Ep. 26: Can't Sleep, Won't Sleep

0:06 Welcome to M4 Medicine, mystery, mayhem, and sometimes murder. I'm Andrea Marciano and RN with 35 years of experience across various fields. From direct patient care in hospitals to home health, geriatrics, and injury medicine, I face life, death, and everything in between. And I'm Crystal Miller and RN with 13 1/2 years of experience. My work spans home health, Hospice, emergency care, geriatrics, and occupational health. From the chaos of trauma based quiet moments with patients, I've seen stories that defy explanations. We've been friends for over 25 years and as nurses we've shared countless stories that have left us and our families speechless. Now we're bringing those stories and many more to you in medicine, mystery, mayhem, and sometimes murder.

0:53 Each week, we'll uncover cases that challenge the boundaries of medicine, sharing the human stories behind the science. From puzzling medical mysteries to shocking real life crimes, we'll bring you stories that'll leave you questioning everything you thought you knew while. We're both experiencing these nurses. We want to make it clear we're not here to give medical advice. This podcast is about storytelling, education and exploration, not diagnosing or treating medical conditions. This is medicine, mystery, mayhem and sometimes murder. Let's dive in. Hey Crystal, how are you? I'm doing well. How are you? I am well, thank you. Anything exciting going on in your life these days? Oh, I was really sick yesterday and I as you recall, we couldn't record this episode because I was too sick to record.

1:36 But I'm feeling much better now, So what a difference a day makes. No kidding. And that's very good news, because the type of sick that has been going around for people involves bodily processes that are less than fun. Indeed, indeed. Well, I'm glad you're feeling better. Thank you, me too. Good. Today I have a topic that I had never heard about until looking at our research sheet of the things that we want to talk about, and this is called fatal familial insomnia. That sounds really scary as somebody with insomnia especially. It is really scary. We'll preface all of this with it's quite rare.

2:17 No panic yet. Thank goodness. Exactly. So my sources are from the National Institute of Health in the part of the National Library of Medicine. Zalancon, Mr. Sankiri and Pradeep Blue wrote an article about familiar insomnia and another article in Institute of Health Library was written by a whole group of people from Italy and it's like 10 different names but the article is 9521 two 57 if anyone wants to go read it. Excellent, excellent. There is an article on rarediseases.org website. That was when I got quite a bit of my information from sciencedirect.com, clevelandclinic.org, and a book called The Family that Couldn't Sleep by essayist and journalist DT Max.

3:15 Those are the things that I used as my primary sources. I had never heard of fatal familial insomnia. I have not heard of it either. I think we think of insomnia and many of us, especially those of us in menopause or perimenopause, experience insomnia. I believe you. Like I have had insomnia issues most of my life. Yes, I have. There's probably a lot of reasons for that. We should. A youngster. Me too, me too. I solved it some of the times by being an avid reader at night and my parents. My parents thought that's why I stayed up but I didn't. I just couldn't sleep. So I read and write. Reading could help me fall asleep, but, and I know that there were times with insomnia that I felt like I was dead.

4:00 For sure or wish I was dead. No kidding. But we're going to find out that this fatal familia insomnia is awful and much, much worse than we have experienced. Fortunately, I did quite a bit of research on this because it was hard to tell what was happening exactly. And this, like many of diagnosis, are based on a certain cluster of symptoms. The hallmarks of this disease include aggressively progressive insomnia. OK. And subsequent autonomic disturbances including tachycardia, hyperhidrosis, and hypertension. OK.

4:42 Right, because of these things, cognitive disturbances happen because nobody can function without sleep. It includes deficits and short term memory and attention balance problems and endocrine dysfunction, which to me it's like, OK, that all really sounds like just having trouble sleeping, right? I mean, I've had trouble sleeping and I felt all of these things, right? Right. But this is on a scale of severity that it's hard to imagine. I just think of times we, in one of our episodes, you talked about the fact that you hadn't slept for like 36 hours or something like that. It was like 12 days, 12 days, a very long time. And you were having issues, right? And, and that's pretty severe.

5:27 And even if you may having not slept meant maybe you had 30 minutes here or 20 minutes there or whatever. These people don't sleep at all. I mean, at all. The disease is currently incurable and has an average duration of 18 months. Wow. And it ultimately leads to death. Wow. So they literally die from this. Some people die faster, some people take a little longer, but the average duration is 18 months from the time that they realize they have it until they're gone, right? This is, we'll talk about this a little in a little bit more detail, but this is called a prion disorder.

6:07 So is amyloidosis, and so is mad cow disease. Exactly. And we'll talk about Mad Cow and and the CJ Khrushchev. I have to read it because I never can remember it, right. Yeah, which is interesting, right. So we'll talk more about Prion. That's funny, I was just thinking about I could do an episode on Prion, but I guess this will be the episode on Prion. Well, you might go to more detail, but I think we'll have enough in this one. That's. OK, I hadn't, I hadn't prepared for it or anything. I was just thinking about because you know the situation with my sister. I was just thinking. About maybe doing an episode on Prion, but I'm happy to let this be the episode on Prion 'cause I want our enlistors to learn about it. Yeah, and it was something I had literally never heard of.

