Hard truths

Unfortunately, fulfilling my prime directive here involves reporting the bad news with the good. I’m in the process of reemerging following a full-on crash. I was down for the count for three days. Worst crash in over a year. I think the culprit was a very long walk at the LA airport where I had to change planes on the way home. It was more exercise than I’ve had in years. When I realized how far it was, I asked for a wheelchair and was told it would take too long. I tried to make it, but ended up unable to take another step, sitting down at the feet of a security guard (yes, lazy, crazy and faking once again). After I talked them out of an ambulance, they got me a chair complete with a lovely young man to push. I won’t make that mistake again. Arrange for the chair ahead of time. I felt fine that night, low energy for a few days but OK, then straight down the tubes. Probably all more familiar to many of you than it is to me. When I was really sick, I wasn’t able to do enough to experience PEM; I had it all the time, so wasn’t so aware of the cause/effect. Before that, I didn’t have it, and could still exercise without adverse consequences. I’m learning what my limitations are at this level of health. Very disappointing that the drugs didn’t prevent it, but facts are facts.

It was classic CFS post-exertional malaise (PEM), in case anyone was doubting my real diagnosis. Magical thinking pretty clearly isn’t going to get me through this one. I have to deal with the reality of my limitations and try to stack the odds in favor of function. It would seem that I’ve become a hothouse flower. I’ll have to figure out how to pace myself to avoid the payback. I guess I needed to be reminded what the stakes are. Maybe I was getting complacent, thinking temperament could win out. It is a formidable opponent, never to be underestimated. Rather, we must use our evolving model of the illness to understand the pathophysiology and fashion meaningful interventions. In hindsight, it was predictable and I’m wondering if O2, IV saline and possibly a pulse of hydrocortisone wouldn’t have headed it off at the pass.

The literature on the pathophysiology of post-exertional malaise in CFS is pretty scanty:

Reduced glutathione (GSH) drops markedly in the liver with strenuous exercise – as a normal consequence. There is substantial evidence that patients with HIV, CFS and autism have GSH depletion. Skeletal muscle competes with the immune system for limited GSH supplies. GSH depletion is immune suppressive and favors viral activation. If the patient is GSH depleted at baseline, then exercise is going to produce marked abnormalities in multiple systems, especially in deconditioned skeletal muscle.

Here’s an intriguing paper with respect to the treatment of GSH depletion in LP-BM5 infected mice:
Inhibition of murine AIDS by pro-glutathione (GSH) molecules. Fraternale

Other simple retroviruses may produce disease in humans in similar ways to XMRV. Some people who seem clinically as if they should have X, are testing negative, even though their diseases look the same as the people who do test positive. It’s very difficult clinically. We know enough to strongly suspect other HMRV’s and possibly other animal retroviruses are present. There is no ability to identify them in humans at this time. The most that can be said is there is or isn’t XMRV detected by culture. The available serology test probably picks up the P variants as well as X, but is negative in some culture positive patients (both very sick and not so sick with this profile). More questions than answers.

