How not to think

Thankfully, I don’t receive all that much blog-related mail.  But this weekend I received several communications about a piece in popular liberal blog.  The piece is (ostensibly) about Lyme disease, which coincidentally happens to be one of the topics of my first post here at SBM.  In fact, I’ve written about Lyme disease a number of times, and Dr. Novella has a very good summary of the controversy at one of his other blogs.  Since we’ve discussed this so many times, I won’t be reviewing the entire controversy, but looking at this particular blog post to examine how our personal experiences and errors in reasoning can distort our view of reality.

The topic of Lyme disease has come up recently in the press, and as the weather improves, cases in the northeastern U.S. should start to increase soon.  Just as a reminder, so-called “chronic” Lyme disease is not Lyme disease at all.  Lyme disease can have early and late manifestations, none of which correspond to the vague, protean symptoms labeled as “chronic” by some.  The disease is often diagnosed without resort to objective evidence, such as reliable, positive lab tests.  But let’s look at the blog post in question and see what’s there.

It sounds as if the writer of this piece has dealt with some terrible suffering, but the explanation she has reached for it is rather odd:

I came by my own ringside seat at these festivities courtesy of a tick bite incurred, probably on a hiking trail somewhere in the Sierra, in the late summer of 1984. I don’t remember the bite. I never saw the tell-tale bulls-eye rash (I’m a country kid — I got bit all the time by one noxious thing or another) that one of the warring camps insists must be present for a Lyme diagnosis to be accurate. But I do know that I went to bed one day in October of that year, and was never the same afterward — and that I’ve been struggling with devastating bouts of exhaustion, body pain, and brain fog ever since.

The narrative sets up a chain of events, then looks for cause.  The chain is “went for a hike” then “felt bad since”.  As we know, it is tempting to employ post hoc ergo propter hoc thinking here,  but is it correct to do so?

There are several problems with this compelling and well-written narrative.  First is the tick bite that wasn’t.  In medicine, we don’t assume an event has happened unless there is evidence for it.  If you have clear evidence for a tick-borne disease but don’t remember a tick bite, then logic would dictate you simply had a bite but were unaware of it.  If you hang your diagnosis on a tick bite, but don’t recall the bite, then your reasoning is circular and nonsensical.  “I have Lyme disease because I had a tick bite, and I know I got bit because of have Lyme disease” is a problematic statement.

Then is the misunderstanding of medical knowledge.  Doctors do not insist on the presence of the erythema migrans rash in order to diagnose Lyme disease.  It is a useful clue, but it’s presence is not required.  The writer’s terrible understanding of medicine and biology truly blossoms later in the story.  (By the way, “brain fog” is a common phrase in the literature of “alternative” diagnoses.  There is no consistent definition, and it is not clear what the phrase represents.)

Over the years, various doctors pinned assorted diagnoses on these symptoms, all of which promised exactly zero hope for a cure.


But it wasn’t until a year ago this past week — nearly 24 years and a dozen or so doctors after my first collapse — that I finally got a firm diagnosis of Lyme disease. Last August, after returning home from the convention in Denver, I started the difficult and demanding high-dose multi-layered antibiotic treatment. The average case of chronic Lyme takes two to five years of treatment to cure. At this late date, though, the odds are only about 70% that I’ll ever be able to shake it. Still, six months in, my joints work again. I can exercise and travel without having to pay it back with weeks in bed. And my mind grows sharper by the day. The drugs are working – and every day I’m better is a day of grace I never thought I’d see.(All emphasis mine. –PalMD)

There are some interesting bits here.  First is the “zero hope for a cure.”  No one likes having there hope taken away. When we tell a patient that we don’t know what’s wrong with them this can be very unsettling.  Of course, even when we don’t have a precise diagnosis, we can still tell patients we will do everything we can to help them feel better. But some people want to hear an exact diagnosis and a clear plan for a cure—this isn’t always possible.  One approach to this uncertainty is to work closely with the patient to help ameliorate their symptoms.  Another is to lie to them.  I find the latter choice to be the easier one, but also the immoral and ultimately unhelpful choice.  Now, let’s see how quickly the writer can fail biology.

