts to it that make up the entire neuron. And part of what keeps the neuron healthy, the inside healthy, is these ion channels. And the ion channels essentially let things in that need to get in and let things out that need to get out. So ions can be things like magnesium or sodium or calcium, which are all very, very important for the neurons or the nerves in your cells to fire properly, to communicate properly.

The interesting thing relating to migraine is that most studies observe a lowered threshold for neuron activity in migraineurs, suggesting that they have this — what we call an altered state of neuronal excitability. Now what does that really mean to you? What that means is normally, it takes a certain amount of input or stimulation in order for a neuron to fire or to communicate. In migraine patients, what happens is that threshold for activation is lowered, and when that’s lowered, it makes the neuron get tired quicker, right? It doesn’t work as well.

So think of it like this. If you were to have a part of the brain that inhibits head and face pain and that area just can’t keep itself healthy, can’t keep itself from failing very well, well, that thing’s going to fail, and now you’re not going to have the ability to inhibit head and face pain, which is where you get classic migraine. Now, we’ll talk in a little bit about how this relates to other types of migraine disorders, but the basic premise is you have this altered state of excitability; things happen when they’re not supposed to happen. That’s the basic idea of what’s going on with the ion channels.

And what this leads to is what’s known as the brain state theory. So the brain state theory states that the brain is altered in migraine to an effect where it’s actually different from most people that don’t have migraine. So if you look on the slide here, it says that while migraine is undoubtedly a consequence of many different things, it’s now being thought by some, including myself, as a purely neuronal disorder.

And there’s a lot of conflict — and there has been for years — about whether it’s vascular or whether it’s neurological or whether it’s a combination. And what we’re really learning is that when it comes to the cause of migraine, it’s neurological. It’s neuronal. When it comes to the effects, to the things that make it worse, to things that affect it, yeah, there’s vascular disfunction, there’s brain disfunction, there’s all sorts of different stuff that contribute. But, ultimately, it is a disorder of the brain, all right? It is a disorder of these ion channels.

And the other reason I think this is very important is if you look at the research on genetics, you’ll find that there’s 50 or 60 different genes that are associated with migraine, but they haven’t been able to nail it down. And, really, the reason for this is all of those different genes are associated with an ion channel that doesn’t work so well, which leads to neuronal hyperexcitability. So it’s not that migraine is just this one gene that goes wrong and then you have a migraine. The reality is there’s tons of different things that can cause migraine, as far as the genes go, and at this point, we don’t know which migraine patient has which genes, which ones are on, which ones are off, which ones are aberrant.

And my personal opinion is as we learn more about this, you’ll understand why people respond better to certain therapies, why some people progress and become chronic patients versus acute or what we call episodic migraine. So, again, this is exciting stuff as far as getting closer to eliminating the symptoms, but as far as understanding migraine, getting the fact that there’s some type of ion dysfunction that leads to neuronal hyperexcitability is what ultimately causes migraine, all right? That’s the key feature there, and that’s kind of what we’re going to be hitting on today.

So another interesting thing, I think, if you’ve had migraine, if you’ve lived with somebody with migraine, is you’ll find that the brains of migraine patients are different than those that don’t have migraine, even when they’re not having an attack. So your sensitivity to light may be heightened, or your sensitivity to sound, the misophonia, may be something that is unfortunately higher even when you’re not having a migraine attack.

So what we want to talk about is the fact that this brain state changes the cellular function, and one of the most frustrating things that I hear with patients is they say, “Well, I’ve had every scan. I’ve had every MRI, CT, all this stuff, and it’s perfectly normal. And so if it’s perfectly normal, what do I do? Nothing’s wrong.” And the idea of migraine is that it’s a functional disorder, all right, just like post-concussion syndrome many times. You’ll do the scans, you’ll do everything, and it looks clean. That doesn’t mean you’re OK; it just means there’s not a brain bleed or a hematoma. With migraine, many times people are looking for the tumor or the obstruction or the stroke that caused this, and that’s not what’s going on.