The hardest truth of all approaching the end of this momentous year for neuroimmune illness patients is that the results of the first informal unpiloted trial of antiretrovirals for XMRV infection suggest that antiretrovirals don’t produce a remission for most. It is clear that they move the illness, but for those who have been sick for a long time, it seems that the drugs don’t fix it, at least so far. There is still very little experience with all three drugs for any length of time, but Ali and I are approaching ten months on treatment and our recovery is still incomplete, especially with respect to our ability to push the envelope. Most patients taking antiretrovirals are reporting very modest or no gains on various combinations of the drugs for various lengths of time. In general, antiretrovirals have been well tolerated. Initially symptoms flare for most, but because of the possibility of encouraging resistance, full HIV doses seem prudent nevertheless. For a small number of people, this period of symptom exacerbation has been prolonged, beyond weeks. There have been a couple of ER visits for early adverse reactions, but both patients ended up tolerating the drugs afterwards. A couple of people went off AZT for possible problems, but went back on. It is still possible that slow improvement will continue over a long period of time, that the drugs will prevent further deterioration or prevent cancer. They are not difficult to take. Neither Ali nor I can tell that we are taking them in any way. In my opinion, clinical trials that don’t anticipate short term problems with underwhelming results at six months, will fail to show benefit. Quantitative measures will be necessary. Adjuncts will be necessary. Rehab will be necessary. It’s going to be a steep climb. But given that these three drugs are the only antiretrovirals we have, it is vital that they not be dismissed prematurely. It may well be worth it for partial recovery. And it is still quite possible that antiretrovirals will prevent activation in the not yet sick or simply work in the newly sick. There may also be a place for post-exposure prophyllaxis. There may be a place for preventing transmission in pregnancy or perinatally. The clock is ticking. Lots of questions. Very few even trying to come up with the right answers.

Here’s the pièce de résistance. Take a look at this paper discussing possible ways that XMRV found it’s way into humans, Of mice and men: on the origin of XMRV. Van Der Kuyl. Of note is that mouse cells were first used in vaccines in 1931. Epidemic neuromyasthenia; clinical syndrome. Henderson. NEJM 1959 documents the first outbreak as having occurred in 1934. An epidemiological goldmine ignored for half a century following the publication of this fine paper. Even now, my email is more informative than anything our epidemiologists have reported in the literature. It is hard to even begin to comprehend the scope of this disaster.

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27 thoughts on “Hard truths

  1. >Thanks Jamie. Sorry you had your PEM relapse. I know how disappointing it is. We have all had them. You get a little wind of energy and off you go! Until the crash. PEM prevention is so counter intuitive. I continually fall off the wagon, so to speak. However, wheelchairs at airports is one rule I have been able to follow, no matter how confident I might feel. Learned the hard way…like we all do.

    I agree that these are early days in knowing in which ways we may be able to use ARV's — in knowing the various ways they may help, even if they do not often provide a full remission. Time will tell. Personally I hold out little hope along those lines for someone like me who has been ill so long. But you never know!

    Ah yes, vaccines. They may have come back to bite us in a way we never dreamed of.

    Hang in there. We so appreciate what you share with all of us and your support for WPI.

  2. >The PEM episode is unfortunately classic, we combat it with Blassi's idea of electrolyte therapy (reCup or Lectrolyte )and glutathione either in the form of IM injection or oral l-cystine and glutatione (www.Immunoprop.com)

  3. >I admit I am disappointed to hear that, so far, antiretrovirals are not the solution for those of us who have been sick for a long time. I hope that with additional research, additions can be made to the protocols which will have more favorable results for long-term sufferers.

    Thank you for your honesty, Dr. Deckoff-Jones.

    Patricia Carter
    XMRV+, 24 years M.E.

  4. >Thank You Doctor! I would give anything for a PARTIAL recovery!

    cfs-28years and 9months

  5. >That is indeed harsh news. I crashed myself after going to the dentist- likely from the local freezing with epinephrine. It's a funny thing because last year I didn't crash with a bigger procedure.

    This proves that we are in urgent need of more research, and extraordinary funding from governments of all countries to get us on the path of recovery. Unfortunately the 4 articles on contamination in Retrovirology is a huge road block on this path.

  6. >So now we start to see why some of the alternative treatments are helpful, though not curative. I am helped by taking non-denatured whey protein. It boosts glutathione levels. B12 shots help some. Graded exercise including walking neck deep in water helps.

    In a strange way this post is encouraging to me since I still test negative for XMRV. I will just keep doing what has worked for me in the past and keep focused on the meaningful things in my life.

    Paula Carnes

  7. >Hi, Jamie.

    I think that you are right on about glutathione depletion being responsible for the crashes that PWCs experience.

