This Podcast Will Kill You - Ep 112 Epilepsy: It’s always the phlegm

Episode Date: February 7, 2023

Only our second episode of the season and we’re already getting in over (and inside) our heads with one of the biggest topics we’ve taken on yet: epilepsy. In this episode, we navigate the constantly changing definitions of epilepsy, make our way through the many different types of seizures, and dig into the inner workings of the brain as we attempt to understand the pathophysiology of this disease. And that’s just the biology section! The history of epilepsy proves to be just as intense, as shown by the multitude of meanings this disease has held over thousands of years. The past merges with the present - and maybe the future - when we delve into some of the technologies that have helped us to gain a clearer picture of this disease and may lead to improvements in prevention, detection, and management of seizures in years to come. See omnystudio.com/listener for privacy information.

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The greatest to ever play the game. Return to finish what they started. Welcome to Survivor 50. I wanted one more shot to play the game that I fell in love with 25 years ago. I want to win against the best of the best. I chickened out at the final tribal. Season 50, it's an honor. Light your torch.

I've got some unfinished business. Be part of history. I have more to play for this time. Bigger than ever. Survivor 50. New milestone season begins CBS tonight at 87 Central. My name is Louise. I live in Johannesburg, South Africa.

I'm originally from Cape Town. In roughly early 2004, I started having what seemed like I would blank out, basically. So I could be doing anything. I might be in the middle of a sentence and I would just kind of stop. So it would seem like I was conscious. My eyes would be open, but I would essentially be unconscious. I did not know what this was. At first, it didn't particularly seem to bother me, but it started happening more and more.

sometimes it was accompanied by what I would now describe as an aura. So sort of a strange sensation almost physically inside my brain. It felt like having an electric shock inside my brain. For a while, we didn't do much about this. I was about 16 at the time. And my mother was of the opinion that this was happening because I was not managing my stress levels. sufficiently. I am not entirely sure what that was supposed to mean. And she was not entirely wrong. Stress was a factor, but this was not actually me not managing it properly. So at the

end of that year, she took me to a psychiatrist to try and see what we could do about this, because, you know, she said to me, if this carried on happening, I would not be allowed to get a learner's license. So anyway, my mother takes me to a psychiatrist and I have a session and he says to her, take it to a neurologist. She has epilepsy. I get sent for an EEG. Afterwards, we go back into the doctor's rooms. He has a look at the EEG and he says, oh yes, this is textbook epilepsy. You had an eight-second seizure while you were during the EEG. I have to say, my poor mother, that was the first time I ever seen anyone's jaw literally drop. She was so shocked. I was just really relieved to know that it's not in fact my fault. So what the doctor explained to me was that I had absence epilepsy,

it used to be called pitymol. I did not know that there was any kind of epilepsy other than the kind where you fell on the floor and shake and that was what was epilepsy in my mind. So I was surprised to discover there was something else. So I was put on medication. The brand name here is epilum or epilazine is the generic. It's sodium velvet. The doctor told me I should be careful because this can increase my appetite and cause me to gain weight. Now I'm a 60, almost 17-year-old girl, so this caused me a great deal of anxiety. And I remember telling my mother, okay, well, you know, help me look out for, you know, am I eating more? Another side effect is developing acne.

I've been quite a lucky teenager. I never had serious breakouts. I had the occasional pimple. And suddenly I was developing pretty serious acne. And again, I'm 17. Suddenly I have acne. I'm gaining weight. It really did a number on my confidence.

In my early 20s, my seizures had been completely controlled since I had initially started on the medication. So 2010, I was 22, and my doctor agreed with me that we could try and lower the dose. And if that goes well, we can stop the medication and see what happens. So I started having brain zaps again occasionally. And I kind of ignored them because I thought, nope, nope, I'm fine, don't want to read the medication. And then one day, it was after class in the afternoon. I was sitting in the computer lab with some of my classmates.

We were busy working on assignments. And the next thing I know, I opened my eyes and I am flat on my back on the floor. And there are several very concerned faces sort of crowding above me. So what had happened was that I had been in front of my computer and I had all of a sudden had a grand mal seizure. What used to be called grandma these days are called tonic clonic seizures. And this is the classic one where you fall on the floor and your body stiffens and then you shake. I later asked some of my classmates sort of what did it look like.

And apparently I had been foaming at the mouth because I bit in my tongue, there was blood in the saliva, which cannot have been easy for them to see, I think. I am very lucky that I did not lose blood or bowel control because that is something that can happen during a tonic chronic seizure. And obviously, you know, it's not something that you can help. It's just a medical thing, but I would have been just so embarrassed. I was incredibly confused after the seizure. I was also completely fatigued. I could barely move my body.

I couldn't walk. So I go back to my previous dose. medication. The year after that, 2011 is when I moved to Jobburg. Things seem to be going fine. I, of course, had to switch to a different doctor. This is also the first time that I find out that you're not supposed to get pregnant while you are on Valpert because it has a potential to be teratogenic, which, you know, none of my previous doctors had told me this. I am a young woman of reproductive age. I'm someone who can get pregnant and no one bothered to tell me this. So I was quite upset. Fast forward to 2016, November, I am freelancing at an ad agency. I'm doing proof

reading for them. I'm sitting in front of the computer and suddenly I opened my eyes and I'm lying flat on my back on the floor and there are several really anxious faces crowded over me. and I've just had another grand mal seizure. Again, I'm very confused. I can barely move my limbs. These are people I don't know. I've only been there for a week. And on my first day, I accidentally got locked in the toilets,

so I'm already known for that. But no, I'm not longer ago who got stuck in the toilets and the girl who had a seizure in the office. So that's fine. So not long after that, I go and see my neurologist. This is the first time in several months that he's had a good look at me, and he says, okay, you have lost a very large amount of weight.

Your body is metabolizing your medication too quickly. That is why you had a seizure. On top of all the stress and so on. So I think actually we doubled my medication. Things have gotten better since then. That was the last seizure of any kind that I've had, my stress level. improved, my acne improved. So things are generally better. Now, I have pressed pause on any kind of reproductive decisions for now. I'm turning 35 now, so I still have a little bit of time,

if I want to think about it. The epilepsy has been under control for several years now, so for the most part, it's not giving me grief. But that was quite an unpleasant experience that realization about just things that I hadn't been told. Maybe it's because I was a teenage goal, and my doctor didn't think that it was particularly necessary to tell me about certain side effects, apart from getting weight, because obviously that's the only thing that could worry me.

For me, my epilepsy experience has been quite a mixed bag. I am technically quite lucky that mine is easily controlled with medication, I can lead a normal life, but it's also been a giant pan of my eyes, and I would prefer not to have it. I don't have any sort of feelings about, oh, it's made me a stronger person or anything like that, and it has also given me some insight into aspects of the medical profession that are disappointing. That's where things stand at this moment. I am hoping for maybe, I don't know, magical, miracle gene therapy or something that will remove this. But we will see where things go.

Thank you so much, Louise, for sharing your story with us. Yeah, thank you so, so much for sharing that. Hi, I'm Erin Welsh. And I'm Aaron Allman Updike. And this is, this podcast will kill you. And today, it's a very big talk. topic we're talking about epilepsy. It's the biggest topic that we've covered in a very long time. Do we say that every single episode? Yes. Is it true this time? Yes. It is absolutely true.

Yeah. Yeah, this is going to be a long but chock full of information and questions episode. I can already tell. And Aaron, you and I talked about this. It was an interesting and difficult balance to strike, between too much detail and not enough detail. Yeah, it was. It was a difficult episode to kind of piece together for me. And I know you said the same. So we'll just see how we did. Yeah.

