Encephalitis Lethargica: The Mysterious Pandemic That's Been Forgotten

Between 1918 and 1920, the Spanish Flu killed 50 million people worldwide.  This pandemic, arrived on the heels of WW1, and between the two events, nearly 5% of the world’s population was killed.  But there was another pandemic occurring, one that is less well known and less frequently talked about, that remains a mystery to this day.  In the winter of 1916 in Europe, people were seeking medical attention for general malaise.  At first, it looked like a mild case of the flu with fever, headaches, and fatigue.  Many would recover, but some would begin exhibiting tremors and many slowed down mentally and physically, until they were completely immobile despite being conscious and alive.  The symptoms presented on a spectrum, but patients sometimes experienced lethargy or even obtundation, paralysis of eye muscles, rigid muscles, frozen posture, loss of speech, and sudden immobility.  In some cases, the progression was overnight.  In others, it took weeks to months.  

Doctors called it Encephalitis Lethargica, but no one really understood it.  Some patients slept for days.  Others stayed awake, trapped inside bodies that no longer moved.  Hundreds of thousands of people lost the ability to walk and talk, and then in 1928 new cases just stopped appearing.  By then, however, there had been more than 1 million cases, and half of those had ended in death.  Those that did survive, often developed a post-encephalitic Parkinsonism leaving them rigid, slow, and unable to move normally for the rest of their lives.

And then, just as mysteriously as it appeared… it vanished.  So what was this disease? A viral epidemic? A post-war complication? Something we still don’t fully understand?  This week, we’re diving into one of the most unsettling medical mysteries in modern history, Encephalitis Lethargica, also known as the Sleeping Sickness.

Transcript

It's Colleen. Hi, it's Kait.
And it's Megan.
And we're the 3SchemeQueens.
Join us each week as we take turns presenting a brand new conspiracy theory or mystery.
From shadowy coverups and unexplained events to viral rabbit holes, we bring the tea, it's piping, the facts, and the tinfoil crowns.
Join the conversation, laugh along with us, and question everything.
When it's all over, we'll tell you what we think, and we'll try to prove it to you.
So grab your drink, hit the follow, and tune in every Tuesday.
Is this thing on? Heya.
Welcome. Welcome back to the 3SchemeQueens.
We're back again.
I hope you enjoyed our last episode on the scientists. Yeah, we're, this week.
We're getting sciency again.
We're getting, yeah, we're getting sciency, but we're getting away from true crime and current events. Is there anything you wanna yelp about?
No, cause we're not allowed to talk about the weather.
And you know what? You can't sing and you can't talk about the weather.
She's taking away our right.
Anyway, it's almost my birthday. As a matter of fact, I believe this episode is coming out the day before Kate's birthday. Happy birthday.
Happy birthday. Everybody have a tequila shot. So yeah, that's the big event is happy birthday to our birthday girl over here.
Yeah, birthday girl.
Taurus. Taurus.
We love Taurus's earth signs.
You know, love and earth sign.
So is it time for our drink check?
Drink check.
In honor of Kate's birthday, I don't know if you guys know this, but Kate loves a bee.
Oh, she does love bees.
I do love bees.
She loves earth.
She, you know, she's an idea girl. So she has a lot of big ideas. And one of her big ideas is to have her own beehive.
Yeah, that is a dream, maybe someday on our compound. Maybe. But I think we could do bees.
I think bees are easy, honestly.
Actually, my mom tried to do bees and they're not easy. You know what, also, I will say bees are probably easier down here because the winter's not as harsh. My mom's bees never made it through the winter.
Yeah, you gotta get it.
She accidentally starved them the first year.
And then the second year, we think they didn't get warm. And then the third year, they flocked to a different nest. Oh, all the bees left.
Oh, well, then their queen must have died. Yeah, I guess.
Yeah, because you know, they never leave the hive unless the queen dies.
And then they always need to queen and that's what they have to go get. They also got too hot because they were flocking outside of their thing.
So did they not have enough water?
I don't know, bees are hard. She got honey though.
I mean, Kait, I can't wait to see your harvest. I'm proud of you on the garden, but you do have a history of getting excited about something.
Yeah, but you know what?
It's because if things have a lot of steps, I don't want to do them. We talked about sourdough for six months. I don't know any girl who eats and loves bread like Kaitlyn.
And I got her a whole shit.
She didn't follow through on that.
No, I didn't follow through, but I'll tell you why. I can never figure out the timing of it. And I honestly could not figure out the timing.
In my opinion, the idea of sourdough, which now I have a sister wife. You've got a dealer now. I've got a sister wife who makes the sourdough.
We've got a bread dealer.
We follow the crumbs, if you know what I mean. Yeah.
The idea of sourdough is what drove me. Well. Process was too much.
Yeah. But the point of all of this was that. I do want to say, I made one loaf of sourdough.
A brick.
It was not well done, but it was a loaf, which means I did have follow-through.
And then I decided, I don't want to do this. Yeah.
Okay.
That's follow-through. She had unfed starter for like a year, and then she just threw it out. Well, yeah, because it had like a lot of, what is it called?
The hooch. The hooch on it.
Yeah.
You can save it, but I don't think, I think Kait had determined this was not going to be her new hobby.
Yeah.
So anyway, it's Kait's birthday. We have a 1920s themed episode. So we're combining those for our drink check, and we're having a prohibition era.
Bees. Knees.
It's good.
It's gin and honey and lemon. Yeah, it's good. Yeah.
Colleen.
I added seltzer water.
I added seltzer shocker, and I subbed vodka for gin. So we're all having a slightly different version of the same drink, but Kait, of course, is having the OG.
