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:
- Postexertional Malaise in Women with Chronic Fatigue Syndrome. VanNess
- Nitric Oxide Metabolite Production During Exercise in Chronic Fatigue Syndrome. Suarez
- Chronic fatigue syndrome… a model based on inflammatory and oxidative and nitrosative stress pathways. Maes
- CBT/GET is … potentially harmful for many patients with ME/CFS. Twisk
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.
- Glutathione depletion in rested and exercised mice: biochemical consequence and adaptation. Leeuwenburgh
- The physiology of exercise intolerance in patients with myalgic encephalomyelitis (ME) and the utility of graded exercise therapy. Pierce (unpublished in the peer reviewed literature)
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.