What’s happening is this brain state. And think of it like this. If you look at the graphic, most people think about neurons as either alive or dead, right? You either had a stroke and they’re dead, or you haven’t had a stroke and your brain’s perfectly healthy. With migraine, what happens is the neuron isn’t dead; it’s just not as healthy as it should be.

And so when you’re doing imaging, it looks like the neurons are there. They’re there, they’re functioning, they’re healthy-ish, and there’s nothing really to see. So imaging and all these diagnostic tests that are out there don’t really account for what’s going on with migraine because the neuron’s still there, it’s still alive, it’s just not as efficient as it should be, all right? So it’s what I call a weaker or a less functional neuron.

So another way to look at this is to go back to that neuron cell and look at these ion channels. So if you look at a normal brain cell, let’s imagine that inside of that cell is negative 75 millivolts, right, because inside the neuron’s always negative. Well, that happens because all of these channels — you can see all the channels there letting those little ions in and out — are allowing it to stay at a negative 75 millivolt.

Well, now imagine if you have a gene alteration of any of those ion channels, as we have in migraine. Now that same neuron may be able to modulate the inside of the cell decently, but it doesn’t have all the tools that it needs. It doesn’t have all the ion channels properly firing, so now that healthy, robust, strong neuron, it’s getting by, right? But if it’s over stimulated, it fails, and now it can’t do its job.

And the thing that I think is really interesting about understanding this whole model is that it explains why a classic migraine and a vestibular migraine and an ocular migraine and a hemiplegic migraine can all really be addressed the same way, because the underlying condition is the same. It’s just a different part of the brain that’s being affected.

So if you have classic migraine, it may be the middle part of the brain, right, that inhibits head — or, middle part of the brain stem that inhibits head and face pain. But if you have vestibular migraine, it may be a little bit further down on the brain stem that’s being affected. Same problem with the ions, same ionic disruption, different part of the brain. Same thing with hemiplegic migraine and any other iteration.

And this is why things like diet, for example, I’ve seen work tremendously with hemiplegic migraine patients. It doesn’t cure them a hundred percent, but I’ve seen tremendous improvements just from that aspect, all right? But how does that make sense if it looks like you’re having stroke? Well, if you go back to how these neurons are modulated and how stress affects them and then they fail when they get too stressed out, that’s how this all makes sense.

So quick question — what do you think the main component is that maintains that negative charge in the neuron? And I know we’ve talked about ions, but the main thing that actually does it is proteins, protein production. Proteins are very negative, and so as the cell’s producing them, that’s what maintains most of the charge. So this is originally where I had kind of my ideas of where we came up with this treatment protocols for migraine, where we went from the receptor-based application, was the idea that in order to produce proteins, you need activation of neurons. In order to activate neurons, they have to be stimulated from a normal outside source.

So for example, if you want to stimulate the vestibular nuclei in the brain stem, you have to do some type of vestibular activity. If you want to stimulate the facial areas, you have to stimulate the facial neurons, those types of things. And what we find is if you stimulate these neurons, you’re able to produce more proteins, and if you produce more proteins, then you can reduce that resting membrane potential or that negativity in the neuron and make up for the genetic predisposition of migraine patients to have this hyperexcitability.

So what does all this mean? Think of it like a weak neuron working out, right? It’s doing bicep curls, or it’s doing pushups. And so it’s just genetically not as strong as its neighbors, for example, but if you exercise it at the right amount, you can produce more proteins, make it stronger and stronger, so now your predisposition or your chances of migraine go down and down and down, which is great news, right?

Now, the problem is the same things that can stimulate and activate these neurons are also the same things that can make them hyperexcitable. So, for example, light therapy can be really, really great for migraine. But if you get too much light therapy and you’re not very stable yet, it’s going to trigger a migraine, and then you actually avoid an activation or a therapy that could be good for you. And this is where migraine treatment can get very frustrating, especially when you get into the chronic stages. So again, I think the understanding of this is the most important thing because then any application you do is to correct this imbalance, to correct this hyperexcitability. All right?

