The sleep switch: hypothalamic control of sleep and wakefulness

[pattismith]

hypothalamus neuroinflammation may be involved in some of us who have Excessive Daytime Sleepiness.

like @Enid, I fell asleep inappropriately several times at the beginning of my illness (which had a progressive onset)

The orexin/hypocretin are associated with narcolepsy. It's now considered an autoimmune disease due to the body attacking and destroying the orexin/hypocretins. It seems like our pituitary/hypothalmus region of the brain just takes a beating somehow.

Several kind of Narcolepsy can occur:

-Primary Narcolepsy: NT1 and NT2
.. NT1 involves cataplexy and low hypocretin / orexin in the hypothalamus (autoimmune)
.. NT2 has no cataplexy/low hypocretin

-Secondary Narcolepsy
Damages to the hypothalamus of diverse origine (traumatic, tumoral, degenerative, inflammatory, infectious...)

Narcolepsy Fact Sheet | National Institute of Neurological Disorders and Stroke (nih.gov)

 

[heapsreal]

hypothalamus neuroinflammation may be involved in some of us who have Excessive Daily Sleepiness.

like @Enid, I fell asleep inappropriately several times at the beginning of my illness (which had a progressive onset)



Several kind of Narcolepsy can occur:

-Primary Narcolepsy: NT1 and NT2
.. NT1 involves cataplexy and low hypocretin / orexin in the hypothalamus (autoimmune)
.. NT2 has no cataplexy/low hypocretin

-Secondary Narcolepsy
Damages to the hypothalamus of diverse origine (traumatic, tumoral, degenerative, inflammatory, infectious...)

Narcolepsy Fact Sheet | National Institute of Neurological Disorders and Stroke (nih.gov)

Interesting reviving this old thread brought back some memories. Struth! 10yrs ago. I sleep better now or maybe regular now that i havent done shift work for 5 yrs but sleep is still medicated. I usually have one bad day a week ie less than 5hrs and suppose to work but have a sickie as we call them down under or its on a day of so i just lounge around, which is not alot different to normal i guess.

I have nights out of the blue where i dont sleep at all but they have become alot more rare maybe every 3 months. Its taken 3 years of no shift work to get to a point of resemblance of a normal sleep pattern , 5hrs plus is a good sleep.

Im abit off topic with this rant but interesting to look back.
Thanks

 

[pattismith]

Hypothalamic lesion and Excessive Daytime Sleepiness (SLE 2018) | Phoenix Rising ME/CFS Forums

Interesting reviving this old thread brought back some memories. Struth! 10yrs ago. I sleep better now or maybe regular now that i havent done shift work for 5 yrs but sleep is still medicated. I usually have one bad day a week ie less than 5hrs and suppose to work but have a sickie as we call them down under or its on a day of so i just lounge around, which is not alot different to normal i guess.

I have nights out of the blue where i dont sleep at all but they have become alot more rare maybe every 3 months. Its taken 3 years of no shift work to get to a point of resemblance of a normal sleep pattern , 5hrs plus is a good sleep.

Im abit off topic with this rant but interesting to look back.
Thanks

Some narcoleptic patients have both Daytime sleepiness and sleep difficulties and take dopaminergic drugs in the daytime and GABA B drugs at night, so as you pointed hypothalamic affection can produce both Wake and Sleep problems.

(Here a clinical evidence of Sleepiness associated with hypothalamic lesion

Hypothalamic lesion and Excessive Daytime Sleepiness (SLE 2018) | Phoenix Rising ME/CFS Forums )

 

[Wisdom]

I sleep better now or maybe regular now that i havent done shift work for 5 yrs but sleep is still medicated.

10 yrs lol
any sleep aid med switch advice now?
baclofen&zopiclone 、&zolpidem 2 options I remember

 

[heapsreal]

Hypothalamic lesion and Excessive Daytime Sleepiness (SLE 2018) | Phoenix Rising ME/CFS Forums

Some narcoleptic patients have both Daytime sleepiness and sleep difficulties and take dopaminergic drugs in the daytime and GABA B drugs at night, so as you pointed hypothalamic affection can produce both Wake and Sleep problems.

(Here a clinical evidence of Sleepiness associated with hypothalamic lesion

Hypothalamic lesion and Excessive Daytime Sleepiness (SLE 2018) | Phoenix Rising ME/CFS Forums )

I think theres a strong link to sleep quality and growth hormone. Growth hormone has so many effects throughout the body which helps regenerate it.
Im not good at directly quoting studies, mostly because i dont have a computer and do everything on my phone now, but gaba B agonists seem to improve sleep and help people get into the deeper stages of sleep need for optimal GH secretions.