But first, we all know what time it is. Is it quarantini time? It's quarantini time. What are we drinking this week? We're drinking the Clonic Tonic. We are. This is one of my favorite names. And we were inspired by,

listener who sent in a very similar suggestion. So thank you, Robin. Yeah. And the Clonic Tonic is a very simple drink. It is simply Campari and tonic water and a slice of orange. And I love this because I think it's actually surprisingly adaptable to a non-alcoholic cocktail because there are bitter non-alcoholic liqueurs or whatever, for lack of a better word, that seemed to really take the place of Kampari, and one of them that I've tried that's delicious is Gia. But anyway, there are options out there. So it's a simple recipe, but we will post it for both the quarantini, as well as the placebo rita on our website, this podcast will kill you.com, as well as on all of our social media channels. On our website, since we're still at the beginning of the

and let us tell you about what you can find there. It's fantastic. It's this podcast will kill you.com. We've got sources from every one of our episodes. We've got transcripts of those episodes as well. We've got links to our merch, which is fantastic. We've got a Goodreads list. We've got a link to our bookshop.org affiliate account. We've got Plodmobile, our music. We've got, there's probably more. Our Patreon, it's there. Check it out. It's all there. I'm wearing one of the very cool new crew neck sweatshirts that you can find on our merch page, and it's the best. You should get one for yourself, everyone. I was actually wearing one of our new sweatshirts recently when I went out to get a milkshake. And somebody was like, I love your sweatshirt. I love that podcast. And I got so embarrassed that I just was like, thanks. Cool. And then I started talking to my dog again. That's amazing. Oh, my gosh. I love that.

It's a great sweatshirt. All right. Well, shall we get into the actual topic of this episode? I think we should right after this break. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients so there's no meal planning and no extra grocery trip. There, assemble and bake meals take about five minutes of hands-on prep.

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Get 50% off your first two orders plus free shipping with code this podcast. Podcast 50. Terms and conditions apply. Visit blue apron.com slash terms for more information. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands

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wide-leg jeans, and they are now in constant rotation. They are so comfortable. The fit is amazing, and they come in a bunch of different washes, so I'm about to go order some more. Refresh your wardrobe with Quince. Go to quince.com slash this podcast to get free shipping on your order and 365-day returns, now available in Canada, too. That's Q-U-I-N-C-E-com slash this podcast to get free shipping and 365-day returns. Quince.com slash this podcast. We said it at the top, and I do feel like we say almost every episode these days what a huge topic we're dealing with. And it's usually true, although we probably also usually exaggerate. For sure.

But when it comes to the topic of epilepsy, this really is something that could probably be split into quite honestly a whole season of episodes, depending on how deep you wanted to get in all of the various types of seizures and types of episodes. and the specific pathophysiology, not to mention history, and epidemiology, and so on and so forth. It really is an absurdly large topic to try and cover in under two hours, hopefully. Overly ambitious of us. So we are not going to cover every detail today, which means that we might not cover any one particular form of epilepsy or type of seizure that, some listeners might be hoping for in the amount of detail that you might want. But the good news is we'll have plenty of resources for you who want to dive deeper. And what I'm hoping that we can all get out of this biology section, at least,

is an appreciation of, first of all, what the heck is a seizure anyway? Yeah. What are some of the various types of seizures? Because spoilers, it's not just what you've seen on TV. How do these seizures differ? and what's going on in our brains during this process? And then what is epilepsy in the context of seizures? Yeah.

So that's where we're going to try to get to. I want to know the answers to all of those questions. I'll do my best. So I'll start out with just some definitions. And for these, I will quote, because I love to have a quote a definition. Epilepsy, the definition, from the international League Against Epilepsy is defined as, quote, a chronic disease of the brain, characterized by an enduring predisposition to generate seizures, unprovoked by any immediate

central nervous system insult. Asterisk, Aaron's words, that part's really important, and we'll get into it. Back to the quote. And by the neurobiological, cognitive, psychological and social consequences of seizure recurrence. So let's kind of just reiterate in maybe more easy language. Epilepsy is recurrent seizures that happen chronically without a clear provoking cause, at least not acutely, like not a single identifiable cause of seizures, and all of the consequences that result from those recurrence of seizures. So clearly, to understand what the heck that means, like what the heck epilepsy is in that context, we have to first understand seizures and realize that not all seizures are indicative of or lead to the disease known as epilepsy. So while all people living with epilepsy experience seizures in one form or another, not all people with seizures or who have had seizures have epilepsy by definition.

Right. So what is a seizure then? And again, the International League Against Epilepsy has a definition for us, and I quote, a seizure is a transient occurrence of signs and or symptoms due to abnormal, excessive, or synchronous neuronal activity in the brain. Episode over, that was so clear, right? I have so many questions already. I do too, Erin. And while that definition might have been helpful for some people, I actually really struggle with that definition. So I'm going to try and really break this down in the way that my brain makes sense of it, which is on a very basic level. We all know, and I've talked about on this podcast before, in other episodes where we've dealt with things like meningitis or other kind of brain-related injuries, that our brain communication. via both electrical and chemical signals. So in general, what happens in our brain is that chemical

signals are converted into actual electrical impulses. And that is what is transmitting information to allow us to do literally everything, like blink, breathe, talk, wave, type, etc. And these electrical signals and the chemical signals as well have to be very tightly regulated, both in their circuits of where they go, and how they go and the timing for us to be able to do all of the things. So what happens in a seizure is that we see a burst of these electrical impulses, an abnormal amount and or abnormal networks or pathways of activity. That is what we are seeing in a seizure, and that is what is picked up on an EEG, when they're hooking up all those electrodes to look at the electrical activity in your brain,

and they say this looks like a seizure. And this abnormal activity, it can start from just one part of the brain, which results in what we call a focal seizure or what used to be called partial seizures. Or sometimes we can see this burst of electrical impulses from both sides, both hemispheres of our brain at the same time.

And that results in what we call a generalized seizure. And because our brain is, suffice it to say, very complicated. It's a complex structure with a lot of different layers between which these electrical impulses have to travel. So these abnormal bursts of activity can happen in any given part of our brain, which means that those signs or symptoms that we might see or associate with the seizure can actually vary incredibly widely depending on where in the brain they're occurring. I have a question about the word abnormal. Oh, yeah.

What is normal? And then how far outside of normal is abnormal? What does the range look like? You know what I mean? Yeah. That is a really, really good question. And I'm going to just say I don't have an answer for it because I don't know enough about EEG readings. And I know that there are sometimes things that can be called by something.

Some people, this looks like what we would call an epileptiform or a seizure-like change in an EEG that maybe by other people would be interpreted as not quite that. So it's a really good question. And I don't think that there, in some cases, is a cut-and-try answer. But what we see on these electrical readings is basically just impulses that often associate with specific seizure-like activity that we'll talk. about in a minute that also correlate with what we're seeing on an EEG that is different than a person's baseline brain activity. Okay, two questions. One, when you're comparing to baseline, is that that person's baseline or like population baseline? And then number two is who is doing the reading? Is it a person or is it a computer or is it both? Like how, who deterred?

what is an epileptiform pattern? Excellent questions. For the first one, I don't fully know. There are, I think, enough EEGs done in the world and being studied for many decades that we have a sense of what typical brain patterns look like across various people. You would still also compare one person's EEG at their baseline when they're not having seizures versus when they are having seizures. So I think it's a little bit of both. Okay. And it is not me. It's a neurologist who is reading the EEGs. Okay, but it is a human.

It's a human. A lot of times there's, you know, just like with an EKG when we're looking at your heart, there's usually a computer readout component. But then an actual human is always going to be the one looking at it and determining a human with a lot of training, a lot. Okay. Okay, fascinating. Cool. But it is also true that because of that, there is a certain amount of subjectivity, right? Right, right, right. Okay, so what then might some of these different types of seizures look like? I think most people listening likely associate seizures with one very specific type of seizure. And that seizure type is called a generalized tonic clonic seizure. These used to be called grand mal seizures, so that terminology might be familiar to some people. These are the kind that you see on TV, where somebody might collapse and is unconscious. and then they have a rhythmic jerking of especially the large muscles of their body.

