Ep 112 Epilepsy: It’s always the phlegm

For a while, we didn't do much about this. I was about sixteen 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.

I was incredibly confused after the seizure. I was also completely fatigued. I could barely move my body.

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 twenty sixteen November. I am freelancing at an ad agency. I'm doing prove fruiting 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 Grandma's seizure.

experience has been quite a mixed bag. I am technically quite lucky that mine is easy controlled with medication, I can lead a normal life, but it's also been a giant Panama ass 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 a magical miracle, gene therapy or something that will remove us, but we will see where things go.

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 Place Barta on our website. This podcast will as well as on all of our social media channels.

got there's probably more. Our Patreon it's there, check it out.

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.

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.

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 experienced 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 neuuronal activity in the brain. Episode over that was so clear.

communicates 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, et cetera. 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 a sonociate with the seizure can actually very incredibly widely depending on where in the brain they're occurring.

cut and dry 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.

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 Mall 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 four, 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 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 of times people do have like prodromes or what we call auras 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.

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 chlonic seizure, Or people could have different fauxci 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 neuuronal 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 twenty or thirty minutes before this became an emergency.

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 so integral in like figuring out what's going on, because you might be having more seizures than you even have very obvious signs.

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, etc.

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 underlying brain changes that can lead to epilepsy to these recurrents 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 their 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.

Most commonly like twelve to eighteen 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 es central nervous 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 febrowse seizures and who later do get diagnosed with epilepsy, that doesn't mean that most kids who have feebrow 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 epilepsy.

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.

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 a 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 genetics. 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.

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.

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 neuro receptors or other neurotransmitters like gabba 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 seizure, we might be able to pick one anti seizure medication over another.

Right and seventy percent remission sounds pretty good, but it also means that right now, thirty percent of people do not or will not necessarily achieve remission.

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 at Kins, there's a

low glycemic index version. But for someone who is living with very frequent seizures, even a small reduction in caizure burden might be a pretty big deal in 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 ketodiet that's on the news throwing that out there. I also am really I just am personally very interested

in the potential mechanisms of the ketogenic diet. So I do 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 keytnes 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, so.

having another seizure over the next ten 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 sixty percent 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.

good and interesting question some people. And maybe it could also be related to if there is an instigating factor, Let's say a meningdroitis 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 twenty four hours apart, so you meet this definition for epilepsy. But over time, maybe your brain remodels itself

enough to then no longer have this epileptiform activity. Huh, then you can, yes, resolve your epilepsy.

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 the 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, interchangeable. 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 trepanation, 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 tripand 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 trepanation in ancient times. The earliest written description of epilepsy comes from Mesopotamia around twenty five hundred 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 with 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. Yep. 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.

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 four hundred 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 phlem. It's always the phlem, and that's part of the humoral theory of disease. In this text called on the Sacred Disease, the author also argue 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, any 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, hm, which is kind of amazing considering that was like thousands of years ago. Yeah, and so much happened in between then and now.

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 eple 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 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 seven seventy 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. But I mean, like, this is something that kept occurring to me, is that we look back at that now and we laughed. But that was science, Like the goddess was the superstition part. The science part was the moon melting your brain. 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. 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 know, something I kept thinking about. Epilepsy was also thought to be from demotic 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 Malias Meleficarum, written by two Dominican friars and published in fourteen ninety four, it was said that seizures were characteristic of witches, and also that witches could cause epilepsy to develop.

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.

like yeah, I don't know, yeah, oh 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 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 onto 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 Aaron, 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. Instance, although descriptions of seizures vary, the common features among them include a 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 twenty years of age. Some writers suggested it was hereditary, while others said it was congenital like. 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. 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, the brain, Yeah, this was in the body. So for instance, there was epilepsy, which was the condition that originated in the head, and then anilepsy 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.

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.

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.

of the ordinary. And while these physician writers certainly weren't right about everything, the extensive writings, with largely accurate representations of programs, range of seizure types, timing of onset, and 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. 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. 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 ten 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.

Avoidance of iron, the first vertebra of a human, drinking human blood, especially gladiator blood. Okay, h lichens of horses or mules. I don't know exactly what that is. I genitals of seals, Nope, testicles of the hippopotamus.

menstrual blood rubbed over the soles of your feet. Just stop it, do 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.

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 eighteenth and nineteenth 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 eighteen hundreds 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 eighteen hundreds, sure some completely unsupported ideas about the underlying cause of epilepsy gained traction, specifically that masturbation led to epilepsy, with some doctors recommending circumcision or even castration

or cletoridectomy 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, idiot pathic 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 grand mal petitemol 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 was being made, due in large part to the rejection of superstitious thinking, the need for science 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 electro and cephalogram by Hans Berger in nineteen twenty nine. I'm not good at like this could be its like 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. Researchers, especially Frederick Andrews Gibbs, Erna Lenhardt Gibbs, and William Lennox, described three major types of clinical seizures using EEG patterns, petitemol, grandma, and psychomotor seizures. These we all call these different things today, and this last one's 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 nineteen sixty four, 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. I 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 eighteen hundreds and into the nineteen hundreds also saw innovation in effective treatments for epilepsy, beginning with potassium bromide and the late eighteen hundreds, phenobarbital in the early nineteen hundreds, phenetoin or dilantin in the nineteen thirties, trimethadone carbamazepine, primidone like soval. The list goes on and on and on, and it's still growing constantly all the time. That and I'm sure we'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 eighteen hundreds and nineteen hundreds were a time of incredible progress in terms of understanding and treatingplepsy. 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 eighteen hundreds and early nineteen hundreds, the United Kingdom and many states in the US 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 will calm you down, God, lead you to not have seizures.

It's horrific. These laws forbidding marriage and permitting sterilization of people with epilepsy weren't repealed in some states until the nineteen sixties.

prohibiting people with epilepsy from marrying repealed. And in the US, up until the nineteen seventies, 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?

prevalence is thought to be about one percent 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 one hundred and twenty five thousand 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.

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 its 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 eighty five. 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 chlonic, very extreme seizures that are the only thing that represents the seizure.

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 ideology 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 cause 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 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 eighties and nineties there was a lot of hype around it, but then in the early two thousands of 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 thirty 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.

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 erin.

these will both be on our website. Both be on our list, as well as a bunch of papers that I also drew from.

published in Nature Reviews Neuroscience in twenty nineteen. 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 dot com under the episodes tap, along with the sources from every other one of our episodes.