Presentation: Paul Cheney, MD, PhD New Insights into the Pathophysiology and Treatment of CFS. October 2001

Date: 11 may 2002

Summary of Cheney lecture

By Doris Brown

Reprinted with permission of Doris Brown
http://virtualhometown.com/dfwcfids/menu.html

Phase 1 - onset or trigger phase - you came down with something, didn't get over it. This is the elevated RNaseL stage. RNaseL fights virus and intracellular bacteria like mycoplasma. Or it can be elevated without cause. This is why you feel crummy, like you have the flu. Also get TH1 suppression, TH2 activation. Perhaps this immune dysregulation causes your infection to not resolve properly, and you move into phase 2.

Phase 2 - Classic CFS (energy, brain and pain problems) 5% don't have pain 99% have cognitive disturbance in areas of the subcortex.

Phase 3 - dynamic injury phase You can have elements from each at any one time, but one is usually primary

In phase 1 and 2 you have symptoms, feel terrible. Phase 3 he calls dynamic dysfunction. You feel relatively ok, but you can't do things because you know you will suffer later. You go through the push/crash cycle enough that over time you withdraw your boundaries. But another thing that happens is the pathology of the illness knocks out the dynamic hormone response, and causes you to be "in a box". This is a lesion of the hypothalamus which downregulates HPA axis, growth hormone is deranged, DNA gene rearrangements occur.

Specifically:

A. Growth hormone allows you to exercise, controls hypoglycemia, helps phase IV sleep which allows you to detox at 3am. Without growth hormone you lose
protein synthesis, so you can no longer heal, exercise or detoxify.

B. Cortisol - is supposed to respond to stresses. So you can't work, deal with complexity, with irritable people or stress. This has the biggest effect on your capacity to work.

C. Female sex hormone go crazy. PMS, infertility, ovarian cysts, bleeding or amenorrea.

D. Anti-diurectic hormone controls your fluid balance. No dynamic response and you pee too much, reduce blood volume.

(Note: it is good to generally stay in your box, but occassionally you should try to push past, so you know where the boundaries are. Then you don't make them smaller and smaller unneccesarily.)

Two reasons why antibiotics might be helping PWC's besides killing bacteria like mycoplasma. One is by killing gut bacteria. In a UCLA study, they killed small bowel bacterial overgrowth and got major improvements in symptoms. Another is that antibiotics like erithyromycin and doxycycline affect gene rearrangements. They could be modulating the illness because they are preventing gene rearrangements.

Phase 1 - high RNaseL destroys human RNA. High RNaseL highly affects liver function, so in phase II your liver is not functioning and unable to handle toxicity

Phase 2 - cellular toxicity due to xenobiotics

Phase 3 - Injury to Central Nervous Systen and DNA gene rearrangement (damage done to brain)

There is a lot about physical exams. Interesting was: 92% of PWC's have poor oxygen transport. If you breathe out and hold your breath, your body should pull oxygen out of your blood. In 70% of PWC's this doesn't happen. There is oxygen in your blood, but your body doesn't transfer it into tissues when it should. This would cause fatigue, pain, microorganisms that live in low oxygen environements to thrive (like mycoplasma, chlamydia pneumonia.)

50% of patients have fingerprint destructions, and 10% have no fingerprints. Studies have shown there is an immune activation in the skin cells, and you
don't make collagen right.

Low body temp 30%
Low systolic blood pressure 50% are less than 100
Orthostatic hypotension 40%
Hypertension is very rare (less than 2%)

Then there is a whole bunch about the biochemistry and what is going on.
Phase I and II are exactly the same things that happen in Reye's Syndrome in children, although slower in CFS.

Using magnesium loading tests (which still aren't totally accurate but the best they can do) 50% of PWC's are depleted, and 50% of those cannot be repaired with any amount of magnesium you give them. So magnesium is recommended even if tests show it is ok. (I wrote a separate email about magnesium and its other benefits.)

Oxygen transport is screwed up
Mitochondrial function is screwed up
Xenobiotic Poisoning (from gut, root canals, jaw, environment)
Heavy Metals (especially mercury which steals the Selenium binding site and knocks out mitochondrial function)
Growth hormone deficiency, by affecting protein synthesis
DNA Gene rearrangement

Discusses mitrochondria and cellular energy
Note: The energy deficit in CFS may be a defense mechanism. If toxins are not broken down correctly, the body will shut down energy production to
protect you from death.

Mitochondrial dysfunction is why exercise makes you worse.

