Sit Down Before Reading: A Memoir by Dave Bexfield
Guinevere was especially proud of her apple orchard. For it grew perfect apples, each identical in size and weight. To celebrate her last harvest of the season, she always sent 11 of the perfect apples to King Arthur on the 11th day of the 11th month. One year, as the carriage arrived to pick up Guinevere and her apples to deliver them to His Majesty’s castle, she noticed that there were not 11, but 12 apples in her pail! Even though visually they were indistinguishable, there must be a bad apple in the bunch, planted by one of her rotten-to-the-core, apple-growing neighbors.
To the south lived Sir Lancelot—admittedly no Johnny Appleseed—who grew apples that were dense and heavier than Guinevere’s. To the north lived Merlin, a crafty magician who grew apples that were airy and lighter than Guinevere’s. The fair maiden, with precious little time before the coach was to leave, brought out her balance scale to weigh a combination of the 12 apples to find not only the “bad” apple, but also discover who the saboteur was. And according to her sundial, she had to solve the caper in just three weighs to prevent her Uber carriage ride from blowing her off for another client and giving her a dreaded one-star passenger review.
How did she manage to figure it out?
The puzzle is a classic. I’ve tasked members of ActiveMSers to solve it over the years, more recently replacing Guinevere and her apples with Homer and his nuclear rods. If memory serves, maybe one person figured it out? In the comedy TV show Brooklyn Nine-Nine, a version has haunted the police captain for over 20 years, so much so that he tried to bribe colleagues with free Beyonce tickets to get the solution.
Some 23 years ago, it haunted me, too. Scott (the PhD wunderkind) dared me to solve the riddle—12 identical balls that time—and then proceeded to chuckle as I spent every waking hour over the next three days trying to solve said riddle. On Day 4 I finally did.
I revisit this puzzler every now and again when there is time to kill, and on the afternoon of January 11, there was definitely time to kill. When Laura and I showed up for our appointment to see UNMH’s chief of infectious diseases, we were met with collective “I dunno” shoulder shrug emojis. I wasn’t in the system, there was zero record of any appointment, and his next available—if I wanted to reschedule—was March. A mild scramble ensued before it was determined that wires had gotten crossed and the doctor still definitely wanted to see me. Could Laura and I wait a couple of hours until he could fit me in at the end of the day? Considering the alternative—uh, March, and a broken promise I made to be treated by our wedding anniversary in less than two weeks—we could certainly wait. In the meantime, I could help Guinevere once again with her apple predicament.
This problem elegantly illustrates lessons in problem solving and how to identify outliers that appear identical to the real thing. With each weigh, you collect troves of data, not just on the apples you’ve weighed, but even on those sitting to the side of the scale. Their absence alone can be informative.
For researchers studying multiple sclerosis, they’ve unwittingly fallen into a trap of their own making. The cacophonous drumbeat driving scientists who were trying to make a landmark discovery—latitude, sunlight, vitamin D!—blinded them to other environmental possibilities. The insatiable verve to grab that brass ring, make history, and prove the true cause of MS—a virus like EBV!—blinded them to the very possibility that they could be looking at two identical-appearing yet different diseases.
That blindness started all those years ago and continues today, as the tools used to prevent this horse-blinder bias only serve to reinforce them. When reviewing conflicting theories, how diligently are researchers going to work to buttress controversial findings that not only will steal valuable time away from their own ongoing investigations, but also potentially doom their life’s research? “Halfheartedly” sounds exceedingly generous. Nobel Prizes aren’t awarded to researchers for double checking someone else’s work. It’s the satisfying equivalent of a participation trophy with all the cachet of a gold-star sticker on your spelling test from third grade.
Dr. Ichelson’s revolutionary discovery of spirochetes in the spinal fluid of MS patients in the 1950s—amid an ocean of pocket protectors, black-framed plastic eyeglasses, and testosterone—was never going to be supported. Even Dr. Kurland’s fascination with Dr. Dean’s discoveries of migrating cases of MS in South Africa was not immune from rejection. The latter two eventually teamed up for what could have been revolutionary research in the field, but those efforts, along with similar studies, were dismissed “because of the relatively small numbers, reliance on medical records instead of personal verification.”
