The Worst Disease You Can Get: Fatal Familial Insomnia and the I-Function
Pierluigi Gambetti, one of the discoverers of the condition known as fatal familial insomnia (FFI), claims that it is "the worst disease you can get." (5) Given the vast number of diseases in the world, Gambetti's claim seems farfetched at first glance, maybe even selfish; who wouldn't want to take credit for discovering one of the worst diseases in the world? But a quick overview of the disease presents solid evidence in favor of the claim- and some interesting insights about the many tasks of the I-function.
FFI has been discovered in only 28 families worldwide; it is an autosomal dominant gene mutation, meaning that a parent with the disease has a fifty percent chance of passing it on to his or her child (2). That much is predictable. But every other aspect of the disease is wildly unpredictable, forcing family members to make difficult decisions. If parents have such a high chance of passing on the disease, one might ask, why don't they simply choose not to have children? The answer: FFI , unlike many other fatal genetic conditions, doesn't appear until the victim is middle-aged, and tests to see whether parents carry the FFI mutation only recently became available (1). Here the first questions of the I-function, and the first paradoxes of the disease, appear. If this disease occurred in childhood, natural selection would have long ago done away with it. Because it does not strike until middle age, however, parents who may be carriers must make difficult decisions about childbirth. Paradoxically, it is in the parents' best interest to have more children, in order to ensure that at least some live FFI free into old age. More children, however, also means more potential FFI cases- a tough paradox for the I-function to work through.
Next, the symptoms. FFI baffled investigators for years, because certain symptoms resemble encephalitis, end-stage alcoholism, and dementia, among other conditions (1). But the hallmark of FFI, which the aforementioned conditions don't necessarily show, is the complete inability to sleep. The brain wave patterns that appear on FFI patients' EEGs go up and down wildly, in a pattern completely unlike the normal sleep-wake cycle; they may still show patterns indicative of REM sleep at night, but they do not pass through the sleep stages that typically precede REM, and they can still move while in the REM stage (5). There are also unbelievable highs in pulse and blood pressure, excessive sweating and an eventual loss of coordination and other gross motor skills (including speech) before the victim finally falls into a coma-like state and dies (1). But, most horribly, the thinking portions of the I-function remain intact, even as the rest of the body deteriorates (4). Because FFI is invariably fatal, patients understand that they will die, can talk and write freely about their coordination deteriorates and understand their fate up until their death (5). Some diseases, like Alzheimer's disease, are tragic because their victims lose the ability to describe their decline; in these diseases, the I-function deteriorates along with the physical body. But FFI is tragic for precisely the opposite reason; it leaves the I-function intact, even when its victims are clearly in physical agony.
Even the agent that causes FFI defies conventions. It is a prion, a form of infectious protein. Humans naturally produce thousands of intricately folded proteins, and the vast majority of them are harmless. But if one protein happens to misfold in a harmful way, it can trigger a chain reaction, leading other proteins to produce similarly harmful forms; the immune system cannot counteract the chain, since it does not see the proteins as infectious agents (4). The exact mechanisms behind this process, and the reasons why it should be fatal, aren't well understood. The effects of prions on the brains of FFI victims, however, are well-documented. In most areas of the brain, FFI victims show remarkably little damage. The thalamus, however, is utterly destroyed, full of holes (3). Given this evidence, one might try to make the argument that the I-function cannot be located in the thalamus; after all, FFI victims remain completely able to think and comprehend the world, even as the prions destroy that part of the brain. However, the I-function isn't limited to one section of the brain, and it does not only control thinking and speech. Indeed the sleep-wake cycle, so damaged in FFI victims, is also regulated in part by the I-function; people simply tend to forget this fact, because sleep feels like such a natural part of our existence. Only in unusual cases, like the severe insomnia of FFI, do we remember the I-function's role in this cycle.
FFI, then, presents yet another example of why it's useless to try to pin down one precise area where the I-function lies. One can see from FFI victims that the parts of the I-function that have to do with language use and comprehension, with naming people and objects in the world, probably aren't located in the thalamus. But the thalamus must play some role in the sleep-wake cycle, judging from FFI victims' brain damage, and the I-function aids in sleep-wake cycles as well; one cannot give an exact location for a function that performs so many diverse tasks.