Studies show low B12 levels and high homocysteine levels in the brain, even though not in the blood.

Kutapressin inhibits all known human herpes viruses in a test tube

TREATMENT OVERVIEW

Phase I: high RNaseL and TH2, coagulation
* Ampligen
* Anti-microbial therapy
* Immune modulation (Th2-Th1 shift)
* Anticoagulant therapy (Berg's SFM model)

Isoprinisine (from Europe) is the best for intracellular immunity

Phase II: xenobiotic toxicity phase
* Attenuate source (gut, teeth/jaw bone, environmental)
* High dose B12
* MSM
* Whey Protein
* Guafenesis
* Growth Hormone (excellent detoxifier of liver)
Doses are very important, can over mobilize toxins. Slow is best.

Phase III: Hypothalmic injury / dynamic hormone response lost / DNA changes
* Growth Hormone Stimulation
* Fetal Bovine Growth Factors (mescenchyime, Thymus)

TREATMENT DETAIL

Add one thing every 2 weeks

Step I Lifestyle adjustment

* Setting Limits (protect mitochondria)
* Oligo-antigenic Diet (eliminate allergens, digestive enzyme support, betaine HCL support (acid)
* Exercise: anaerobic and rebound exercise (rebound chair) Limit aerobic exercise to tolerance.

General metabolic support

* Blood volume (gookinaid)
* Oxygen transport (Weil Breath exercise; Diamox Long Acting 500mg twice a day - this helps oxygen transfer, manipulates acid / base balance in blood
which is off, helps pressure headaches)
* Autonomic Nervous System Regulation (reound exercises, body work, accupressure, stress reduction, etc.)

Step II Neuroprotection via Threshold Potentials

The subject was "Neuroprotection via Threshold Potentials" and is based primarily on research in Scientific American over the past 10 years.
There are NMDA blockers: Parenteral Magnesium and Taurine, Histamine Blockers (Doxepin Elixir). There are Gaba Agonists: Klonopin, Neurontin, GABA, Valerian Root.

These receptors opose each other and create an electrical potential, a set point where your brain works optimally. The response of the brain to injury is to drop the threshold potential. This causes a number of problems such as lights are too bright, noises are too loud, people are irritating, etc. You also don't sleep well with a lower threshold potential.

On a straight line of threshold potentials, at the left side is Seizure, and at the right side is Coma. Coma is actually a very healing state. (2 Cheney patients went into unrelated Coma's and CFIDS improved dramatically.) So for many reasons you want your threshold potential higher. In CFIDS people it tends to be low, and we need to raise it.

The best drug to raise it is magnesium. This is an NMDA blocker. Also at least people with 50% of people CFS are low in magnesium in their cells (even if it measures ok in the blood), so you get two benefits from magnesium.

Cheney says if you come into the hospital with severe brain problems and they can't figure out what is wrong with you, they inject you with magnesium to raise the threshold potential and protect the brain until they figure out what is wrong. This is the same reason he recommends magnesium, to protect the brain in this way.

(Note: One thing he didn't address and I am not sure of, is he also recommends klonopin which appears at the other side of the equation. So I'm not sure how that fits in. I have seen literature that klonopin is believed to reduce small seizures and thus contribute to better sleep, which would imply it moves it up the threshold potential curve also. But I thought he said "NMDA blockers and Gaba agonists opose each other..." So I am a little confused on this.)
>
How he implements magnesium: Start with shots every day for a month. Then twice a week for a month. Patient takes tablets also the whole time. After the 2 months, the patient decides based on how they feel with and without the shot whether to continue. He says 70% decide to continue with daily shots, which is amazing because it is painful. However he has added the taurine to make it not painful. Dose is 1/2cc magnesium sulfate 50% (which is about 250 mg), 1.5cc taurine. Inject high on the hip, pushing in 1/2cc at at time, slowly. For tablets he uses magnesium glycinate, as
it is the smallest molecule and most likely to get intracellular where it is needed. Dose is 100-200mg am, 200mg, pm. Then the shot at night.

Step III DNA Protection

* Antioxidants
* Bioflavinoids (important to take with antioxidants or they can make you worse)
* Extra vitamin E
* CoQ10
* ALA (keep low because of mercury)
* Omega 3 and 6 oils
* Melatonin (powerful antioxidant.)

