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Article: Proteins on the Brain': A Breakthrough for ME/CFS?

Discussion in 'Phoenix Rising Articles' started by Phoenix Rising Team, Apr 2, 2010.

  1. bel canto

    bel canto Senior Member

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    Cort - Are you aware of the tremendous potential upset regarding the underlying cause of multiple sclerosis?

    Researchers in Italy, with some recent support here in the US, believe that MS is triggered by the blood brain barrier being compromised, resulting in buildup of iron deposits on veins. That then triggers the inappropriate immune response which destroys the myelin sheath and damages the nerve. They believe that many or most MS patients have abnormalities in the major veins that drain the brain and spinal cord - internal jugulars and azygos.

    Hundreds of procedures (venoplasty - opening up the veins with a balloon and/or stent) have been done, with some dramatic results being reported. Stanford did thirty-something procedures, but have suspended them due to potential technical difficulties with the stents.

    One of the thoughts is that if blood can't leave the brain adequately, it is not entering the brain adequately, thus producing some level of something like hypoxia - thus, the fatigue, brain fog, etc. which are not tied to specific brain lesions.

    The condition absolutely exists where veins are malformed or blocked or collapsed, etc. The big questions are, of course, IF and HOW that condition might relate to MS. The condition is known as CCSVI - chronic cerebral-spinal insufficiency.

    Due to the substantial overlap in symptoms (many sources believe that the great majority of ms patients fit the criteria for cfs), the similarity of viruses being associated, and after reading the above discussion of possible microbleeds in cfs patients, I thought I would just throw it out there. There are some people with CCSVI who do not fit MS diagnostic criteria. I wonder if they're totally healthy, or have other problems not described in the studies so far.
  2. lucysun

    lucysun

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    They don't need patients - but still need healthy controls

    Cort,
    I am pretty sure they have all the patient participants - last time I saw them they had started crunching the data! Yay! I was called in for a lung function test to add to that data. They were also debating whether I was indeed a CFS or Fibromyalgia patient - indeed - it seems that there is a big overlap. I never have considered myself a CFS person, as pain is my chief complaint, not fatigue. Whatever. What they call me makes no real difference, they can call it whatever they like - doesn't change things much for me.

    But they still need healthy controls. I understand why it is so hard to get them - I was one of the participants who had the dreaded "spinal fluid leak" headache, and while I was fine with it, my family was not too pleased - that certainly didn't give them any incentive to sign up!

    BTW - I had a high pressure reading (21 I think) , and that relief feeling immediately after, as well, but they caution that there is really no good "standard" for what normal is. Not like they have a lot of opportunity to get readings from healthy people, after all. So while it was a concern for me for a while after, I have let that little "finding" go - not sure it is really significant.

    Dr. B and Dr. R are indeed special people - their dedication and empathy are amazing. I look forward to their final results.

    Thank you for sharing this information and your experience with the study.

  3. Cort

    Cort Phoenix Rising Founder

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    I think this is so interesting...look at Dr. Perrin's theory - that lymph flows from the brain are impaired causing the system to back - causing toxicity in the brain (1'm sure I got some of that wrong :)) but the jist impaired circulation from the brain to the body.

    Then you at evidence suggesting there are problems with circulation in the body and the blood vessels - then throw in low blood volume - a further circulatory stressor - Dr. Baraniuk's findings that blood vessels are tightening up instead of opening - it just seems like there are all sorts of the ways to get the blood vessels and blood flows to the brain involved.

    I wonder if alot of the problems are occurring in the small blood vessels that researcher have trouble imaging. I read that women tend to have more small blood vessel problems - and this is a female dominated disorder.
  4. Cort

    Cort Phoenix Rising Founder

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    Glad to hear they're crunching the data!
  5. August59

    August59 Daughters High School Graduation

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    This may be more of a question for RichVank, but I'm sure others have a good handle on this discovery. This seems to make the case for getting the methylation blood test done so that you can get your strategy for treating a methylation block, if present.
    My biggest question is - What would be the best supplements to try that may help reduce these affects from this process if in fact was taking place. Carnosine supplement? Looks like it makes the case for a good anti-oxidant, but which would be better? I already take Klonopin and it definitely makes a difference and in small doses too (I take .25 mg twice a day and .5 mg at bedtime).:confused::confused:
  6. richvank

    richvank Senior Member

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    Hi, August59.