So how to do we active the brain? And we’re going to go through this pretty quickly because the main idea is understanding the hyperexcitability. There’s a million different things that we can do for it, OK? The other thing I want to make clear is — as far as, well, what part of the brain is impacted, where do I activate? Well, the research so far has shown all of these areas to be implicated in migraine.

So we have these few nuclei in the brain stem — the pons, the medulla, and the midbrain, so that’s the lower, middle, and upper part of the brain stem. We also have the hypothalamus, the thalamus, many different areas in the cortex, including the frontal, temporal, and parietal nuclei.

So what is this to say? Not that you need to memorize all this stuff or know what all this means, but anywhere from the bottom part of the brain stem all the way up into the entire brain, there have been implications that that’s what’s affected and helping to cause migraine.

So the point here is there is no one activation or one therapy that knocks out migraines so that you don’t have to worry about anymore. So the idea is how do we identify what area to treat, because otherwise we’re just kind of shooting in the dark, right?

And so what we started doing over these past number of years is starting first with a comprehensive exam, all right? And, remember, we’re looking at this functionally. So, for example, if you were to do a test we call a Romberg’s, where you put your feet together, you close your eyes. If you fall all the way over, that’s what we call a positive test. If you don’t fall over, it’s considered normal, right?

But I’ve done thousands of these at this point, and you can see that not everybody sways the same direction, right? Some person might be perfectly still. The next person might sway really, really far to the right over and over again. The next person might go in an ellipse pattern, OK? So why doesn’t everybody sway the same way, right? If it was a normal test, they should all do the same thing. And what you’re finding is that there’s a big gray area between abnormal, which is falling over, and normal, which is being pretty solid.

And so what you do is you take all of the tests that you could possibly do, and based on the aberrancies or the area of the brain that’s dysfunctional, you’ll start to see patterns in the way that eye movements are dysfunctional or balance or posture or gait patterns. And so when we do this test, we’re looking at all these different signs, and you’ll start to get an idea of what part of the brain could contribute or could be responsible for all of these different things that I’m seeing on this examination.

So, for example, I started taking blood pressure on the both sides of every migraine patient for years, and what we started to see is there’s these really subtle differences from side to side in migraine patients. We call it dysautonomia. And classic dysautonomia is something like POTS, where you stand up and you almost pass out. Well, that’s not what’s happening in all migraine patients — it happens in some — but what you’ll see is smaller differences in these patients. So you start taking that from side to side, then you look at how their balance is or how their eyes move in different directions, and you can start to narrow down, it’s more that upper brain stem or the lower brain stem or more that right frontal area.

And, again, it’s not that there’s a tumor there or there is a stroke there; it’s that those areas are functionally not as strong, or weaker, because of this lack of ionic control because of the genetic predisposition that happen with migraine.

And so whether it’s in the midbrain or the medulla or the cortex, it doesn’t matter, because all of those things take different input. So if I see somebody that has right-sided mid–brain stem dysfunction, that’s going be treated very differently than an right-sided lower brain stem or a right-sided cortical dysfunction. And so once you identify what part of the brain is impacted, then you can figure out what types of therapies to use and be a little bit more specific, all right?

The good news is there’s tons of these things that are already being researched. So if you look at receptor-based applications, you’ll notice that many of them will show efficacy. They’ll say, “Hey, 30 percent of people showed improvement,” or, “50 percent of people got half better.”

That’s great. But it’s never much more than 40 or 50 percent, right? It’s always this lower amount because all of the different modalities, they implicate or they activate different parts of the brain. And when they’re applied to a whole bunch of people, well, if half of them had dysfunction in the area that, say, vagal nerve stimulation activates, well, they’re going to do really well. But if this other half, they didn’t have dysfunction in those areas and it’s getting stimulated, well, it doesn’t really help them at all, right? So it’s not a bad therapy; it’s just not really being applied appropriately for that person.