6:50 Now people might say well you're a nurse of 30 plus years and you haven't heard of it, right? Because while I am a nurse, I have not specialized in every possible discipline in medical issues most. Of us will. Right. Most of us, whether we're nurses or physicians or any anyone in a medical field will do a specialty of some sort, whatever that looks like. And we can't possibly know everything, although some people think we should. And even sometimes when we learn about things like say in school, for example, because we do learn a lot of broad topics and, and things in school, but then once we do specialize, it's easy to let that specialty kind of take over. And some of those things that don't apply to the specialty kind of fall to the weight side.

7:37 You mean perhaps things I regurgitated for a test and never thought about again? Precisely what I mean. All those right, Right. Well, memories do have limitations at any rate. This prion disorder, and all of them apparently from what I saw, are characterized by long incubation periods and short clinical durations. Short can mean different things, but it's short generally, considering what most chronic illnesses have. This means the abnormal prions may accumulate for many years without causing symptoms, and that's the long incubation period. But once symptoms begin, the disorder rapidly worsens. The earliest description of the disease dates back to 1765. Wow.

8:24 I know I looked but there wasn't much about this. But there was a report of an Italian man with symptoms suggested suggestive of FFI, fatal familial insomnia. So we'll call it FFI most of the time from now. Sure, forget and say the whole name might do. But the disease was formally identified and clinically described in 1986 by Ligerisi ET All, followed by subsequent studies further describing its pathophysiology, etiology and clinical course. And again, they had reference to this guy in 1765, but I never saw anything that specifically said This is why, although he fit into the bucket of FFI and but this study in 1986 appeared to be the first really broad study giving some further information about it.

9:19 It said over and over again in the things I researched that the most important thing is a detailed history and neurological examination, because these are the things that start narrowing down what it is. Because we know that with neurological concerns, there are several types of neurological things that will indicate this sort of thing or that sort of thing or different diagnosis. So it's a rule out, as is most of what medicine is. Yeah, it's a rule out. It's not this. It's not that. OK, what else do we test? And we'll talk a little bit more about what other things can be tested. And as I mentioned, their treatment essentially focusing on symptomatic relief and of care because again, there's no cure.

10:01 We'll note that in these prion diseases, that's the case. As far as we or them, I'll say it many times, but it's extremely rare. So if you're hearing this and you have insomnia and any of these symptoms sound like they could be you, ask your provider about it and know that it probably isn't that. Well, if it's familial, you'll probably have seen it in your in your history, right In your history. Probably we'll talk a little bit more of that in a minute. But worldwide, there have been hundreds of cases of FFI documented, predominantly in Europe and Asia. What's interesting is, yeah, and there's a notable increase in recent years, particularly in China. A total of 131 FFI patients were identified and reported, including 57 women and 72 men.

10:53 And that was in China. As far as I know, they don't know why yet because this is still kind of emerging information. And this is one of those disorders that is rare enough. And we know that rare things don't get as much money because they're a total of, you know, few 100 people in the whole world versus things that have a whole lot more people affected. But I think that we're finding there are more and more things that may involved this disease pathology. But the average disease onset was 47 1/2 years old. Wow. OK. But it does range somewhere as young as 17 and somewhere as old as 76. Now, when we see this, the person that was 17, I would think either presented with really strong symptoms or their personal provider watching for this was really aware of the disorder. Because I can see many people being sort of pushed off from other sorts of problems before they really got to the bottom of it, which can happen when you have a disorder that's unusual. Maybe a person has never heard about it. But this report that they're referring to for these cases of FFI noted that 106 of these patients of 131 passed away and the duration average 13 1/2 months with a range of 2 to 48 months.

12:16 As we talked about South, initially they were saying 18 months. This study showed 13.2 months. The connection between variations and characteristics across regions and genetic makeup is subject to a scientific interest because there are some differences depending on where it is found and the genetic makeup of the people involved. There was a small study that was done and I didn't see who did the study. It just referenced this send this article by Legarracy and in his study at 86, they said that there's a study that suggested that a particular genetic difference at now you're going to really want to memorize this at codon 129 might be linked to the features of FFI disease. We kind of laughed at ha ha yeah, I don't know. However, this is a genetic code that are that is now being looked at.

13:11 So they may be able to see that it's coming. Like many of these neurological disorders or things that carry hereditary pieces, They're starting to find more of the gene markers that will say, OK, you may be coming up with it or this is in your family. You may not want to have children or whatever it is because this more likely to occur in your gene pool than it is in somebody else's. So they're starting to notice that at this 129 gene, there may be it might be linked to the genetic features of the FFI disease. Now again, this is a maybe they're not sure they have such a small population to look at.

13:55 They're having some trouble finding a true connection. But from the research I did, it looks like that Creon map is where it is. They say that in among Asians there's an occurrence of symptoms like movements, sleep, breathing difficulties and laryngeal strider, which was not noted in other genetic makeup. Why not really sure. Another separate displayed hypertension, excessive sweating and weight loss. Another group of Asians had double vision, so it looks like they're connected, but they can't, it seems, map it exactly. But the genetic prion disease again are very rare, 1 to 1.5 new cases of genetic and non genetic prion diseases per 1,000,000 people.