    I want to emphasize that I have offered the hypothesis that Dr. Baraniuk's observations of misfolded proteins can be explained by glutathione depletion, which is tied to a partial block in the methylation cycle. However, at this point, it's an unproven hypothesis. I just want to make that clear.

    With regard to treatment of the partial methylation cycle block and glutathione depletion, I do recommend getting the Vitamin Diagnostics methylation pathways panel run first, to see if these features are indeed present, and to get baseline data for use later in the treatment. Contact info for getting this panel is pasted below.

    With regard to treatment, the protocol for the Simplified Treatment Approach is also pasted below. As I wrote there, my position is that it is necessary to work with a licensed physician while on this treatment.

    Best regards,

    Rich

    Methylation Pathways Panel




    This panel will indicate whether a person has a partial methylation cycle block and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block. I am not associated with the lab that offers this panel.

    The panel requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on a clinician’s letterhead.


    Available from:

    Vitamin Diagnostics, Inc.
    540 Bordentown Avenue, Suite 4930
    South Amboy, NJ 08879
    USA
    Phone: (732) 721-1234
    Fax: (732) 525-3288

    Lab Director: Tapan Audhya, Ph.D.

    Dr. Audhya is willing to help clinicians with interpretation of the panel by phone.



    April 18, 2009


    SIMPLIFIED TREATMENT APPROACH
    FOR LIFTING THE METHYLATION CYCLE BLOCK
    IN CHRONIC FATIGUE SYNDROME (Revised)

    (Extracted from the full treatment program
    developed by Amy Yasko, Ph.D., N.D.
    which is used primarily in treating autism [1])

    SUPPLEMENTS

    1. FolaPro [2]: tablet (200mcg) daily
    2. Actifolate [3]: tablet daily
    3. General Vitamin Neurological Health Formula [4]: start with tablet and work up dosage as tolerated to 2 tablets daily
    4. Phosphatidyl Serine Complex [5]: 1 softgel capsule daily
    5. Activated B12 Guard [6]: 1 sublingual lozenge daily

    All these supplements can be obtained from http://www.holisticheal.com, or all but the third one can be obtained from other sources.
    The first two supplement tablets are difficult to break into quarters. We recommend that you obtain (from any pharmacy) a good-quality pill splitter to assist with this process. They can, alternatively, be crushed into powders, which are then separated on a flat surface using a knife or single-edged razor blade, and the powders can be mixed together. They can be taken orally with water, with or without food.
    These supplements can make some patients sleepy, so in those cases they take them at bedtime. They can be taken at any time of day, with or without food.
    GO SLOWLY. As the methylation cycle block is lifted, toxins are released and processed by the body, and this can lead to an exacerbation of symptoms. IF THIS HAPPENS, try smaller doses, every other day. SLOWLY work up to the full dosages.
    Although this treatment approach consists only of nonprescription nutritional supplements, a few patients have reported adverse effects while on it. Therefore, it is necessary that patients be supervised by physicians while receiving this treatment.


    [1] Yasko, Amy, and Gordon, Garry, The Puzzle of Autism, Matrix Development Publishing, Payson, AZ, 2006, p. 49.
    [2] FolaPro is a registered trademark of Metagenics, Inc.
    [3] Actifolate is a registered trademark of Metagenics, Inc.
    [4] General Vitamin Neurological Health Formula is formulated and supplied by Holistic Health Consultants LLC.
    [5] Phosphatidyl Serine Complex is a product of Vitamin Discount Center.
    [6] Activated B12 Guard is a registered trademark of Perque LLC.
  7. August59

    August59 Daughters High School Graduation

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    Thanks Rick, I certainly appreciate the feedback and am completely on track with the "Simplified Approach" and what I was trying to ask (bad day) was if anything else would be recommended based on this study? Thanks
  8. richvank

    richvank Senior Member

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    Hi, August59.

    I don't know of anything else to suggest based on the results of Dr. Baraniuk's study. If my hypothesis is correct, lifting the methylation cycle block and bringing glutathione up should allow the cells to fold the proteins properly. But again, it's an unproven hypothesis at this point.

