Told Ya So

Depression and suicidal thoughts in untreated and treated narcolepsy

Conclusions: Depression, depressive symptoms, suicidal thoughts and SR were frequent in patients with NT1, especially without treatment, and were associated with NT1 severity. Depressive symptoms and suicidal thoughts improved after NT1 management.

So cool.

'Waves' of fluid clear the brain of toxins during sleep. 

 This is why most illnesses induce sleep... 

(P. Gingivalis induces insomnia) (Uh-huh)

EFFIN AY!!! HERE IT IS!!!!!

Effects of Very Low Calorie Ketogenic Diet on the Orexinergic System

Orexin-A levels significantly increased after dietary treatment.

Grazie Italia!

Yo Dr. Mignot

Fuck You, Motherfucker.
We told you over a decade ago it was gastrointestinal.
See the Fucking Vortex.

Lipopolysaccharide Challenge Reduces Orexin Production

Lipopolysaccharide (LPS) is a microbial toxin, produced during gram-negative bacterial infection.
Injecting animals with LPS reduces Orexin production, just like an infection.

**New Research** Orexin-A Prevents Lipopolysaccharide-Induced Neuroinflammation at the Level of the Intestinal Barrier 

Low orexin levels allow LPS from your microbiome to leak through your intestine into the bloodstream (endotoxemia),  which causes even more orexin dysfunction.  (!!!!!)

Hypocretin/orexin loss changes the hypothalamic immune response

The hypothalmic response to LPS challenge in orexin deficient animals is to cease orexin production altogether.

Effects of inflammation produced by chronic lipopolysaccharide administration on the survival of hypocretin neurons and sleep.

Long term endotoxemia kills orexin cells.

Three Strikes and You're OUT

Infection with the influenza virus causes massive lung damage, raising endotoxin levels drastically, which lowers orexin levels.
Endotoxin reduces the immune response to many bacterial infection, so those are common afterwards.

Strep and staph bacteria then give you another big dose of endotoxin by causing open lesions.

And then the antibiotics they give you burst the bacteria and release A LOT more endotoxin, which shuts down your orexin production completely.

Low levels of orexin impairs healing and promotes intestinal permeability which allows all that endotoxin to leak into your bloodstream constantly,  finally killing the orexin cells.

Why I am Obsessed with Dehydration

BECAUSE I CAN'T FEEL IT.

This study was just published, it shows that rising orexin levels are a trigger for thirst.
That as a rat gets dehydrated it's orexin levels rise and this motivates it to seek water.

I find this does not happen for me.
If I am outside and sweating I will just become more and more focused and obsessive on finishing my task instead of seeking relief.   I think this is because the stress hormones are being activated instead...


Orexin neurons couple neural systems mediating fluid balance with motivation-related circuits.

During extracellular dehydration, neural systems that sense deficits in body fluid homeostasis operate in tandem with those that mediate motivation and reward in order to promote ingestive behaviors that restore fluid balance. We hypothesized that hypothalamic orexin (Ox) neurons act as an interface to couple brain regions sensing and processing information about body fluid status with central nervous system motivation and reward systems. An initial set of anterograde and retrograde tracing experiments suggested that structures along the lamina terminalis (LT), a region of the forebrain that serves to monitor and integrate information reflecting body fluid balance, project to hypothalamic Ox neurons that, in turn, project to dopamine neurons in the ventral tegmental area (VTA). A second set of experiments determined whether Ox neuron activation is associated with extracellular dehydration and the seeking out and consumption of water and saline. An elevation of Fos-like immunoreactivity in Ox neurons was observed in fluid-depleted rats that were allowed to ingest water and sodium. A final experiment was conducted to determine whether Ox release in the VTA promotes thirst and salt appetite. Bilateral microinjection of the Ox Type I receptor antagonist SB-408124 into the VTA prior to acute extracellular dehydration attenuated fluid intake. Together, these studies support the hypothesis that structures along the LT modulate activity in the VTA through actions of orexinergic neurons that have cell bodies in the hypothalamus. This pathway may function to facilitate sustained consumption of fluids necessary for restoration of fluid balance.

Anyhow, I'm pretty sure that explains a whole lot of my problems since I moved here to the desert.
I'm crispy as a tato chip... 
And I don't want to take a frakkin shower.

