27 replies to this topic

[petra]

I just wrote far too much about all this - just trying to get my own head clear on it - anything I've got wrong it'd be really useful to know.

You know how the hypocretin system is partly about how we decide when to stay awake to eat or when we've had enough to eat and can go to sleep? Cortisol (natural steroid we make in adrenals) is a lot to do with energy and sleep control too and the hypocretin system is connected up to all the bits of us that affect energy balance and appetite, and the bits that "decide" when and how much cortisol we make - pituitary, adrenals, pancreas, GIT, all the rest of the autonomic system, (stress response - fight or flight or rest and digest bit)
So if there's no, or not enoughhypocretin to give (strong enough) messages to these bits, then it would make sense to me that cortisol regulation is all mixed up and steroids could help short term.
Sorry, I don't know if steroids is going to be our long term answer - one of the side effects of increased natural cortisol or longterm synthetic steroid use is insomnia.

I had the best morning in I don't know how long after I'd had this early morning test to see if my adrenals could make enough steroid - they use a synthetic homone to stimulate adrenals - I was awake, my head was clear, eyesight sharp, didn't feel on the point of collapse, lost that feeling of struggle, made me think "oh this is how most people live - it's SO easy! "


From what I've read adrenal glands make a bit of their own hypocretins. I'm not sure if that stops in N, or in some people with N.
Hypocretins (in plasma? made in the adrenals?) can act directly on both adrenal cells that make cortisol, and
The pituitary gets hypocretin nerves from the hypothalamus and it also makes a bit of it's own hypocretins. The cells in the pituitary that make ACTH - the hormone that stimulates the adrenals to make cortisol.

I'm not sure I've made proper sense of the research - I'm only semi science literate, so it's a bit murky, and my language skills are just crappy cos of dreaming and HHs all night (a gorgeous black leopard kept coming through the window and chewing my head) - so let me know if I've got things wrong - it helps. And if I'm saying things too simple - that's for my own benefit!
If anyone speaks science and would like to help me make sense of this stuff, let me know and I can send on all the references

I know from that test that whatever increases cortisol in the morning helps me stay awake and function that day - we are supposed to have a peak in the morning to help us wake and get moving - in normal people it starts before waking and reaches maximum just before or soon after waking up.

And it is supposed to go down at night just before sleep. And I know that whatever increases it overnight - like too much excercise in the day, starting to get a cold, allergic reaction - makes my sleep worse and tips me into sometimes quite a long spell of bad days.

adrenal glands and pituitary both make a bit oftheir own hypocretins. And there's hypocretin in the blood, so it's not all working through the nerves, but I don't know if that all gets lost in Narcolepsy, as well as the hypocretin nerves stopping working. I think the plasma hypocretin goes.

In stress we make CRF. CRF neurons act directly on hypocretin ones which help us stay alert to danger, maintains the stress response, makes a sympathetic (fight or flight response in our brains, and acts on the pituitary which makes the hormone ACTH which tells the adrenals to make cortisol.


We make more cortisol in response to allsorts of physical and emotional stresses, - it helps us handle it. But when we're living with chronic stresses this reaction happens all the time and it causes us lots of different health problems.
And the system that regulates it - the hypothalamus, pituitary, adrenal axis - the HPA - is sort of complicated, and it can get trained into an individual pattern of responses, or set of habits, by all sorts of environmental factors from before birth through life. It looks like it often gets set in a pattern fairly early in life, and we're all a bit different. Some illnesses, whatever age they come on at will interact with and make big changes in that basic pattern - and it looks to me like Narcolepsy is one of them.


Cortisol potentiates, strengthens some of the effects of adrenaline and noradrenaline and increases the rate of synthesis of adrenaline - so that would feel good in the short term for tired people.


When we sleep bad our immune system goes a bit haywire too. Some of the inflammatory cytokines can make us sleepy, (maybe like normal people get sleepy with a cold) and I know that bit of the immune system is all a bit messed up in PWN. I don't know whether that's caused by changes in the HPA functioning in narcolepsy, or is an effect of never getting a proper sleep or both. It would make sense to me if steroids reduced those particular proinflammatory cytokines that make us sleepy - but I'm too sleepy to go and read to check it, so it could be nonsense.


Too much cortisol/steroids, or wrong time of day for peaks in secretion of cortisol, lands people in that increased abdominal weight, insulin resistance/poor blood sugar control, poor sleep, exhausted state - heading towards diabetes II and CVS and immune/inflammatory problems.