The treatment takes so long because Lyme is the most cunningly persistent bacterium known to science. In its native state, it’s a spirochete — a cousin to syphilis. But if you hit it with penicillin, it will convert in a matter of minutes into an intracellular form that’s more like a mycoplasma, which will only respond to a macrolide antibiotic like azithromiycin or Biaxin. Or, just for fun, it will roll up into a hard cyst form that can hide, dormant, in the macrophages of cells, and then emerge to re-infect the host years on down the road. This well-armored third form responds — only very reluctantly — to Flagyl and a couple of the TB drugs. Curing the disease means taking large doses of several classes of antibiotics together for months at a time — either orally, or through an IV — so the germ will have nowhere to hide. And all the while, we also need to be carefully watching for and mitigating the drugs’ own very real consequences to the body.

I’m not sure what it means that Borrelia is “the most cunningly persistent bacterium known to science.” I mean, I have opinions I suppose. Mycobacterium tb is a clever fellow, as is syphilis. I’m not sure what makes Borrelia the most anything. A micro-organism can be the most prevalent, or the smallest or largest, but it can’t be the most cunning. “Persistent” is an interesting one. I’m not sure what makes her think it’s particularly persistent. Tuberculosis is very persistent, as are many of the human herpes viruses.  As to the different supposed phases of the bacterium, it is not an obligate intracellular organism, and it is in fact not clear if it even can perisist within cells.  As far as antibiotic sensitivity, I am not aware that this changes, although some antibiotics are better at different stages of disease.  What is very clear from randomized controlled trials is that: 1) the somatic symptoms described by those with “chronic Lyme disease” are no more frequent in people who have had Lyme disease than in matched controls; 2) randomized controlled trials have failed to show any efficacy to prolonged antibiotic treatment in those who are described as having “chronic Lyme disease”.  The only source I could find that describes this particular “life cycle” of the spirochete is in the quack journal Medical Hypotheses.

To complicate matters further, the ticks that deliver Lyme usually deliver other diseases, too: babesiosis (a form of malaria), ehrlichiosis, mycoplasma, and others that also must be found and treated for a full cure to happen. Though these are nominally “deer ticks,” entomologists have found Lyme-bearing ticks on birds, dogs, rodents, horses, and many other animals. Last week’s chimp attack is also being blamed on a form of Lyme psychosis. It’s probably true that veterinarians have a better handle on this disease than the doctors who treat humans do.

Ugh. I don’t think she’s ever taken a biology course. Babesiosis is not a form or malaria. Also, I don’t doubt that veterinarians have a handle on animal diseases—I do doubt that they have a better handle on human disease. It’s just not their thing.

I’m loathe to continue the line-by-line analysis of the piece, as I don’t want to lose you here, so stick with me as I wrap this up.  The article continues the pattern of conclusion—>evidence.  Whatever the author may wish, we cannot do science by forming conclusions and then twisting the facts to fit these conclusions. For example:

However, once some strains of Lyme get dispersed and embedded in the body’s tissues, the standard treatment won’t touch them. Worse: the standard Lyme tests won’t, either, so the results will likely come back negative. The shady politics of how the approved Lyme tests were developed would take a whole separate post to explain; but suffice to say that they’re only 70% accurate on their best day, which would make them patently unacceptable as a diagnostic tool were it any other disease. Far more accurate and sensitive tests are available, but insurance companies won’t cover the $400 fee.

These alternative Lyme tests are usually not covered because the are inaccurate.  The chronic Lyme advocates have sought out shaky labs that will give them the results that they desire, rather than the ones with most accurately reveal the biologic facts.  This leads directly into the Connecticut debacle.

Last year, the Connecticut attorney general actually harassed the Infectious Disease Society of America over their official treatment recommendations for Lyme disease.  In a classic, but strangely backward Pharma shill gambit, the ISDA was accused of being in cahoots with various forces to deny proper treatment to people with Lyme disease.  Part of the idiocy is that it is the chronic Lyme advocates who make millions administering expensive and disproved treatments.  The ISDA guidelines are both evidence based and cost-effective.

This particular piece, posted on a popular blog, is a horrible piece of medical writing, but a perfect example of what can go wrong when a reporter doesn’t understand science.   The diagnosis and treatment of disease is supposed to be based on science, not on wish-fulfillment.  It’s difficult to have unexplained symptoms, but giving them a false label and subjecting oneself to fake treatments helps no one except the person receiving the check.