14:45 So I'll say that again, 1 to 1.5 people have this per 1,000,000 right in the pot. Well, we know someone who has one of these prion disorders. It's very, very rare, right? These people are very often genetically tested and studied to see if it's hereditary or if it is non hereditary because there are some cases where it's non hereditary because there is a mutation in that 129 freon. They think, I guess the good news is it's very rare. There's approximately 50 to 7070. There are approximately 50 to 70 families worldwide who carry the mutation that caused the condition. Now, because it's familial, 50 to 70 families may sound kind of like.

15:35 I mean that can propagate though. Exactly. Yeah, it can because it's familial, right? Hopefully these people are, I mean, just. Consider a just consider a family tree, right? Like think about the top and how far out a family tree can go. And so when you're saying 50 to 70 families, that could be 50, that could be one at the top of each of these huge trees. And again, I'm not saying, but I'm just saying that's not like 50 to 70 people. That's what I'm saying. Exactly. And remembering the average incidence of symptoms showing up is 57 years old. So these people have probably already had children, right? Their children may not have, but these people have. So it will start to spread in a reasonable way because nobody knew, right?

16:23 Because. We're doing genetic testing. We weren't doing genetic testing 30-40 years ago for this sort of thing. Also, again, so rare, they wouldn't test everybody cause genetic testing is still very expensive and you have to know what you're looking for. It's not just throwing a net out there and see what gets caught. You're like, OK, I'm looking for 1/29. Is it there? Right, right. Things like the bracha genes, now they really know what to look for. So it's faster, it's easier, it's cheaper, but it took a long time to get there and there's been millions and millions and millions of people dealing with breast cancer and the cancer's associated with a bracha gene. Not to say that this doesn't warrant study, but I can see how it would go a whole lot slower if for no other reason study groups are so small and it's really hard to get a valuable study with three people. Right, they're going to die in 18 months. Right, exactly.

17:15 I mean, what are you going to do? What it does, as I mentioned, causes progressive, untreatable insomnia, and I can't even imagine what that could feel like. I can't either having you had insomnia that ends I can't imagine. Yeah, some of the things I was reading about it, it feels like there there is some indication that there are sarcoses that end up being involved because the person just can't, can't, Yeah, anything. So this gene that is involved, the prion gene, causes misfolded proteins to accumulate in the thalamus. So the protein is there. It's either the way I understand, it's either extra or it's building up in a weird way and it basically eats the brain and the thalamus area primarily. And then it affects other parts of the brain and it destroys the sleep wake regulation because the thalamus is what controls that.

18:15 So if the thalamus is turning into Swiss cheese, then it can't do its job. Again, not determined until symptomology happens. So Speaking of symptoms, the characters to symptom is as I said, progressive insomnia. It often begins during middle age, but can occur earlier or later in life. And at first it may be mild. So you get somebody, you get a 45 year old woman who says I have insomnia. They're like menopause, good job, all right. And if you think about it, if they're getting their first symptom at 47 and it's insomnia and they're told for six months or more, it's menopause while they're dead before they realize it's not right, right.

19:01 Again, very rare, not going to happen to very many people, but still, I can only imagine how difficult this must be. So it becomes progressively worse until the individual gets very little sleep, sometimes literally no sleep. It can become suddenly and rapidly worsen over the next few months. And when they fall asleep, if they're able to, vivid dreams may occur. It's not, it's just different sleep if they're able to. The lack of sleep just leads to so many difficulties. Insomnia is usually the first symptoms, but they also have progressive dementia and worsened problems with thought, cognitive, memory, language, and behavior.

19:42 Initially the signs may be subtle, which again makes it difficult to diagnose because you've got a 47 year old woman who's having some little types of dementia, memory issues, things like that. Menopause, OK, for sure. Get to dig a little deeper initially. Like I said, they could have other things going on too. Unintended late weight loss? I'm really waiting for that one. I really want something for weight loss, but not that indicates a real illness. Just want weight loss that I don't have to worry about anyway. So unintended weight loss, forgetfulness and inattentiveness problems, concentrating or speech problems. Now I wonder if the unintended weight loss could be partially because of the forgetfulness, inattentiveness and things like that.

20:29 Because I think of people, people who have, say, Parkinson's that I'm familiar with, they don't think about eating because they don't either they don't feel hunger or they don't remember they're hungry after they feel it or whatever. So a lot of people who have Parkinson's or other types of dimensions still live on their own, literally starve to death because they don't take care of it, and after a while they just can't take care of it. These can be, to me, cascading problems, right? Because one will create the next and the next and the next. Still possible with these sorts of things pushing it off to something else because it's rare. People aren't necessarily going to be checking it now because some of the incidents in in China is increasing. I wonder if that makes it more commonly tested for. But it's still a very, very small population. So I'm not sure.

21:21 But some individuals may also, as I mentioned, have double vision or jerky eye movements. You've got someone, we've talked recently about people with tardive dyskinesia, some different types of medications that could, that could be something that gets pushed off on that or maybe they're testing for other types of things. They can have swallowing problems and slurred speech. They eventually have trouble coordinating voluntary, voluntary movements. They can look like they do have Parkinson's, right? Those symptoms will show. And maybe it's that many of these things can't be tested until the person has died, right? Like Alzheimer's? Yes, they have more and more physical tests and more cognitive tests that they're being able to narrow some of these dementias down. But it's still, I can see in this 18 month window how people may not have even gotten to the proper test yet with the things that are going on just because they're so diffuse and so unclear.