If research doesn’t line up with expectations—it contradicts that latitude theory, it blames a bacteria and not a virus—scientists can usually conjure other confounding circumstances, even those of the ticky-tack variety, that can torpedo a study quicker than the Lusitania. Sometimes, though, those “confounding circumstances”—the bad apple in Guinevere’s pail—ironically contain the very clue that breaks the case wide open. There can be two opposing truths operating simultaneously: as Lyme disease is being mistaken for MS at a horrific clip, MS may indeed still originate from the Epstein Barr virus, a popular hypothesis. By isolating the confounding problem (e.g., Lyme disease), suddenly even conflicting theories can crystallize in ways never before envisioned.
Crystallization
As discussed in Chapter 32, adding a substantial chunk of Lyme disease into MS cases rather effortlessly explains the inconsistent latitude gradient in the US and around the world, the unmistakable ability for cases of Lyme disease to migrate (e.g., to South Africa via Europe), and that confounding steady rise in the age of diagnosis for multiple sclerosis. But accounting for this misdiagnosis wrinkle also unlocks a host of other mysteries that have plagued researchers studying the demyelinating disease for as long as MS has been studied.
Is it genetic? Researchers had come to a consensus that “MS isn't directly inherited, but people who are related to someone with the condition are more likely to develop it.” This may still be true—but these loose genetic connections easily could be explained by patterns of Lyme infection. How is that possible when Lyme is spread by ticks?
Meet Zoe, a 79-year-old woman who was diagnosed in 1981 with multiple sclerosis. Today she lives in Albuquerque, but she grew up spending her summers vacationing with her family on Townline Lake outside of Aitkin, Minnesota. Despite her diagnosis, Zoe has continued to make annual pilgrimages to the private compound, inviting friends and extended family to experience the serenity of the fabled lakes of her home state, “boating, digging a waterway between lakes, and hiking in the woods,” recalls her friend JoAnn, a frequent companion on these jaunts.
The odds of getting diagnosed with MS after visiting Zoe's lake house are astronomically, improbably high.
JoAnn, 76 and also a resident of Albuquerque, was diagnosed with primary progressive MS in 2006 at the age of 59. Zoe’s daughter-in-law, an occasional lake guest, was diagnosed with relapse remitting MS that same year. Four years later, based on optic neuritis and brain lesions, so was Ginger, another guest who spent time with Zoe at Townline Lake. But in Ginger’s case, there was a fortuitous mistake made at the hospital after she experienced an especially rough relapse soon after her diagnosis. Instead of receiving the prescribed intravenous high-dose steroids, a confused nurse started her on a different medication. Nearly an hour later arrived “another nurse who discontinued the infusion, telling her it was a strong antibiotic that shouldn’t have been used.”
Ginger never had another episode again.
While these women are not related by blood, there is a high degree of probability that their blood has fed more than a few hungry Minnesota ticks. The same is true of families who live or vacation together in known blacklegged tick haunts—that aunt who lives in rural Wisconsin, the brother who hunts in Pennsylvania, Mom and Dad who purchased a cottage in Maine for memory-building retreats. It makes perfect sense that the risk of “developing MS” has a vague but statistically relevant familial relation—these are, after all, the people you tend to spend the most time around: siblings, parents, aunts/uncles, cousins, grandparents, and typically in that order. The more time you spend in an environment with Lyme-infected ticks that may have already triggered one case of misdiagnosed MS, the higher the risk you and the people around you may also become infected with the same illness.
But what about the noted increased risk of identical twins, which seemingly proves a hereditary component? Not exactly. Although it happens infrequently, Lyme disease can be passed down in the womb from a pregnant mother to her child or children. Even the CDC acknowledges this fact in their health fliers. “Untreated Lyme disease during pregnancy can lead to infection of the placenta,” warns the CDC. “Spread from mother to fetus is possible but rare.” Complicating matters, when this happens, the mother may not know that she herself is infected and may have few, if any, symptoms.
Authors of these research studies consistently find “modest familial risk” for MS, but researchers studying the genetic connection in Sweden admit that they “cannot exclude the possibility that MS is an infectious disease determined by host characteristics and ubiquitous exposure.” But c’mon, like that would ever happen, the researchers intoned. “The parable of the shepherd crying wolf comes to mind, since so many putative viral associations have been declared present, causal, and then summarily excluded.”
Researchers shouldn’t use carnivorous parables that could turn around and bite them in the ass.