Posted in: Science and Medicine

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16 thoughts on “How not to think

  1. David Gorski says:

    Unfortunately, there has been at least one other time I’m aware of when Sara Robinson has been prone to poor reasoning and accepting bad studies because they confirm her bias:

  2. storkdok says:

    I have heard this before. A couple of years ago someone got onto an autism mom’s group and started touting that autism was caused by chronic Lyme’s disease. It took me about 10 minutes to debunk that theory, but the uproar it caused lasted for days.

  3. daedalus2u says:

    I think that what is called “chronic Lyme” is a persistent state of neuroinflammation and that this chronic neuroinflammation is a final common pathway for “brain fog” and other persistent cognitive difficulties not associated with damage. That can be caused by real chronic neural infections, such as neurosyphilis, or by other inflammatory agents, such as amyloid, or just a chronic movement of the “oxidative stress setpoint” in the brain to a more inflammatory state (in autism I think that is due to epigenetic programming of the brain in utero). Hemoglobin in the brain can cause it too (or the degradation products of hemoglobin if they are not cleared properly). Once that state occurs, it can be persistent long term. Oxidative stress in the brain does produce characteristic mental states, to some extent idiosyncratic, but in general the same as are produced by high stress or the fight or flight state, a bit of paranoia and scattered thinking and in some cases belligerence similar to what is associated with hypoglycemia and/or acute psychosis of stimulant abuse or roid rage. This shows up as white matter hyperintensities on MRI.

    Neuroinflammation is necessarily a delicate balance between NO production and superoxide production. How delicate this balance has to be regulated is not well appreciated. The inflammatory cytokines (such as TNF-alpha) are what (mostly) regulate the level of superoxide production. When TNF-alpha activity is blocked (as in the Etanercept effect in Alzheimer’s), the neuroinflammation can go down very rapidly (minutes). I think the acute resolution of Alzheimer’s due to perispinal Etanercept is a real result, but the effect is mediated through a reduction in superoxide (which causes a corresponding increase in NO).

    I suspect the anecdotal reports of resolution of symptoms with chronic antibiotic use may be correct. I think the mechanism attributed to those antibiotics is not correct. Long term antibiotic use will either clear the infection, or the organism will become resistant and the antibiotics will have no effect. Any effect of antibiotics that persists with continued use is likely not an effect on an infectious agent.

    I think it is a Jarisch-Herxheimer reaction, not from an infectious agent being killed, but from normal gut commensals. Even after prolonged antibiotic treatment there are still many susceptible bacteria in the gut. When those are killed, they lyse and the lytic products are immunogenic and will cause a Jarisch-Herxheimer reaction. A component of that immune system stimulation is the induction of iNOS and the production of NO as well as other pro and anti-inflammatory cytokines. That NO from iNOS acts as an anti-inflammatory cytokine and temporarily resolves some of the symptoms of neuroinflammation. Chronic antibiotic use is a bad way to achieve this result.

    Autism is associated with chronic neuroinflammation and some of the symptoms of autism can be temporarily resolved with fever. The brain has to be capable of balancing very high levels of NO (as during sepsis or cerebral malaria) with superoxide to maintain neuronal mitochondria function at all times. My hypothesis is that it is the NO from iNOS associated with the immune system activation that causes fever that causes the temporary resolution of some autism symptoms. I have a long and detailed analysis of that and the connection to fever therapy which was the “standard of care” for neurosyphilis for a couple of decades. Before antibiotics, the “standard of care” was to give people with neurosyphilis malaria, and let them go through 10 or so cycles of fever.

    It turns out that to clear intracellular infections; cells need a high ATP level. That increases autophagy, and causes the cell contents to turn over more rapidly. Cells can replace everything but the nucleus with newly synthesized proteins, so increasing turnover of cellular contents is a good idea if there are unwanted guests. A high ATP level is turned on by a high NO level. Sepsis is a very high NO level which produces a very high ATP level.

  4. Mojo says:

    By the way, “brain fog” is a common phrase in the literature of “alternative” diagnoses. There is no consistent definition, and it is not clear what the phrase represents.

    I’m trying to resist the temptation to comment on the connection between “brain fog” and alternative medicine…

  5. weing says:

    “brain fog” Isn’t that what Tom Hanks’ character had in Joe vs the Volcano?

  6. daedalus2u says:

    I get it when I am under really high stress. Thinking becomes very labored and complex ideas can’t be thought of at all. It is a little like being very distracted, but there isn;t any apparent distracter.