They'll be kind of rigid and then have muscle convulsions. They might bite their tongue during this process. They might have loss of bladder or bowel function because of autonomic nervous system involvement. And then usually when they wake up, they have a period of confusion where they're not quite sure what's going on and this might take some time to resolve. That is one type of seizure, but it is just one, and there are so many more than that. And that makes sense, since now we know, that any part of the brain can be affected. So let's get into how we can classify seizures. We define seizures first from their point of origin.

So like I said before, seizures can be focal, which means they start from one part, one hemisphere and one little part of the brain. Don't ask me how little, Aaron, just like one area of the brain. Okay. Or they can be generalized, meaning that they're starting at onset from both hemispheres of the brain. And a lot of times we actually don't know. We don't know necessarily what that pinpoint origin is. And so then these seizures are classified as unknown origin. And then we can further classify them by what signs and symptoms we see after that. Then, to further break this down, there are also motor and non-motor seizures. So motor seizures have like physical skeletal muscle involvement. So moving of usually the extremities or something in some way. This can look like spasms.

It can be like a hyperkinetic or a myoclonic like stiffening and tightening of muscles. It could be a tightening and relaxing very rapidly, which is what results in that tonic-clonic description. That's what tonic-clonic means. It's alternating between tensing and relaxing of muscles with this like jerking motion. It could also be much smaller twitches of muscles just say of the hand or the face. Or it could also be a sudden weakness. So rather than a tension of muscles, it could be a sudden flacidity of.

muscles. And that's all just within motor seizures. It could also have none of that and be a non-motor seizure, which could have a huge variety of symptoms. It could have cognitive symptoms like just a blank stare where people just suddenly like have no emotion on their face. It is a blank stare and is unresponsive. It could be sensory symptoms that might even be something that people are feeling or are aware of sudden sensory changes. Or it could be a complete loss of activity all of a sudden, which is called behavioral arrest, where someone just suddenly stops exactly what they're doing. And a whole bunch of other things, even within that. And when we especially talk about focal seizures, this is not true for generalized seizures, but then the third step that we have to look at is whether awareness

is intact or impaired. So because a focal seizure happens in only one part of the brain, someone may or may not know and be aware that they're having a seizure at the time that they're having it. And so we say that their awareness is either impaired or intact. With generalized seizures, awareness is not intact because it's happening in both hemispheres of your brain at the same time. But a lot of times people do have like prodromes or what we call oras prior to a seizure, so they might know that one is coming. And before you ask, because I know you're going to have a million questions. I do. You can already see one on my face. Yep, I can. All of these different seizure types are not mutually exclusive. Different types of epilepsy or even a single seizure episode can have multiple of these forms within them. So for example, something could start as a focal seizure, but could then generalize and become bilateral and then end with something that looks like a generalized tonic-clonic seizure. Or people could have different foci of seizures throughout their brain that result in throughout their lifetime having seizures of multiple

types or multiple forms. And my last important note before I let you ask questions that I hope I can answer, is that one of the things that's very important to know about seizures is that these are brief episodes. These are brief episodes of this intense neuronal activity. And when I say brief, I mean on the order of seconds to one to two minutes. Because any seizure lasting more than five minutes, or if you have multiple seizures happening within a short time frame where someone does not return to full consciousness in between, that results in something known as status epilepticus and is a major medical emergency. We thought, I think, for a long time in the kind of history of epilepsy, that it was 20 or 30 minutes before this became an emergency. But it's not. If seizures are happening,

for five minutes straight, that's a medical emergency because there's so much brain activity that can result in long-lasting damage. This is rare. Status Epilepticus is rare. It most often happens with generalized tonic clonic seizures. So that seizure that's happening on both sides resulting in that convulsive whole-body seizure. But it's also possible to have non-convulsive status epilepticus. And that's, I think, really important where EEGs can be.

be so integral in like figuring out what's going on because you might be having more seizures than you even have very obvious signs or symptoms of. Right. That makes sense. Okay. I know you have a million questions. Yeah. Okay. I want to I want to start pretty general. Okay. We have all of these different seizure classification types. There can be overlap. There can be multiple descriptors for a certain type of seizure. That is important information. What does that information help you decide to do? Does it have an impact on treatment, on prognosis, on, yeah, like what sort of information do you get from that beyond just what type of seizure it is? Excellent question. It has implications for kind of so many different things. So for example, especially when it comes to focal seizures, if we can identify that

a seizure is coming from one specific focus, then there are potentially treatment options that might be very targeted. Let's say that a seizure is emanating from a particular area of the brain where there is a tumor. That's something that we're going to be more easily able, potentially, to target and to treat directly. It also does affect what medications might be used, and I don't have a lot of details on that because there are so many different anti-epileptic medications and anti-seizure medications, but there are different ones that have maybe been shown to be more beneficial in certain types of seizures than other

types of seizures. So it's important to note and be able to kind of identify what type of seizure to be able to pick the best medication. And then when you have, say, focal seizures, whether there's an impairment of awareness or not, that also is going to be important for not only just a person's general life, but also determining if it's safe for them to be doing activities like driving, et cetera. Okay. Okay. That makes sense. Yeah. So there's kind of a lot of layers of why it's important, not just medications, but also additional treatments that might be available and just kind of determining what somebody's prognosis might be and things like that as well. Okay. My other question is about something that you mentioned, and that is the damage that

can result from status epilepticus. But I also wanted to know, first of all, how does that damage occur? And does that damage happen in people who, for instance, have epilepsy, not status epileptychus, but repeated seizures throughout their life? Yeah, absolutely. Excellent question. So the short answer is yes, there are changes in the brain that are going to happen with epilepsy and with recurrent seizures. And one of the things that I always try and touch on it in all of our episodes is the pathophysiology of whatever recovering. And so that usually means trying to get into some of that nitty-gritty detail, like what is happening in our brain during this process. When it comes to epilepsy, it's really difficult to get super into the nitty-gritty details, not just because I'm not a neurologist, but also because the under-and-a-neurgy-a-narrows. but also because the underlying brain changes that can lead to epilepsy to these recurrence of seizures are manyfold.

There's a lot of different potential changes in the brain that can result in epilepsy. So then it makes the specific details of what's causing seizures also really varied. And so it's hard to kind of generalize it. But I'm going to try. So the leading hypothesis is that when it comes to epilepsy, when it comes to recurrent unprovoked seizures, what happens is that you end up with an imbalance of excitatory and inhibitory currents at its most basic form. And we've talked on this podcast before about how in our brain we have neurotransmitters and electrical signals that are promoting action like bend your arm. and we have pathways in our brain that are inhibiting action, like unbend your arm, right, or stop bending. And there's a lot of different neurotransmitters and ions and receptors that are involved in all of this complex signaling

and converting these excitatory and inhibitory signals into that electricity, right? So epilepsy arises when those signals are malfunctioning, but that can happen through any of those particular pathways, through changes in ion channels, through changes in the concentration of neurotransmitters, from changes in receptors in our brain. And there's some hypothesis that part of the recurrence of seizures in epilepsy is due to inflammation that happens during this seizure process. And it might be that inflammation as well plays a really big role in the kind of perpetuation of epilepsy and seizures.

I don't know if that fully answers your question. But the truth is that it's because seizures can occur from so many different possible sources, it can also result in so many different changes in the brain, both changes in things like our ion channels or the concentration of neuron transmitters. It can result in changes of the structural cells, the glial cells, within our brain. It can also result in changes in the actual connectivity of our neural networks themselves when you have seizures and when you have recurrent seizures. So any and all of the above are possible. Does having one seizure make you more likely to have a second seizure?

That's a good question. I don't think that we can 100% say yes. or 100% say no. There are a lot of ways that you can have a seizure that you may never have a seizure again. For example, febrile seizures, which happen in kids, usually young kids, most commonly like 12 to 18 months, but usually anywhere from six months to five years, can have a seizure in the context of an acute illness where they have a fever that's not from a central nervous system infection, because that would be something else entirely. And these most often resolve spontaneously. We don't usually see any permanent or residual damage.

