One of the best parts of this journey from a medical point of view is that it is based in hard science. It is the first time in my career, including training and sixteen years of emergency medicine, that voodoo has taken a backseat to the basic science. If one applies the knowledge we have about HIV to CFS, we have a pretty good model from which to consider our approach to treatment.
Read the Mogensen paper linked on the sidebar. Then read it a few more times. The keys are in that paper. It’s all the result of persistent immune activation (plus gene modification?), however it may manifest in a particular individual. I came up with the following system based model, better than symptom based, but still more complicated than it needs to be in order to consider therapeutics.
The myriad symptoms of CFS can be sorted into general categories based on pathophysiological groups. Here is my first pass at this, with examples of symptoms, not close to exhaustive, in parentheses. The categories provide a framework for considering pathogenesis and may present strategies for a multi-pronged approach to therapeutics.
- Vascular spasm (migraines, flashbacks, black outs, dysautonomia, microvascular angina, dysrhythmias, GI symptoms, Raynaud’s)
- Inflammation (depression, sleep disorder, cognitive deficits, fibromyalgia, malaise, OI, IBS/IBD, “swollen brain” possibly related to CCVSI, interstitial cystitis)
- Neurodegeneration (sensory overload, sensory neuropathies, cerebellar degeneration, neuropsychiatric manifestations, neuropathic pain, MS)
- Immune activation, derangement (activated viruses, tick-borne diseases, almost autoimmunity, antiphospholid syndrome, Hashimotos’s thyroiditis, late neoplastic transformation)
- Hormone depletion and receptor insensitivity (cortisol, androgens, insulin insensitivity, LH insensitivity leading to progesterone deficiency in women and testosterone deficiency in men, hypothyroidism)
- Cellular hypoxia, mitochondrial defect, methylation defects (shortness of breath, mini-clubbing, “fatigue” or energy currency deficit, heavy metal toxicity, MCS, oxidative stress)
- Push-crash (short term, days, post mental and physical exertional malaise; longer term, weeks or months, post trigger activation- physical, emotional, infectious- physiological explanation is obscure)
- Gene activation/repression (Marfan’s, Ehlers-Danlos, other connective tissue disorders? Susceptibiltiy to neurotoxic illnes? Cancer?)
But each piece of this list can be explained in terms of the downstream effects of the virus. The hardest to explain mechanistically is push/crash, but some sort of abnormal response to stress hormones is probably involved, thus likely one more manifestation of diffuse hormone abnormalities. There are many questions of course, why hormone depletion, the exact nature of the receptor abnormalities, what exactly causes the hit to the nervous system, but if you consider it piece by piece, all can be explained by the uncontrolled replication and persistent presence of the virus. The body knows it’s there and is doing exactly what it’s supposed to. If it weren’t for the immune response, mucking up the works, it might almost be a commensal. There is no immune deficiency as there is with AIDS, even with advanced disease. Immune deficiency and long term survival are not compatible.
My medical mind was shaped by surgeons. I prefer to treat with my hands than my prescription pad. Not so useful for dealing with chronic disease, but I keep seeing ways in which that approach is needed for the current situation. In many ways, the simplistic ED mentality is what’s called for. It’s an emergency. People are trapped and suffering, with no help, or worse than no help. Triage, best guess, compassionate care. ABC’s.
We have a way to think about it now. No more need for all those black box protocols. It’s pretty simple all of a sudden. Unfortunately there are very few therapeutic modalities worth considering, but at least we finally know what not to do. We need reliable detection from more than one commercial lab in the world. We need viral load measures so we can figure out what we’re actually doing with antiretroviral therapy. We need specific drugs. But considering what’s available at this moment, the options are limited and therefore not complicated.
There is a slowly growing coalition of doctors with sufficient critical thinking skills to consider what to do now for thousands of XMRV+ patients who have already been tested. Only a very few, but it’s a beginning. Doctors who are willing to try to figure some of it out, even before the scientists get the years of controlling the show that they seem to want. The patients don’t die after all. What’s the hurry? And after the detection issues are worked out, in a year or two, then they have to prove pathogenesis, not just association. Then after a few more years we can start to think about whether the drugs we already have are safe enough to try in clinical trials. The usual path to clinical trials is a case study, then a pilot trial of carefully selected cases, before a large scale clinical trial. We are the case study. Patients are lining up to be included in pilot trials, formally or informally. Where have all the doctors gone?
I was an alternative doctor, of sorts, in my last medical incarnation. Patients from that practice keep coming to mind. Many of the patients currently seen in alternative practice will turn out to be X infected. The alternative medicine community has come very far in identifying the metabolic defects and how to think about treatment without doing harm. Many people have written to me that if I would only consider this or that supplement, it would help us. This is at the heart of the problem with treating CFS. The disease is a relapsing remitting process all on it’s own. Everyone naturally attributes their improvement to whatever they were doing when they got better. I recovered the first time for almost a decade with no pharmaceutical treatment at all. In fact, my health would likely be better than it is, had I never seen a doctor at all.
Not in any way interested in increasing our pill burden, we are starting to add back in a few supplements, in the hope that they will be more useful than they have been in the past. Here is a useful review article about neutriceuticals for HIV:
Nutrients and HIV: N-Acetylcysteine, Alpha-Lipoic Acid, L-Glutamine, and L-Carnitine. Patrick
We’ve tracked our TGF beta-1’s and C4a’s from baseline in an attempt to monitor something useful, though viral load, if it were available, is probably the only meaningful thing to follow. These labs do reflect what has happened experientially, though I think it lags behind the clinical picture. It looks like the drugs flare inflammation, consistent with our experience, though Ali didn’t think they made her particularly worse, sick as she already was. Our C4a’s were both normal initially, went sky high when we started treatment, have been coming down and were normal again when we were drawn the end of Sept. My TGF beta-1 was 25,000+ at baseline and has been coming down the whole time, most recently 6000+. Ali’s was 9000+, went up to 28,000+, has been drifting down and was 7000+ last check. We need a few more data points to know if it is meaningful.