22:19 And maybe it's better one day, worse another day. They can have fevers, heart rate increasing, you know, tachycardia, high blood pressure increase sweat, sweating, which we talked about, the hyperhidrosis, which can be very unpleasant. Again, menopause, right? Menopause increase production of tears. I never saw why except for thalamus also has because of the automatic autonomic nervous system that thalamus runs. It is just probably one of those things that the body says OK, time to cry, time to do this. They can be constipated. They have also they can be increased have it increased heat or fever, but they can have decreased body temperature.

23:02 Interesting. So they can feel cold and sexual dysfunction, including erectile dysfunction, anxiety and depression are also common findings as well. Back to the age these symptoms typically manifest can be written off for so many rays. You've got a guy with erectile dysfunction dysfunction that's in his 50s. That's not that atypical. That's yeah, right. That's so. Do you worry about it? Is he going to mention it? Who knows, right? So that's kind of how the symptoms can look, which is a little bit all over the board. Pathophysiology is these misfolded prions. I tried to find a picture or something of what that could look like, but I didn't see anything and I didn't honestly try terribly hard, but I wondered what it could look like.

23:47 But it just does. Basically the picture that I saw, I saw an MRI and it was showing how the brain just didn't look quite right. And it would be more obvious to someone who's really well versed at this, but I can. Say we could read an MRI. That's right, those, those people. But you know, most of us have seen enough imaging that we go, well, that's not right. But they also note that the paradial temporal and frontal lobes have shown higher involvement than the occipital lobe. So it starts in the thalamus and then kind of goes out. Like many of these degenerative disorders, they'll start somewhere and they get worse and worse. The involvement of the brain cortex in almost all cases is positively correlated to the duration of the disease. So to me, what that means is the longer a person has this disease, the more parts of the brain, including the brain cortex are involved.

24:47 The prion proteins pattern in the brain are, as I mentioned with thalamus being the most effective by degenerative changes. Now it doesn't mean that everything else is left alone, but the thalamus was the most involved and has the most problem with what the ultimate decline is. And everywhere it says it's poorly understood. They don't know. They don't really. They don't really know what the triggers. I mean, like I said, it's hereditary, so the genes are there. But if the genes are there and it's been there for a long time, they were talking about how the protein starts to kind of pile up. So that's why it takes a while to have an onset. It didn't say in what I read why maybe it goes faster in some people than others.

25:36 It didn't. It didn't indicate that to me. I don't know if maybe there's greater genetic material that has it positive on both sides or something that maybe that could increase it. I'm not really sure. No known care exists. Again, palliative care. People almost always go on to Hospice right away because they're doing that palliative care. So now I'm curious, if you go on Hospice and they give you say oxycodone or Oxycontin, and why can't I think of the other one, Anxiety medication, Ativan, is that going to put you to sleep? We'll talk about that in a minute. Oh, OK. OK.

26:17 Yes, not those drugs specifically, but generally clinical presentation as we talked about are sleep disturbances, disruption of normal sleep architecture. So there will be when a person sleeps, they go through different phases, right? And in case of his sleep disturbances, they have an increased frequency of leg movements. They have central sleep apnea was reported in 40 to 60% of patients. We both clutch our pearls going sleep apnea. I know I'm like, that's it, I've got it. I'm dead. I know any minute now, but but so can you see how this can be really dangerous thing to know about like some of the things like no any minute now I'm going to anyway, I feel I'm probably safe as I'm 60 and has passed the window and I'm still alive most days.

27:04 I know I feel pretty proud. But I did think it was interesting that that sleep apnea was reported in 4640 to 60% of patients and the sleep apnea they speak of is central. So that's the brain controlled breathing. So when the brain is air quotes offline during sleep, it's like, yeah, breathing, not breathing, whatever. Breathing. What else? What do we need that for? And that's part of I have central and obstructive sleep apnea and that's what my brain says now we're we're good. We don't really need to worry about that whole breathing thing. And because of the central sleep apnea. Now it did make me wonder, is there something neurologically that could be addressed in in a situation such as myself with central sleep apnea or not? Don't know.

27:50 I did as I always do in our very intensive studies, I thought about it, don't know why. All right, moving on. We have to be so careful not to go down rabbit holes. I get it because when I was first researching for this I'd be I'd spend 5 1/2 hours researching something because I went down 5 rabbit holes. I know. It's an easy trigger. Highlighted text going, oh, what's that mean? You know, it's so true. It's so true. But in this case, I really thought that was an interesting finding. As the disease progresses, it can disrupt the sleep wake cycle, leading to a confused state during wakefulness. So usually we're on the circadian rhythm.

