Missed Diagnoses in History Part II: Joan of Arc and King George the III

[00:00:00] She says, like the voices always remind me of the sound of church bells. I knew that's the soul is like this religious defined angle that they play on that. So what do y'all think she had? Let's pause for a moment like Dora. What was the diagnosis? How patient. Welcome back to having patient with, I'm your host, Preston Roche, and I've got another solo episode for you here today.

But before we get into the solo episode, I want you to look at the background behind me. It's different because I moved, I have been going in and out of a U-Haul all week, and I've finally moved out of the place this morning. I got up at 6:00 AM and I spent the last five hours moving boxes, and I have a flight in an hour.

So let's get this done. You know what I mean? I'm in a very like, get stuff done kind of mood and if there's a window, we're just gonna tackle it. And I feel kind of exhausted, so I'll probably crash little plane. But that's the break, you know what I [00:01:00] mean? it's, the trip is when the break starts. At least that's how it feels when, you have a lot stacked on your plate.

But enough about my story. We have some really interesting stories coming up today. So y'all really seemed to like. The, stories throughout history that I did last time. So if you're interested, it's the episode called, missing Diagnosis in History. And we did, we covered the Glass King And we covered Mary Todd, talking about two kind of interesting potential psychiatric episodes, And we all really, like, liked it.

We, we have some good Spotify comments here. So somebody said this would make a really good series. Thanks Sean Jordan Music. I agree. And we're making it a series. So this is episode two. Mira said thank you so much for the crash course lessons on Mary Todd. Now I know what I'm getting into when I see the Broadway show.

Oh, Mary and I haven't seen that [00:02:00] show, but I should watch it. It's a good follow up. And then Katie said, does this mean we're finally getting a Mercury episode? Katie, I'm, working on it. You know, it's my Mercury, it's, in retrograde right now, so I can't cover mercury yet, but, after my Saturn finishes return, it's return then, we'll cover Mercury.

So, Kate, don't worry, it's coming. Good stuff's coming down the pipeline. So, going on with today's episode, we have two very interesting cases, and I'll read you guys a little teaser for each of them. So the first one is a king. Sits strapped to a chair and he calls his coronation throne. He's been talking for 16 hours without stopping, and he's not, you know, he's not Bernie Sanders doing a filibuster.

He's just on one more. So they thought his urine is the color of port wine. This doctor think that this is good [00:03:00] news. Proof finally of what's wrong with him. But they're about to be wrong for several hundred years and 300 years before. That is our second case. This is a teenage girl. She's kneeling in her father's garden, and there's a flash of light to her right and a voice, and that voice will speak to her almost every day.

For the rest of her short life, it will tell her to crown a king and lift a siege. She'll do both of them. Then that voice will be used to burden her alive. So we have two different patients. Two very different outcomes. Well, I guess same outcome. Argue if you extend the timeline long enough, you know, everybody dies.

Two patients, same outcome, different arcs. One of them literally had an arc and two completely different ways that history got this diagnosis wrong. So let's get into it. We are gonna take a quick break and when we come back we will be talking about the first case.[00:04:00] 

So. Last time we did a king, we did King Charles, who is afraid of glass, and we're doing another king this time. So this is gonna be one of the most famous, wrong diagnoses in the history of medicine. Probably, I don't know, we've been getting stuff wrong for a long time. And, actually I would say this is one of the most wrong diagnoses that we discovered so far, because if you get it wrong, but never figure out you got it wrong, it could be arguably more famous.

And it was put on the world stage. Got a lot of attention in the sixties and eighties, so, so let's get into it with George third, which I imagine a lot of the audiences aren't familiar with. So, George, I third rained from 1760 to 18, 20, about 60 years, and it's one of the longest in British history.

He was a British king. So couple important points on his resume. He lost the American colonies. He reigned during the Napoleonic Wars, and he's famously known as Mad King George, [00:05:00] but. Before he got the title of Mad King George, he was kind of a born dude and for like a majority of his life leading up to the kind of, when the madness came out, he was pretty uneventful.