    As you may know, some of us have found, after trying this over a five year period, that though direct support for glutathione can help temporarily, the partial methylation cycle block must be lifted in order to bring glutathione up to normal on a steady basis.
    The biochemistry behind this, the treatment protocol, and reports on clinical study of the treatment can all be found at http://www.cfsresearch.org by clicking on CFS/M.E. and then on my name.

    Best wishes for a healthier New Year!

    Rich Van Konynenburg, Ph.D.

  8. >Jamie, I recall you not responding to glutathione IV, but were you using Wellness or Medaus? They're the best, proprietary stabilized reduced glutathione. I have tried other ones that feel like water to me (nada). And when I'm under extreme stress, like I've been lately, I can't "feel" the glutathione. It seems to get used up instantly. Whereas when I'm in a good situation, I actually feel it as it a kind of "happiness" in all my cells. And I have heard others say that.

    Any plane flight, you should Rx oxygen. It's low oxygen in the cabin and bad air generally.

    I don't know what to say about the retroviruses and whether they are causative, hitch-hikers or, as I've felt all along, work synergistically and are switched on by another contender that is more virulent. Time will tell. Thanks for your honesty, rest up, keep in your window, so you can go back to practice.

  9. >Jamie, I''m so sorry to hear that you've had this crash, but thank you for relaying your experience honestly. All accurate information is good information and helpful. All in all, to me it sounds like two steps forward and one back, not the other way around. I'm not abandoning hope yet. I hope you feel better soon.

  10. >"It was more exercise than I've had in years."

    Deconditioning can't be reversed in a few weeks of otherwise increasing function. But you knew that. So, you just added to the evidence of PEM and how important pacing is. I assure you temperament doesn't win out.

    If ART only stops the progression of illness it would be worth it. To be here when/if they come up with something better is still the dream of many of us. But even to improve function by 20% would be worth it to me.

    I hope you will take really good care of yourself and come out of this crash feeling better than before.

    I hope you won't feel pressured to do, do, do for all of us who are cheering you on. Take good care of YOU.

  11. >This must have been quite disheartening for you Jamie. My experience may be helpful in some way. I made significant progress being on IV anti-viral tx (not arv's) for a year. In spite of tremendous healing of the primary symptoms (OI, sleep problems, brain blur, etc), the PEM has not budged. If not for the PEM, I would be almost fully functional. I was told by a seasoned ME/CFS physician that the PEM is last to come along. That's surely been true for me.

    Rather than this crash putting a shadow over the potential for healing with ARV's, maybe it's just revealing the need to fine tune complimentary Tx.



  12. >Jamie,
    A few thoughts:
    One, could it be possible you are experiencing mitochondrial toxicity from the drugs, particularly AZT, that is just starting to catch up to you? Have you considered doing a Sinatra protocol-style cocktail of mito supplements?

    Two, I think you excluded a very important paper in the field of PEM: Sarah Myhill's paper on mitochondrial damage as a marker for CFS. I believe it is available as a download from her website. Myhill feels strongly, I believe, that PEM is inextricably linked to mito damage.

    Three, I have been thinking lately about PEM as (at least in part) a post-ictal state. I know of at least two patients who have had very significant recovery with large doses of anti-seizure meds administered at just the right times. Post-ictal fatigue/confusion/etc. actually sounds a fair amount like PEM, or aspects of PEM, and I wonder if anyone is exploring this angle. Patients with a lot of seizures and prolonged post-ictal states seem to experience not only "chronic fatigue" (not CFS) but cognitive problems as the brain recovers. Dr. Cheney used to talk about ME/CFS patients being shifted toward a seizure-like state in the brain, hence his feeling that klonopin was neuroprotective. As this relates to XMRV, though, I wonder if XMRV might colonize in the temporal lobes, as HIV does. There is evidence that HIV evolves up to 100 times faster in the temporal lobes: http://www.aidsmap.com/Genetic-study-reveals-how-HIV-causes-dementia/page/1422083/

    I think this could explain why, for some of us, PEM from sensory stimulation over time becomes exactly like PEM from exertion.


