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"An antidote for hypersomnia" - possible PEM clue ?

xchocoholic

Senior Member
Messages
2,947
Location
Florida
My editor had brain fog so bear with me .. Title should say antidote not anecdote .. lol ...

I get hypersomnia when I get PEM so maybe this could help explain why. Or at least provide a treatment for this.

An antidote for hypersomnia

http://news.emory.edu/stories/2012/11/antidote_for_hypersomnia/campus.html


Researchers at Emory University School of Medicine have discovered that dozens of adults with an elevated need for sleep have a substance in their cerebrospinal fluid that acts like a sleeping pill.

The results are published in the journal Science Translational Medicine.
Some members of this patient population appear to have a distinct, disabling sleep disorder called "primary hypersomnia," which is separate from better-known conditions such as sleep apnea or narcolepsy.

They regularly sleep more than 70 hours per week and have difficulties awakening. When awake, they still have reaction times comparable to someone who has been awake all night.

Their sleepiness often interferes with work or school attendance, and conventional treatments such as stimulants bring little relief.

"These individuals report feeling as if they’re walking around in a fog — physically, but not mentally awake," says lead author David Rye, professor of neurology at Emory University School of Medicine and director of research for Emory Healthcare’s Program in Sleep.

"When encountering excessive sleepiness in a patient, we typically think it’s caused by an impairment in the brain’s wake systems and treat it with stimulant medications.

However, in these patients, the situation is more akin to attempting to drive a car with the parking brake engaged. Our thinking needs to shift from pushing the accelerator harder, to releasing the brake."

In a clinical study with seven patients who remained sleepy despite above-ordinary sleep amounts and treatment with stimulants, Emory researchers showed that treatment with the drug flumazenil can restore alertness, although flumazenil’s effectiveness was not uniform for all seven. Alertness was gauged through the psychomotor vigilance test, a measurement of reaction time.

Flumazenil is usually used in cases of overdose of benzodiazepines, a widely used class of sedatives such as diazepam (Valium) and zolpidem (Ambien).

Evidence in the paper suggests that the sleep-inducing substance in patients’ cerebrospinal fluid is not a benzodiazepine drug, even though flumazenil counteracts it.

Identifying the mysterious "somnogen", which appears to be produced by the body, could give scientists greater insight into how our brains regulate states of consciousness such as alertness and sleep.

"Primary hypersomnias are disabling and poorly understood. This study represents a breakthrough in determining a cause for these disorders and devising a rational approach to therapy.

Further research is required to determine whether or not the results apply to the majority of patients," says Merrill Mitler, a program director at the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health.


The team of researchers involved in this effort includes Rye, Andrew Jenkins, assistant professor of anesthesiology, and Kathy Parker, previously at Emory and now at University of Rochester Medical Center.

The paper describes how samples of patients’ cerebrospinal fluid (CSF) contain a substance that enhances the effects of the brain chemical GABA (gamma-amino butyric acid). GABA is one of the main inhibitory chemicals of the nervous system — alcohol, barbituates and benzodiazepines all enhance the effects of GABA.

In the laboratory, the size of the effect on GABA receptor function is more than twice as large in the hyper-sleepy patients, on average, than in control samples.
"In some of the more severely affected patients, we estimated the magnitude of the GABA-enhancing effect as nearly equivalent to that expected for someone receiving sedation for outpatient colonoscopy," Rye says.

"This is a level of impaired consciousness that many subjects had to combat on almost a daily basis in order to live their usual lives."
The ICSD-2 (International Classification of Sleep Disorders) terms this disorder "primary hypersomnia" and the proposed DSM-V describes it as "major hypersomnolence disorder." Its prevalence is unclear.

The Emory team’s findings could potentially provide a biological definition and a treatment for an under-recognized sleep disorder.

The patients in the group examined in the paper have received a variety of diagnoses, including idiopathic hypersomnia and narcolepsy without cataplexy.

Cataplexy is a sudden loss of muscle tone, sometimes triggered by surprise or strong emotion, characteristic to narcolepsy.

Other members of the group are simply considered "long sleepers" (more than 10 hours per day).
In addition, the identity of the GABA-enhancing substance is not yet known, although Rye and Jenkins are devising strategies to pin it down.