The gaba B drugs are things like baclofen, phenibut as well as GHB which the prescription version is xyrem and dam expensive, if you can find a specialist to prescribe it and jump through the hoops. XYREM is actually mainly prescribed for narcoleptics which i assume works for this condition as it helps narcoleptics to reach deeper refreshing sleep, so less day time sleepiness and maybe less need for stimulants during the day.

My experience with baclofen and phenibut is they definitely help appear to improve sleep quality but for me dont help me fall asleep, so i need a typical sleep med to initiate sleep. I have a hunch that lyrica/pregabalin may work the same for deep sleep and better GH secretion??

I have heard of people on GH therapy sleep better but usually dont have sleep issues. Theres been a few cfsers over the years report that using GH mostly hasnt really improved sleep. So i think the deeper sleep and GH connection is a factor, theres still other processors from deep sleep we must get thst GH alone doesnt do.

I think the mecfsers that arent tired and wired but appear sleepy all the time and dont use sleep meds, probably dont reach deep stages of sleep but more in a light day time nap stage all the time and totally fogged out or constant pain.

 

[heapsreal]

10 yrs lol
any sleep aid med switch advice now?
baclofen&zopiclone 、&zolpidem 2 options I remember

Lol you pretty much have my sleep stack.
Benzos like a Z drug ie zopiclone or zolpidem to fall asleep and antihistamines like diphenhydramine, doxylamine, phenergan or periactin or some could use a low dose trycyclic like doxepine or amitriptyline . To help maintain sleep. Plus im on lyrica for nerve pain/RLS.

Reminds me there was some research on periactin helping improve stage 4 deep sleep.

Obviously one should work with their dr, but its smart to try all the natural things tryptophan, melatonin, withania etc. Then if no luck try the antihistamines first and have drug free nights etc. Extend possible tolerance and use of meds as long as you can. If one eventually ends up on a benzo or z drug, try to alternate them as much as you can and have drug free nights if possible or go back to melatonin etc. Delay tolerance to meds as long as you can.

I think its been a big part of helping me to keep working 3 to 4 days per week mostly. The amount of days ive missed of work due to insomnia id hate to imagine, but probably enough if i did work thst money would have covered my iherb orders

 

[heapsreal]

Forgot to mention one thing that has greatly improved my sleep but isnt a sleep aid and probably another sign of the hpa axis is dysfunctional.

Getting up to pee constantly throughtout the night and the day too. It slowly creeps up on you and i didnt realise how often i was going until my wife and kids kept mentioning it. I also had a few blood tests where it indicated i was slightly dehydrated and my dr said to drink more. I was already drinking heaps of fluid.

So the average person pee's 1.5 litres in 24hrs. So i decided to measure my output over 24hrs. I was shocked, 10 litres. So i was getting plenty of exercise running to to toilet and then to the fridge or tap for a drink etc. After telling my dr this, i then had my vassopressin levels tested which controls the kidneys urine output and did a 24hr urine collection.

The vassopressin was within range and my dr said its not really an accurate test as this hormone fluctuates alot throughout the day. The 24hr urine collection was 10litres, the look on the pathology labs face as i handed over 4 x 3litre bottles. Alot of people pee even more, i have heard from others. They test the urine and basically said it was very diluted so in one end and out the other.

A diagnosis of diabetes insipidus was given and i went on minirin/desmopressin as synthetic form of vassopressin. OMG ! The first night i took minirin with sleep meds and i slept through the night maybe 7hrs. In my mind i thought i got up to pee normally about twice per night but after taking minirin and sleeping so well i realised i was getting up alot more then twice, i was probably too tired to really take notice or id just be awake after 4hrs and just pee lol.

So thinks like peeing that interrupt and disrupt sleep quality. Things like pain, sleep apnea etc are other issues that severely stuff up sleep.

I still required meds for sleep but the minirin actually allowed the meds to work as my bladder wasnt kicking me in the you know what every hr to get up and pee.

Theres a cfsme specialist that wrote we drink like fish and pee like race horses. That was so true for me although Im more of a clydesdale than a race horse.

 

[pattismith]

@heapsreal
taking Minirin was a real relief for you!
Did you try GABA supplementation to help falling asleep?

 

[heapsreal]

@heapsreal
taking Minirin was a real relief for you!
Did you try GABA supplementation to help falling asleep?

Yes minirin was a relief.
After the intial onset of cfs where the viral infections are new and typically just sleep, after that in the post viral stage was when sleep issues started worsening.

Because of the work i do ive seen many people using sleep meds. Usually its just one and they continually take it and increase the dose etc until they are on such a high dose that stopping it would give them severe withdrawals. So knowing that i start on things like gaba and many other natural sleep aids. I found them not very effective.

So when i knew i had to go down the medication side for sleep i was aware of withdrawal and dependency issues. I guess thats why i have many threads where i say i alternate many different meds to avoid tolerance. But i also add natural substances from time to time. Last night for example i also took the herb withania as well as 5htp and melatonin plus sleep meds.