The Bees Knees.
This is the Bees Knees, if you know what I mean, Maggie. So that's what we're having, and let's get into it, shall we? Between 1918 and 1920, the Spanish flu killed 50 million people worldwide.
Pause.
You know who was killed by the Spanish flu?
Edward Pellin. This pandemic arrived on the heels of World War I, and between the two events, nearly 5% of the world's population was killed.
But there was also another pandemic occurring, one that is less well-known and less frequently talked about, and that remains a mystery to this day.
At the same time?
In the winter of 1916, in Europe, people were seeking medical attention for general malaise. At first, it looked like a mild case of the flu, with fever, headaches, and fatigue.
Many would recover, but some would begin exhibiting tremors, and many slowed down mentally and physically, until they were completely immobile despite being conscious and alive.
The symptoms presented on a spectrum, but patients sometimes experienced lethargy or even obtundation, paralysis of eye muscles, rigid muscles, frozen posture, loss of speech, and sudden immobility.
In some cases, the progression was overnight, in others, it took weeks to months. Doctors called it encephalitis lethargica, but no one really understood it.
Some patients slept for days, others stayed awake, trapped inside their bodies that no longer moved.
Oh my God. What?
Hundreds of thousands of people lost the ability to walk and talk, and then in 1928, new cases just stopped appearing. By then, however, there had been more than a million cases, and half of those had ended in death.
You know what it sounds like? Gillian Barr.
Gillian Barr. Gillian Barr.
Yeah. You know what I mean. Oh, that was good.
I'm not wrong, though. It does sound like it.
But yeah, it sounds like Jilly. Let's be clear. Those that did survive often developed a post-encephalitic Parkinsonism.
We mean them rigid, slow, and unable to move normally for the rest of their lives. So what was this disease? A viral pandemic, a post-war complication, something we still don't fully understand.
This week, we're diving into one of the most unsettling medical mysteries in modern history, encephalitis lethargica, also known as the sleeping sickness.
Here are my thoughts already.
Yeah.
I'd like to know the age frame of people affected. I'd like to know-
All ages. All ages.
What environmental toxins have they been exposed to? And then when it ended, was there some other type of vaccine created? Like around the time frame of it not stopping?
And have we never seen it ever again? We've literally never seen it again?
My question- So encephalitis was their actual like-
Proof, proof? Well, yeah, proof that it was like- Doing lumbar punctures?
Yeah. Inflammation of your brain.
You guys, I have answers to most of those questions.
And you're sure this is separate from the movie where they throw a ball and they catch it?
That is, but that's not the same as brain on fire.
Oh, I'm talking about the one where they catch the ball.
The same one. What movie is it? The Awakening?
I've seen it a few times.
It's really good.
It's Rod Flames.
He was the doctor.
Yeah. And it's based on a true story, but I'm going to talk about all of that.
They kept their instinct.
They're frozen.
But if you throw, they hit.
But if you like threw a ball at him, he'd catch it.
Wow.
That's so interesting. Okay. We're getting ahead.
Okay.
I know what this is.
So really what this disease led to was like people being what we say, like locked in, which we see.
My biggest fear.
That's my biggest fear. Yeah, my biggest fear.
Do you think that with like when people get like chiropractic adjustments or whatever, they get posterior circulation strokes, and then they're completely locked in, so their brain is fully functioning, but they are like completely paralyzed, and
often maybe can move their eyes and that's it. Okay. So the disease in of itself, that it's like their statues and locked in, that enough is terrifying, right? That would make it a podcast worthy creepy discussion.
But on top of that, we don't know what caused it. Yeah.
It was like a post-viral syndrome.
That's a question. Was it somehow related to the Spanish flu? Because it seemed to be around the same time as the Spanish flu.
Do these people also have the flu?
These are all great questions.
I'm going to get to. Did everyone have FC bar? Yeah.
Was it an anatomy reaction? Was there some unlike you guys mentioned exposures? Was there some kind of like neurologic pathogen?
Right. So again, terrifying disease. The people were frozen for decades.
When you say frozen, were they able to breathe on their own? Was there diaphragm? They were able to breathe and they were able to...
You could feed them and they would instinctually swallow, but they're just sitting in chairs. Like catatonic. Like catatonic.
Okay.
Yeah.
Okay.
All right, all right.
I'm picturing.
I'm cracking.
All ages, like young people and old people.
It was all ages.
Also, we are three healthcare workers. We all just survived a pandemic. Wild.
Other than you see in the movie, Colleen, did we ever learn about this in school?
No.
No. Have you ever even heard of this?
No.
When you said Sleeping Disease, I feel like I had heard of it in some form, but that's it. Just the term.
I want to say I watched the movie in school though, in high school.
I just feel like decades of education, and I don't believe I ever heard about this huge global outbreak that occurred, which might have just been because while it was massive, it was not quite as massive as the Spanish influenza, which kind of
occurred at the same time. So maybe that just kind of overshadowed it, but I'm like, weird, this disease is weird. The fact that we don't know about it is weird. The fact that in answer to your question, have there been cases?
There hasn't.
There have been cases.
Oh, there have.
Cases still pop up today, but it's like one a year.
Oh my gosh.
So, fear unlocked.
Oh my God. So this pandemic ended 100 years ago. We don't know why it ended.
We're still kind of getting some very rare cases.
So they have been popping up to date.
But like one a year. So I feel like there's not enough. No one is like really invested in researching this because it's like the pandemic happened, it ended.
And then it was like, okay, not an active issue anymore. And so then we just have like, yeah, like one or two cases a year that pop up. Why?