Based on its size and sensitivity to certain enzymes, it could be a peptide, similar to but not the same as the hormones oxytocin or hypocretin.

In the laboratory, Jenkins and his colleagues have shown that the sleep-inducing substance can act on GABA receptors that are not sensitive to benzodiazepines.


"Previous studies with flumazenil indicate that it does not have a wake-promoting effect on most people, so its ability to normalize vigilance in this subpopulation of extremely sleepy patients appears genuinely novel," Rye says.

Other Emory authors include postdoctoral fellows Amanda Freeman and Jacqueline Fairley, data analyst Prabhjyot Saini, Donald Bliwise, professor of neurology, Michael Owens, professor of psychiatry and behavioral sciences, Lynn Marie Trotti, assistant professor of neurology, James Ritchie, professor of pathology and laboratory medicine and Paul Garcia, assistant professor of anesthesiology.

Parker, Rye and Jenkins are co-inventors on patent rights held by Emory University. Emory and the inventors could potentially receive royalties derived from the intellectual property related to this research.

The research was supported by the Woodruff Health Sciences Center Fund, the National Institute of Neurological Disorders and Stroke (NS055015 and NS050595) and the National Institute of General Medical Sciences (GM073959), James Sumner and the Arthur Williams
 

Little Bluestem

All Good Things Must Come to an End
Messages
4,930
Very interesting. I can not help wondering if in our case the hypersomnia is secondary to the ME/CFS. It could be the brain's way of making the body stay within its energy limit.
 

Gavman

Senior Member
Messages
316
Location
Sydney
Some doctors when approached with cfs want to stimulate an energy drained person when the opposite is more likely to help. Those who get over sharp illnesses aggressively rest. The body of one with chronic problems is unable to rest properly and improving that may improve recovery - if it is a virus that the body can't defeat it will erode it and until antibodies are created or given the body systems will deteriorate and make it harder to deal with the initial virus.
 

xchocoholic

Senior Member
Messages
2,947
Location
Florida
Hi,

I take Klonopin, a benzo, nightly for myoclonus so I struggle with waking up in the morning.
I have energy but my brain is hanging onto the benzo and making it hard for me to think. Feeling
sleepy or drugged and uncoordinated is different from feeling fatigued.

This drugged feeling clears on it's own after awhile. I've tried various supplements, coffee, etc but haven't found a way
to force the benzo out of my brain. Which is what I "think" they're talking about. Only these
people didn't take a benzo.

My brain hangs onto other sedating chemicals too. It took me 3 days to wake up from taking
1 Vistaril. So there's some kind of chemical my body is missing that should eliminate this.
I'm thinking it could be the same chemical causing hypersomnia during pem.

I'm still looking for whatever enzyme or
peptide they found. Maybe it's a liver enzyme ? ? Or connected to mast cells / histamine clearing ?

Provigil and Ritalin sped up my thinking and my motor skills but kept me awake all night. I don't understand the difference
in these chemicals and the one they used yet.

The cause could be from allergies too. I used to have narcolepsy until I went on the gfcfsf diet. I suspect this is my reaction to wheat. Chicken and turkey knock me out if I eat them a few meals in a row. So maybe, mc meds and / or avoiding triggers is the answer.

My pem has lessened on the mc meds but not consistently. I'm still experimenting tho. I'm allergic to most things on the planet so finding and eliminating all of my triggers is impossible. I suspect many of us canaries are like this.

Tc ... X
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
One candidate for hypersomnia I am looking at is PGD2. The counter-treatment is resverotrol, though its use is problematic taken as an isolated supplement. It can also prevent sleep as I am finding, though there are ways to counter this based on the biochemistry. If I succeed I will blogs about it.
 

xchocoholic

Senior Member
Messages
2,947
Location
Florida
Hi Alex,

I did a little googling on pgd2 and prostaglandins. It's going to take more than a little googling for me to
understand this. I'm not sure I want to get into all the terminology but I did see a mast cell connection,
niacin and nsaids block pgd2s.

What do you think of our body's abilities to convert sunlight to vitamin d ? Could missing out
on allowing or bodies to do this be messing with our fat regulation ?

Fwiw, I took Resvinatrol for a few months because it worked great. But like everything else, it stopped
working.

Tc .. X