Web Sources:
1) Case Study: Fatal Familial Insomnia; Location: Venice, Italy; To Sleep No More
2) Dying for Sleep: Researchers Track the Cause of a Rare but Fatal form of Insomnia
3) Fatal Familial Insomnia
4) Biofundamentals: Protein Folding and Turnover
Non-Web Source:
1) The Family That Couldn't Sleep: A Medical Mystery, by D.T. Max. Random House Publications, New York, 2006.
Freaked out
I have had some kinda weird insomnia and it has been going on for 7 days now. it's really freaking me out and it's weird. NO BENZO's work and the 15mg remeron doesn't even work. and i ain't one to take much meds.... no one in my family has this or even regular insomnia so i don't know what to do... i just started taking LOPRESSOR about a month ago and it's 50mg a day. maybe it's my LOPRESSOR? i have to take that for my inappropriate sinus tachycardia syndrome............
FFI is EXTREMELY RARE
To the above comments, believe me, the chance that you actually have this problem is 1 in billions, so relax and take an ambien ;)
At medical school I had read a chapter on this and had chills sent up my spine. I think I would rather poke hot needles in my eyes than suffer from this. I would be interested to know if there is any treatment available for it by now, as I remember no medications seemed to show any significant signs of treating it.
And I think that given the possibility I could hand this down to my children I would certainly think twice before having kids.
this is a horrible disease
this is a horrible disease and i wonder why on earth there is such a horrific thing like this? who made this disease? they did not have this before the 1900's did they???? well i have insomnia... i have a hard time falling asleep at night so my doctor put me on remeron and it helps a lot so now i get 9 hours of sleep each night... maybe y'all should try remeron??
You DON'T have the disease
Ok RELAX! no one here has the disease. You all just suffer from Chronic Insomnia. Yes not sleeping is terrible. I've had insomnia before for about 4 months but I didn't die! If you has FFI you would be showing other symptoms such as loss of coordination so RELAX! that is the key word
me too
I'm going through something like this too. Harley, are you still having your symptoms?
i have been unable to sleep
i have been unable to sleep since may 08, now its sept im possitive i have some form of ffi, i had all the symtoms from supper panic attacks for two months with no help from sleeping pills, sweating and weight loss and motor skills are getting worse, my head feels like jello but i still can remember and think as good as ever which is the worse part of this hell, i have enough money to last till june but i dont think my body will last that long its in gods hands now
You don't have FFI
OK let's go through some facts. FFI is gentically inherited. Do you have parents? Did they have FFI? Did they have Insomnia? Did they develop Insomnia around 40-50 years of age then 5-6 months later slip into a coma and die? If you said yes to ALL of these questions then you can CONSIDER the SUPER ULTRA SLIM POSSIBILLITY that you have FFI!!!!! When you sleep your body becomes paralysed and therefore the brain does not have to worry about you physically and it rests and recharges ready for the next day. When you don't sleep your brain is trying to work at normal capacity but it can't as it is not "recharged". When you have not slept for a pro longed period your brain is trying to work fully at "Low battery" so yeh as a result PHYSICALLY your body is slowed as the brain lacks general motor skills. But phsychologically its still functioning pretty much the same. So memory is not affected. You've put yourself into a psychological state where you BELIEVE you won't fall asleep and therefore you won't but if you tell yourself you WILL fall alseep then you will. Try sleeptracks. This is NOT an advertisement
FFi non inherited form
I to may be going through this, my body has not fallen asleep on its own for 3 months.I', loosing weight memory and motor skills.My eyes aren't tearing. Did you know there was a Noninherited form of this disease?
How are you doing?
Harley
Extraordinarily unlikely that anyone writing here is affected
For all of you suffering with the fear that you have this disease, you should be assured that you most certainly do NOT.
Only a relative handful of people on the planet have ever had this disease. You are more likely to win the lottery WHILE being struck by lightning after tripping over a hunk of a fallen meteor on the way to go pick up the new car you won in the latest radio contest.
i know 2 ppl with it
in responce 2 the comment titled "Extraordinarily unlikely that anyone writing here is affected" he/she said "Only a relative handful of people on the planet have ever had this disease. You are more likely to win the lottery WHILE being struck by lightning after tripping over a hunk of a fallen meteor on the way to go pick up the new car you won in the latest radio contest."
yet i know 2 ppl that have it in fact one of them was my girlfriend and she died from it and her sis has it and she is now haveing a kid so even that kid might have it.