Why so many?
This is all part of the mystery.
And so we don't know where it came from or where it went. Was there like a pathogen that mutated? Did it just die out?
Did something about our environment change? These are questions.
And they were scattered over the countries. Like, it's not one particular area.
Yeah, it started in Europe, but then it moved. And so yeah, you think if it was like an environmental thing, that's weird. Yeah, right.
But there was no common denominator.
Did some bug, like, migrate?
Like get on a ship and migrate?
Like a bad bug or something. Yeah, the Chinese lanternflies, you know?
So let me start with just telling you a little bit more about the disease.
Okay.
The diagnostic criteria for encephalitis lethargica is an acute or subacute encephalitic illness, which Kait pointed out, encephalitis just means inflammation of the brain.
Like so many things can cause inflammation.
An acute or subacute encephalitic illness, which has as part of its clinical picture, at least three of the following, signs of basal ganglia involvement, oculogyric crises, ophthalmoplegia, obsessive-compulsive disorder, achinetic mutism, central
respiratory irregularities, insomniac and or sleep inversion. So these people might have had like...
Basal ganglia is gait.
Yeah, like balance and like level of consciousness. It's like you're deep. So your level of consciousness, your gait issues, non-verbal, eyes aren't moving.
Could they blink?
So sometimes they could have, which also to, that's like when you're locked in from like a posterior circulation stroke, you can have vertical eye movement and that's it.
And when I'm, this seemed to have more of like a horizontal eye movement, like they could, they would look side to side maybe, but like they weren't really, like some of these nurses said it was like, you would just be walking and this patient would
Oh, that is so creepy.
That's some horror movie.
Yeah, I would never work at night.
Well, do they sleep? Are they always awake?
Well, they get sleep wake dysfunction.
Okay. Yeah, they're all delirious.
In the acute phase, the patients will present with a prodrome of flu-like symptoms including headache, malaise, generally not feeling well, low-grade fever, and then they would get this rapid onset of neurologic symptoms, and there were three
subtypes. So the most common subtype was somnolent ophthalmoplegic. So these patients got extreme sleepiness, confusion, delirium, had amyloid eye movements, about half of them died, but those who did survive tended to have a full recovery.
They didn't have kind of the long term.
Sounds like mono.
Well, it sounds like a lot of things. It sounds like vixidemicoma.
It sounds like mono. It sounds like the sleepiness.
Ion bray. It sounds like those types of like polio. There's a hyperkinetic subtype where the patients got manic and had involuntary twitching, like tetany, hallucinations, pain in the face and limbs, and circadian rhythm disruption.
So again, sleep, wake, dislike. That sounds like mania, petany.
This is weird. This is very odd.
And then there was a amyostatic achinetic, which is like rigidity and lack of movement, and you've got like the Parkinson's mask. The mask face got no emotions.
Okay.
So these are sort of like the three subtypes. So you would get this rapid onset of one of those kind of clusters of symptoms.
Okay.
And then many of these patients would recover, but some would develop a chronic version of the disease called post-encephalitic Parkinsonism.
Which is what these patients had.
Yes. Which is what the patients in the movie you're talking about. Those patients had.
So that's when these patients would be unable to initiate movements, but could be prompted into movement through reflexes or posing. So they could sit in a chair. If you threw a ball, they would catch it.
That's what we saw in the movie, The Awakenings we're going to talk about. Or if they're sitting in a chair and you lift their arm up, they'll keep their arm up.
Oh.
They said you could put them in an uncomfortable position and they would hold it, but they wouldn't initiate the movement themselves.
I hope nobody abused that.
So they called that waxing flexibility. Some patients develop psychiatric conditions and personality changes with pediatric patients especially prone to psychosis because you asked age range. All ages got this.
Patients typically entered this chronic phase one to five years after the acute phase. So imagine you have this syndrome, you have gone through one of these phases, right?
You recover and then five years down the line, you develop this post-encephalitic Parkinsonism, and you're back in this locked in state.
That is so weird.
So generally, again, it was one to five years, but they said that there were cases where it developed as soon as six months or as late as 30 to 45 years later.
I wonder how long it took the scientists to connect it to that original acute phase, if it happened decades after like that.
They had records. They do have records. Yeah.
Yeah. Somebody did a study, someone did a retrospective study, and I'm going to talk about it. Okay.
No, I meant Colleen. She's like, five years later, they-
Okay. No, she said 40 years, right?
Oh, I said that, well, in very rare cases, we've seen it as far as 45.
That is a huge gap that I wouldn't even cover.
But generally, it was the one to five years. One to five year rate. Yeah, but you know what?
That's what ID, like infectious disease doctors do.
They're literally- They haven't.
They're like the detectives of medicine.
I guess you're right. Yeah.
Especially if you don't know what's causing it.
It's like constant surge.
So do you know who else loves to pontificate?
Who? House, MD.
Neurologists.
Oh, yeah. Yeah. So-
Nerd alerts.
So mystery number one.
Number one.
Where did this come from?
A virus.
Okay. That's what you're thinking?
A virus. I can't remember what the movie said.
I don't think the movie told- No one knows. The movie really focused on the scientist later who tried to cure this.
Yeah. That was really the focus. Okay.
This is like such a 10 percent that she's like, I've seen the movie, and now it's like-
Multiple times.
And they catch baseballs, and they catch baseballs.
Yeah, they catch baseballs. I've seen the movie like three times. Anyways, 10 percent.
I think to me, it sounds like a post-viral syndrome.
Okay. Or like something that- When you say that though, do you think it's like the actual virus is attacking the brain, or do you think it's like an inflammatory-
Like an autoimmune.