28:32 We it's based on light, dark, etcetera, and the air quotes, normal sleeping pattern. Now you've got people who are working overnight shifts. Well that all bets are off of that case because they have to shift, physically shift their rhythm because they have to be up all night. I was never capable of doing that without being sick. But because of this disruptive sleep wake cycle, there's a confused state during wakefulness, as I just mentioned and people reported as being a dreamlike state. So if you ever, I think of it, maybe as I, I'm sleeping deeply and I wake up suddenly I'm like, what, what, where am I? What am I doing? That's how I envision it. I don't know if that's really how it works, but that's kind of how I envision is that the whole time that the person is awake, they're sort of not even really awake because they haven't really gotten grounded themselves or yeah, or whatever.

29:26 And because even if they're air, quote, sleeping, their body is still not really reaching those R.E.M. states that we're all supposed to need. Some of these other symptoms, the autonomic dysfunction, can be things that will mimic other, other disorders. As we talked about the hypertension, tachycardia, things like that can mimic other things. So there could be a whole series of tests that are unrelated to this disorder, again, possibly not being completed before the person has died and the death is diagnostic, right. Then they know. Yeah, I guess that was it. You were talking about how if it runs in families, so there are times where if there have been enough in a family, they'll go, OK, well, we know right away what this is. But if it's a family that has not ever had an onset of it or maybe people died early enough that they weren't involved yet because what if a person died before they were 76 and they weren't going to manifest until after 76? They didn't know, right?

30:25 So that group is gone. There are multiple cranial nerves potentially affected because of the involvement of the brain stem. Some of those things are the double vision early in the disease. And that actually can be diagnosis to diagnostic to having that double vision or swallowing difficulties in gay gaze abnormalities. Those are those can be diagnostic in this situation. They can also have hallucinations after many people. The median point of this disorder is 12 weeks. After they've had this disorder for 12 weeks, they can start having hallucinations. They start having a loss of orientation about where they are in space.

31:08 They start falling over. But what does it sound like? Parkinson's right, or all kinds of other things, Yeah, yeah. Again, could be a problem. They have the gate difficulty ataxia, which is that sort of odd gates going on, and the gate changes though in this can when they know this is what it is. The gate dysfunction will reflect the spread of the neurological degeneration though. The worse the gate gets the more down the path they have gone and ultimately they can have a delirium condition that goes on. And again I I think that even without the brain dysfunction, just a delirium from a lack of sleep for heaven's sakes would just be so intense. One thing though, while they do mention that behavioral and intellectual capacity can be altered, and many many of the cases it isn't altered until the very end. To me, that means the person was aware of what was going on and. And that would be hard.

32:12 Yeah. Behavioral and intellectual capacity tends to worsen, of course, as the disease progress and people can become depressed or apathetic as the insomnia worsens. Again, to me, a natural course of insomnia. I agree. We talked about the mental health problems, and I think to me, these mental health issues, especially the depression, would be so hard to watch as a family member because it's really nothing that can be done. And just that support and palliative nature of care is what's really important.

32:52 The person will have progressive fragility, so they'll have weight loss. And again, this can mimic things like Alzheimer's, any other kind of dementia where they stop eating, Parkinson's and stuff like that. But these people that are down this road are typically positively diagnosed and they know what's happening, what's going on. In order to diagnose these things, they've got the typical work up, CB, CS, different types of blood tests going into liver function, ammonia levels and blood cultures for suspected bacterial infections, because those sorts of things can be the cause of dementia just off the top. So these things are the easiest things to test for. They run these tests and that would be a common diagnostic tool and anybody coming in with some of these sort of disorder questions.

33:43 And then they look at reversible causes of cognitive decline, including thyroid function test, vitamin B12 and folate levels, which all can cause cognitive changes, right? They also test for sexually transmitted infections such as syphilis and HIV because they can cause some of these symptoms. So you can see each step is going a little deeper into more unusual sorts of territory. And then they'll do sleep studies and find out where they are in their actual sleep. Because I how many times you said or somebody has said to you, gosh, I had such a hard time going to sleep last night. I think I have insomnia.

34:28 Oh, really? And he asked a little more about it. Yeah, it took me like 5 minutes. Right. Or even like I leave it for 30 minutes. Oh, did you? Yeah, gosh, that's hard. But then also, so if everyone who had those sorts of statements went in and got tested for sleep studies, well, it would become obvious that it was probably just a regular sleep situation. And so that's got to be tested. See if they really do have a sleep disorder and what is the potential dysfunction between the transition of sleep stages. As I mentioned, the REM sleep will be affected and it makes the sleep efficiency, it's called reduced. Slow wave sleep is reduced as well. So those things are actual demonstrative testing that can be done and then the EEG can show some different changes in the study and they can have sharp wave complexes which I'm unaware of what that looks like.

35:27 Have you ever seen that with your kids 'cause I know your kids have had some EE GS done for seizure type activity. Do you have you ever heard of that sharp wave complex? No, I've never had the EE GS interpreted for me. I haven't either. I didn't know what that was. But it does suggest that the prion disease could be there, but it's only seen in a small percentage of patients with the genetic form of prion disease. So while it can indicate it, it's not always there. So it's still just more information. It doesn't rule something in or out completely at that point. And then that'll go a little bit deeper, right? There are spongiform degeneration like Crusof Jacob disease, which have similar presentation that is likely to have a an abnormal EEG.