Coming Into Focus
The inclusion of Lyme disease also makes clear the disease latency factor thought to be an indicative pattern of MS. While the CDC touts an incubation period of 3-30 days for the tickborne illness, the reality is far hazier, as the experts at Columbia University report. “Symptoms may develop quickly or not until many months or years later as the spirochete can evade the immune response and remain dormant in the human host for long periods.” How long? Even decades potentially, hibernating undisturbed until something triggers the spirochetes to start doing the two-step, typically following an illness, severe stress, surgery, or a traumatic accident, particularly a head injury. Essentially, the bacterial invaders are taking full advantage of those opportunities when your immune system is distracted or preoccupied, when—to parlay an overused sports analogy—it takes its eye off the keeping-you-healthy ball.
That tracks. I was under significant work pressure at the time of my first relapse in 2004, and the day of my attack I recorded in my diary that “I played tennis w/Lenny & Claudia and got plugged in head.” It was such a memorable thwack that I wrote it down.
No, my head was not bandaged from a tennis ball to the head, but I do have a knack for the dramatic.
Some may be wondering about the patterns between MS and Lyme disease regarding gender. Although the CDC reports that the majority of its reported surveillance cases of Lyme are male, 58%, insurance records tell a far different story. FAIR Health analyzed more than 29 billion private claims data for a 2019 report and found that women outnumbered men nearly 2 to 1 in claims related to Lyme—more comparable to MS gender inequality, which is estimated to be closer to 3 to 1 female or higher. FAIR Health documented that “in 2018, more claim lines for Lyme disease were submitted for females than males in every age group from 11 to 70.”
Researchers are uncertain why there is such a disparity between sexes, but myriad explanations have been proposed: women may attract more ticks (playing outdoors with their children, gardening, etc.), their rashes may be more atypical (and therefore missed), the traditional 2-tiered testing may not be as accurate in females, and they may not respond as well to treatment as men. More body fat for the spirochetes to hide out in may be a factor as well. And then there’s the bias issue that practitioners are unlikely to shake anytime soon. “Illnesses with a female preponderance, such as fibromyalgia, chronic fatigue syndrome, or depression, may be misdiagnosed as chronic Lyme disease,” warns a study notably dismissive of someone with two X chromosomes claiming Lyme disease. It's got to be something else affecting these women. So, really, it's just a girl thing, not Lyme.
The presence of Lyme-infected ticks even explains some of the most bizarre and bewildering findings from MS studies, like the odd fact that people who are wealthier and more highly educated are more at risk for contracting multiple sclerosis. A 2011 Australian research study recounts that “a study of enlisted men who had served in the Army of the United States in World War II had found a very strong correlation of the risk of MS with high educational level and socioeconomic status of preservice occupation: highest quartile 2.3 times the lowest. A similar correlation of higher MS risk with higher levels of education and socioeconomic status has also been found in over 2,000 Australian cases.” A 2016 French study cited in Chapter 28: Hidden in Plain Sight also concluded that “the latitude gradient is not uniform depending on the socioeconomic status of the studied population” backing up similar research around the world that “socioeconomic factors may be related to the likelihood of developing multiple sclerosis and to its subsequent course.”
Reading the hypotheses of flummoxed researchers trying to rationalize why this is happening is almost painful. Access to proper medical care is a popular guess… except the argument falls apart in areas with universal healthcare. Cleanliness, then! The richer you are, the more you wash, and the more you wash, the more you wash away the good stuff, which is problematic, “because of poor standards of hygiene in those of lower socioeconomic status” and because increased dirtiness “may result in relative immunity to a virus infection that triggers disease in later life.” The authors even made a point to say that “the possibility of common genetic factors linking intelligence and personality traits with susceptibility to multiple sclerosis cannot be excluded.”
In what can only be described as a miracle or a glitch in the matrix, I could find zero studies attempting to connect the consumption of Russian caviar and freshly shaved Italian white truffles to multiple sclerosis. (And I don’t think it was an issue recruiting volunteers.) Researchers, quick and before you overthink this, what common thread is associated with more education? Higher income! And what do people with money do more frequently than those who lack the funds? Travel! There’s a blissfully straightforward reason why most of Africa and Latin America have lower rates of MS, but you see upward blips in more affluent countries in those areas, like South Africa and Argentina. People have the cash to explore North America and Europe, and then inadvertently pick up a pesky tick infection that will be misdiagnosed as MS sometime after they return home, just as Dr. Dean discovered in his South African research all those years ago.