I think it's an inflammatory response.
It could be, and it could be like when you have Epstein-Barr and then years later, you can get a cancer.
But I know at one point in the movie, they were able to temporarily relieve symptoms. So it's something that can respond to something. Like steroids?
And I feel like viruses run their course. You know what I mean? Okay.
Wait, wait. IVIG.
Post-viral inflammatory response, autoimmune.
Yeah.
That's what I think. And that's what we- Well, I've got news for you without me even giving you the facts.
The three of us are all on the same page. Yeah.
Okay.
So the leading scientific theory- And so the disease was connected to the 1918 influenza pandemic, which makes sense because the encephalitis lethargica pandemic surged during and after the flu, so they overlapped on the back half, sort of.
And then as the Spanish flu ended, we had the ending of this pandemic. Right. I see what you're doing with your hands.
Thank you. She's drawing the waves. I'm trying to make a timeline.
The prodrome of flu-like symptoms was suspicious too, right? Because most of these people reported having a fever, malaise, and then they got this. That's like an inflammatory response.
Yeah, you're right.
Yeah.
The movement control centers like the basal ganglia would become inflamed, and that would explain the Parkinson-like symptoms, which is not dissimilar to subacute sclerosing hand encephalitis, where years after contracting the measles, a mutated
measles virus will attack the brain, leading to personality changes, myoclonus, it's like, you know, twitching, seizures, dementia, Rye the movement's, coma and death. But scientists have never discovered the influenza virus in the preserved brain
samples from patients. So they've actually gone back in the loop and they couldn't find that. So that was like, that's like kind of the one theory, is like the infection from the Spanish flu later on infects the brain. Yeah, right, right.
But again, we have no proof of that. A newer theory is what we all think, autoimmune related.
Right.
So there are other recognized types of encephalitis today that are caused by the immune system attacking the brain. So the big one, the movie I thought you were talking about was Brain on Five.
Yeah. Which I've seen that too.
And that's a great book. I think I've mentioned that on this podcast before.
She gets tetra, tetra, what is it called?
Yeah, teratoma.
Teratoma.
So anti-NMDA encephalitis, which is what, this is what I thought on the pit when the guy had schizophrenia.
That's what you thought he had.
I thought he had this and I still maintain that if I was writing it, I would have written it. That would have been way more interesting than just schizophrenia. Agreed.
So a lot of these patients present like they're schizophrenic, and then when you go back, it is like an actual medical condition that's causing these psychiatric syndromes. Right.
Which in general for the listeners, whenever people come with psych symptoms, you always rule out any possible physical medical condition first. If you have depression symptoms, they're going to check your thyroid, things like that.
Which they did do in the pit. They did an LP, a lumbar puncture on the patient before they diagnosed him with, and I don't think they ever said schizophrenia, but that's sort of what they ended up saying.
So in 2007, this anti-NMDA encephalitis though was discovered. And usually what Kait was getting to that these patients have some sort of teratoma, ovarian or testicular usually. So some kind of germ cell tumor.
And that the germ cell tumors contain brain tissue, and it triggers the immune system to attack the NMDA receptors in the brain.
And they attack themselves.
And the NMDA receptors are like the primary excitatory neurotransmitter. So your immune system cranks up and tries to fight this tissue, which means it's also fighting your own brain.
Yeah.
And these patients develop inflammation and then present with them. Again, it usually starts, we would get a lot of patients who were like, found wandering naked in the street.
So it's like sort of like some kind of weird psychiatric like presentation. Right. That then progresses to cognitive changes, movement disorders, seizures, autonomic dysfunction, if left untreated, death.
And the treatment, besides removal of any tumors, is aggressive immunosuppression.
And that's different or well, that all of that is for the Brain on Fire movie.
Well, it's an anti-NMDA encephalitis, which is a type of autoimmune, which I'm trying to say, I'm just trying to kind of link the comparisons because I think this sounds similar to our theory, our theory, yes, that like this is the body's attacking
the brain and that's what's causing the encephalitis. Yes, yes. And the treatment for anti-NMDA receptor encephalitis, like Kait mentioned, is you do like a lot of immunosuppression.
So you give IVIG, IV immunoglobulins, you do plasma exchange where you filter the blood and you do very high doses of steroids. And then a lot of times you put them on like biologics, you know, right.
It's a general autoimmune treatment. Don't you have to remove the...
Yes, if they have it. I've also seen a lot of cases of ADEM, which is, we see this a lot in kids, but it's the same thing. It's a post-viral encephalitis where again, this hyperactive immune response from a previous virus causes demyelination.
You get this acute disseminated encephalomyelitis, you get inflammation of the brain, patients present with memory loss, personality changes, seizure, severe fatigue. Again, treatment for these are all like, let's turn off the body's immune response.
Again, I think this feels very similar. So it's possible that these patients had the Spanish flu, and it wasn't that the Spanish flu infected their brain, it's that they had this over-the-top response that led to an attack on the brain.
Unlucky.
The problem with this theory though, is that the tracking, if you track the outbreaks of encephalitis lethargica geographically, and you track the outbreaks of the Spanish flu, there's no overlap.
So these people weren't getting the flu.
It wasn't like everywhere we see the flu, a year later we saw encephalitis lethargica.
But that didn't happen.
No.
So was there any pattern?
Colleen, that was such a good question. In answer to your question, I told you that there's still kind of modern cases popping up, right? So researchers looked at 20 modern cases.
They found that out of these 20, 13 had strep antibodies indicating a recent strep infection. And almost all of them reported a sore throat. So were they all having like a strep outbreak?