Poor blood sugar control and poor sleep also tip people into this same kind of/ or same area of problems - where they are making too much cortisol or at the wrong times of day. It's a bit of a vicious cycle.

And I think a lot of the metabolic abnormalities in narcolepsy - means that a lot of us are already in that same/similar area of problems. I think it maybe worsens Narcolepsy.Sorry - hope I'm wrong, but it looks to me like longterm steroid use maybe wouldn't be so good for us.


I was thinking - that if there's a vicious cycle in N with all these different factors worsening it, then maybe that also gives us lots of ways, routes in to change it for the better, turn some of it around.
Some people found low GI diet helps reduce EDS. there was some study on it - they found it reduced it in that group by 18%, which doesn't sound huge but it's nearly a fifth better. I found out by experimenting about 10 years back that I was less sleepy the less carbs I ate.
Diabetes II is more common in PWN. Heard someone saying they felt more awake when they took metformin - a drug for diabetes type II.



There's research saying the hypocretin system acts directly on all parts of the HPA, and it was a bit complicated but I think it was saying that we make the same amount of cortisol overall. And we have our peak secretion and lowest secretion at the same time of day as other people.
And that ACTH the hormone made in the pituitary has it's peaks and troughs at the normal time of day, so our overall daily clock on all this stuff isn't broken.
We make ACTH throughout the day with one peak and one trough, and in between little pulses of secretion. This paper was saying that people with narcolepsy in their study had lower basal, constant background levels of ACTH than controls, and that they (PWN) made less overall in a 24 hour period but they still released it in pulses.
It also said that their adrenals still managed to make the same amount of cortisol overall and have our peaks and troughs in the right time of day,
but that they had 'reduced secretory process regularity' which I still have to look up to find out what it means.

" The reduced basal secretory ACTH secretion and the diminished secretory process regularity of the ACTH/cortisol ensemble conjointly suggest that hypocretin deficiency induces changes in the interplay between pituitary adrenal hormones"

My head is mush just now, so I know I haven't got this bit clear - can anyone put that bit into english for me? Thanks.

Another study found hypocretins increase both cortisol secretion directly and pituitary secretion of ACTH


Sorry all this is sort of garbled - best my head can do today.
Looks like some of us with N gets into a bit of vicious spiral with blood sugar control, and weight gain and pro inflammatory cytokines from poor sleep and increased HPA dysregulation.
and finding things that help with all that side isn't going to make the basic problem go away, it could ease things a bit for some like me that have got in that spiral.
If they could find something that could act on the HPA changes, and made it all more normal - that might help. Maybe that's going to have to be the hypocretin treatments when they come through.
I'm going to do all I can to work on blood sugarcontrol/weight, allergies, stress response. Even if all I do is stop things getting worse that'd be worth it.


Sorry that was way longer than I meant. And I have no way of working out if I've made any kind of sense.

If anyone's into putting together research, and putting it into english - it'd be lovely to talk.

Petra

[Chuck Z.]

I had the best morning in I don't know how long after I'd had this early morning test to see if my adrenals could make enough steroid - they use a synthetic homone to stimulate adrenals - I was awake, my head was clear, eyesight sharp, didn't feel on the point of collapse, lost that feeling of struggle, made me think "oh this is how most people live - it's SO easy! "

I have yet to read the rest, but I must jump on this!

OMG -- An endo that I was sent to was SO arrogant to me. I had an ACTH stress test done, but my Cortisol response was "normal". I was yelling (literally) that something was wrong because I felt like a million bucks! (Too bad it only lasted about 5 hours). For me, when the test was done, I fell asleep during the injections of ACTH. I was then more sleepy than normal for about 5 hours and then I caught the glorious "second wind". Oh, to feel like that again.

Ok, Now I'm going to read the rest.... hehhee

[Chuck Z.]

Petra,

That was more than wonderful -- of my years of research, I ran across the ACTH (as mentioned), my glucose tolerance hit 28 in an hour (reactive hypoglyglemia), autoimmune was always a question to me (chronic strep and ear infections). I dare say you have fully defined narcolepsy to a "T" (eg. the HPA going haywire because of inadequate hypocretins). Before joining this group, I had never heard of hyprocretins -- I so wish I ran across it -- all my dancing around research of symptoms was "around" hypocretins. Ah, but as usual, I must digress before I start "dancing around" my own circles.