So this is where I always go back to every migraine patient must be treated extremely individualistically, all right? So you got to treat every migraine patient as if they’re the only migraine patient, OK?

So there’s tons of different types of neuromodulation, and it can be anything from electrical stimulation to tactile stimulation, like massage or acupuncture. There’s even a new thing we’ve been using called insufflation, where you help move the eardrum with air. It looks pretty wild, but I’ll tell you, it works so well in many, many patients. And this can even be classic manual therapy like chiropractic or physiotherapy, and now they’re looking at things like magnetic stimulation, direct-current stimulation, laser therapy, all sorts of cool stuff. But again, all of this can be helpful, but until you do an exam and see what areas are affected, you don’t really know the best way to apply these therapies.

So, for example, this is where I first kind of got an eye-opening experience, where you hear acupuncture works great, or chiropractic works great, or massage is awesome, or exercise or whatever. And there was this paper that said, “Well, for massage, average relief was about 45 percent.” So, OK, that’s pretty good. Let’s use massage. Well, for acupressure, it was about 44 and a half percent. Well, that’s pretty close to massage. OK, well, what about chiropractic? Well, chiropractic was about 45 percent effective. OK, well, what about physiotherapy, osteopathy? Well, they all have these very similar percentages of being effective. And the first three are a little bit more direct, manual, hands-on. Some physiotherapy, you may not maybe exercise, right? You don’t know what they’re doing.

And the point is all of these are effective, all right, because for the percentage that is was helping, those people had these areas of the brain that were dysfunctional, so these things can be beneficial. The point is there is no one specific therapy that’s perfect for it. It has to be dependent on the patient and their area of dysfunction.

So let’s take an example. There’s been some new research out there, new devices that are doing stimulation to the vagal nerve. Well, what you can see is the vagal nerve is right here. The NTS is really the input. There’s another one below it that’s kind of the output. And so you would think, OK, the vagal nerve, it shoots into that lower brain stem, so I would just want to use vagal nerve for the lower brain stem if I find dysfunction there.

Well, you can see by this chart here that not only does the vagal stim go right into that lower brain stem where the nucleus is; well, that nucleus also projects to the upper brain stem, to the thalamus, to the forebrain, the basal ganglia, all these different areas of the brain. And so not only will it help people that have this lower–brain stem dysfunction; it also helps people that have dysfunction in these other areas.

So, again, it’s not that one therapy does treatment to one area of the brain and that’s what you have to do. The nervous system communicates very robustly, and the idea is what is the most efficient way that we can get to that area of the brain, provide stimulation — but not too much — that stimulates those nerves and reduces the probability that you’ll have migraine?

So insufflation was another one. We think that it affects multiple areas of the brain. So you’ve got the fifth cranial nerve, which is in the mid–brain stem. You got the other nine and ten cranial nerves in the lower brain stem. So, many areas that you can impact just from insufflation.

Trigeminal nerve stimulation stimulates the nerves up here. Well, obviously, they go to that direct input into that pons, which is that midbrain, but they also go up into those frontal cortices and the anterior cingulate. The reason that’s important is those areas help with pain control, all right? And the orbital frontal cortex helps with pain modulation.

So, again, these are all different modalities that stimulate specific areas and then also kind of kiss other parts of the brain to a lesser degree. So, again, this is part of the art of figuring out not only what stimulation is good but also what amount of stimulation and how much and how long to do these things.

Another cool one that I’m really excited about is laser therapy. This is a really small but cool study they did in, I believe, Brazil, where they were finding that specific points with laser — they did exactly the same as Botox for that amount of time. But once they stopped, the Botox still did pretty good, maintained that reduction in pain days — that’s what we’re looking at here. But the laser continued to see a reduction in pain days even after they started, which, again, without getting into the mechanics of how laser works, makes a lot of sense, right? It helps to stabilize neurons by stimulating the mitochondria, gives it more ATP production, which again can help to lower that resting membrane potential. So really, really cool stuff.