Hold on.
There's a question I have.
There's a case in kids that when they get treated with antibiotics, is it strep?
They get treated with the penicillin.
And once they get the penicillin or amoxicillin or whatever they get, it's like they have this hyperactivity.
H-O-I-G-N-E Hoyng's Syndrome, characterized by severe agitation, confusion, visual and auditory hallucinations, and fear of impending death has been reported after penicillin, G-prokane administration in children.
New fear.
Well, you're not a child.
No. New fear. Why did I know that?
Oh, and then PANS or PANDAS.
Oh, I know PANDAS. Yeah, some children develop acute onset neuropsychiatric symptoms, including mood changes, anxiety, OCD, and behavioral regression, following infections, particularly strep infections.
This syndrome is termed pediatric acute onset neuropsychiatric syndrome, PANS. But PANDAS is like that. But it's, yeah, these kids get...
Again, with strep.
And you can eat them as an adult, but it just is more often seen in children.
Strep causes scarlet fever.
Yeah, strep is no good. I've had strep before. Am I going to get this?
So yeah, strep is no joke, guys.
Take your antibiotics, take your full course. That's why we don't mess around with sore throats. You got a sore throat in the temp, you better go get swabbed.
Period.
There's a theory that this was just a virus, but not the influenza virus, its own separate virus that is now extinct.
So maybe something that circulated in the 1900s, hidden the body for years, forcefully destroying the brain and causing bizarre behavioral movement symptoms, because we have CJD, Creusfeld-Jakob disease, which was a prion disorder where the proteins
Yeah, I was thinking prion disease, but you would be able to see that in the brain, right?
Yes, yes.
If you've looked at brains now, it progresses dementia, weakness, coma and death. Yeah, it feels like the book we read. What was the book we read?
Yeah, it did feel like the book we read. The line between. Yeah.
Yeah.
We read that book.
No, we read the book. We read the book.
Why?
Because she said, I was on vacation, and she said, I need a book suggestion. It was, it was met. The first book was better than the second book.
But pretty much the premise is-
I have FOMO.
Is that in this book, someone in Alaska eats brain. He's like a cattle guy who eats brain. He doesn't know it, but then the issue is that he goes and gets surgery.
They aren't disinfected for the prion, so then it's spread through the hospital, and then it becomes like a zombie apocalypse.
This is real?
No, this was a novel, a dystopian novel. And then you guys had mentioned, before we all jumped to autoimmune, your first thought was environmental exposure.
Yeah.
So the thought was, you know, World War I had just ended.
I'm thinking chemicals, bio warfare.
During and after the war, were people exposed to chemical weapons, industrial toxins, heavy metals, and new pharmaceuticals? Or did massive exposure to toxins trigger neurologic damage or immune reactions?
You know what though, I don't think that theory works because US wasn't a part of World War I, right?
Yes, we were. We were a part of it. We didn't end it like we ended World War II.
But we started World War II by ending World War I.
Yeah. Where would the chemicals be in Europe? You know what I mean?
Well, we were in Europe fighting.
Oh, children weren't.
Old people weren't. You know what I mean? Like they wouldn't, it would make sense for a whole bunch of young men to be the main population, but they weren't.
It's the airplanes.
Chemtrails.
Well, I think we've kind of touched a little bit on how this was very kind of Parkinson's-esque, except, yes, it's really more, Parkinsonian is the term we should use because it was not Parkinson's disease.
But similar presentations.
It was a more rapid, more severe presentation than what you would typically get with Parkinson's.
And young people.
Exactly, Parkinson's usually in older people.
But if we look at Parkinson's because there were similarities, we know 15% of Parkinson's disease is caused by hereditary gene mutations.
And the rest, we believe, are associated with exposure to environmental risk factors, like pesticides, rural environment, consumption of well water, exposure to herbicides, and exposure to dry cleaning chemicals.
And did you guys know that caffeine and tobacco have a protective mechanism against Parkinson's?
So we're drinking coffee, we're good? Yeah. And tobacco, say less.
Isn't CT and Parkinson's correlated?
Let me open my open evidence.
This is my favorite episode.
Oh, you are right. They're strongly correlated with Parkinsonism occurring in approximately 25 to 30 percent of individuals CTE diagnosed on autopsy, particularly those older than 50 years.
Yeah.
Look at you, Colleen.
I only know that.
That is a fact. Yes. So those are the theories about where it came from.
But as I mentioned, while we have these random cases now, the last survivor from that original pandemic died in 2002.
But they still froze them.
He had contracted it when he was 11. He lived in a facility in near Catatonia for over 70 years. So there's just like not a ton of interest.
It's kind of like it happened. It went away. And now people are like, this is not what we're going to invest all their money in researching, right?
Because I'm shocked he lived so long without getting like pressure injuries.
Okay.
You guys want to know about court. Did anyone just go back and look at this and find connections, right?
Yeah.
You asked that. What a retrospective study. The retrospective analysis, you are correct.
And in 2024, one of those occurred.
Where? What university?
They took, well, it was like within a single center in England, where that used to house a lot of these patients. I took care of these patients. And so physicians looked at case notes from 1918 to 1946, and they compared 614 cases to 65 controls.
And they noted that about 32% of the patients had a febrile prodrome in the year preceding their illness. So almost a third of patients had a fever before, but not all, only a third.
Oh, okay.
They found that only 37% had had a case of the flu documented. So if we were like this, again, trying to be like, did they all get the flu and then get this disease, doesn't sound like it.
And they felt these were statistically significant compared to the control group, the febrile prodrome and the previous flu. But again, about two-thirds of patients didn't experience these things. So that's hard to say this caused this.