Severe Insomnia following stroke
Does anyone know if it is possible to stroke your ability to sleep? None of the docs can tell me. In the rare instance that I do fall asleep it lasts less than 45min and I have terrible hypnopompic hallucinations with no paralysis.
The brain has many sleep
The brain has many sleep centers, and it is certainly possible for a stroke to damage any one or more of these. I would suggest you consult with a neurologist for an examination and have an MRI done. It may or may not be possible to gain help for whatever you find, but it may also give you a modicum of peace to know what has happened. Don't lose hope either! The brain can take a long time to heal, but it's ability to overcome injury can also be quite remarkable. Best wishes to you.
The short answer is that I
The short answer is that I don't know. But I had a stroke and still have trouble sleeping more than one year later, though my problems are not nearly as severe as yours. In my case, I believe it was caused by the nurses in hospital continually waking me up to check if my brain was still functioning normally in the weeks following the stroke, and after that my own worry about not being able to sleep keeping me awake. So what I'm saying is it's possible your insomnia could be caused by something other than the stroke, though it could be related. I also have heard that people who have had their brain 'interfered with' often suffer from insomnia. I was told just to 'be patient', and it should settle down eventually. Not very helpful advice, IMO, but just passing it on.
Thank you for the voice of reason Philip
In the world we live in today, It is really a shame that people are still so quick to assert their archaic religious beliefs as being the answer to everything. This disease is one that will most likely evolve itself to extinction as I'm sure many other rare genetic diseases have done in the past. This is simply a genetic disorder. It is not a "punishment" from God... just to humor this concept, wouldn't only the worst "sinners" in the world be struck with such a devastating disease? We understand exactly what causes this and unfortunately until gene therapy becomes a reality it's virtually untreatable.
Throughout history we have had a countless number of problems there was no answer to. Naturally when there is no easy answer, It's simple to blame it on a supernatural entity that is all-knowing and all-powerful. As we progress through history these problems get factual, scientific solutions that allow us to conquer them and succeed as a species. Because of this It is truly sad that there is ridiculously large portion of society that is stuck in the dark ages. Perhaps that sort of thinking is easier to grasp then how complex the world actually is. Whatever the reason, please, do the rest of us a favor and keep it to yourself. The people that can look outside the box will be out solving the worlds problems while the tunnel-vision religious group is waiting till 2012 to prove us all wrong.
I take a dim view of the above assertion......
We are living in an era where we understand more now than we have ever understood about the workings of the human body, about the origins of the universe, about the formation of galaxies and other celestial bodies, and the world in which we live. This is not to state or to imply that we know everything that there is to know, or that we are even close to understanding everything that there is to understand -- but we are in a position now to understand that physical diseases have causes that can be determined, and that many of these diseases can be treated.
I suffer from an inherited genetic disorder too. My disorder is not nearly as horrible or as terrible as FFI, but it has caused me a great deal of physical pain. In short, my connective tissue is insufficiently elastic. This leads to serious impacts to multiple organ systems, including my bones, my heart, my joints, my skin, my skeletal structure, my eyes, and other systems. I have been placed on an aggressive pain management schedule involving oxycodone and other opiates / opioids, and I undergo regular CT scans, MRI scans, and echocardiograms to diagnose and monitor any potential cardiac abnormalities that may arise (and are eventually likely to arise).
This is not a punishment from God, and it makes me cringe to read accounts by other people who revert to the archaic belief that physical illness is a form of punishment for sin. I am openly gay, and have heard fundamentalist preachers and ignorant laypersons assert that HIV infection is a form of punishment from God (I am lucky in that I learned about HIV and its transmission before coming out and before becoming sexually active – knowledge of how to prevent infection combined with a determination never to engage in unsafe sex was the only thing that kept me from becoming infected). Physical diseases are not punishments – they are processes. Some diseases are caused by microbes. Other diseases are caused by faults in the genome of the patient (as in my case). People living in Africa who suffer from such diseases as cholera, kwashiorkor, and malaria are not being punished for sins; they are the unlucky victims of poverty and starvation.
This is not the time to browbeat a person suffering from FFI – or to browbeat yourself. FFI is a prion disease caused by two point mutations resulting in two amino acid substitutions that should not occur. That is the bottom line. FFI is a tragedy, and it should be acknowledged as such. The last thing that persons suffering from this disease (whether directly or indirectly) need is pious sermonizing by people who wish to return medical understanding to the dark ages.
PHILIP
This illness is from Satan.