  7. Karl Withakay says:

    # weing, I think that was a brain cloud; it must be a more severe form of brain fog. Maybe if it gets bad enough, it actually becomes good and turns into a brain storm.

  8. weing says:

    I always thought fog was a cloud on the ground. But you’re right. I get it when I’m sleep deprived and try to read or write. I find I’m stuck on reading or writing the same word and can’t grasp the meaning of the sentence or even know what I’m writing.

  9. hardindr says:

    Mrs. Robinson responds to this post:

    Sadie and Kim: If you think I’m so damn smart, go follow storkdok’s link for another view of my relative intelligence.

    This reviewer missed the point that this was a political piece, not a science piece. I’m not going to dignify it with a response, save to say that I don’t have to defend my “brain fog” or my “feeling bad” when I’ve got six inches of files documenting some pretty serious issues. If Dr. Science-Based Medicine wants to review my strangely-flecked SPECT scans and bizarre blood work and the musings of my doctors, he’ll first need to persuade me that he’s actually capable of addressing my issues. He’ll also need to explain why, on the basis of no exam, he’s willing to diagnose me as not having Lyme (diagnosing without actual examination is malpractice, dude) — despite my recent positive Lyme test and the patent fact that Lyme treatment is actually fixing me. Until then, he may be qualified to hold forth on his own blog, but he’s not qualified to be my doctor.

    I do appreciate his thoroughgoing demonstration of everything I was talking about, though. You don’t have to take my word now for what pluperfect jerks these guys are.

    Pattoye, that debate has been had — over and over — by people with far stronger scientific chops that I have. SBM, like his ISDA friends, is willfully choosing to reject piles and piles of peer-reviewed research that more than amply proves the existence of chronic Lyme. The studies run to the hundreds. If he’s not going to believe them, he’s not going to believe me. And so there’s absolutely no reason I should engage him at all.

    As for the “miracle test”: I referenced it up above in these comments. Even the CDC is quite clear that the western blot is too flawed to be relied on. The Igenex panel tests for the outer surface proteins — OSP-A and B — that the Dearborn meeting refused to add to the western blot because they were locked up in patents owned by people who were looking to make vaccines out of them. That’s not a good reason to leave off the two most definitively diagnosic Lyme bands and leave patients at the mercy of a crippled test. (I would refer you to Pamela Weintraub’s discussion of Dearborn in “Cure Unknown” for a full examination of how this happened.)

    SBM also completely failed to address my main thesis point, which is that the way the research system is organized creates huge splits between researchers, clinicians, and patients that lead to precisely the kind of debates we’re seeing. His choice here was to waste his breath getting all defensive and telling the world I’m wrong — thus proving my exact point, and providing and excellent example of this conflict at work– or he could have addressed that point by offering some constructive ideas for fixing this split.

    His overheated attack made it very clear where is bread is buttered. If he really, truly wants to understand our side of the story, I’d be happy to put him in touch with scientists who’d be glad to explain it to him in terms he’d find satisfying.

    The offer extends to you, too. Go ahead. Prove me wrong.

    For the interested, comments for the original blog post can be left here

  10. starling says:

    Okay, before this discussion gets any more foggy (heh), I’d like to float this name on this blog in the context of “chronic Lyme disease” and science-based medicine:

    James L. Schaller, M.D.

    Reactions? Responses? Let ‘er rip.

    I am a Ph.D.-level ecologist (not a medical scientist) with a personal interest in the “chronic Lyme disease” discussion, and the only rational exchange I have found so far on the internet is at this site.

  11. davidp says:

    I have a good friend who has exactly the same symptoms as Sara including “devastating bouts of exhaustion, body pain, and brain fog” ever since a bout of viral pneumonia in 1988. It can’t be Lyme disease because 1) we don’t have that in Eastern Australia (a few people disagree) 2) he hadn’t been in tick infested areas and 3) Lyme disease is not viral pneumonia and vice-versa.

    The quoted two to five years of treatment to cure with 70% chance of success sounds just like the chances of recovery from a chronic condition without treatment.

    Finally, I am not a biologist or doctor (although half my relatives are), but I thought hiding “in the macrophages of cells” was funny, since macrophages are cells, and engulf cells, but are never (?) in cells.

  12. weing says:

    I just had a patient come in with this diagnosis that he has had for the past 1.5 years. Unfortunate for him and now for me. I’m still trying to sift out all the data from the various specialists he has been seeing and make sense of what appears to be a fragmented workup. Is anyone aware of what the most common diagnoses are in these patients after a comprehensive evaluation?