And while there may be some association between kids who have febrile seizures and who later do get diagnosed with epilepsy, that doesn't mean that most kids who have febrile seizures are going to develop epilepsy by any means. Okay. Same thing if you think of someone who's a child or an adult who ends up having a seizure because of metabolic derangements like severe hypoglycemia in the context of something like diabetes. Oh, okay. That can result in seizures, but this would be a reflex or a provoked seizure due to that clear factor, hypoglycemia, causing that seizure. And no matter how many times you might have a hypoglycemic seizure, that doesn't necessarily mean that you have.

have epilepsy. That was my other question, which was unprovoked. What is provoked versus unprovoked? Okay, got it. Exactly. Yeah, the same is true for something like alcohol withdrawal, which is a very common cause of seizures. So if your seizures are only and exclusively in the context of alcohol withdrawal, that doesn't necessarily mean you have epilepsy. Right. And so when you're talking about unprovoked. You're not talking about triggers for epilepsy seizures, like flashing lights or, which I know is not very, yeah. Okay. Yeah, actually, that's a really good, important point. Yes, I'm not talking about that, which can trigger someone who has epilepsy. And one thing I think is really important that I saw in a paper that I never thought of that way is that epileptic seizure. So people who

have epilepsy, their seizures are not random. Like, seizures are not entirely random. We might not know by any means what any provoking factor is for any given particular seizure that someone has, but something is going on in a person's brain that ends up leading to a seizure in a person who has epilepsy. Okay. So they're not entirely random. Gotcha. Yeah. That's honestly most of what I have for the kind of biology of seizures and of epilepsy. Okay, so then I do have more questions. Great. I was going to talk about treatment, but I want to know if you have any more questions first. So you went through a bunch of different types of seizures.

Epilepsy also comes in many different forms. What are some of those forms? Yeah. So, and I will say that the terminology surrounding epilepsy, much like the terminus, surrounding seizures themselves has changed a lot in recent years. I'm going to talk about the most current terminology that we have. So in general, today, epilepsy is classified as either genetic, meaning predominantly arising from an identifiable genetic cause, be that a single mutation or multiples, or structural or metabolic, which means it's caused initially at least by something like, say, stroke or a trauma, like a traumatic brain injury, or a tumor in the case of structural, or even a malformation of the brain itself, which might be congenital, or various metabolic

syndromes that might lead to seizures, which can also be genetic, so it gets a little confusing, or instigated by something like a meningitis or an encephalitis that later leads to recurrent seizures. And then if we can't pinpoint any of those, then an epilepsy would be classified as unknown. And a really big proportion of epilepsy, and I don't have an exact number on this, is actually unknown origin. So we don't always know what the instigating factor was. Okay. And then what about different types of epilepsy? Yeah, I know. I mean, this one is hard, I think, because I think it was more common in the past to separate out very specific forms of epilepsy. And now I think we have started lumping a lot more of them together based on those classifications that I mentioned.

Like, what type of seizures do you have with your epilepsy? Okay. So I know when I was in med school, I had to memorize. a whole bunch of different seizure types and a whole bunch of different types of epilepsy. And it seems like the trend now is more to focus on what seizure types does a person with epilepsy experience and classify it based on that. So as an example of that, a lot of people might have heard of temporal lobe epilepsy. Temporal lobe epilepsy means seizures that are arising from the temporal lobe, which is one lobe of our brain. We have one temporal lobe on each side. So now it would be more common to

classify that as a person who has epilepsy whose seizure type is a focal onset, impaired awareness seizure originating from the temporal lobe with motor symptoms of various forms. Okay. Does that make sense? So it's like more cumbersome, but a lot more specific. Right. I mean, and it makes sense in terms of, treatment too, I would imagine. And then within that, you'll still be able to classify the type of epilepsy based on whether it's genetic or whether it was from a structural change or a metabolic disorder, et cetera. Right. Important also that genetic does not mean hereditary necessarily. Yes, absolutely. Speaking of treatment. Yeah. Let's. What treatments are there? How do they work?

Great question. There are. a whole host of anti-epileptic or anti-seizure medications. And the good news that I have is that most data that I saw suggests that up to 70 or some places, say 80% of people living with epilepsy will achieve remission. And often this happens with the first drug tried, the first anti-seizure medication that somebody tries, regardless of what one they end up trying. There are too many different antiseure medications for me to list. Some of them act, for example, on sodium channels, and so they're modulating some of those chemical signals.

Some of them might act on certain neuroreceptors or other neurotransmitters like GABA or glutamate. So I'm not going to get into the nitty-gritty of how each of these different medications work, but you can imagine that if we can pinpoint any specifics about a single, seizure, we might be able to pick one antiseasure medication over another, right? And 70% remission sounds pretty good, but it also means that right now 30% of people do not or will not necessarily achieve remission. What proportion of that is lack of access versus not finding the right drug? That's a good question. That's not counting lack of access. That's people who are tried on antiseasure medication, yeah, which is really important because we'll get.

into lack of access later. Yeah. This is where it becomes really important to be able to identify as much as we can about seizures, because for some people who can't achieve remission with medication so far, there may be surgical options depending on the focality of their epilepsy. So surgery might mean resection or destruction of an area of epileptic focus, or it might be nerve stimulation, usually peripheral nerve stimulation, rather. than deep brain stimulation.

Various forms of this have been shown in some cases to lead to a reduction in seizure burden, maybe not complete remission. Another treatment that a lot of people have probably heard of because it's all over everything is a dietary control known as the ketogenic diet. The ketogenic diet is very interesting and probably could be its whole own episode. In general, the quality of evidence that we have, is not all that great, but likely because of small sample sizes. But it has been shown for treatment-resistant childhood epilepsy to improve the chances of

seizure reduction or remission. There's a lot less evidence for less restrictive diets, like there's a modified Atkins. There's a low glycemic index version. But for someone who is living with very frequent seizures, even a small reduction. and seizure burden might be a pretty big deal and pretty life-changing. But the data that we have is just not all that strong. And a true ketogenic diet, like is used in these studies, to look at epilepsy, is incredibly difficult to achieve. It is very, very restrictive. So it's not the keto diet that's on the news. Just throwing that out there. I also am really, I just am personally

very interested in like the potential mechanisms of the ketogenic diet. So I do have to, have a couple papers if people want to read more about it. Spoilers, we don't know. But there's a lot of different hypotheses with various levels of potential theoretical and actual support on how this change in forcing our brain to use ketones rather than glucose might shift basically metabolism or mitochondrial function to then change the way that electrical impulses are generated. It's pretty cool, but it's all kind of theoretical at this point. Yeah, yeah. Okay, interesting. It's interesting. There's more if you want to read about it. But that essentially is what I have, at least, about epilepsy and seizures. I have two questions. Okay. My first question is how many recurrent seizures does it take to be diagnosed as epilepsy?

Oh, great question. Two. Oh, really? Okay. Two or more, I can give you like a full, even more formal definitions. Two or more unprovoked seizures greater than 24 hours apart, so not within the same day. Or, and this part's very interesting and has really huge implications for the treatment of people with epilepsy going forward. It can also be a single unprovoked seizure. in a person who has a greater than 60% risk of having another seizure over the next 10 years. And the way that they determine that is by looking at an EEG to see if the findings on there look like there are changes in the brain already that have the potential to result in seizures. Or any epileptiform activity that you can see on an EEG even if you're not having seizures at the time. And so those two things with a 60% probability would then, even with a single seizure, mean that you have epilepsy. Okay. And then the third thing would be also if you have an epilepsy syndrome.

So like a genetic or other disorder that is known to be associated with epilepsy. Gotcha. Yeah. My second question is, you know, you talked about how epilepsy a lot of the time we don't know what causes someone's epilepsy. Yeah. A lot of the time also epilepsy can just stop. Yeah. Why?