And then even modalities you never really think about, like vestibular rehabilitation, where traditionally you think about just kind of spinning around. Well, not only does it have to do with motion; you can also use treatments where you put hot water or hot air or cold air into the ear, which stimulates the vestibular system. You can use eye movements in many different iterations. We actually find that there are a number of eye movements that work really, really well to help with migraine, and that’s something that we’ve been exploring for about six or seven years now that we’ve been playing with this, and we just see phenomenal reductions just from getting the eyes to move appropriately.

And, again, think about this from a activation standpoint. If those neurons are being stressed out because they’re working super, super hard, the chances of migraine go up. So I’ve seen a number of patients that when they just follow a target, they can’t follow the target without their eyes skipping all over the place or they jump ahead or they lag behind. And so imagine if you’re just going about your day looking at things, your brain’s working extra hard just to focus on a target or to follow a car or to do very simple, seemingly innocuous activities. And once you correct that, the stress on the system goes down so much, you see a reduction in migraine days.

Most of what I talked about today is therapies, receptor-based things, but that’s not the whole picture, right? So I just want to put this all in context here because when I work with migraine patients, what I like to start with is an exam, if we can, because we see people coming in from all over. And so if they’re local, we try to do the exam first. If not, we try to work on other things that are challenging the patient, so diet, exercise, hormones, things like that.

So in an ideal world, we do an exam; then we figure out what areas of the brain are the targets for that application. Once we identify those targets, the next thing you want to do is identify other sources of stress, so whether it’s dietary considerations, hormonal issues. Whatever it is, you want to identify those and reduce the things that are contributing to migraine.

Once you’ve done that, you want to evaluate the types of receptor-based treatments you’ve used. So say you’re seeing a chiropractor, and they’re doing something on your neck or your back. Well, if that’s helping you out, great. It’s probably an appropriate application. But I see a lot of patients that have gone, and maybe it didn’t help, or they’ve gone and actually made them worse.

Well, I actually like the patients that made them worse, because what that tells me is it’s activating a part of the brain or a system in the brain that’s just not ready for that much stimulation, but it’s impacting their migraine. So we may start with a similar activity at a much lower amount or much slower approach until we can build them up to handling that type of stimulation. So, again, the idea is evaluate, and then you want to make changes as needed.

So as you see that treatment’s going on and you’re doing well or not well, you want to reassess and say, “OK, is something good happening?” Then you’re probably doing something right. Is something bad happening, which means you might be doing something right but too much of that thing, right? And that’s also OK. And if you’re just not seeing much of a change, we may be barking up the wrong tree, all right? So the idea is you want to continually kind of reevaluate this idea but always go back to what areas are we targeting, how can I better stabilize them, and what other things are contributing — other stressors are contributing to the probability that I’m having migraine?

And that is the way that we look at it at our locations. This is what I teach other doctors. This is why I wrote a book about this, because this is such an important concept that if you prescribe medicine or do surgeries or do physiotherapy or whatever, all of those things can absolutely be helpful, but how is it servicing this underlying problem, which is the migraine? So that’s always what we want to go back to.

So I really hope you enjoy this. I know we’re doing a Q and A after this, so I’m really looking forward to your questions. And, again, I’m bummed that we don’t get to meet everybody in person, because this is a great discussion that I hope continues to be ongoing. So thank you so much for your time today. I hope you enjoyed it. And I look forward to your questions soon.

This podcast is sponsored in part by Lundbeck.

*The contents of this podcast are intended for general informational purposes only and do not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The speaker does not recommend or endorse any specific course of treatment, products, procedures, opinions, or other information that may be mentioned. Reliance on any information provided by this content is solely at your own risk.