Here, some more links to add to my list:

Dehydration alters human brain shape and activity, slackens task performance
Next 5 years predicted to be abnormally hot
The Arid West Moves East, With Big Implications For Agriculture


Expect more, I'm on a hot trail now...

oh my...
Drought In Central Europe Reveals Cautionary 'Hunger Stones' In Czech River
"Over a dozen of the hunger stones, chosen to record low water levels, can now be seen in and near the northern Czech town of Decin near the German border," the AP writes.
One of the stones on the banks of the Elbe is carved with the words "Wenn du mich siehst, dann weine": "If you see me, weep."

KNOW HOPE

Brain never stops growing, scientists find, as elderly shown to have same number of new neurons as teens 

I have waited several years to state this definitively:
There is every reason to believe Orexin cells will repopulate in your brain- if you stop killing them.

Mapping the Darkness

These gifs are as close as I have ever come to my hallucinations.   I see patterns of light when I close my eyes. The overall effect is really similar, but the things I see are less distinct than actual lines.  Just swirly shadows.  And the motion seems to go the other way.   I have to figure out what that means...

This was my most common configuration while falling asleep
two sources, seemed to be located at the eyes.

This is what it looked like when I was a child.
one source.  off center.

This is very similar to what I had right after my tooth extractions
Definitely emanating from the upper jaws.

If my tear ducts are clogged and my eyelids are really puffy and I squeeze my eyes- I get something like this, but infinitely fractal in the center.

As I Was Saying

Morbidity and mortality of middle-aged and elderly narcoleptics.

Middle-aged and elderly patients had more health contacts before and after their narcolepsy diagnosis with respect to several disease domains: infections, neoplasm, endocrine/metabolic diseases/diabetes, mental/psychiatric, neurological (including epilepsy), eye, cardiovascular (hypertension, ischemic heart disease), respiratory (upper-airway infections, sleep apnea), gastrointestinal, musculoskeletal (including discopathies) and skin diseases. Narcolepsy patients had lower reproductive rates. Furthermore, patients showed significantly more health contacts due to the evaluation and control contacts for disease and symptoms. Patients suffered from significantly more multiple diseases than did controls.

See the vicious circles.

How Narcolepsy Works- in less than ten sentences.

Open wounds in the mouth allows Bacterial Endotoxin into the bloodstream.
Bacterial endotoxin slows down orexin cells.
Prolonged endotoxemia kills orexin cells.

The wounds may be caused by injury, teething, infection, or surgery.
And although oropharyngeal infections seem to be the most common in acute narcolepsy,  other chronic injuries and infections will also trigger this process.

Sugar promotes microbial activity and glucose lowers orexin levels directly- triggering sleepiness.
The reason gluten increases symptoms is it promotes the translocation of endotoxin going through your intestinal wall into your bloodstream- it increases your burden.  So does alcohol.

And in the wickedest irony ever-  the most common treatment for wounds and infections is also the most powerful trigger of orexin cell loss-
Antibiotics cause Acute Endotoxemia while they destroy bacteria in your body.

(very long version)

THIS IS WHY

THEY NEARLY KILLED HER.
SHE PROBABLY NEARLY KILLED HERSELF.
SHE STILL HASN'T RECOVERED.

Narcolepsy-cataplexy and psychosis: a case study.

A 14-year-old girl was referred to Sleep and Epilepsy Unit for excessive daytime sleepiness, impaired nocturnal sleep, binge eating and weight gain, over the last year. After being diagnosed with a NT1 the patient was treated with modafinil and sodium oxybate. She was hospitalized for psychotic symptoms after starting NT1 treatment. Withdrawal of the narcolepsy treatment and initiation of haloperidol 1 mg/day (the only antipsychotic treatment she could tolerate) improved the delusions, hallucinations and dysphoria but worsened the narcolepsy symptoms. Polysomnography showed fragmented nocturnal sleep and five sleep REM onset periods in MSLT. Positive HLA-QB1*06:02 and undetectable level of hypocretine in the cerebrospinal fluid were found. MRI and CT-scan were normal. Diagnostic Interview for Genetic Studies Adapted for Narcolepsy (DIGSAN) questionnaire confirmed that patient presented a dual diagnostic NT1 and psychotic symptoms. The last sleep follow-up while on psychopharmacological treatment, showed an increased sleep efficiency index. She currently has severe somnolence, obesity, and partial cataplectic attacks along with normal mood, academic failure and social isolation.