So he, he was a pious guy, which was not the standard at the time. Like he was really faithful to his wife Charlotte, across their 15 children. He was dutiful, he was obsessed with agriculture. They nickname him, farmer George. Before that he was a modest guy. I remember like, let's compare him to some of the other kings, like, what was this?

The Church of England. So I'm pretty sure like, you know, even being a king doesn't mean you're gonna be a moral dude. Even you're like the leader of the church. Like, so remember Henry VIII made the Church of England just so that he could go do some extra marital stuff and make up his own rules. So the fact that like.

George II [00:06:00] is staying on track, like he's a level guys, is the point I'm trying to make and is he has a good or an upstanding personality. Then the reason why we're building up how upstanding he is, because this is such a sharp departure in midlife. So around age 50 is when we start to see, a difference here.

So here's the kind of the picture that I want in your brain. it's around the age of 50, and then he starts kind of. Repeating these persistent behaviors. He starts speaking for hours until he's hoarse sometimes, until he's filming at the mouth and the content of his speech is what's really scaring people.

So this kind of previously, Temperate, like religious faithful man. he's become grandiose. He's become lewd. Like he, he's, saying these crass things. there was like a courier out in the, courtyard and he's like, oh, I want to marry you. Like, come here, you know, [00:07:00] let's, get it on. And everyone's like, George, what?

What's going on? Like, where's Farmer George that I knew before? And then on top of this. He's not sleeping at all. He's, going out and looking through the telescopes in the courtyard, and he's like, oh, I can see Hanover from here. Like, I'm the best, I'm the best astronomer to ever do it before. And they're like, this is like making no sense.

they actually ev eventually strap him to a restraint chair, and then he like sarcastically renames his coronation chair because they're, trying to hold this dude down. They're like, stop trying to marry. Every, assistant that you have, and then his doctors are now taking a crack at him. So we have his doctors, Francis Willis and his sons, they're the, he's celebrity madness doctors.

And they handle madness with a, strict regimen. they do intimidation. They blister you, they force you to take a medics, like anything to kind of purge it outta you. So. [00:08:00] You asked me, I'd say that's pretty hardcore psychiatry in 17 hundreds. And I, don't even give people four se medics. I just hit him with the Zofran, kind of take him the other direction, but more onto Francis will and his hardball style.

So when we're, looking at his assessment, and remember we have this kind of unstoppable speech. We have the lost need for sleep. We have this guy who thinks he's. Way more grandiose than he was before. And he's becoming really impulsive and hypersexual. But, we still don't have like a good idea of where the madness is coming from, right?

Because this isn't making much sense. So Francis w and his sons, they're playing the intimidation game with George. They're basically like, George, stop being mad. You know, we're gonna make you vomit. We're gonna blister you, we're gonna hit you where it hurts, and then maybe you'll stop being mad.

and so. While they're kind of doing the full physical work up on George, they notice something and that's he's developing port [00:09:00] wine, urine, and he has some abdominal pain or it's discolored urine, right? So then they go, okay, this is exactly what's going on. He's actually, he's having some kind of poison inside of him and when we figured it off, and he has a couple like.

Mild relapses after that, but then he slowly starts to get better. Right. So let's pause for a second. What kind of stuff is coming up on your differential? We have this guy, he's in his early fifties. He's going mad. He's exhibiting all these signs of mania. We can just jump to that part. But then he has these physical signs, these like abdominal pain, poor wine, urine, and then he's also getting this really crazy treatment from the, psychiatrist at the time.

So first [00:10:00] things first, when, whenever you have someone develop a mood episode in midlife, you need to do a full workup on it. And this is some, like, interestingly, this is kind of something that we, I think, got wrong in history where you could argue that we did, because everybody made the claim that this is like 100% metabolic and they said, oh, he's got acute intermittent porphyria and he had a porphyria episode, and that caused his mania.

It's like the fort one urine, the abdominal pain and everything else. So, and I guess it's possible. So I was looking into the, neuropsychiatric symptoms of acute intermittent porphyria. And so heme is when you have enough, unconjugated heme or like early precursors of heme buildup, they are neurotoxic and they can cause mania, orps, psychotic symptoms.