I believe phenibut is gaba attached to an amino acid. Picamilon which is gaba attached to niacin, which helps it cross the blood brain barrier, is on my radar to try.

Apologize if i waffle on abit

 

[hapl808]

http://www.psychology.uiowa.edu/faculty/blumberg/course_docs/seminar.2008/readings/mignot.2002.pdf

An encephalitis epidemic in 1918-1926, the hypothalamus was recognised to be the problem of major sleep problems in these people. I wonder if it was an ME outbreak. Other articles i have read have mention the hypothalamus being injured in me/cfs patients. A specific part of the hypoth was injured, maybe this is the part of the brain injured in cfs/me that have sleep problems. people that dont have sleep issues didnt have an injury to this part, probably other parts of the hypothal?? interesting.

cheers!!!

I'm new-ish to the forums and wouldn't have seen this thread before anyways, but also in light of the current situation, I wonder if the 'encephalitis epidemic' in 1918-1926 was a result of Spanish Flu? The link doesn't work anymore so maybe a totally different thing, but the date stuck out.

 

[pattismith]

I'm new-ish to the forums and wouldn't have seen this thread before anyways, but also in light of the current situation, I wonder if the 'encephalitis epidemic' in 1918-1926 was a result of Spanish Flu? The link doesn't work anymore so maybe a totally different thing, but the date stuck out.

yes it might be.

Encephalitis lethargica - Wikipedia
The relationship between encephalitis lethargica and influenza: A critical analysis (nih.gov)

 

[heapsreal]

I'm new-ish to the forums and wouldn't have seen this thread before anyways, but also in light of the current situation, I wonder if the 'encephalitis epidemic' in 1918-1926 was a result of Spanish Flu? The link doesn't work anymore so maybe a totally different thing, but the date stuck out.

Its interesting hearing that many long haulers from covid are having sleep issues. I think its more clear that many symptoms of cfsers are from the initial damage the virus does but persists after the infection has cleared. Known as the hit and run theory.

 

[pattismith]

Front. Synaptic Neurosci., 04 February 2021 | https://doi.org/10.3389/fnsyn.2021.622405

Orexin-A/Hypocretin-1 Controls the VTA-NAc Mesolimbic Pathway via Endocannabinoid-Mediated Disinhibition of Dopaminergic Neurons in Obese Mice

Lea Tunisi1,2, Livia D'Angelo2, Alba Clara Fernández-Rilo1, Nicola Forte1,3,

Fabiana Piscitelli1, Roberta Imperatore4, Paolo de Girolamo2, Vincenzo Di Marzo1,3,5* and Luigia Cristino1*

Disinhibition of orexin-A/hypocretin-1 (OX-A) release occurs to several output areas of the lateral hypothalamus (LH) in the brain of leptin knockout obese ob/ob mice.

In this study, we have investigated whether a similar increase of OX-A release occurs to the ventral tegmental area (VTA), an orexinergic LH output area with functional effects on dopaminergic signaling at the mesolimbic circuit.

By confocal and correlative light and electron microscopy (CLEM) morphological studies coupled to molecular, biochemical, and pharmacological approaches, we investigated OX-A-mediated dopaminergic signaling at the LH-VTA-nucleus accumbens (NAc) pathway in obese ob/ob mice compared to wild-type (wt) lean littermates.

We found an elevation of OX-A trafficking and release to the VTA of ob/ob mice and consequent orexin receptor-1 (OX1R)-mediated over-activation of dopaminergic (DA) neurons via phospholipase C (PLC)/diacylglycerol lipase (DAGL-α)-induced biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG).

In fact, by retrograde signaling to cannabinoid receptor type 1 (CB1R) at inhibitory inputs to DA neurons, 2-AG inhibited GABA release thus inducing an increase in DA concentration in the VTA and NAc of ob/ob mice.

This effect was prevented by the OX1R antagonist SB-334867 (30 mg/Kg, i.p.), or the CB1R antagonist AM251 (10 mg/Kg, i.p.) and mimicked by OX-A injection (40 μg/Kg, i.p.) in wt lean mice.

Enhanced DA signaling to the NAc in ob/ob mice, or in OX-A-injected wt mice, was accompanied by β-arrestin2-mediated desensitization of dopamine D2 receptor (D2R) in a manner prevented by SB-334867 or the D2R antagonist L741 (1.5 mg/Kg, i.p.).

These results further support the role of OX-A signaling in the control of neuroadaptive responses, such as compulsive reward-seeking behavior or binge-like consumption of high palatable food, and suggest that aberrant OX-A trafficking to the DA neurons in the VTA of ob/ob mice influences the D2R response at NAc, a main target area of the mesolimbic pathway, via 2-AG/CB1-mediated retrograde signaling.