The biggest question in my mind, with respect to the use of antiretrovirals, is whether it is necessary to be blasted right off the bat with a full HIV dose, because of the experience with HIV drug resistance, having nothing to do with CFS or X. We have reason to believe that flaring inflammation is counterproductive and we have clinical and lab evidence that full doses of the drugs flare inflammation. We may be setting off exactly the reaction we are trying to turn off, and that may be why some early results have been less than impressive. If I were starting now, I might try starting low and going up as quickly as possible. Certainly after an unsuccesful attempt at getting going. I took tenofovir at half dose for a week, after being unable to start the first time, then went up to full dose without problems. That said, we don’t want to find out in a few years that people who tried treatment early on wound up with resistant virus. Another possibility, especially for patients who have been sick for a long time, is pretreatment for a more rapid beneficial response.
I wonder as much as anyone, especially sometimes in the middle of the night, if it is Deplin, stopping antibiotics or the power of positive thinking that has made us better rather than antiretrovirals? It doesn’t seem likely, especially since there are two of us, but I do hear occasional reports of spontaneous recovery even after a long time. For now, we have to live with this uncertainty, until we have more clinical and laboratory evidence. I thought there would be a large amount of clinical anecdotal data by now, but the powers that be seem to be getting their way, with a stranglehold on the option, due to physician fear, ignorance, self-interest. I would like to modify something I’ve said in the past. I’ve referred to the use of antiretrovirals as an experiment. From my current vantage point, taking antiretrovirals for a retrovirus doesn’t even constitute the usual and customary off-label prescribing. It is a valid option, until evidence shows it isn’t. It is unbelievable that people write to me every day because their physicians seem unable to write prescriptions when they have been prescribing much more dangerous drugs routinely for many years. Not that prior harm justifies a new round, but I believe a trial of antiretrovirals can be a rational medical choice at this time, on a case by case basis. And my daughter and I have put our bodies and privacy on the line to demonstrate that. At the very least, even the most skeptical will have to accept that we are doing extremely well, outside of the CFS bell curve, despite antiretrovirals (three drug combination) at full HIV doses for nine months.
I have received quite a few letters from people who crashed for the first or subsequent time after a vaccination, including flu shots. In my opinion, at this point anyone with a CFS history or the offspring of anyone with a CFS history, should not be vaccinated. It may be that it is the immune challenge that sets off the disease (as it would seem from listening to case histories of autistic patients). But there is an even more pressing and insidious consideration. I have been reading the animal retrovirus literature to find clues for understanding and dealing with HMRV’s.
The literature is vast. Amazing what they know about chicken retroviruses (ALV’s)! Simple endogenous retroviruses. Can infect cells of other species in tissue culture. Recombination events play a part in pathogenesis. Cause tumors of various sorts. Sounds familiar…
There’s literature about breeding in and out certain endogenous retroviruses in chickens. You can breed in compulsive overeating (like OCD) caused by a particular endogenous retrovirus. And you can selectively breed out the ones you don’t like.
- Proviral integrations and expression of endogenous Avian leucosis virus during long term selection for high and low body weight in two chicken lines. Sojeong
- Extremely Different Behaviours in High and Low Body Weight Lines of Chicken are Associated with Differential Expression of Genes Involved in Neuronal Plasticity. Ka
- Methods for evaluating and developing commercial chicken strains free of endogenous subgroup E avian leukosis virus. Bacon
Guess what! They grow live attenuated vaccines in all kinds of animal cells, commonly chick and duck embryos. I’m not a conspiracy theory type. I usually think stupidity explains most of the disasters. But in this case, it is more about arrogance and hubris. They’ve known all along that various endogenous retroviruses were present in the cells they were using, but decided to go ahead and do it anyway. I’m not saying that ALV related viruses are involved in the chronic neuroimmune illnesses the way that the murine retroviruses likely are, but it certainly seems possible. At least worth considering until we know more. It appears that there is more than one MuLV related virus. Could there be other animal retroviruses involved?
- Endogenous retroviruses as potential hazards for vaccines. Miyazawa
- Risks linked to endogenous retroviruses for vaccine production: a general overview. Dewannieux
- Isolation of an Infectious Endogenous Retrovirus in a Proportion of Live Attenuated Vaccines for Pets. Miyazawa
A paper that takes arrogance to a new level. Absence of proof is not proof of absence.
- Identification and characterization of avian retroviruses in chicken embryo-derived yellow fever vaccines: investigation of transmission to vaccine recipients. Hussain/Heneine
Here’s a good one…
- Quantitative detection of RT activity by PERT assay: feasibility and limits to a standardized screening assay for human vaccines. André
And here is a little good news (we’re overdue). AZT inhibits this group of retroviruses also. They knew that before I had Ali. AZT really is a very broad spectrum drug.
- 3′-Azido-3′-Deoxythymidine Inhibits the Replication of Avian Leukosis Virus. Olsen
- The effect of 3′-azido-2′,3′-dideoxythymidine on experimental viral infections. Shneĭder
- Inhibition of the avian leukosis-sarcoma complex with 3′-azido-3′-deoxythymidine (AzT); a model for screening and evaluation of chemotherapeutic agents against retrovirus infections. Kavsan
And look, they know more about another simple retrovirus that infects fish than they do about what’s wrong with millions of people. This one makes tumors that wax and wane and doesn’t kill quickly.