However, it, would be unexpected for someone at his stage in life to develop such, like an [00:11:00] acute episode of porphyria. It's usually between like the ages of 18 and 40. So it's was possible because he's kinda like outside of the, standard range there. But everyone I think throughout history is kind of just like, oh, this is like obviously porphyria and we're gonna like see if we can trace it throughout the rest of his family.

But there's some other interesting things here. So the, I know we're all used to anti-medics, but the pro medics that his doctors were giving them, they contained arsenic. And they started treating him, and then they saw the port wine urine come through. And, arsenic is important here because it also disrupts hemo synthesis.

And so some people argue that actually he was just experiencing a manic episode. And then while they were treating his mania, they induced. Essentially an iatrogenic porphyria. And then as he's responding to the peds developing abdominal pain and then you, and then having the port [00:12:00] wine urine, that was all atrogenic and that his psychiatrists were just making it worse, so to speak.

So you could argue that, you know, maybe he did have a manic episode later in life and developed some form of bipolar disorder because he does like return to this like normal level lucidity, but then has a couple more manic episodes later in life. The other thing that I would be like interested in looking out for in someone who's developing bipolar disorder this late in life is that I don't think it's like a primary psychiatric illness.

Like he may have, may make episodes, but it's, I wanna say it's like from something else going on. So for example. Like you're not, it's unlikely that you develop primary epilepsy later in life, but if you have a tumor, for example, like a meningioma or something that's pressing on a portion of your brain, that, that, irritation of the cortex could cause seizures.

So even though you have like intermittent seizures that would respond to [00:13:00] anti-epileptic medication, you don't have like epilepsy now you have a tumor. So he could, have a similar thing that's inducing mania. he could also have had a stroke. So you can have, post-stroke mania, even like some early forms of frontal temporal dementia, which I would say he's like right in the range for between like 50 and 64.

So as that tau protein builds up in the frontal and temporal lobes, you can start to degrade the interior c like cortex, which can also lead to manic like symptoms. I feel like I'm leaving, for those of you who are watching a video, I feel like I'm like slowly leaving the frame here and I'm gonna myself really quick, so.

I think those are all the other things that I would consider. I think as we revisit the madness of King George and before said it was all acute intermittent porphyria. I think we're coming back to saying like it was probably that he had bipolar disorder, but we're not sure, sorry, not bipolar disorder, but that he was experiencing episodic [00:14:00] mania due to probably some other medical illness that is unclear.

So, and I guess, but, finally. Even though I've been like hating on it being primary bipolar disorder this whole time is because you can still technically develop these mood episodes that late in life. If you look at the bell curve for like first break psychosis and first spec mania, it's still a, it's still a bell curve and it, peaks around like 25 to 30 for men.

But as it kind of flattens out on the side, there's still like a small sliver that's gonna be like touching into like middle age. And he might be like a standard deviation and a half or two standard deviations to the right of the norm, which decreases the probability. You know, he might be in the like, I don't know, 98th percentile of age to develop the illness, but that doesn't make it impossible.

It just means it's [00:15:00] like, oh, well the people that develop bipolar is like 2% chance or something. So. that's like one thing I get into a lot with psychiatry is that like, just because it doesn't fit our, like usual age parameters doesn't make it impossible. And I'm not saying that to encourage you to think that, you know, your 89-year-old grandma who's having hallucinations in the hospital is developed a nuance at schizophrenia, but that it's not impossible.

and you have to remember that as you're like ruling out all of the other like medical causes that. Sometimes it does happen And we have to take that into account And we can't just like give someone a bunch of arsenic, watch them piss blood and then go, oh, it was porphyria all along. And that's all I have to say about that.

So we are gonna take a quick break and when we come back we're gonna roll into the second story.

Okay. And we are back [00:16:00] to talk about Joan of Arc. I'm gonna say that. Out the gate, but let's tell her story first before we kind of get into all the medical mumbo jumbo. I feel like we kind of went straight to Adam King George. I wanna let this one build up a little bit more. So let me set the scene for you.

We're on a place called Don Reia Village that's kind of, cling to the, eastern edge of France. And this is important 'cause it's about the worst stretch of the a hundred years war. And Joan is the daughter of this tenant farmer. He, she's not noble. The, dad is not literate and no one in the area, is educator if you read or write.