  13. >Has anyone been tested for d-lactic acidosis, as it is said to be strikingly similar to CFS according to the Sheedy paper? It can occur without an increase in the anion gap, see link below. Symptoms of dla are severe lethargy, changes in gait, slurred speech, or difficulty in speaking, hyperventilation, confusion, disorientation, dizziness, the feeling of being drunk without having had a drink, headaches, nystagmus,jaw clenching, carb craving and irritability. It is not seen in routine blood tests, and a d-lactate assay kit is required. It is seen as a complication of a shortened bowel, but in the link below it states that is calves it is seen as "viral infection–induced villous atrophy rather than surgical removal of the small intestine."

    It goes on to say

    "There is a possibility, although it has not been described, that a similar scenario could occur in diarrheic monogastrics, including humans"


    The anion gap



  14. >Jamie, curiously, 1931 that was about the time they also began using thimerosal in vaccines. Leo Kanner wrote about his first 11 cases of autism in 1943. All of the kids Leo profiled were born around 1931-1933. (coincidence?) One of the boys, Donald T- was diagnosed with rheumatoid arthritis as a child and treated with gold salts- a primitive form of chelation. He recovered from RA, but also- many autism symptoms went away. Was the cure from RA from the chelating properties of gold salts, or was it the reduction in oxidative stress and increase in glutathione? (Dr James Adams found one dose of DMSA normalized glutathione in ASD kids). Dan Olmsted, who has documented the roots of autism, suggested it was the chelation (of thimerosal). I was thought the same, but now I'm not so sure of that. Perhaps you would find more clues in his recently published book "Age of Autism" ? (co-authored with Mark Blaxill).

    On glutathione- now that Labcorp tests for this, I'd like to see that test added to the regimin of diagnostics on CFS/ME. (Kids with autism are most often found to be critically low.) Has anyone in the CFS/ME world used glutathione levels to direct treatment protocols? What about combining Phosphatydil Choline with GSH for better absorbtion?

    Tami G

  15. >I'm wondering if you've been in touch with Dr Timothy Luckett, virologist whose sister has ME/CFS. On his blog he mentions receipt of a report from a 36 year old woman, former marathon runner, sick w/CFS for 12 years, disabled for 3. After 4 months on Isentress and Viread she was able to return to work full time and can exercise an hour/day.

    He doesn't say whether she was positive for any retrovirusus or viruses, but he does say she sought a doctor who would prescribe ART after hearing about the WPI findings.


  16. >I appreciate your candor. If AZT and other drugs work well in the lab against XMRV should we necessarily expect that they would work in the body?

  17. >We already have clinical evidence that they do work in the body, but the drugs we have can only inhibit early stage events of viral replication. Latent provirus can still activate and generate new viral particles, fueling persistent immune activation. This type of chronic immune activation is now known to be very important in the progression of HIV infection to AIDS. Unfortunately, we don't have a protease inhibitor that works in vitro against XMRV, so we are limited to other strategies for maintaining latency. We need specific drugs.

  18. >Hi jamie I dont know what your IL-6 and TFN alpha levels are like but they can be very high.This raises glucose metabolism to the point that available glucose becomes depleted if demands on ATP are high that coupled with damaged mitochondria as a result of raised TFN alpha may lead to a state of ATP exhaustion The details are too complex to post but basically the mitochondria need time to regenerate a supply of ATP. I dont know what your glucose intake during this period was like but it may be worth looking at

  19. >Jamie, I too appreciate your candor and am sincerely sorry that your health has worsened.

    To me it suggests that while XMRV may still play a part in ME/CFS, perhaps it isn't 'the' cause that so many seem to think it is, and comparing it to HIV is a mistake, in my opinion.