This illness is from Satan. I might have it. I lost ability to sleep in 2006 after a terrible sin I committed. I felt how God left me and Satan took over my body, soul and spirit. He tried to kill me but God came back to stop him. But he left me and left me some of his demons and this (FFI?) illness. My doctor refuses to have some test done about this FFI. No sleeping pills have helped me. Seroquel and Lorazepan are the only pills that are helping me have a 2 to 4 hours sleep since 2007. Just pray, repent and ask for forgiveness and lets see if it is the Will of God to save us or to let Satan kill us for our sins. Nobody wants to beleive in God anymore and Satan is taking over. He made me see and feel HELL when he entered my body. It was horrible. Maybe you might consider deliverance ministry or exorcism. They didn't work for me...and I feel like dying little by little every day. I am so sorry I left Jesus of Nazareth when I had the chance to be with Him. This illness could also be the result of generational sin.
FFI
look I'm not saying anything mean or that god isn't real or shit like that, but this god figure, is said in the bible to love you for your ideas and way of thinking, he doesn't punish until your dead therefore your comment is invalid, also, its rude and inconsiderate for people to say out load how people are wrong to not go to god, i don't believe in him and its awkward for people like me who aren't in that religion to read this stuff, and i would hope that all people would try to keep shouting there religion at a minimum.. because not everyone is of one religion, there are to many religions out there for you to assume all religions are your own
You are horrible
I can't stand people who are willing to spout psychobabble over the internet on a serious forum. God doesn't exist and neither do demons or the devil. Grow up and stop believing in imaginary friends.
Hopefully there aren't too many gullible people out there who will listen to you.
You don't have FFI, youd be pretty much dead by now and even the most intense drugs wouldn't work to give you those 2-4 hours per night. You don't have a disease you're just insane. :)
Heres hoping you wake up from your crazy jesus-coma
Even Peter was forgiven after he sinned knowingly 3 times
Don't loose faith, my brother, God can forgive you. There is not a sin in this world caused by our weakness that can't and won't be forgiven. Only direct sins against God are unforgivable.If you repent, there is no problem.
And about the other comments regarding the "call to reason": I wish you would never have to find out that God exists by Satanic possession.
We don't know squat about the human body or the human spirit. The "modern" science doesn't recognize the existence of the spirit, so, the modern science doesn't know anything about what makes us what we are. the bible is to be trusted more than any science book.
Modern medicine only gives pills that annihilate the symptoms or help the body get well by itself. And when that is not possible, we take the organ out.
Modern medicine can't treat the cause of a disease.
No sin is unforgiveable.
God is a spirit of forgiveness, he will accept us if we come to him.
Comment about FFI
I have a client and friend who is suffering with chronic insomnia and severe depression. Her insomnia has been since December, and here it is April. She tells me she cannot sleep at all, and that she feels that she has lost the ability to sleep. I was searching the internet trying to find something to help her. Sleeping pills don't work...nothing seems to give her any sleep...day or night. After reading about FFI, I wondered if possibly this could be what is wrong with her. She seems alert for someone who has not slept in so long. I would be a walking zombie after just a few days without sleep. I am desperate to find help for her. The doctors just keep prescribing narcotics to make her sleep, but they do not help. And she is really scaring me with her talk of not being able to take it any more. I have no idea if there is anyone in her family who has had a similar condition. I will be asking her some questions in this area tomorrow. I do not plan to share anything with her about the FFI until I see if she has this in her family history. And then it would be something that I would have to really put some thought into how to get her the blood tests without telling her about the fatality of this condition.
Today I awoke and she was very much on my heart. I prayed that God would help her, and that if she did have FFI, He would not allow her to suffer a very long, drawn out death. After praying, I layed there a little while. Then the thought came to me that systemic enzymes could be the answer. They help the body to breakdown and utilize proteins....and we loose the ability to manufacture enough of these enzymes as we age. So maybe the reason FFI doesn't strike people till they are around 50 or 60 is because they have enough enzymes in the body most of their lives, and it takes this long for the body to become depleted and the damage to start displaying symptoms. I have no idea if this is totally off the wall. Possibly it is. I am not a medical professional. I am only someone who tries to do things naturally, and I read a lot and try a lot of things to help seemingly hopeless conditions. I just wanted to find someone to tell this to so it could be looked into to see if it made any sense at all. If this could help these people, then I would be so wrong in not sharing this idea.
Hopefully someone who can truly determine if this could be helpful will read this or it can be passed on to someone who can.