So she's kind of hanging out in this like little peasant region. The English, they hold the north and King Charles, you remember from before. He's been, disinherited. He's un frowned, and he's like [00:17:00] basically losing to the English right now. So this is the context of where she's in France. So now she's about 13 at this time, and she is in the garden and she hears this voice and she sees this light, and, she knows that the light it's to, to her, right?

And then. the voice comes over her, and it's kind of like whole sensation. This happens all of a sudden, like, like within the snap of a finger. And she was really afraid that the first time this happened. But then, the voice itself, it, comes back and she hears it again when she's in, you know, other random situations like doing chores or, walking to town.

But it's not, the voice isn't constant. It like goes and then we'll come back all of a sudden and then. it for, also for context, it is like a formless voice. So it's like mumbles. [00:18:00] That's how I imagine, Lisa, or when patients tell me that they have voices they can't articulate. That's, usually what they say.

it's like kind of Gru or it's far away. hey. But she can't make it out. And then it does start to resolve into these like voices that she can't distinguish, show. She, names them the first Michael being a saint. And then there's Catherine and Margaret. And they don't rant.

they're not yelling at her, not telling, she's about to counsel her and they start to comfort her. So she was afraid by these, like, rumbling voices at first, but now she finds them to be helpful. So this is the part that, Should really kind of amaze you or because it amazed everybody at this time the, this kind of teenage peasant girl on the [00:19:00] authority, that she can hear voices or is being told voices.

She, talks her way up to, the Dolphins Corp. And she gets in front of the king and, tells him that a voice is sent her to put a crown on his head. Catherine and Margaret said. You know, we need to get, we need to get dolphin a, crown and put this guy in charge and then somehow it works. she, so she rides the siege of Orleans.

This is in, 1429. So she's at the court of the, dolphin and he, she tells him about this kinda like divine prophet, his voice. And then he's like, wow. We need to start putting this into action. And so he puts Joan on the front of a, relief force party and sends them to the siege of Orleans, and she shows up with this, fervent confidence and calm leadership, armed with this spiritual [00:20:00] God-like voice calling her.

And this actually works so it galvanizes the troops, the French gain all this confidence. Word gets around that. They have, like, essentially the French have God on their side and the British, in the area, they, start to lose confidence and then like they, they went, they turn over the city. A few months later, she gets to stand beside Charles at his coronation in reams, which is exactly where she said she'd be.

Now she's in the center of the nation's conflict, but a year ago she was just standing in the garden and getting shot with a bright light. This all happened in 1429 and in 1430 she's captured in Compen and she's handed over to the Burgundians and then, they sell her to the English. They don't want a soldier or any anything, but they see her as the symbol and they want to destroy that story that she's bringing with them.

So they [00:21:00] want to declare Joan to be a heretic and a witch, and they want to unmake his kingship ultimately. So. They run through this whole trial of condemnation at Rowan. it's not really about Joan. It's a, it's really, it's a political demolition and a chance for them to attack everything. The French that the French had at this point, they make her into this devil, this witch.

And then in, 1431 at the age of 19, they burned her alive at the stake. And I think that's, the story that most people know. So I'd actually didn't really know the full story of Joan of Ark. I knew that. She was a young teenage girl who played a role in helping motivate the troops of France to win a couple in court in battles, and I knew she got burned.

that was about it. But I didn't really know before reading and prepping for this episode, I didn't really know much about kind of this, the divine interventions that she was experiencing. It also the, different like the of it. So [00:22:00] now let's kind of get back. The clues as to what Joan might have had.

And the most interesting thing here is actually we can read from the, testimony of the trial that they had because it, it was a sham trial and they're accusing her of being a witch, but she still has a chance to tell her story and that allows the nerdy neurologists and psychiatrists are history to go back and kind of reanalyze it.

So going back, it's a 13-year-old girl, no significant traumatic event sleep up to this point, she's hit with this episodic, sudden great light and then auditory hallucinations that also are episodic and come and go. She doesn't have any impaired cognition, between them. When they ask her how long these periods last, they're brief sci, they come and go.