  13. daedalus2u says:

    It is my understanding that the authors of Science Based Medicine don’t dispute the presence of individual symptoms in individual patients (when properly documented). What is being disputed in this and other posts on what some call “chronic Lyme” is the unifying idea behind those symptoms and what treatment modalities that idea suggests.

    The idea that a bacterium can change and morph into different things in minutes is simply wrong. If anyone could demonstrate that, it would be a first class ticket to Stockholm. It would be front page news in every science journal in the world. SBM would have multiple posts about it. It would be the most startling discovery in biology and medicine in the last 100 years. There is not a hint of how such an occurrence might be possible. Everything that is well known about DNA, protein synthesis, etc. suggests that such an occurrence is not possible. It has never been observed and everyone who studies such things appreciates that if it were observed and documented it would be a ticket to Stockholm. The idea that many thousands of scientists would ignore such observations is preposterous.

    It would be an extraordinary claim. It requires extraordinary evidence. What has been provided isn’t even ordinary evidence. If a person has one infection, and then following treatment develops another infection, and then following treatment develops a third infection the most likely explanation is that the first infection was cleared, a second organism then became dominant, when that organism was cleared a third became dominant. The idea that the first organism changed into the second and then changed into a third is simply preposterous. The infectious agent changing during the course of an infection is not unknown or even rare. It is common for viral infections to become bacterial. Viruses don’t mutate into bacteria, rather the infection by the virus opens up the host to infection by bacteria.

    Infections containing many different organisms are the rule rather than the exception. Humans have at least hundreds, more likely thousands or tens of thousands or hundreds of thousands of different bacteria living in our bodies. Here is an example where they followed the change in bacterial diversity during the course of an infection effectively treated with antibiotics. There were many hundreds of different organisms.

    That the symptoms of “chronic Lyme” can be caused by multiple different organisms indicates to me that it isn’t caused by an organism, but is instead caused by the body’s natural reaction to something. If it isn’t caused by an organism, treating it with antibiotics isn’t going to fix it. There is no known organism that is not susceptible to antibiotics in the short term that is susceptible to antibiotics in the long term. TB is susceptible, but it is so slow growing that treatment has to continue for such a long time. In TB, the patient becomes asymptomatic after a short course of antibiotic treatment. The long course is required to prevent relapse, not because symptoms continue.

    I happen to think that low NO would produce symptoms characteristic of what is called “chronic Lyme”. The comment on the other thread about how intestinal parasites can relieve symptoms is completely consistent with that. Intestinal parasites activate the immune system and cause expression of iNOS. Inflammatory diseases are essentially unknown in the rural undeveloped world. No MS, IBD, allergies, asthma, diabetes, heart disease, etc. No “chronic Lyme” either.

  14. vannin says:

    I’m a bit late to this one. When my patients talk about “brain fog”, what they seem to mean is concentration and working memory problems – forgetting what they went into the kitchen for, for example. Concentration is affected by a variety of factors, including fatigue, anxiety, and depression. Indeed, the effects of depression can be so severe that they look like brain injury.

  15. I had Lyme disease about 15 years ago—got it in a Lyme-rich location (Cape Cod), self-diagnosed and treated (yeah, yeah, we’re not supposed to do that, but I had everything: myalgias, fever, slightly stiff neck, photophobia, all lasting almost two weeks without getting worse or better, before I bothered to look at my crotch one morning and, lo and beheld, there was a fading bullseye rash, and I was far from home and couldn’t bother looking for a doc, which would have been a pain in the ass). I started myself on doxcycline and within a few hours I knew I was getting better (even had a moderate Jarisch-Herxheimer rxn, d2U!). All symptoms except photophobia were gone for good within a couple of days. I continued the doxy for 25 days.

    The photophobia lasted about 10 years. Never did I imagine that this was evidence of persistent live organisms, but assumed it was some persistent manifestation of whatever anatomico-physiologic change had triggered it in the first place. I didn’t even notice when it finally went away; I merely realized, at some point thereafter, that I no longer couldn’t stand going outside on a sunny day without shades. If during those 10 years I’d been a worried, medically unsophisticated person and had seen a doc who assured me that I had chronic LD, I may have taken antibiotics for years and eventually become convinced that they had cured me.

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