36:13 Again, that would take further testing. But this CG day, CG day, I'm like you're a fan. CG Day CJD is considered to be a prion disease and we'll talk a little bit more, as I mentioned before, we'll talk a little bit more about what that is. But again, it can overlap, right? Another difficulty in diagnosis. Cerebral spinal fluid can be studied for biomarkers and apparently there's a 1433 protein that can show up in the cerebral spinal fluid. But they're they're also nonspecific and can be part of various diseases. Jeez. Exactly.

36:53 This protein, while it can be pride of the cryon disease, can cause neuronal neuron death and still not be that. Can you see how difficult this? Is yeah, I can. All of these things have to be true in order for it to be a positive test. But all of these can be true and still not a positive test, right? Right. Why is this hard to find? Can't imagine they'll do some CT scans and have some Mris, but they're also in limited value for diagnosing it. But it can help rule out other neurological pathologies. Again, rule out is where we're going. There might be some reduce diffusion in the thalamus when there's AMRI, but it might not be.

37:42 And yeah, it really is. A PET scan can sometimes aid in diagnosing it because it can reveal hypo metabolism in the thalamic region of the brain, which basically means it's not doing quite as well as it should. It can so sluggish or things like that, but it might not. Anyway, there's a lot of things that it could look like, but one of the things if they really suspect it, they'll do some genetic testing and they will find potentially they'll find that gene sequence. They're starting to notice that there may be another gene sequence that can be involved, but most of them have that 129 segment that is a problem.

38:28 And then once they're gone, they can do some brain biopsies. Most people don't get a brain biopsy while they're alive because, you know, it's not really indicated for good results. This comes to the medications. So treatment and management, palliative care, as we discussed, because there's no cure, right? Different treatment modalities that were mentioned are discontinuing medications that may exacerbate confusion, memory and insomnia is essential. So you asked about anxiety. Yeah, that can cause confusion, memory problems and in some people, insomnia. So probably not the best choice, although it feels like it could help.

39:12 But it sounded like with my research, I was looking at some of these medications have what is called a paradoxical effect where it's supposed to put some people to sleep. We'll talk about melatonin in just a minute. And it doesn't for these people because it reacts opposite, for example. Yes, yes, it does that for me as well. And so they show an inadequate response to sedatives like the barbiturates or benzos. And what's interesting is they've studied these having people take the barbiturates or benzoids and do an EEG and instead of sedating the hyper excite. Oh, wow. Oh.

39:53 Jeez. They may need a feeding tube ultimately because of the difficulty in swallowing, which is in itself a problem they're finding. Some studies are showing that the using of GHB gamma hydroxobitrate can help with the sleep disruption, but it might not the things that they've studied. Again, because of the small pool of people involved, they just. Don't have enough concrete evidence that anything particular works. They have some evidence that some things don't work most of the time, but they don't have anything saying this is exactly what we need to do.

40:35 There is a study that is being conducted in Italy that might prevent the onsider prion disease and individuals who are carriers and this gene that they may carry includes the M129 we're talking about and D 178 N you may know where these are. I do not, I do not. The study involves administering antibiotic doxycycline orally daily for 10 years to 10 carriers and comparing the results with a control group of 15 non carriers from the same family. So we've got the families, some are carriers, some are non carriers, some are positive for the disease.

41:17 The positive for disease aren't involved in the study because it doesn't matter anymore because what we're trying to do is can this prevent them. Trials are ongoing and nobody knows the outcome of the study yet because it hasn't gone on long enough. Although if you think about it, administering this antibiotic, the doxycycline 100 milligrams daily for 10 years, think of all the potential problems that can cause. Well I take an antibiotic every day now since my hip replacement went bad. So, yeah, and you know, and you have probably some gastrointestinal things to show for it, but I didn't see why they thought the antibiotic could help, but I know that especially. Where it's genetic, That's what's interesting. That somehow they think that it might prevent the onset. Maybe they think that if the environment of the body is hostile with an infection, that maybe it provides this opportunity.

42:15 Because many of the genetic disorders that can that happen, you know, take bracha, because I'm more familiar with that than a lot of them. There is a reason that the defective gene basically got turned on. They a lot of times think it's related to an immune system problem. So in this case, maybe the immune system problem they're looking at is infection. I didn't go down that rabbit hole as far as I probably could have because I didn't want this to last three episodes like our last one lasted 2. But immunotherapy has reported promising results in vitro. So if you have two parents that are carriers and they have a child, especially before they realize they're carriers, they're doing some in vitro studies and clinical trials, but they're doing it in animals right now because obviously people don't like babies to be messed with. There's some whole ethical stuff going on there. These immunotherapy research, research studies are focusing on antibody vaccines, dendritic cell vaccines. You know, dendrites are the nerve endings that pass the nerve impulsive along.

43:27 So they're checking to see if those cells can be saved, I guess, or transfer the protein that can repair the damaged protein, things like that. They're not sure yet. They're just trying to figure it out because whatever causes this folding, this misfolding of the prion protein is, as far as they can tell, the problem, right? One of the last things that they talked about as far as treatment is psychosocial therapy. And it's essential for both the patient and the family because everybody's going through some stuff, whether it's because the family is feeling helpless because they can't do anything or the patient is having all of the things that can come with that, including the the depression and anxiety that comes with the disorder itself. So it's very important to have that psychosocial and support aspect for the patient and the family. The Hospice care can be beneficial, as I mentioned, because it is focus on palliative care, right? There's a study of a man who is 58 and he was admitted in the hospital in March of 2023.