    Perhaps your 'prime directive' should be taking care of yourself and your daughter, instead of playing the role of the brave, heroic warrior in this battle against something which may not even be causal. As others have said, please don't feel pressured or obligated to report anything. Take six months "off". You owe nothing to us, but everything to yourself and your daughter.



    p.s. I also agree with posts by Rich Van K, and Tami G above. It might be very helpful to look into both methylation and environmental toxin exposure.

  20. >The mistakes people are making is assuming a human gamma retrovirus behaves like and induces pathology in the same way as HIV. it does not. A HGRV is a gene maipulator and by being so disrupts immune homeostasis which in turn leads to cytokine induced pathology including oxidative stress. Hence they can induce pathology when inserted into DNA. If one considers the situation in other mammals then XMRV is very likely to be one of many xenotropic polytropic and amphoteric strains. those testing negative with CCCME/cfs should bear that in mind.The other mistake people make is thinking that CFS as defined by Fukuda actually exists in scientific terms in the absence of PEM it is just a metaphor treated as though it is an objective diagnosis

  21. >Healthy New Year to all of us who are part of the JDJ blog community. I owe a great debt of gratitude to you, Jamie. Based on your comments about Actos, I've been on Actos (15 mg per day with another 15 mg added prn) since December 3rd. That afternoon after the first dose I chose to sit up and read. Since January of 2010 when I became ill, I haven't chosen to sit up for anything. I have been on Valtrex since mid-August (tested positive for XMRV in Sept.) and was seeing some incremental improvement in function after I started that. The Actos has improved my functional capacity by 80 – 90 percent. With the exception of exercising as exercise, I was able to live normally through the holidays, using 30 mg of Actos each day. This week I've been back in fog and PEM land but as evidenced by the fact that I'm sitting at the computer, I've already regained function.
    I never would have known to ask for Actos without your blog.

    It is scary and deeply disappointing to feel the symptoms re-surge. Like other readers, I am sorry you are going through PEM and grateful for the gift of your sharing your experiences and knowledge.

  22. >so sorry you're not feeling well, it is frustrating to have PEM, and an unpleasant reminder of our "energy envelope" limitations. i have recently started inhaling h2o2 3% thru a nasal spray and have gotten excellent results with that, as a quick pick me up. i used bill munro's protocol. just throwing out an idea here..feel better jamie and everyone , hopefully a healthier year ahead of us..

  23. >Dr. Jamie,

    your experience in the airport mirrored one I had almost exactly. I was returning home form seeing Dr. Goldstein in CA in 2003, and knew it was the last time I would be able to travel.

    By the time I returned to DIA (Denver International Airport), I knew the walk to my car would be a heroic measure on my part. when I got there, i could barely stand; my muscles were convulsing and my heart was battering my chest wall.

    My auto-unlock didnt work. I used my key to get into the car. Tried to start the car and then my world fell apart. The battery was dead. There was nothing else I couuld do but reconcile that I Had to walk back to the terminal area, and find help. It still brings me to tears. I made it there, only to be told I had to walk the distance of half a football field and talk to a security guard to get jumper cable help. I asked for help. I asked for a cart to take me. They said no. I asked them to please call them for me, they said no. I knew what I looked like walking (kinda) to the security center. People stared at me. None stopped to help. I'll never forget it. The fact that I made it is beyond me. It's such a testemant to sheer will and inhuman grit. I don't know how I did it. I don't think I did. I think a hundred angels did it for me.

    Bless your heart, and I hope you are better.

  24. >Yes, big airports are no fun. We only tried flying once since I got CFS. It was not worth it. Crying together in a food court did bring a lovely child to our table to show us her new doll. We are sick, but, children carry a magic we have forgotten. I am happy WPI is starting to function. Don't worry, even if we are all completely cured, we will still have bad days, just like everyone else.

  25. >Your story sounds way too familiar. PEM is a rather rude reminder for us to "excersize within our limitations." Unfortunately that is much easier said than done.

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