It can happen in the daylight, but also can happen while she's sleeping and bring her out of sleep and wake her up. So. Of her own lines, she says, is, I was asleep. And the [00:23:00] voice awoke me. they ask her how often this happens, and she says, usually it's like a few times a week, but then it gets onto the point where she says, there's never a day.

I do not hear them. And the, tone underneath all this is that she always associates the voices with bells. She says like the voice is always remind me of the sign of church bells. I knew that's the soul is like this, religious defined angle that they play on that. So what do y'all think she had?

Let's pause for a moment. My Dora. What was the diagnosis? Okay, let's talk about it. So do you think she has a primary psychotic disorder like schizophrenia? She have any like paroxysmal psychosis? I don't think so. And if, she had schizophrenia, I wouldn't expect her to be so, cognitively organized in between and also not progressing, so severely [00:24:00] that she, would be able to like work with all these, troops and political leaders.

I think she would be cast aside as mad, probably pretty fast. And I don't think it would take her to get to the trial to, to be killed or burned or something. I think something bad would've happened earlier. So. But it does fit the timeline. You can develop schizophrenia, you know, between ages of 13 and 19.

Know would make a lot of sense. I don't think it's mania, like I don't, it doesn't really seem that she has any like, mood episodes associated with it. I think it's actually kind of like outside of the, realm of the DSM and I think it's some other like, neurologic event that's having some psychiatric symptoms going on.

So it could be like, do you think it's like a metabolic disorder that's at the up or down? I don't really, it doesn't like make sense to me. I'd also expect her to start getting more severely sick. And have like more somatic illness, which I don't think we detect any evidence of. And it, could be something autoimmune.

So like lupus for example. The, primary symptom can be [00:25:00] psychosis, but I don't think that was going on either. I would also expect it to at least eventually start having some other issues that I also don't think it'd be like as episodic. or if it was episodic, it'd be like. Months of psychosis and then it remits and then another couple months of psychosis.

But this is like momentary throughout the day, like your heart skipping a beat. So, so even like kind of the episodic nature of lupus doesn't quite match this episodic nature. so that's where I think we move towards something or like some kind of epilepsy. And this is fascinating to me because there's a couple specific signs that it could be a type of epilepsy, which he does experience it.

If you, there's like frontal lobe epilepsy, you can get like confused and you can, become disinhibited aggressive. if it's, you know, like diffuse epilepsy or, it comes from like an epileptic foci, but then it spreads the rest of your brain. You'd have a full [00:26:00] tonic-clonic seizure. Then like obviously that happens episodically, but it wouldn't result in this.

But you can have temporal lobe seizures, so. Temporal lobe seizures, can be contained within the, that region of your brain, and they cause a couple different like auras. So your temporal lobe that's in charge of, your, or your amygdalas is right next to it. Your thalamus is right there as well. It also has a large control over language, over kind of like your sense of perception and, Your memory. So those are all things that would be, you'd expect to be affected by a temporal seizure. So you can have like sudden strong, emotional changes. So sometimes people can fear, feel unprovoked fear or even intense joy or confidence you can experience like really sudden, illusions of taste or smell.

So like, gustatory and olfactory [00:27:00] hallucinations are common for temporal lip seizures, but you can also have visual hallucinations. So. you can also get this kinda like rising feeling inside of you. Like you're, like, you're slowly building up. You can also have sudden onset deja vu or jamiah vu, jamiah fu being that something should feel familiar, but it's not like you've forgotten about it.

This could happen episodically lasting for moments and then going away. So what I think might have happened is she has a temporal lobe seizure, and that's where she sees the bright light. And then she has the auditory hallucination with the temporal lobe seizure. And because her epilepsy is untreated over the next couple of years, it's causing like hyperexcitability and irritation within the temporal lobe.

And her brain is also trying to make sense of this seizure input. So that leads to her starting to like articulate what the voices are saying. And the fact that they're encouraging too is [00:28:00] also kind of. Pushes against psychosis, which it's almost always like a negative or like a paranoid, voice or a voice that makes you feel less confident about yourself.