    Recently, I've been suggesting some other supports for the methylation cycle treatment in cases where it has not been effective. These include amino acids and vitamin and mineral cofactors for the enzymes in the methylation cycle and related pathways. The latter include the B-complex vitamins, magnesium, zinc, manganese and selenium. I've also suggested that some might benefit by some direct support for glutathione when starting this treatment, because stimulating the activity of methionine synthase in the methylation cycle may temporarily lower glutathione even further, before it eventually rises to normal. Such a drop could contribute to the excitotoxicity that several people have reported, which manifests as a "wired" feeling, anxiety, insomnia, or hypersensitivity of the senses. I have suggested these things apart from Dr. Baraniuk's research, but I think that they can help to get glutathione up sooner, and if my hypothesis is correct, that could correct the protein misfolding sooner, also.

    Best regards,

    Rich
  9. Noah_Scape

    Noah_Scape

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    MS treatment

    I was wondering about this too, since there was recent media coverage of two Canadians who went to Poland to get the "neck vein treatment" for their MS. They claim to have been helped greatly [too soon to pronounce a cure though].

    And it all just make so much sense, from the point of view of a Fibro victim, my symptoms match the description of symptoms of the "protiens on the brain" condition.

    My question is [for Cort?] -
    "Does this relate to the work of Dr.s Light [Alan and Kathleen?] who found sensory neurons monitoring muscle status that are "overactive" when Fibro patients exersize?"
  10. Athene

    Athene Never give up

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    Aberrant prion disease?

    I am just wondering if this is the same discovery that Kenny De Meirleir made and called aberrant prions? He has already patented the name "Aberrant prion disease" (as a new,proper diagnosis for CFS patients) so he must be pretty confident about this.
  11. alice1

    alice1 Senior Member

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    Toronto
    Thankyou you Cort and richvank for all this great information.
  12. doug

    doug

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    San Rafael, CA
    Thanks for posting this interesting story. I'm a layman not constrained by medical knowledge, so can make wild guesses about the cause of amyloid plaque. Possibly XMRV impairs immunity, causes secondary bacterial or viral infections which lead to antobody and cytokine overload, impair renal function. Proteins and toxins don't get eliminated correctly causing amyloid plaques/vasculitis. When this happens in blood supply to the brain, leading to neuron breakdown in the Hypothalamicpituitaryadrenal axis, along with hormone imbalance.

    There is also a theory that narrowing of veins leading from the brain causes iron deposits in the brain and MS:
    http://jnnp.bmj.com/content/early/2008/12/05/jnnp.2008.157164.full.pdf html
    The cause of artery narrowing is yet to be identified, but maybe amyloid plaques? Chronic infections can cause vasculitus

    Amyloid plaques are caused by antibodies (Glycoproteins) that cannot be broken down and accumulate. Secondary amylodosis can be caused by chronic infection.
    http://www.mayoclinic.com/health/amyloidosis/DS00431/DSECTION=causes
    The kidney filters proteins and removes toxins. Infections can cause abnormal kidney function or subclinical glomerular disease:
    http://www.uptodate.com/patients/content/topic.do?topicKey=~cxxxdQH6Eb6H/_
    and
    http://en.wikipedia.org/wiki/Glomerulonephritis

    Curcumin and Vitamin D3 reduce amyloid plaques:
    http://news.bbc.co.uk/2/hi/health/1668932.stm
    and
    http://www.sciencedaily.com/releases/2009/07/090715131558.htm
    "The team discovered that curcuminoids enhanced the surface binding of amyloid beta to macrophages and that vitamin D strongly stimulated the uptake and absorption of amyloid beta in macrophages.
  13. August59

    August59 Daughters High School Graduation

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    Elimination of Toxins produced in the lifting of methylation block


    Hi Rich (or anyone else that might have very good perspective on this)

    When starting the treatment and with the expectation that at least a partial methylation block is lifted, how are the majority of these toxins eliminated? The liver, kidneys or other?
  14. slayadragon

    slayadragon Senior Member

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    twitpic.com/photos/SlayaDragon
    As some folks here know, I have been pursuing what might be called "extreme mold avoidance" to address my long-standing (14 years), severe, wholly classic ME/CFS. Insofar as I manage to avoid mold toxins at a high enough level (a task FAR easier said than done!), I am wholly well.

    One thing that I have found to be interesting is that almost immediately upon getting a big mold exposure, I get feelings of swelling and inflammation in my spinal cord. This especially is noticeable at the back of my neck, eventually (if the exposure is bad enough) leading to headaches.