44:36 He had this is a case study. I, I probably said that wrong. He he's just a case they were talking about and not that he was a study, but it was a case study about his disorder. So sorry about misspeaking on that, but he was 50. Eight. I'm pissed. I know you are, you're so mad, but he was in the hospital in March of 2023. He had a 7 month history of walking and stability and just sort of general you've heard the symptoms. So just problems with sleeping. He had light sleep, frequent awakening, shortened sleep duration, daytime drowsiness, and poor response to insomnia medication. As I said, that paradox or response like melatonin didn't work because it made him more awake. The other sorts of things could have that paradoxical effect. Anyway, he was diagnosed with depression because of the adverse events, like he was a truck driver. So I think with all of these symptoms, I imagine that would make it, if not difficult, certainly nearly impossible to do his job.

45:38 Yeah, without. It's certainly unsafe if he was right. That was another story though. He, so he was diagnosed with depression and he presented in 2022, almost a year before being admitted to the hospital with progressive date gait instability and hyperhidrosis symptoms. Again, that could kind of just look like a lot of different things. He did have a genetically confirmed case of FFI. He had both maternal and paternal transmission within the family. So importantly, they knew that this family had FFI. So he was diagnosed quite quickly really based on all of the potentials and these these features in these declines had been moving fairly fast and he had some of the abnormal abnormalities in the cerebral spinal fluid and some electrolyte imbalances that can come with this disorder. He had therapeutic measures with a ganglion block because they wanted to try to see if that helped with some of these symptoms.

46:45 And he had, they wanted to regulate the hyper sweating as it were, with the ganglion block, and they wanted to try that to see if it helped to manage it. At first it looked like it was helping, but ultimately it didn't look like it did any good, which is unfortunate. And so his prognosis didn't improve, but they were hoping it could give him a little relief. And I guess it did for a minute, but not, not anything too significant. The book I was telling you about by journalist DT Max called The Family That Couldn't Sleep was a book talking about this, just the whole thing. There was a family, an Italian family who for 200 years had suffered from this inherited disease. They didn't know what it was yet, of course, but it struck their family members in middle age and it said it stole their sleep, eating holes in their brains and ended their lives in a matter of months.

47:42 Wow. And this was a very known family because it was 200 years. Makes me wonder a couple things because some of these historic families enter bred quite a bit. Wonder if that has something to do with this disorder. I wonder. Yeah. I mean, it makes sense, but I don't know. The other thing that he talks about in this book is in Papua New Guinea, a primitive tribe is nearly obliterated by sickness whose chief symptom is uncontrollable laughter. Now this is an FFI, but this is part of what happened, what he was mentioning, and also he mentions across Europe, millions of sheep rub their fleeces raw before collapsing.

48:23 And in England, cows attack their owners in the milking parlors, while the American West, thousands of deer starved to death in fields full of grass. And he noted all of that. And I've heard of a few of these things, but one is bad cow disease. Right? Exactly. And this narrative that this Mr. Max person centered on this Italian family. And one of the things that he noted is that this Italian family had rapid deterioration. As we talked about, they suffered from sweating, pinprick pupils, tremors and hallucinations. They after months of merciless limbo between sleep and wakefulness, victims die from sheer physical exhaustion.

49:06 That's not entirely true, but essentially true. The cause eventually traced to these prions misfolded proteins that he kills in thalamus in the brain sleep center. Like we mentioned, the other strange conditions which we talked about were Peru, which was the one with New Guinea, Scrapey is. Which one do you think? I'm going to guess the scraping of the. That's right. That's right. And mad cow disease, They all seem to share the prion disorder and they're the proteins that sometimes go wrong. This is what he said in his book, resulting in neurological illness that is always fatal. Even more mysterious and frightening, they're almost impossible to destroy these prions because they're not alive and have no DNA.

49:53 So when you think of things that might attack, say the infection or something like that, it's because these are living air quote bodies. And they really truly are. They're not the same as you and I walking around, but they have something that can, a nucleus and things like that, that can be stopped. These prion cells cannot, which is one of the reasons they haven't been able to find a cure, because they can't stop them from doing what they're doing, even though they've tried a variety of things. One of the things that when we were talking about this disease is about the Papua New Guinea folks, this cure happened because they had ritualistic cannibalism eating the brains of the deceased. Oh, wow.

50:33 They think the disease was in these brains they were eating and then not transmitted. But that more to me supports maybe a bacterial component, but I don't know how. These mad cows bacterial so. Yeah. And but they still affect the prion, which is chicken before the egg situation, right. So it seems that whatever it is affects the crion and then the prion grows basically out of control in the form of a cancer type growth as we've talked about with some disorders we know about and the mad cow disease disease was in the 80s and 90s primarily. And the big outbreak was the feeding the cattle from the feeding cattle of the remains of the other cows. Yeah, feeding cows. Cows.