I have given this lady some systemic enzymes to take between meals, and am going to monitor her progress.
Sincerely
Jean Terry
She does not have FFI
The reason she is alert during the day is because her brain is producing seratonin, the "stay awake" hormone. Perscribe her melatonin. It is the opposite of Seratonin. It may help
Jean, systemic enzymes would
Jean, systemic enzymes would be unlikely to work due to the blood brain barrier. Additionally, prions are protease resistant. In case you're unfamiliar, proteases are enzymes that break down proteins. Consuming enzymes will only aid in the digestion of dietary protein.
FFI
I suffer from severe insomnia as well. I have had an episode where I literally went 6 months without sleep while pregnant. I am seeing a specialist tomorrow, hopefully he can find out if I have FFI. Is there anyway I can contact your friend, it sounds like we would really be able to support each other. Not sleepig is surely the ultimate form of uncontrolable torture. I haven't found anyone to talk to who's suffered like I have and can share their experience. I've had severe insomnia for 7 years. I understand her talking about not being able to take it anymore. I feel that way too.
Insomnia for 4/1/2 months, can't take it anymore!
I feel the same way I can't take this awful insomnia
anymore, and I've had it much less of a time period then
you, so I really feel bad for you. I've been on all kinds
of sleeping pills, and none of them give me more then 4
hours, once in a while a little more. This may sound vain
but I hate always looking so tired! I'm 41 and feel like
I'm really going to age from this awful insomnia. Does
anyone else feel this way? I'm also very alert during the
day, and at night before going to bed. Is it possible that
it's from stress? The adrenal glands are on the fight or
flight response constantly. I'm don't really do much during
the day, I'm not working right now, but still I should feel tired right? Or could it be this awful
disease? My parents are in their 70's and are both still
living. I'm also on antidepressants for depression. But
they just help me from commiting suicide from this. I'm
almost always down and don't like to do things anymore.
It's helpful but not good that others can't take it anymore
I thought I was the only one. Because everyone that I talk
to, says there are much worse things out there and don't
and can't understand because they don't have it. Any reply
would be great.
insomnia
I have said the same thing, I just can't take it anymore.
I've been taking sleeping pills for about 4/1/2 months.
I havn't really tried sleeping on my own to much. But I'm
in a deep depression over this And this may sound vain but
hate always looking so tired. It just keeps getting worse
and worse. I'm worried I'm going to age a lot from not
sleeping more than 4 hours a night sometimes less, and
it's with sleeping pills. I'm 41 years old so I could
definately age from this. If I was younger I'd have a
better chance. I'm also very alert during the
day which everyone I knows thinks it seems odd, although
right now I'm not working so I don't have much to do, but
still you would think I'd be tired. Is it stress
adrenalin running through my body causing me to not feel
tired but look tired. I also thought I might be bi-polar
because they don't get much sleep and still are alert, but
besides depression I don't have any of the other symptoms
If anyone's depressed and feels alert during the day, maybe
should check into bi-polar if you have other symptoms.
I just hope I don't have this awful disease. But it's
helpful to hear others say they can't take it anymore
because when I tell people this they just say, oh there's
much worse things you could have! They just don't and
can't understand.
ffi
Hi ,thanks for your writing, I am suffering from horrible insomnia for most of my life, and I now going through the worst of it, not being able to sleep at all for the last 6 weeks, so I now know that I have FFI which is a real punishment and will aventually destroy me , I am 61 years old and parts of my life where really beautiful but others where not good at all, as I was anoraxia and ,ccleptomanic ( not for many years) and always talked lies, so I think part of the sickness is from really bad conscience,
P erhaps you can give me some advise, ,as doctors don't know how to help us with such an horrific condition. thanks
Listen, I had beyond severe
Listen, I had beyond severe insomnia. I would go for 7-8 days at a time with zero sleep. I was a zombie and I eventually lost my mind. it lasted for months but it came back. It seems like your only concern about this is aging. Its really not a concern. stress and aging is kind of a bs thing promoted by cosmetic industries. Youre much more likely to show signs of aging due to overdone sun exposure and smoking. So as long as you avoid those things you should be fine. Im 22 years old and have been dealing with insomnia for my entire life. I go through bouts of severe insomnia in between a regular condition of mild insomnia with just a few hours a night. If my insomnia were going to age me, id look older then 22 but i promise you i am wrinkle and age spot free.
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