How? When does that happen under what circumstances? How often? Yeah. If I had those answers, Aaron. It is more common, I believe, with childhood epilepsies that they may resolve over time. Why? I don't know. And beyond that, it's just a really good and interesting question. Some people, and maybe it could also be related to if there is an instigating factor, let's say a menendritis infection or a traumatic brain injury, something that changes the brain enough that you have this chance of recurrent seizures or you've had two seizures greater than 24 hours apart. So you meet this definition for epilepsy.

epilepsy, but over time, maybe your brain remodels itself enough to then no longer have this epileptiform activity. Then you can, yes, resolve your epilepsy. That's fascinating. Yeah, and that's also part of the change and the definition of epilepsy that happened relatively recently is that it can be a disease that is also resolved. Okay, okay, a temporary chronic disease. Yeah, yeah.

Well, and also a something that is classified as a disease, and, not a disorder. And that was a very intentional change when they kind of updated these definitions, which I think is very interesting. So, Erin, that was a lot. It was. And also probably not enough. Yep. So tell me, where did all of this come from? How did we get here? Have we always had epilepsy? What? I will. Start the deep, deep dive into the history section right after this break. Anyone who works long hours knows the routine. Wash, sanitize, repeat.

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Lift to 32 32 32 32. Quote, a history of epilepsy seems a premature, perhaps even a doubtful enterprise. There is no unanimity about the range of the concept of epilepsy and the nature of the disease is as yet obscure. end quote. Wow. So the end, huh? The end. Yeah. I borrowed this quote from a book called The Falling Sickness by Osset Temkin, considered to be the authority on the history of epilepsy in the Western world. These words mark the very beginning of the first edition of this book, published back in 1945. And when 26 years later, the author revised and published a second edition, they stayed right at the beginning. And I think they were even in the fourth edition published in the mid-90s. Oh, no. Yeah, because when that fourth edition came out in 1994, they remained just as true as they were in

1945. Wow. And now in 2023, I feel like there's still an accurate description of the mystery that surrounds epilepsy. So that's why I thought it was the perfect way to start the history section. Great. Even though we've come a tremendously long way in our understanding and treatment of epilepsy since those words were first written, as the biology section just demonstrated, there are still so very many unanswered questions. But having unanswered questions isn't a bad thing necessarily. look at the nature of those questions and how specific they are. That alone, I think, shows incredible progress in our knowledge of epilepsy. And that progress, along with the historical social perceptions of epilepsy, is what I want to talk about today, particularly in the Western

world, since that's where most of the sources that I found concentrated on. When did humans first recognize epilepsy? How did the meaning of this condition shift over time, what did people think caused epilepsy, and how did they treat it? This is a massive topic, like we keep saying. And I'm going to try my best, but there are parts that I simply won't get to or won't go into in great depth. And like we keep saying, the good news is that we will give you plenty of material to read on if you are still curious. Always. Always. Other challenge, or maybe not necessarily challenge, but something that I want to note is that the

definition of epilepsy has changed substantially throughout history. And even at any one given point in time, you would probably get a dozen different answers if you ask a dozen different people what epilepsy was. In ancient times and into the Middle Ages and the Renaissance, epilepsy, seizure, attack, convulsion, many different words or terms were all used interchangeably. So while today we think of epilepsy as a chronic condition, in the past it could have meant that or it could have meant an isolated seizure. So keep that in mind. I usually try in these history sections to talk a bit about the evolutionary origins of whatever topic we're covering. But I decided not to attempt that for epilepsy for several reasons. There is still so much unknown about its pathophysiology. You can't even

really say it's pathophysiology, since there are so many different types of seizures, each with different histories and causes and triggers. And so I felt that a discussion of each of those evolutionary histories would probably have been more confusing than enlightening. I will go so far as to say that it's likely that humans have experienced epilepsy for as long as we've been human, and probably long before that. And instead, I'll start with the very first observations of epilepsy, which come from the ancient world. Some researchers have speculated that trepination, which is a practice that's been performed for thousands of years where you make a small hole in the skull and remove the bone, that was done to treat epilepsy and that ancient trepaned skulls

indicate their knowledge of the disease. But this remains controversial, and it's something that we're never going to know for sure, why people use trepination in ancient times. The earliest written description of epilepsy comes from Mesopotamia around 2,500 BCE in an ancient Sumerian text describing, quote, a person whose neck turns left, whose hands and feet are tense and eyes wide open, froth flowing from the mouth and consciousness being lost. Which pretty well describes a focal unaware tonic seizure. This condition was called antisubu and was thought to be related to the hand of sin, the god of the moon.

And already we have our first theme in the history of epilepsy, a theme that kind of, I think, overshadows most any other theme that I would call attention to. the belief that the condition had links to the supernatural, to religion, to magic of some sort, that it was more than a physical condition. As we'll see, this gave epilepsy a whole host of different meanings, some positive, like, oh, you are prophetic or you're a chosen genius, and some most negative, like it being a sign that you're possessed by an evil demon or spirit. I feel like that is the one that I think of the most when you think of like historical associations with epilepsy or seizures.

Yep, for sure. And we'll get into all of it. But a big part of this theme is that these beliefs about the supernatural cause of epilepsy were in continuous conflict for much of history with scientists or physicians who believed that there was a physical, biological explanation. for what was happening. Sometimes superstition, dominated popular thought, and other times, science. This dichotomy is an oversimplification. It's much more nuanced than how I'm presenting it, but I wanted to point it out because it shapes the prevailing perception and treatment of epilepsy over the next several thousand years, give or take. For instance, in one of the Hippocratic texts written around 400 BCE, it is said that the seat,

of the disease is in the brain, it's a hereditary condition, and that an excess of phlegm in the blood is what leads to seizures. It's always the phlegm. It's always the phlegm. And that's part of the humoral theory of disease. In this text called on the sacred disease, the author also argues against the labeling of epilepsy as a divine disease, quote, I am about to discuss the disease called sacred. It is not, in my opinion, and more divine or sacred than any other diseases, but has a natural cause, and its supposed divine origin is due to men's inexperience and to their wonder at its peculiar character. But if it is to be considered divine, just because it is wonderful, there would be not one sacred

disease, but many. Which is kind of amazing, considering that was like thousands of years ago. Yeah. And so much happened in between then and now. Yeah. And this isn't to say that the science behind what these ancient Greek physicians believed caused epilepsy was sound by today's standards. You know, for instance, it was caused by the weather, hot wind, dry wind, whatever. But it was a clear and important distinction to them, to many physicians at that time. And I think that's really interesting.

Yeah. However, that was certainly not the case as we move on to ancient Rome and then especially the Middle Ages. In ancient Rome, the scientific lens through which many Hippocratic-era physicians viewed epilepsy shifted to one that was a bit more supernatural, or at least one where a supernatural explanation was more willingly considered. An epileptic seizure could be a bad omen, and it was often thought to be brought on by an unwelcome God or demon.

A person who had epilepsy was considered unclean and their condition contagious by touch or by sharing food or drink. While occasionally it was viewed as a blessing or a sign of prophecy, by and large it was a negative stigmatizing disease. The meaning that epilepsy held or the importance with which people viewed it can be seen in part by looking at the names that it has had over time. Let's start with the word epilepsy, which has roots in the Greek verb epilambanian. I'm probably completely destroyed that, but that word means to seize or to attack. So epilepsy seems to have been used in these ancient texts simply to mean seizure, a single medical event without any connotations of supernatural or magic elements. The chronic condition was often referred to in ancient Greece and ruse.