Right. They could not find any evidence of a common exposure, but they did compare, they looked through like what all these patients experience. And I'm going to preface this by saying, you guys asked about lumbar punctures.
They were doing lumbar punctures at this time, only about 177 patients, less than a third of them got LPs.
Anything conclusive in all?
What's interesting is that almost all of them had clear CSF, and only 12% had a white count.
For the reader, can you tell them what CSF is?
Cerebral spinal fluid is the spinal fluid that coats our brain and our spine. A lubricant, if you will. Correct.
And when you have like an infection in the brain.
It would be cloudy.
It would be bloody, could be cloudy, depending on what is going on in the brain. You might have white blood cells in there. But you would expect with an inflammation of the brain encephalitis.
There would be something.
To have white cells.
So you could see white cells if it was a bacterial infection in the brain, you should see white cells, even if it wasn't infectious, but it was just inflammatory. But only 12% actually had white blood cells in their CSF.
12% of the 100 something that they did. And they didn't lumbar puncture every patient. So that's hard to even say if that's enough data collection.
Yeah, and MRI was not widely available until the 1980s, so we can't really take that into account.
But if we look at the current diagnostic criteria for autoimmune encephalitis, which is what we think it is, the diagnostic criteria requires three of the following to be met.
A subacute onset, meaning rapid progression in less than three months, with short-term memory loss, altered mental status or psychiatric symptoms. New focal CNS findings, so any kind of new neurologic deficit.
Seizures not explained by a previously known seizure disorder. CSF pleocytosis, meaning that there's white blood cells in the CSF, which again, we said most of the lumbar punctures did not demonstrate.
And MRI feature suggestive encephalitis, which again, we can't really use that because we didn't have MRI. And then reasonable exclusion of alternative causes.
So when they took this study, if we had all this information on these patients, these 600 plus patients we looked at, how many of them would have met diagnostic criteria for autoimmune encephalitis? More than half of them.
And again, I'm like, would that have been even more if we actually had LPs on people and if we had MRI capability, maybe we would have had more than that.
So it seems like we don't have a definitive answer to that question, but my money is still on an autoimmune. But again, to what?
You said that there's still like one a year or whatever. Are they doing all of this? Like, do we have anything new from the...
Well, yeah, any other thing.
Honestly, the way I looked up, I was like, how are they treating these one to two patients a year? And they're treating them with IVIG, plasma exchange, high-dose steroids, which is how we treat autoimmune encephalitis.
So if that's what they're seeing the response, then we can make it clear. I feel like that sounds...
But we just don't know what they're autoimmune responding to.
Hold on. With modern medicine and the development of medicine, how many people recover after, or is it still the same?
They still become catatonic.
Yeah. I don't know. There were so few cases that didn't look much into it.
I will say there's videos online of people who have this, and they are up and walking and doing things. And it's like they're still having maybe gait issues, but they're not in this frozen statue like they were in the 20s.
Interesting.
Where it came from, we don't know. We have our theory, right? Question 2, how do we treat it?
So in the 1960s, as I mentioned, a lot of these patients now were 40 years, 30 years out from this pandemic, but there were a lot of these survivors who remained hospitalized and they filled entire wards for decades.
Yeah.
Neurologist Dr. Oliver Sacks began going into these wards.
So this is where the movie comes?
Yes. He said, they would be conscious and aware, yet not fully awake. They would sit motionless and speechless all day in their chairs, totally lacking energy, impetus, initiative, motive, appetite, affect, or desire.
They registered what went on about them without active attention and with profound indifference. He described them as being ghost and zombie-like.
In 1966, he had moved to New York and was working at Beth Abraham, which sounds like was like a rehab, like a long-term care facility in the Bronx, and they had 80 chronic patients who had been suffering for decades.
He wondered if new developments in Parkinson's management could be utilized in the encephalitis lethargica population.
Because they had such Parkinsonian symptoms.
Exactly.
Now Parkinson's, again, we're talking about not encephalitis lethargica, but actual Parkinson's disease is a neurodegenerative disease in which neurons or nerve cells in the brain slowly break down and patients develop tremor, bradykinesia, where you
get really slow movements, muscle rigidity, gait and balance issues. They have difficulty with memory, language, and reasoning. Mood disorders like anxiety and depression, dysphagia, so difficulty swallowing and chewing, and dysregulated sleep.
So when researchers looked at the brains of deceased Parkinson's patients, they discovered they were deficient in dopamine, which makes sense since the neurons that produce dopamine were being destroyed.
Dopamine is a neurotransmitter that aids in communication between nerve cells. So researchers wanted to supplement dopamine into these Parkinson's patients and see if they got better.
But dopamine administered to patients could not cross the blood-brain barrier. So they said, I wonder if we could give Dopa, that's like the precursor of dopamine to these patients.
If we give to them, we're going to see a benefit in Parkinson's patients.
Lividopa.
Exactly. And so that's how the drug L-Dopa or Lividopa, they started giving that first to animals in the 50s and they saw a benefit. And so this was life-changing for Parkinson's patients.
And Dr. Sacks is like, I wonder if it'll make a difference in this population. He selected an experimental group of six patients.
He gave three of them Lividopa, and then we had a control group who received a placebo. And he administered the medication for a 90-day observational study. The findings were remarkable.
Remarkable.
Remarkable.
The study group woke up.
Movin around.
With many of them speaking and walking for the first time. Wow. And that's why, like, really these people didn't have, like, muscle atrophy.
And they had memory.
Yeah.
Like, they, it proved that they were in there.
Yeah.