This young lady was suffering from a systemic infection and they gave her Xyrem and modafinil which suppressed the immune symptoms and made her manic.  And then they took her off and she went septic and psychotic.
And then they gave her Haloperidol which drastically worsens strep infections.

She's fucking lucky to be alive.

Bigly

Our friend Gina has been interviewed for Sleep Review Magazine.

Food as Therapy for Narcolepsy Patients

“I hit ketosis in seven days and it was like a fire was lit inside of me,” says Dennis, referring to a metabolic state characterized by raised levels of ketone bodies in the body tissues. “I was awake, I was cognizant, and it was such a huge difference from what I’ve felt before.”

ICYMI:  This is the video of her presentation at the NN conference.
I was there.  It's my favorite memory.

Oh Really...

Low cerebrospinal fluid Orexin levels in infants during SIDS risk period.

Hmmm, well-  low orexin levels are caused by infection and impaired breathing.
I suggest sucking the boogers out of kids noses before they sleep.
Oh, and SLEEPING ON AN INCLINE.

(this advice goes for adults with breathing problems too...)

See the Pathology

I saw this picture on the internet yesterday and can't stop thinking about it.
This is not a sweetly sleeping baby.     This baby is in the middle of a narcoleptic sleep attack.
He has infected and swollen adenoids. He can't breathe through his nose.
And his tear ducts are clogged. That's why his eyelids and brows are swollen.
That hand under his face is to hold his mouth open and soothe the the pain in his cheeks.

He's oxygen deprived and mouth breathing because he's been laid down flat.
The resulting orexin deficiency has made his muscles slack and locked him in sleep.
Look at the furrowed brow, he's trying to move but can't.

He's already insulin resistant.   Chubby, smooth and pink...
I'm guessing somebody just fed him some cereal.

It's the stuff like this that gets me the most-  the things that everyone else thinks are cute and funny and make me feel like I've been gut punched.

CHA CHING!!

Peripherally administered orexin improves survival of mice with endotoxin shock.

Sepsis is a systemic inflammatory response to infection, accounting for the most common cause of death in intensive care units. Here, we report that peripheral administration of the hypothalamic neuropeptide orexin improves the survival of mice with lipopolysaccharide (LPS) induced endotoxin shock, a well-studied septic shock model. The effect is accompanied by a suppression of excessive cytokine production and an increase of catecholamines and corticosterone. We found that peripherally administered orexin penetrates the blood-brain barrier under endotoxin shock, and that central administration of orexin also suppresses the cytokine production and improves the survival, indicating orexin's direct action in the central nervous system (CNS). Orexin helps restore body temperature and potentiates cardiovascular function in LPS-injected mice. Pleiotropic modulation of inflammatory response by orexin through the CNS may constitute a novel therapeutic approach for septic shock.

The Brilliance of the Cognitively Impaired

It's just fascinating how really sick narcos can come up with complicated excuses to continue the status quo.
One of the most common arguments comes from people who have had their orexin levels tested and show no measurable levels.   They claim there isn't any reason for them to restrict their diets because they won't produce more orexin anyway.

Yeah, not so much.

1, You probably do still have viable cells, and will produce more orexin if you don't suppress them via diet.   Please read my post on The Finer Points of Progressive Cell Loss

2. If you truly don't produce any orexin, that really messes up your glucose and insulin regulation- and that makes you tired and fat- so you should eat clean anyway to compensate for that effect.

3. Your pathology is showing.  Welcome to the club.  This is a Symptom. We'll come up with any reason to keep eating carbs.