Rome as the sacred disease or the great disease, which eventually turned into the Latin Morbis Meyer and then into the French Grand Mal, which is also a term that we used to use for a certain type of seizure. In the Middle Ages, the name most commonly used to describe the condition was something involving falling. The falling sickness, the falling evil. Catechus, meaning falling, something that falls. And I will also note that the falling sickness was what the disease was called in the first descriptions in ancient Chinese medical texts dating back to 770 BCE. But also in the Middle Ages, the disease began to be associated with more loaded words,

such as demonicus and lunaticus, referring to the belief that epilepsy was a type of madness or that it was a sign of possession. Speaking of lunaticus, I don't know if I'm saying that right, probably not, which is where the word lunatic comes from, it originates from the Latin Luna, meaning moon, since it was believed that the moon could cause bouts of insanity or epilepsy. During this time period, people with epilepsy were often described as being seized by, quote, the disease of the moon. Why the moon? Well, perhaps it was the vengeance of the goddess of the moon, or you could go with a scientific explanation that, quote, the waxing moon heated the atmosphere surrounding the earth and consequently melted the brain, thus provoking an attack. So, but I mean, like, this is something that kept occurring to me is that we look back at that now and we laugh, but that was science. The goddess was the superstition part.

Right. The science part was the moon melting your brain. Yeah. There are many different ways to distinguish between superstition and science or wishful thinking or magical thinking and science. And some was done at the time of the writings. And some is done from our perspective today. Right. So we could look at that and go, oh, well, both of those are definitely superstitious beliefs.

How could you ever think that the moon would melt your brain? But back then, that was science. I don't know, something I kept thinking about. Epilepsy was also thought to be from demonic possession or caused by the devil, and its reputation as an evil disease gets a mention even in Dante's Inferno. Many people with epilepsy were forbidden to go to church, or if they were allowed, they could not take the Eucharist or touch anything in the church, because, again, people thought it was contagious.

Epilepsy was linked to witchcraft, and in the handbook on witch hunting, Malia Smellifakarum, written by two Dominican friars and published in 1494, it was said that seizures were characteristic of witches and also that witches could cause epilepsy to develop. Yeah, a lot of feelings there. Mm-hmm.

But again, I will say that there was no, overall consensus on epilepsy as an evil disease at any point in time. There were also mentions of it as a saintly disease. St. Valentine is the patron saint of epilepsy and one that marked you as chosen in a good way or a genius. Continuing into the Renaissance, epilepsy was still a disease fraught with meaning, and it was still the doctor or the priest or society that got to choose what that meaning was. Priests were sometimes called in to determine whether someone was possessed or simply had epilepsy, and people with epilepsy were believed to have the power of prophecy, but that their prophecies should be taken with a grain of salt. I suspect it was something

along the lines of we should believe them if it's a favorable prophecy, and we should shun them otherwise. I'm so curious if there was any correlation between like different seizure types and whether someone was considered to be demonic versus saintly or possessed versus, you know, a fortune teller. Like it's, it's so interesting to try and we can't know, I guess, but we can't know. And as I'll talk about, people did recognize many different seizure types. Yeah. But I'm I think it was so difficult to spread this information, but also to look back now and go, oh, that was this type of seizure. Right, right, right.

Oh, they were seeing this. Was what they were writing about even a seizure? Right. You know, like, I don't know. Yeah. Ugh. Yeah. But it is around this time during the Renaissance that scientific thought and the medical writings

of ancient physicians like Hippocrates and Avicenna began to. to experience a resurgence as people became more and more skeptical of supernatural or magical explanations. And this led to epilepsy being viewed and researched with more of a medical lens rather than solely with a moral one, which isn't to say that epilepsy became a neutral disease, not at all. As one author put it, superstitions were exchanged, not discarded. But before I continue on to that, I want to go back and ask not what epilepsy meant to people from ancient times to the Renaissance, but what people actually knew about what epilepsy was. As I'm sure you'll talk more about, Erin, epilepsy in its many forms is incredibly prevalent. And this likely isn't a new phenomenon

given the extent to which epilepsy was written about historically. Even some of the oldest descriptions of epilepsy that we have, talk about different forms of the condition, variations in seizure appearance and duration, and they do a pretty good job of recognizing patterns in its epidemiology. For instance, although descriptions of seizures vary, the common features among them include fall to the ground, unconsciousness, insensibility to pain, and no recollection of the attack upon regaining consciousness. They observed that epilepsy, most often occurred early in life, especially during teething, and that it was uncommon for it to first show up after 20 years of age. Some writers suggested it was hereditary, while others said it was congenital.

One of the more popular and persistent superstitions from the Renaissance was that if a pregnant person saw someone having a seizure, that baby would develop epilepsy. Oh, my gosh. Eventually, yeah. Okay. Yeah. Not what happens. No. Writers early on recognized that a seizure was often preceded by what they called and what we still call an aura, meaning breeze, which got its name when a young boy described a sensation like a cold breeze entering his head right before he had a seizure.

A range of pre-seizure signs or symptoms was recognized, slow speech, headache, dizziness, stiff hands ringing in the ears, just to name a few. And beginning in the Middle Ages, major divisions in epilepsy began to be made, often associated with where it was thought to originate in the body. Which I think is interesting knowing that that's how we characterize a lot of seizures types as well as like where it originates in the brain. In the brain, yeah. Yeah. This was in the body. So for instance, there was epilepsy, which was the condition that originated in the head. and then analypsy, the form arising from the stomach, and then catalepsy was from any other part of the body.

Epilepsy was also linked to hysteria when the seizures were thought to originate in the uterus, and eclampsia was also thought to be a special form of epilepsy arising from a pregnant uterus. Yeah, I mean, that's interesting because that is still just – it's not epilepsy, but yeah. Yeah, yeah. But it's a seizure. Yeah, that's really interesting. Yeah. And then divisions were made more along the lines of major versus minor. Platerius in the 12th century wrote, quote, major epilepsy is a complete obstruction of the principal ventricles of the brain.

People suffering from it fall down quickly. The mouth and face are distorted, and there's also a trembling movement of the neck and of the whole body and clenching of the teeth. Sometimes they pass urine, feces, and seed involuntarily. They snore and froth, and when the froth has been wiped off, they froth again. Minor epilepsy is an incomplete obstruction of the ventricles of the brain. People suffering from it sometimes fall down. Sometimes they do not fall down, but faint. The froth, once having been wiped off, does not reappear and they are quickly relieved. Hmm. Interesting. Yeah. Although physicians from the Renaissance largely echoed what the preceding generations

had written about epilepsy, particularly ancient Greek physicians, they did make one important observation that broadened the concept of the condition, that epilepsy or seizures could result as a complication from another illness such as smallpox or scurvy or measles or the newly emerging syphilis. Essentially, the idea that epilepsy could be a symptom or a complication and wasn't just a disease unto itself. That is super interesting. Isn't that? And as this definition of epilepsy expanded, the classification came to be more about perfect or simple epilepsy, the most common form, the form that you see the most. And then there was imperfect epilepsy, anything that was out of the ordinary. And while these physician writers certainly weren't right

about everything, the extensive writings with largely accurate representations of prognosis, range of seizure types, timing of onset, an association with certain traumatic events such as a head injury shows that these physicians were thinking about the disease and writing about it in a systematic way. Yeah. What they did struggle with was the ultimate cause of epilepsy, which I think we can empathize with, given just how many things can cause epilepsy, how much of the time we don't know what causes it, how many different types of seizures there are, and how we are still struggling

to understand the pathophysiology of this condition. Right. scientific explanations were varied. Hot weather or dry weather or too temperate weather, drinking too much alcohol or not enough, exercising or lack of exercise, too much sleep or not enough, anger, fright, bad smells. Anything could be blamed for epilepsy. And we've already gone through some of the moral explanations. Nothing seemed to fit.

Nothing seemed to be a satisfyingly consistent answer. And so is it any wonder, really, that we have a million and one. explanations for epilepsy from these times. And for every one of those explanations, we have at least 10 cures. Our favorite. And that also makes complete sense, given that epilepsy can sometimes resolve on its own, like we talked about. Medications can work differently from person to person and from type to type, and it can take a long time even today to see whether a medication for epilepsy is actually effective. I don't know, though, if I have ever seen as extensive a list of cures and treatments for any illness as I have for epilepsy.