    I discussed this on another board with a CFS specialist, Keith Berndtson, M.D., of Park Ridge, Illinois. I am going to put his summary hypothesis on the post below. (This was prior to the announcement about XMRV, so that virus is not included. It would be consistent with his other comments though.)

    Dr. Baraniuk and Dr. Mavrindrin have done studies in which spinal taps temporarily relieved patients' symptoms. This would be consistent with my experience (and that of a number of other CFSers pursuing extreme mold avoidance) that reducing the swelling relieves a variety of symptoms in this disease.

    Mycotoxins (especially the ones made by Stachybotrys, which appears to be by far the worst mold for many of us) have been shown in lab studies to be extremely good at causing oxidative stress and inflammation. I've yet to see any research suggesting that any other toxic substance that people are likely to come into contact with is as good at doing this.

    Insofar as viruses like XMRV also contribute to oxidative stress and inflammation, a combination seems like it may be a "perfect storm" leading to a disease as serious as this one.

    Rich and Cort (and others), I'd like to hear your comments.

    Best, Lisa
  15. slayadragon

    slayadragon Senior Member

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    twitpic.com/photos/SlayaDragon
    With the increased spinal fluid pressures, the temporary relief after spinal tap, the questions raised about whether Chiari malformations are causative or merely associated chronic recurrent severe headaches, the progression from an initial stage (depression, short fuse, cognitive dysfunction, etc.) to "migraine" headache make you wonder whether brain capillary endothelial membranes can become leaky from mold exposure.

    Daniel Amen, MD, has documented regional brain blood flow patterns in patients with various diagnoses (though not CFS). Certain symptoms correlate with reduced flow in certain brain regions. For example, if you experience decreased blood flow in your dominant-side temporal lobe, you may experience aggression (directed externally or internally), reading difficulties, word-finding problems, or increased sensitivity to slights, or emotional instability.

    We know that mold toxins create a leaky blood brain barrier. We also know that the choroid plexus of the brain filters brain blood and lymph into CSF. It also makes beta-2-microglobulin, a protein whose grab free toxins in this filtrate and escort them out of the CSF compartment.

    Let's say a biotoxin exposure creates a sequence of cytokine release, MMP-9 release, and a patch of leaky blood brain barrier. The cytokine response moves into the brain. Depending on which part of an individual's brain is affected, and depending on the relative state of neurochemical balance or imbalance in various parts of that person's brain, you might experience a sudden quickness to anger, reversible paralysis, brain fog, depression, or something else.

    Meanwhile, the choroid plexus is receiving more toxic shipments, so it is to crank up the volume of CSF production. The intracranial and/or spinal CSF pressure builds, creating deep pain at the base of the neck, top of the head, above the eyes, spine swelling, etc. You have what almost everyone would agree is a migraine headache, but it's really driven by the increased CSF pressure that occurs when the choroid plexus is trying to mop up after another toxic spill type of exposure to brain tissue. We do a spinal tap and the pressure is abnormally high, but tapping 30 cc of fluid out of the CSF space relieves the pressure on your brain and spinal cord and you feel better - until the pressure builds up again.

    You learn that mold is a trigger, so you avoid it as best you can. The avoidance slides you toward the part of the CFS spectrum where cytokine activity is quiet enough for you to tolerate exercise well. You exercise regularly at high altitudes and the EPO effect does wonders for your system.

    There may be "priming" triggers - or antecedent changes exposures to (reactivated HHV-6a, leaky gut-derived toxicities, parvovirus, Lyme, toxic fat stores, heavy metals, solvents, pesticides, etc.), and there may be "cascade triggers" (biotoxins, chemical exposures, food sensitivities, etc.).

    We should get the idea that there would be dozens of biomarker abnormalities floating through the bloodstream and CSF of CFS patients. The question is, is there a set pattern of abnormal biomarkers that a) place people on the CFS spectrum of illness, and b) sort them into specific types somewhere on the spectrum.

    We shall see. But if CFS patients remain something like a black box (or a dark gray box), as long as we can devise inputs (care plans) that produce reliably good outputs (clinical outcomes), then the pathways and mediators can unfold at the pace of academic research.

    -Keith Berndtson, M.D.

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