I said, hurt. Healthcare must have been better in the 60s than I imagined if these patients could walk after four years.
It probably was. It was better.
He started giving it to other patients. And while they had initial improvements, he noted that over time, they required increasing doses to receive the same results, eventually developing side effects and relapsing.
So this, there's a book you can read, The Awakenings. There's a film that Colleen and I watched. It's great.
Robert De Niro?
No, it is Robert De Niro and Robert Williams.
So Robert De Niro plays Leonard, who is the most famous case that Dr. Sacks talks about.
Because he's young.
He was young. Before treatment, he had been frozen in a near catatonic state for decades, unable to initiate movement, almost completely still. He remained alert, but frozen in his own body.
After levodopa, he awakened rapidly, regaining speech, humor, and sharp intelligence. He picked up life exactly where he left off, but became intensely aware of all the lost time leading to restlessness, obsessive behaviors, and ticks.
I mean, this guy was like a teenager.
When he got sick.
And then it's like 40 years later, and you come to, and it's like you just missed. Yeah, but like- All things that had happened.
Yeah.
You know what I'm thinking about? Like if you've missed your like crazy face. I'm thinking about-
Adolescent years.
Yeah.
I'm thinking about all the things that were invented in the 50s, like cereal, like cornflakes.
That's what she's thinking about.
And suddenly like the breakfast options. Like that's crazy.
So he struggled with impulse control, he experienced emotional highs and crushing lows, and eventually his condition deteriorated as side effects worsened, the drug lost effectiveness.
Also, levodopa makes them feel high. Like-
I mean, dopamine is also-
It's the happy drug.
Yeah. Rose R was passive, almost entirely withdrawn with minimal movement or expression. After levodopa, she became lively, expressive, even joyful with a strong personality.
She became overwhelmed with the passage of time as the drug's effectiveness fluctuated, so did her condition. And she would cycle between clarity and immobility. And so she was like very vital after levodopa.
Then as she started to relapse, she became very distressed about like losing that vitality. And ultimately she did not sustain her improvement. Another case, again, there's a whole bunch of these you can read about in the book, but Mrs.
O, she was completely immobile and unresponsive. She was able to express what she experienced during those silent years. That's how we know again that she was in there.
She was fully internally conscious observing everything but unable to act. She described being trapped in her own body.
But in addition to the burst of energy, she became hyperactive, talkative, and euphoric, developing a type of mania, fluctuating between periods of normal function and dyskinesia, like involuntary movements.
Again, she had these profound side effects and her improvement was only temporary. So sad. But here is the deal too.
Yeah, like the movie ends and they're all back frozen.
Like kind of a really sad movie.
It's like, yay.
You learn about them.
And then it's the struggles that it's not as easy. Like, yeah, Leonard's mother was like his caregiver. Now she's like, what do I do?
She's 90, doesn't need me.
And then my thing is like they woke them back up after decades of being locked in, which is like is a miracle. But then I'm like, is it worth it? Because then they all became so depressed of what they missed.
They're like, wait, my husband divorced me.
My family is dead.
Pros and cons.
So the story was that like he couldn't get this work published because it was this small single center observational study. So he ended up writing a book about his work. He wrote multiple books.
The book Awakenings included the case reports that I kind of touched on. There's more than that. It talks about individuals that he had treated.
And then that was adapted into the 90s film starring Robin Williams, Robert De Niro. But I have an update on this. And it's not good news.
There was an article in New Yorker in December that painted a different picture of Dr. Sacks.
Don't tell me he was abusing them.
Well, he was a, no, no, but he was a troubled man. He was a gay man. And his mother told him homosexuality was an abomination.
And then she died. So then he was like grieving his mother. He was like all messed up from, you know, hating himself.
And he spent a lot of his life living in a celibate state. He went through extensive therapy. And in his journals, he admitted that he had fictionalized or embellished his medical reporting, adding background and details to make for better stories.
Oh no.
And adding abilities and depth that patients did not experience.
It's like the way he was trapped in his life. He could see in these patients that were trapped.
So it ruins all the data.
So he claims that this patient got better and this one didn't, that that is all accurate. And the thing that he altered was more of backstories of the patients, and to make them more reader-friendly and dramatic. Yes.
His journals described his books as half-report, half-imagined, and he wrote about the guilt he felt over the lies.
But again, he says that the lies were limited to subjective background experiences, but the data was true and was validated by other research.
This article also revealed that again, in his attempt to paint these pictures of these patients, in a way that we all want to read and root for them, he made Leonard this young kid who was this really great guy, and as a child was turned into this
statue. But Leonard was not a good guy.
Oh, no.
Because after the Levadopa woke him up, he wrote an autobiography and he talked about his childhood before getting sick, and he bragged about having raped his cousin and girls that he was babysitting in the movie back in the day.
Yeah, so I'm like, not a daring guy that Robert De Niro portrayed in the movie.
Imagine waking up after decades of being in a catatonic state only to think you're flexing.
Yeah, well, she'd be like, you missed the beginning of like, women are people. Right. And you think that you're going to write a book and be like, people are going to think I'm BA that I raped the little child I was babysitting.
Instead of just being like, maybe you're better off locked in, sir. Right.
Lock him back up.
Yeah. So that's kind of what I have. There is one weird mystery I want to add.
So where it came from?
No idea.
I mean, we think it's a post-viral syndrome. Yes. But we think it was like they all got, or some kind of post-infectious.
Are we thinking they all got strep throat and then got this? But then even if you say that, why people get strep throat now and they don't get this? I know.
We're stronger now and we get treatment.
But before that, this wasn't happening.