Excellent Documentation of the Obvious

High Rates of Psychiatric Comorbidity in Narcolepsy

RESULTS:
The final population included 9,312 narcolepsy subjects and 46,559 controls . All categories of mental illness were significantly more prevalent in patients with narcolepsy versus controls, with the highest excess prevalence noted for Mood disorders, Depressive disorders, and Anxiety disorders. Excess prevalence of anxiety and mood disorders (narcolepsy vs controls) was higher in younger age groups versus older age groups. Psychiatric medication usage was higher in the narcolepsy group versus controls in the following categories: selective serotonin reuptake inhibitors (36% vs 17%), anxiolytic benzodiazepines (34% vs 19%), hypnotics (29% vs 13%), serotonin-norepinephrine reuptake inhibitors (21% vs 6%), and tricyclic antidepressants (13% vs 4%).

CONCLUSIONS:
Narcolepsy is associated with significant comorbid psychiatric illness burden and higher psychiatric medication usage compared with the non-narcolepsy population.

Update-  don't forget Narcolespy is also comorbid with lots of "Physical" illnesses.

Piping Fresh Hypothesis, right off the griddle

A Vagal Infection Mechanism of Cataplexy

If you are familiar with my writing, you know that I think strep infections are a big cause of Narcolepsy.  My main thesis is that chronic long-term infection causes less orexin production, orexin cell destruction and drastic metabolic changes that we experience as sleep, eating and mood disorders.
But I haven't really had a good explanation for how a systemic infection could cause cataplexy. A constant low level of orexin doesn't really account for the sudden onset of cataplexy.

I read something that flipped a switch in my brain though.
Look at this:

The Vagus Nerve Infection Hypothesis for Chronic Fatigue Syndrome

Location, Location, Location.
VanElzakker proposes that an infection triggers CFS, but if his theory is right the most important thing about that infection is not what it is but where it is. That ‘where’ is the biggest nerve in the body; the vagus nerve – a ‘wandering nerve’ that stretches over much of our torso and sends its roots into most of the organs of the body.
The vagus nerve isn’t just any nerve; it’s the nervous system’s immune conduit to the brain. VE believes that an infection there doesn’t need to be large to cause havoc in the brain; it just needs to be present.

This may be what is going on with cataplexy.
Strep infections result in chronic throat biofilms from either nasal or tonsillar ulcers.  Pathogenic bacteria create mucous coverings in the throat near the ear canals.   And these persistent colonies are antibiotic resistant.

The branches of the vagus nerve run down both sides of your neck,    They run right next to the ears and down the front of your chest and all through your abdomen.
The vagus nerve controls a lot of things.  Your heart rhythm, your digestion, all the way down to your reproductive organs.   Not to mention it is wired to the Locus Ceruleus in the brain- which triggers cataplexy.

I am pretty convinced that if you have a chronic biofilm near the ears, the bacteria can infiltrate and affect the nerve-  and when you stimulate the the nerve via stress, you trigger a neurological short-circuit.

Orexin cells also directly control heart rhythm by direct contact with the Vagus.   I would guess this causes that feeling that someone is sitting on your chest during panic attacks.   And maybe some of the heart fluttering that happens when we're hypoglycemic.

Anyhow-  the Vagus nerve is in the throat.   It seems to cause the panic problems.
Trigeminal nerve is in the nose and mouth.  Infections in those places seem to cause the headaches and hallucinations.

(For the record, a good portion of my certainty comes from attending Narcolepsy conferences.   I watch the audience.  In one afternoon session, at least 80% of the zombies were rubbing their necks behind the ear, the others were asleep.  We also tend to pierce our ears and faces a lot.)

Vagal Stimulating Devices are all the rage these days.   I think that might be promising.  
But you should probably try this first.

Beauty and Joy

THIS IS WHY.  THIS. THIS. THIS!

Gina's Video is Online  (Get some tissues.)

I would gush over it, but she speaks better for herself.
I do agree with the commenter who wishes she had more time...

And if you have the means, please go over and donate to her GoFundMe drive, she has worked for years studying and organizing and getting this ready- and we really need her to take this show on the road!

Big Thanks to Glenn who did all the audio modulation and merged in the graphics.   He totally rocks.

Yo Sleep Doctors

Recent reports of  Steroid therapy ameliorated cataplexy should not be assumed to be evidence of an Autoimmune reaction... this result could also occur in the event of an active Infection.

This therapy obscures the source of the symptoms..
I suggest you check those kids for chronic Strep Throat before you put them on immunosuppressants.