I have to ask though, as I've stated in other posts, I suspect that anesthesia plays a part in amplifying symptoms. I suspect, and yes I assert that our clocks or *not* in sync and anesthesia is to blame -- I think narcoleptics get "stuck" in a sleep mode as a result. And thinking out loud, I'm starting to think that time of day of anesthesia is critical and also could explain the variations in symptoms. Again, I digress before I start to ramble, hehehe

You did a brilliant job of putting all of it together! In fact, I'm printing it out and I'm gonna hand it out to my GP, Neuro and especially the arrogant Endo. God bless for all the hard work of compiling it all into one place.

[petra]

Hi Chuck,

That's very kind! I'm really glad some of that made some kind of sense to someone ! you know those old TVs when you turn them off and the light shrinks down to a little dot in the middle and stays like that a moment before it disappears into the darkness - that's my head these days. I think 'chronic embarrassment' should be added to the symptom list of N. Don't know if I'll ever stop being embarrassed over strugglin to communicate.

I'd be worried your doctors would laugh at that but I could try write something properly if that's any use - tho it might take me a while!!
I'm thinking all that stuff I was on about is just one part of N. Whatever I do, the sleep switch is going to stay broken, and maybe some aspects of HPA function are damaged for good by the initial damage/ autoimmune process. And some bits of HPA function get worse because of longterm huge demands on the body of living with the illness, and then because it's not working so good already ordinary stresses get sort of amplified and feed into whole spiral, worsening symptoms now and speeding up development of longterm problems - diabetes etc. That last bit, the ordinary life stresses and food is the little bit I can work on - easier said than done tho.
What got you interested in anaesthetics and N? I'd never thought about it before, and now I'm curious. getting curious is fab for staying awake - thank you!
In some of that animal torture stuff they do to research hypocretins, I think(have to check it) they they use same kinds of chemicals used as anaesthesics in humans, to stop the animals hypocretin neurones working.
And then some of those chemicals aren't so different from some agrochemicals, that can cause, or help tip people over into some autoimmune diseases, or worsen them when they already have them.
And there's people who've got symptomatic N from getting short of oxygen and that can happen sometimes in anaesthesia. I'm wondering are people with sleep apnea - like lots of PWN - more vulnerable to that? Not saying any of that is what happens, just thinking aloud.
From what you've come across do you think anaesthetics can start N, or do immediate damage and sudden worsening of symptoms, or slow worsening? I'm off to google around about anaesthetics.

Thanks Chuck for lovely answer and for getting me thinking!

petra

[Chuck Z.]

Please see my latest post in the Anesthesia survey. I was so shocked that he called (after I gave a message a couple days ago giving a short explanation of my theory) that I was not able to think or talk sense for close to an hour, LOL.

Wrapping steroids into the mix does make sense *if* the assmption is given that anesthesia is causing some sort of autoimmune response.

I know I will be watching for any papers coming from UCLA!

[shallow_water]

I am so relieved to see this post. I am not alone! I have had several infections over the last few months and always feel better with anti-biotic treatment as well!

My latest infection includes lyme and strep. I am having a difficult time getting rid of the strep and am on a different anti-biotic now as well as a 5day dose of prednisone for the inflammation in my neck glands.

My doc believes the infections have to due with the chronic fatigue in N which lowers the immune system.

So interesting that other PWN have the same issues and once again only a PWN can completely understand.

[xiola23]

Very interesting theory. Steriods are used in alot of treatment of auto-immune diseases and antibiotics (long term) are used to treat lyme disease and all the other fun strains of certain bacterias.

I saw a documentary that talked about new treatment in the UK that a couple people are participating in. I guess it's still in the trial phase, but they went on to explain that you get a 3 day course of IV meds every month that are used to help protect the remaining hypocretins in the hypothalamus. So far, from what the documentary stated, people are responding very well. I'm just wondering if this IV med they are referring to, isn't some sort of steroid or sister/cousin drug.

This documentary stated as well that it is difinitive that Narcolepsy can be caused by genetics, head injury or by an auto-immune disease reaction. If we could all figure out 'how' we got narcolepsy I think it would be easier to break us each down into that category and treat as such. Be it steroids/IV meds or surgery. The differentials in hypocretin levels and such can be explained with this to. Someone with Narc can have a normal level of hypocretins, but the hypothalamus is not using or housing it properly because of a defect from head trauma or auto-immune disease. If it's genetic, then it would make sense that there would be little or no hypocretin or the production would be malfuctioning.

now that i've went off on a tangent..LOL..sorry about that, I just hope all this comes to a head SOOOOOOON and much better treatment and/or a cure is found!
Thanks for stirring my brain Chuck!

[Chuck Z.]

Now you have my interests piqued kat! What was the name of the documentary? I'd love to view!