After this, it wasn't happening, which is like this window. I guess the issue would be like, I'm like, yeah, my money is on this as an autoimmune response to something, but how was it a pandemic?
Like, you know, when you don't get autoimmune pandemics.
No, that is weird.
It's got some kind of...
The cause was an etiology. The cause was a pandemic, but we don't know what.
I'm surprised Colleen has not brought up that this could be like a psychiatric. I've been waiting for her to say, were they all...
Sounds so clear that they are reacting to something.
Yeah, I thought she was gonna be like, were some of these people faking it? Was a lot of this like psychosomatic? Yeah.
It was a traumatic time, and maybe they were predisposed to psychiatric issues. I really also thought that's where I was gonna go with it. Yeah.
I mean, they're locked in.
That is not like a menti bee. Well, catatonic. Yeah.
That's kind of like...
A lot of these people were...
Catatonic with reflexes? You can't fake that.
Okay. So yeah, such a mystery still on what caused all of these to happen. Now, just something interesting to add to this story, because we like a good mystery, we like a good conspiracy theory.
So do you remember in our Hitler-Argentina episode?
Oh, no.
We talked about how Hitler likely had Parkinson's.
Yeah.
And we said, we all agreed, we didn't think that he made it to Argentina, and if he did, certainly didn't live long because...
Yeah, because he was on all those meds.
Yeah. Well, there is evidence that maybe he didn't have Parkinson's, maybe he had encephalitis lethargica. So the evidence is that his symptoms started as tremors in 1923.
He had left-hand tremors and he would hide his hand in his pocket or behind his back, but he was only 34, which is really too young for Parkinson's. I mean, it would be like early onset Parkinson's, but Michael J.
Fox.
Very rare, yeah, very rare. In the 1940s, he had rapidly progressed and was hardly ever seen in public. And there were documents of abnormal eye movements, which would be consistent with encephalitis lethargica.
So did he have encephalitis lethargica? That's just like an interesting question. And then Woodrow Wilson, he went to the 1919 Versailles Peace Conference.
We're trying to wrap up World War I, right? They said that he got sick while he was there, and then he started having weird personality behavioral issues.
So when he had gone into the Peace Conference, he was like, I don't want any reparations from the Germans. We need to just end this war without any bad blood and move on. And then after he got sick at this Peace Conference, he flipped.
He ended up voting to approve or to enforce harsh punishment on the Germans, including accepting blame for World War I, paying massive reparations and shrinking military losing territory, which led to German resentment and economic collapse, thereby
allowing for the rise of Hitler, which then led to World War II. So one of the theories like, why did this guy who was so, Woodrow Wilson was like, we're not gonna come down hard on the Germans.
And then all of a sudden he gets sick, he flips, and he has behavioral and personality changes. And so some people are like, did he have this? And is that what caused him to change his mind and led to World War II?
So those are weird mysteries.
Yeah, that is a weird mystery.
Sounds very conspiratorial. Yeah. Anyway, that's all I have.
Again, I just think it's interesting that like, we don't really talk about this. It was a whole pandemic.
And nobody started it.
We still don't know why it started, why it ended, and what exactly it is. But it's terrifying that people spent decades locked in, in psych hospitals, you know?
Crazy sauce.
Anything else that anyone wants to say?
No, I just, again, they still don't know what causes it. Is it a tick-borne illness? Oh, good thought.
There's probably an infectious disease doctor out here who's thought about that.
Well, you know what? Also, we'll find out if there's a resurgence now that we have more ticks from the Lyme disease vaccine. So, the current cases are being treated with immunosuppression.
So, IVIG, plasma exchange, high-dose steroids, and then also levodopa, just like Dr. Sacks did.
Well, and again, I don't know, I think we see, again, I've seen videos of patients rehabbing from this and they look better than locked in, but they still haven't like have a gait issue, that kind of thing.
But I just feel like with an N of one a year, I don't know if we can really say like, oh, we're treating these patients and they're getting better. No other thoughts from you?
No, I just think the movie's good, but now I'm tainted knowing that he was an awful person. Not Robert Wigley.
Not an awful person, he just had issues. He just raped his cousin. No, you're talking about Leonard.
Yeah.
I thought you were talking about Dr.
Sacks. I'm like, Dr. Sacks?
No.
The thing just got a little bit, had just a flare for the dramatics maybe, and had a rough life.
But yeah, Leonard, again, I feel less bad that Leonard relapsed and ended up locked back in. Okay. Well, something a little different.
I just thought this medical mystery might speak to our strength. Guys, just a reminder, don't forget to check out our Facebook and Instagram pages at 3SchemeQueens. That's the number 3SchemeQueens, all one word.
We're also on Reddit, same username.
If you want to check out our website, go to 3schemequeens.com, and you can find links to our social media accounts, our Buzzsprout page, all of our episodes, additional content, and our contact page, where you can engage with us and share any updates
on the topics that we have discussed. Let us know how we're doing and what you want to hear next. There are also opportunities to financially support us with links to buy us a cup of coffee and links to our merch store.
As always, if you choose not to financially support us, we appreciate the follows, the downloads, the listens, the likes. Kait, what should the people do?
Yeah, I want you to take out your phone right now, and I want you to text three people who are interested in medical mysteries.
Yes, who are interested, who liked HouseMD. Because this feels very HouseMD.
It does feel very HouseMD.
And after, I would like you to scroll on down, leave us a five-star review, leave us a comment, share us on your social media platforms, interact with us on our social media platforms, send us an email, send us anything that you want us to chat
And yeah.
You're in. And otherwise, we will see you next Tuesday.
Next Tuesday. Next Tuesday.