I loved this quote from neurologist Edward Seve King in 1861. Quote, there is scarcely a substance in the world capable of passing through the gullet of man that has not at one time or another enjoyed the reputation. of being an anti-epileptic. End quote. That's really funny. I feel like that's honestly, like, still true sometimes. Right? And I won't go through this absolutely massive list,

because I eventually just stopped writing them down. I was like, I can't, this is all of my notes now. And it would be an entire episode. But I did want to go through a variety of them. Missletoe is commonly featured, especially mistletoe collected at the new moon. An amulet containing coral, peony, and the root of strychnose. Peony also shows up frequently. An iron nail or weapon.

Avoidance of iron. The first vertebra of a human. What? Drinking human blood, especially gladiator blood. Okay. Likens of horses or mules. I don't know exactly what that is. I, mm-mm.

Genitals of seals. Nope. Testicles of the hippopotamus. No, also no. Also no. Blood of the tortoise or of the flatfish. Oh, what? The skin of a lizard.

This lovely combination. Feces of the land crocodile, the heart and genitals of the hair and blood of the sea tortoise. I, I. Uh-huh. A frog's liver. Burned human bones in a cocktail. avoidance of goats menstrual blood

rubbed over the soles of your feet just stop it two more kill a dog and let the patient have its bile and my absolute favorite is quote to let the person who first saw him fall urinate into his own shoe

stir the urine and give it as a drink to the patient Aaron Like, I know we talk about not, like, judging people back then, but, like, come on. I know. It's the, it's really, I mean, there are lots of things like burned human bones and pea shoe. Pea shoe. Like, that's not ever going to be a thing.

Mm-mm. Mm-mm. I mean, I think it does demonstrate how desperate people were. for a cure. That seems even beyond. Yeah, I also wonder sometimes, like, were any of these ever written as a joke? And we're just, like, they're like, ha, ha, look at these ridiculous things that people have tried. And it's not actually, no one actually has ever done any of these.

That's what that one feels like, quite honestly. It feels like what you tell, like, your little brother to do, you know? Yes. And then you're like, I didn't mean for you to actually do it. it, dude. Mom! Yeah, yeah, 100%. Well, fortunately, as we move on to the age of enlightenment and beyond, so like the 17th, 18th century onwards, epilepsy becomes less about drinking someone's pee from a shoe

and more about systematic study. Okay, love it. One thing that helped tremendously with this was the rise in anatomical dissections, which which I think we've talked about before, for hundreds of years prior had been viewed as sacrilegious. And so for the first time, anatomists were able to link certain diseases with observable changes in the structure or function of body parts. And that included epilepsy and changes in the brain, such as an abscess or a tumor or a hemorrhage in someone with the condition. And the rise of statistics had its own role to play, something that we've talked about in several other episodes of the podcast. In the case of epilepsy, institutions were created to house and care for people with the disease,

since it was believed that they could or should not live independently. And these institutions were viewed as opportunities to collect medical data for statistical purposes, which did lead to advancements in understanding the hereditary nature of some forms, characterizing the age of onset, patterns and seizure triggers, incidents of certain forms, and also rejecting some of the long-held beliefs, like the phase of the moon, affected the likelihood of a seizure. But they were 18th and 19th century institutions nonetheless,

and likely pretty miserable places to be forced to live. Demonic possession or association with, quote-unquote, insanity, continued to be used as a justification for locking someone with epilepsy away, and it was only in the early to mid-1800s that separate buildings were established for people with epilepsy and people deemed, quote-unquote, insane, with one major distinction between the groups being that the epilepsy group could attend mass, while the quote-unquote insane group could not. Clearly, the stigmatization of epilepsy didn't lessen over time. It just changed in flavor, despite the many medical advancements made throughout the 1800s.

Sure, some completely unsupported ideas about the underlying cause of epilepsy gain traction, specifically that masturbation led to epilepsy, with some doctors recommending circumcision, or even castration, or clitoridectomy, to literally no effect. Yeah. Oh, gosh. But overall, the rise of experimental observational science and the specialization of medical branches like neurology led to tremendous progress in our understanding of seizures and epilepsy. What had been previously divided into two main groups,

idiopathic epilepsy originating in the brain, and sympathetic epilepsy originating anywhere else, soon became more and more complex, with terminology developed to describe different types of seizures, like Gran Mal, Petit Mal, and Absence. The physiology of nerves and reflexes, began to be uncovered, and that helped to better understand why seizures looked like they did, and experiments altering blood flow to and from the brain showed how unconsciousness or convulsions

could result from the duration or intensity of blockage. Slowly but surely, scientists were chipping away at the mystery that was epilepsy, and finding that with every question answered, ten more sprung up in its place. Inevitably. Inevitably. But the questions were becoming more targeted, more detailed, revealing just how quickly progress is being made, due in large part to the rejection of superstitious thinking, the need for scientific claims to be supported by observational or experimental data, and a tendency to look at everything with a healthy dose of skepticism, including the teachings of the ancient Greek physicians, which previously had been taken more or less as gospel. Perhaps the biggest turning point in the history

of epilepsy during this time came with the invention of the human EEG, electroencephalogram by Hans Berger in 1929. I'm not good at, like, this could be its own episode really. It could be. Maybe someday.

But what it did for epilepsy was allowed physicians to diagnose a type of seizure or epilepsy without actually having to observe the person having a seizure. Mm-hmm. Researchers, especially Frederick Andrews Gibbs, Erna Lennhart Gibbs, and William Lennox,

described three major types of clinical seizures using EEG patterns, Petit Mall, Grandmall, and Psychomotor Seizures. We all call these different things today. Mm-hmm. And this last one, psychomotor seizures, or in today's terms, focal seizures arising from the temporal lobe, prior to this, most of the people experiencing one of these seizures were labeled as hysterical. And the application of EEG to animal models also really opened up the world of epilepsy, making it very clear that we desperately needed to revamp our classification system. And so in 1964, the International League Against Epilepsy proposed a new classification system,

which has since been continually revised and refined with big changes occurring every few decades. And I kind of love that it's constantly changing because it's like, hey, let's reconsider, maybe we should change this word or that word. Maybe there's a, you know, that's how progress is made. I love it. Cellular and molecular advancements have also vastly improved our understanding of the underlying pathophysiology of seizures and have shown some promise for novel therapies. The late 1800s and into the 1900s also saw innovation in effective treatments for epilepsy,

beginning with potassium bromide in the late 1800s, phenobarbital in the early 1900s, phenotoyne or dilatin in the 1930s, trimethyone, carbamazepine, primadone, like, sodium valproate. The list goes on and on and on. And it's still growing constantly all the time that, and I'm sure you'll talk about some more that are on the horizon. And then there was non-pharmaceutical treatments that were also successfully applied, including vagus nerve stimulation and some surgical procedures. I hope that I've shown by now that the 1800s and 1900s were a time of incredible progress in terms of understanding and treating epilepsy.

But the rise in quote-unquote scientific or rational thinking didn't mean that the stigma of epilepsy disappeared. In the previous centuries, epilepsy had been feared or looked upon negatively, likely because it was a mystery. You fear what you don't know. No one knew what caused it. No one knew why it happened, when it happened, and so science couldn't answer it. It must be a devil. It must be a god. It must be whatever, the moon. But when we finally gained enough concrete knowledge about epilepsy to conclude that it wasn't demonic possession, that knowledge wasn't used to dispel the harmful stigma surrounding epilepsy, but rather to perpetuate it. Beginning in the late 1800s and early 1900s, the United Kingdom and many states in the U.S.

created laws for the sterilization of people with epilepsy and laws forbidding marriage if you had epilepsy. I know. I know. At the same time, I will point out that marriage was often prescribed for women to cure their epilepsy. Stop it. Not pregnancy necessarily, but just marriage. Stop it. We'll calm you down and lead you to not have seizures. Oh, no. No.

These sterilization and marriage laws were bolstered by some of the earliest research into the genetics of epilepsy. which was done in the early 1900s. And if all of this screams eugenics to you, that's because it is. It is. This is straight from the eugenics handbook. A horrifyingly prevalent opinion, the 20th century's demonic possession, held by so many people who were making the policy and healthcare decisions for these people. It's horrific.