But these like articulate voices that are giving her counsel that only lasts for a few moments, that sounds like an epileptic, event. And then the fact that she's lucid in between these episodes where things are like otherwise. Okay. That also points towards epilepsy. It's like she's kind of has these like discharges and then goes about her day.

Now, the final thing on the differential that I guess I didn't include is maybe God was talking to her. I don't know. Like you could, I'm not a religious person, but really strange things do happen and I'm like, well, you know, if, I was gone and I wanted to talk to Joan of Arc, maybe I could induce temporal lobe seizures.

In her and then [00:29:00] use those as the medium to communicate with her. So I think, like if you do have this like strong like religious view of Joan of Arc, there's probably a way to, to marry both kind of the medical interpretation and philosophical, spiritual interpretation of 'em without them necessarily being mutually exclusive.

But kind of coming back to the end, I think this is. Temporal lobe, epilepsy. I wonder if we got her on an anti-epileptic drug, if this would stop. So if I remember right, I think for partial seizures, things like oxcarbazepine can be a little bit better. I don't know if you would start out with that.

We'd probably start with Keppra or something and, like Keppra, Keppra might make her more angry. Then she gets some, that cap rage takes that into Ballers, starts to take it to the, King of England. So I think that's what, that's, I think I would probably start with that. You know, I'd come [00:30:00] in, I'd say, Hey, I'm pressing 'em from the future.

I brought this bag of k, K stands for Kepper with me, and I'm gonna give it to Joan just to see if it's SSA voices. But I know the voices are good for You'all and I'm worried it might be this thing called temporal epilepsy, but you guys don't have to worry about that right now. Just that. I'm just curious, you know, so we'll give her some kepper for a little bit.

If the voices stop. Cool. I'm actually gonna take it back. Let her go back to hearing the voices, because y'all need that to win the war kind kinda makes sense. You know, like, like do no harm. Right. So it's like if the patient's, no one's just doing something for 'em. I'm not one to, stand in there. Just we're serious or I'm, not trying to, you know, change course history.

I just, wanna find out for myself because I'm like, I'm a curious guy and I think that's, all I have for today. I thank you for being patient with me. I guess this whole thing is called How to Be Patient. [00:31:00] I like put together like the outline for these episodes, and then I went back to moving.

So I've basically, I feel, I felt like I was a little, like under-prepared for this one, but I wanted to kind of get through the story for y'all and then so we, made you like more of a coverup, like a fill in the blanks type episode later. thank you to everyone who's been like, enjoying the history episodes, who's been commenting.

I know Margaret is still on the break, but she is slated to come back in early July. We do have a neuropsychologist coming on soon, so that, I think that'll be kind of fun. We'll be able to get into more of like the ID aspect of things. if you have any interest in that. Thank y'all again for listening.

let us know how the show was. Shout to everyone who put out those Spotify comments like we opted five Spotify comments on the last one. So like, oh my God. We're gonna be viral this, see, it's popping off. You can, if you're not on Spotify, you can always contact the team directly at how to be patient pod.com or on Instagram and TikTok [00:32:00] at Human Content Pods.

Hi Matt. It's Prerow on Instagram or just prerow on TikTok. You can also find full videos on my YouTube channel each week at its prerow. thanks again for listening. I'm your host, Preston Roche. Margaret Duncan will be back in July. Our executive producers are me, Preston Roush, Margaret Duncan, Will Flanary, Kristin Flannery, Aron Korney, Rob Goldman, Hanzi Brook, our editor and engineers, Jason Portizo, our music bio Mayor Ben-Zvi.

To learn more about our program, disclaimer, ethics, policy submission verification, licensing terms, and our HIPAA release terms, go to how do patient pod.com or reach out to us at how to be patient at. Human content.com with any questions or concerns. How to be patient is human content production. Bye.[00:33:00] 

Thank you for watching. If you wanna see more of us or if you wanna see, this is lilac. She's my cat. She's gonna be waving her hand at one of the floating boxes, which will lead to more episodes. Lilac Point to the other episodes. Lilac doesn't know what the internet is, but I swear they're, they've. They probably exist for real.

But in the meantime, I'm just gonna pet lilac and then I'm gonna go dance in the background.