Neuroprotection from CNS toxicity

* CNS xenobiotic detox: B12 hydroxycobalamin 10000mcg IM a day
* CNS Homocysteine detox: P5P, Folic Acid, Trimethylglycine, L serine

Step IV Toxic Source Attenuation

GI Tract - microbial toxicity

* Olive leaf extract
* S Boulardi
* Organic Botanical Extracts (1 month at a time)
* Glutamine Source
* Polymicrobial protiotics without FOS which just makes the bad guys grow faster

Oral Cavity: microbial toxicity source

* herbal tooth and gum tonic
* remove or detox root canal and caviations

Heavy metals (metal load is different than how toxic the metal is to you.)

* amalgams (be careful revmoving)
* fish
* water supply

Home environmental

* home mold plate testing ($10 test kit, sherry rogers in syracruse NY)
* air duct inspections and cleaning
* electronic air duct inserts (for mold)
* Hepa/Hega air filters
* Personal VOC badges by 3M, you wear around for 2 days and measures the amount of volatile organic compound you are exposed to
* CO detectors

Cheney likes chlorella tablets for mercury. Start slow and work your way up. Believes is safer than pharmaceuticals. If you take 2 chlorella and
get sick, you probably have mercury.

Step V

Detox:

* B12 shots: hydroxycobalamin start at 10000mcg/day
* MSM @ 6-12g/day
* Whey 10-20g/day
* Guaifenesis short acting, start at 300mg (Q12H, I think means twice a day?)
* Growth Hormone .2mg SQ miniquick a week

Beware that detoxification can immobilize toxins too fast. MSM is particularly troublesome that way. Go slowly.

STEP VI

Other novel forms of detox he touched on and said he is starting to investigate are:

* colon hydrotherapy (should be time limited),
* hydrogen peroxide/epsom salt bath (twice a week),
* infra red light pads over lympathic drainage sites (20-40 minutes twice a week to activate nitrous oxide enzyme),
* deep tissue massage,
* infrared sauna at low temp twice a week.

Step VII

Enhancing Phase III recovery trajectory

* Growth hormone injections
* Fetal Bovine Growth factors

Teenagers get better much more than older people. Why? He believe growth hormone. A 10 year old has 10 times the growth hormone as a 30 year old.

6 of 9 in study were good to excellent responders. Other 3 were in the group that didn't get immune modulation, and they had joint pain especially in wrists. At least 3 are back to work in demanding jobs.

Growth hormone must be kept a low dose once or twice a week, or patients get worse patients must be immune modulated before starting GH or GF

Risks of GH: If you have cancer, it mayincrease the growth rates (it does in test tubes, not so clear in animal studies where sometimes the immune system
improvement shrinks the tumor) He gives miniscule amounts once a week to reduce this risk. GH also can activate a virus, make it grow faster. And once you trigger it, you can't turn it off by stopping the GH.

He gives 0.2mg once a week. This is low enough that isn't a problem in 99% of people. Some people can take more, but is riskier.

The more well the patient is, the better they do. GH is best for people who have gone through the worst, come back up, but are still 30-40% away from
better. This helps them the most.

Growth Factor seems to activate the immune system, cytokines, which causes joint pain.

Functional response of GH and GF are much better if you take them together. But GF is packaged in packages large enough for 10 doses and can only be
used once. So unless manufacturer repackages, it isn't economically feasible.

Interesting things from Q&A

Q. Should high cholesterol be treated with drugs?

He thinks no except in extreme risk cases, especially do not use those drugs that inhibit liver synthesis. Also drugs that lower cholesterol also lower
CoQ10, and PWC's are already low. INTERESTING: Your body uses cholesterol to make steroids like testosterone, aldesterone, DHEA, cortisol, estrogen, etc. So your body might make more cholesterol on purpose to try to fix the fact that these have been screwed up.

Tests he orders:

Elevated RNaseL
Pathogens
SFM (soluable fibrin monomer)
TH2 activation, TH1 suppression
Toxins in urin that correlate with gut bacteria
Mercury in stool, and how respond to chlorella
Growth Hormone (exercise test, see if rises)
Insulin Tolerance Test
24 hour urnine test for GH
Cortisol response to exercise

He has kits sent to you in the mail so you can get them done cheaply, then you see him when results are in.

Q. Oral Thymus?

He has used glandulars in CFS. Thymus glandular makes sense to him. But they are derived from animals, so you have to worry about mad cow, etc.

Q. Does CFS affect aging?

Some of his patients look much younger than they are, others look much older than they are. The ones that learn to stay within their boundaries look
younger. Ones that always break through the boundaries look very old.

Q. EEG Neurofeedback?

He has done and he thinks it can work, but in his experience it doesn't seem to stick.

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