These laws forbidding marriage and permitting sterilization of people with epilepsy, weren't repealed in some states until the 1960s. I somehow knew that you were going to say the 1960s even. By 1966, three states, West Virginia, North Carolina and Virginia, still had eugenic marriage laws, and 13 states still had eugenic sterilization laws against people with epilepsy. 13 states. The last law was repealed only in 1980.

Oh, no. Uh-huh. Only in 1970, in the U.K., was a law prohibiting people with epilepsy from marrying repealed. And in the U.S., up until the 1970s, it was legal to deny people who had seizures into public spaces like restaurants, theaters, recreational centers, and so on. And even though we now have laws in much of the world, prohibiting. such discrimination, that doesn't mean that it's not done. Nor does it mean that stigma disappeared overnight. In fact, people with epilepsy today often report feelings of stigma and the negative impact it has on overall quality of life, which I'm guessing you might talk more about. The story of

epilepsy is huge. And it's so much more than how we learned this or that, how the EEG came to be, how we decided that this seizure was different than this seizure. It's a story about the meaning that diseases can hold, how science can be manipulated to perpetuate discrimination, and how there's never an end to the questions we ask. Speaking of questions, Aaron, where do we stand with epilepsy today? Oh, I can't wait to tell you right after this short break. Epilepsy is so much more prevalent than I realized before researching this episode. Globally, more than 50 million people worldwide have epilepsy. What?

50 million people worldwide. And overall lifetime prevalence is thought to be about 1% on average. Wow. I know. Right? Whoa. Disproportionately, epilepsy affects people living in low and middle income countries, and there's probably a whole myriad of reasons for that. And we'll get into a lot of issues associated with that as well.

And another statistic that I think is important is that worldwide, there's an estimated 125,000 deaths each year related to epilepsy. And I think we often don't think of epilepsy as a disease causing death. Yeah. Because most of the time it doesn't. But the risk of premature death for people with epilepsy is estimated to be three times higher than that of the general population. And in low resource settings, this risk may be up to seven times higher. Can you talk about why? It's a whole lot of different reasons.

It could be things like drownings or car accidents, like traumatic incidences that happen in the context of a seizure. Okay. It could also be due to infections that result perhaps like following a seizure that isn't adequately treated or as a result of status epilepticus resulting in certain brain changes that might make you more susceptible to infection later on, things like that. Huh. Which is why I think we see such high. higher burden in low and middle income countries where you're maybe not having as much diagnosis or access to treatment, especially in the cases of things that get more severe. We can look at the statistics for epilepsy, both in terms of adults versus children, as well as

by different seizure type or different epilepsy type. And so we can just kind of briefly go over that because I think it's always an interesting part. Prevalence overall, unsurprisingly, for a chronic disease is highest in adults, right? Far more adults are living with epilepsy than children just because of the numbers of adults that exist. But when we look at incidents, so new diagnosis of epilepsy, it's highest in the youngest and the oldest age groups, which is really interesting. So it has kind of a bimodal incidence. Yeah. where you'll see an increase, especially in the first year of life, although in low and middle

income countries, it's maybe the first few years of life. And then a decline in the incidence, so new rates of new infection throughout adulthood, and then a subsequent increase again in people who are over age 85. Now, the types of epilepsy are going to be very different in those two age groups. where older adults, it's more likely to be as a consequence of something that happened, say, a stroke or a trauma or etc. If we look at epilepsy by seizure type, one thing that I think is really interesting is that it's actually focal seizures that are the predominant seizure type in both children and adults. Despite the fact that popular media would make you think that it's these generalized tonic-clonic, very extreme, seizures that are the only thing that represents a seizure. But the most common type overall is focal

seizures, usually focal impaired awareness seizures, which account for about 36% of people with seizures. So this would be a seizure that starts from only one place in the brain, may or may not have motor involvement, but does result in the person being unaware of having the seizure at the time of the seizure. Okay. So again, it can look a lot of different ways, but focal seizures are more common overall. So interesting. And overall, unknown etiology of epilepsy is the most common. So even though we know that epilepsy can be genetic, it can be from structural or metabolic changes, it can be the result of a trauma. Most of the time, we don't know what the actual underlying car. is, which makes it really difficult.

So then that brings us to where we go from here. Yeah. And I honestly didn't even know where to start when thinking about this, like current future directions, because there's so much ground to cover. In terms of therapeutics, there has been a huge amount of advancements in recent decades. There are dozens of new medications that are safer, that we have better monitoring for. But I don't have any, like, here's the newest, most exciting thing to tell you about because we don't have, like, one single mind-blowing new drug.

One thing that I thought was interesting was the idea of seizure prediction, which is something that people have been working on for a very long time. And I think in the 80s and 90s, there was a lot of hype around it. But then in the early 2000s, a review came out that was like, yeah, all that data was actually really flawed. and we are nowhere closer to a model to be able to predict seizure onset than we were like 30 years ago. But since then, people are still working on it, which I just think is very interesting. There's a lot of kind of flaws with the data that exists and the ways that people are trying to do it thus far. But with advances in EEG technology, it's more likely, I think, than it ever has been, which is really, really fascinating. because so much of the burden of epilepsy is this recurrence of seizures that you may or may not know are coming, right?

And so being able to predict seizure onset could have huge implications for quality of life. Right. And speaking of quality of life, I think one big takeaway from all of this is just how far we have to go, especially in low and middle-income countries when it comes to not only the treatment but also the identification of epilepsy. Yeah. So just last year in December 2022, the World Health Organization published a brief that was titled Improving the Lives of People with Epilepsy.

And most of their biggest points were all focused on addressing the treatment gap and integrating the treatment of epilepsy into a primary cancer. settings since so much of the world doesn't have access to these specialized neurologists and epileptologists. So I think that that is kind of one of the things that I'm most excited for going forward is just getting this knowledge to a place where it's more applicable to people who are already living with this. So that's epilepsy, Aaron. It's such, I mean, we covered so much ground, Erin, but... But I know nothing. I know nothing. Oh my gosh. I know. I mean, I know a lot more. Same. Same. But not everything. And I feel like that's how we could sum up epilepsy and seizures in

general. It's so true. Wow. Wow. Well, speaking of learning more... Let's all do it. Let's talk about sources. So I had several. I'm going to shout out just one, and that is the book that I already mentioned called The Falling Sickness by Ossay Temkin. And I also want to shout out a book that I have not read, but is on my list, has been for a really long time. And it's supposed to be an incredible work of nonfiction called The Spirit Catches You and You Fall Down by Anne Fatiman. And these will both be on our website, both be on our list, as well as a bunch of papers that I also drew from. I also had quite a number of papers with so much more detail for those of you who want that nitty-gritty. I promise you, I have it. Some of the papers that I really loved were one that was kind of pretty basic, but it was titled the Epidemiology of Epilepsy. It was published in neuroepidemiology in 2020. You can't get more effective than that. Perfect.

There was also a really interesting one that has a lot more detail on how we think epilepsy develops over time. time that was published in Nature Review's neuroscience in 2019. And then I've got details on ketogenic diet, if you want more of that, more on where we stand with the pharmacology of epilepsy, and then of course a link as well to the World Health Organization brief that I mentioned. All of these are on our website, this podcast will kill you.com, under the episodes tab, along with the sources from every other one of our episodes. Thank you again to Louise for being willing to share your story with us and with everyone. Thank you also to Leanna Skulachi for help with our audio mixing for this episode.

And thank you to Bloodmobile for providing the music for this episode and all of our episodes. And thank you to Exactly Right Network. And thank you to you, listeners. There's so many thank you. So many thank you. But we don't want to forget about you. You allow us. to make this podcast happen.

Seriously, we love it. Thanks for listening. A special shout out to our patrons. It means so much to have your support. It really does. Oh, big topic over. We're done for the season. We're done for the season.

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