Simply Remarkable
Randall’s email to me was short and to the point. His trial run with doxycycline, the typical first-line antibiotic to treat Lyme disease, started on a distinctly positive note. “Yesterday saw my MS bladder disappear. Went every 4 hours with zero urgency. I’d say that’s a positive for Lyme. Thank you. Still haven’t discussed with my wife. Waiting for test results on the off chance they will be positive.”
They weren’t. He had a lone band on his Western blot: good ole #41, the same generic Journey cover band that showed up for me. That did Randall no favors, other than now he can boast that the two of us are, officially and forevermore, blood brothers. His next message was more revealing, picking at the scab of many of the same question marks that had engulfed me in the early days of treatment, too.
Day 16 on Doxy and I continue to enjoy a much longer fuse on my bladder than I have known for over a decade and there seem to be muscles in my [rear] and thighs that have awakened allowing me to raise myself up and transfer much easier. My neuropathy has also been massively better from almost the first dose (except for a couple of days of burning and stiffness). All of this is not very visible to the outside observer and so [my nurse practitioner wife] remains skeptical. I find myself vacillating between doubt and belief on a daily basis. Perhaps it is placebo or (as the constant chorus goes from everyone in the medical community) the “anti-inflammatory properties of antibiotics....” Honestly, are they more anti-inflammatory than the massive doses of steroids I’ve been subjected to? None of those steroids ever stopped the urinary urgency one iota! And so the debate goes round and round in my head.
I know just how Randall feels, settling my own internal debate after my gains held, and then kept holding. Only then was I able to accept that the infrequent hiccups—I peed more often today than yesterday!—were just that, hiccups (or Herxheimers, the temporary increase of symptoms due to the antibiotics). Indeed, I was eager to discuss my clear antibiotic successes in great detail with my new infectious disease doctor and was prepared to make my case that I, without question, was fighting Lyme disease and not a form of multiple sclerosis resistant to all medication.
As I sat in the hospital waiting room, after trying for over a year to see an infectious disease specialist for my suspected Lyme disease, and after solving Guinevere’s rotten apple conundrum in my head and re-reviewing copious case notes I had printed out for my doctor’s edification, my name finally was called. I had been girding for this moment, lining up every duck I could find into a tidy row. Daffy, Donald, Dewey, the AFLAC one, giant inflatable versions, the entire Anaheim professional hockey team, all of ’em. What was going to be the hangup? How were my concerns going to be dismissed? What perfunctory lecture was I going to be given? Wait, wait, let me guess how this is going to go….
“Mr. Bexfield, I’ve examined your medical history, and I see that you do not have the requisite number of bands in your bloodwork required to receive a Lyme disease diagnosis. And that your MS specialist agrees with that assessment. Have you heard about the anti-inflammatory properties of doxycycline? The placebo effect can be quite powerful you know….”
Laura and I thought we had prepared for every possible contingency, but not for this. Definitely not for this.
“I’ve reviewed your case file and what you’ve written in detail, and I’ve made the decision to treat you with IV antibiotics on a compassionate use basis,” said the ID doctor moments after introducing himself to us. Moments. I hadn’t even had time to hand him my curated folder of overwhelming evidence, which was now as useful as a folder of future paper airplanes.
“To be clear, I am not saying that I believe you have Lyme disease,” he continued. “And it remains the policy at UNMH to treat Lyme disease only after a positive test. But I am going to override that policy and give you ceftriaxone. Is that suitable to you?”
I held on tightly to my wheelchair and dared not risk looking at Laura. Squeals of delight at that moment would have been highly inappropriate and unprofessional. As the room quietly spun joyous ribbons of imaginary confetti, I expected to see a large, floating bagel appear as everything, everywhere, seemed to be happening all at once. My desperate quest to get treatment appeared to be coming to an end.
It took the Chicago Cubs 108 years to finally win another World Series, Captain Raymond Holt 20 years to solve that brainteaser, and Odysseus 10 years of wandering before he made it back home after the Trojan War. Me to get treated? Only 14 months and 33 chapters.
What could possibly go wrong?