51:13 Right. They were trying to increase the protein. They tried, it said. And one thing it said tried to make the meat meteor like what? And I could. See. Maybe that it could make some sense, but you know, things die for a reason. Yeah, yeah, exactly. So it later spread to humans as variant, which is the truth felt Jacob sees the CJD. So remember this comes from mad cow and it's a variant from that. And CJD is also a rare, rapidly progressive and fatal neurological disorder caused by infectious misfolded proteins called prions. This case is non genetic because we talked earlier about what was genetic and non genetic.

51:58 This would be non genetic because it came from infectious proteins. It causes the severe dementia, muscle jerks and vision issues, with most patients dying within a year of onset. And there's no cure for this either. Effects people mostly in their 60s. What? Yeah. I can't eat anything now. Mad cow. Nothing forever. That should lengthen my life anyway. And then the Scrapy that we were talking, I mean, you get names of things that are some weirdo who thought of this. And then scrapy, well, that's really obvious. But it's really silly too. Yeah, exactly. It causes the sheep to completely rub their wool off.

52:38 To me, that sounds like maybe maybe the sheep are having hallucinations. Maybe they have dementia. I don't know what would make them do that. I doubt there's been as much study of that than other things. It sounds like it is also a non genetic form of one of these prion diseases because it probably is environmental from whatever bacteria that they get. It's just super intense. In this book, the family that couldn't sleep. Max said that he did a lot of interviews and he read archival research, and he said that the story's connection to human greed and ambition from the Prussian chemist von Leyburg, who wanted to make the meat meteor had a lot to do with it.

53:24 And also the natives who had the custom of eating the dead brain nearly wiped them out. And these afflictions are definitely not normal, but they can often be described based on what something Mr. Max said was because of financial greed, maybe trying to save a buck here or there, things like that. I didn't see that that was substantiated in anything that I read. But that was his opinion. He did this book, he said, because he has inherited neurological illness. They did not talk about what it was, but he has something and that's what brought this information to his, his mind. That's what he wanted, why he was focusing on it. These are just really, really interesting cases. As I said, they just don't have a cure. There are different things that I talked about this on almost everything I say where they're noticing that there's, there might be more and more things that are related to these prion diseases because now they're starting to know where to look for them.

54:28 And, and that could be good because if they're looking, they're going to find potentially cures. It doesn't look like it's coming really fast, but but it looks like at least it's becoming known. I think that's really good. And if it can save even one life, then it's moving in the right direction or even ease the suffering of people who are experiencing it. That would be huge. Yeah, I agree. Yeah, I had a thought while you were talking about the old 200 year old family of the going through generations and I, I couldn't help but wonder if they had some sort of colloquialism for what they called it. Like, you know, it's like come down with the family, sleep, death or something like that, you know? Exactly because it seems like partially in those times people didn't live as long.

55:20 So I wondered when I thought about that 200 your span, they must have had an earlier onset because people just didn't live past 30s in most cases in that kind of time frame. And does that mean the onset has extended based on our life expectancy? I mean, or are people still dying out of early and they just don't know that's what happened? So that's actually a common misperception. The life expectancy back then was the same as our life expectancy for the most part, give or take 20 years. The problem is that the infant mortality rate was much higher. And so they were, the figures were coming out of an average life expectancy. But when you take 30 babies that have died and 70 people that have lived 70 that, then you get 30s really. I didn't know that.

56:16 I know, surprise. Surprise, that's an interesting take then, but on Little House on the Prairie when I used to watch. I mean, they weren't living to the 90s like they like people are now, but it was more like the 60s, seventies, 50s, sixties, 70s still. But on Little House on the Prairie, this is what I base all my information of. You know, Laura Ingalls Wilder is definitely the expert on all things longevity. Exactly, exactly. That's really interesting. That really gives me a whole different perspective on how these paths went. So maybe they really weren't as young as I may have imagined, because they weren't as young as I had imagined. And of course, people had a lot more things they died of that could not be controlled infection one of them. That's really interesting.

57:08 Anyway, I think this is a fascinating topic. Very sad. I. Agree totally fascinating and really sad and really I honestly by the way knew all about prans and Pran disease. Why on earth did your daughter Odyssey know about? I mean. I haven't. She's probably something like, and This is why we drink the podcast, something like that. Oh OK, I haven't heard that one but that's why. We drink, I guess. That's there's a lot of a lot of podcasts covering all kinds of different stuff. It's just really interesting to see how people, what people's take on different topics are. Anyway, if you know of a familial trait or disorder that your family has and you'd like us to look into it, let us know.

57:50 We check our ear. We'd love to hear. All right. Thank you. All right, if you've made it this far, clearly you like a little mayhem with your medicine. Or you just enjoy hearing us ramble about weird medical mysteries. Either way, we'd love you for it. So hit that follow or subscribe button wherever you're listening. And toss us a rating or review while you're at it. Helps other curious weirdos find the show. And we know there are a lot of you out there. Oh so many. Come join the chaos. Thanks for listening to Medicine, Mystery, mayhem, and sometimes Murder. Do you have an idea for an episode of this podcast? Just want to say hi? You can get in touch with us at our M4 pod.

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