Sit Down Before Reading: A Memoir by Dave Bexfield
I stared at the gaudy numbers in disbelief. Those couldn’t be right, but they had to be right. Randall, my actuarial angel, had simply done what I asked: plugged a nationwide 30% MS misdiagnosis rate into his spreadsheet of the regional and national prevalence of US-based MS cases (based on the 2019 study) overlayed with the CDC’s Lyme disease prevalence data by state, nothing more. He didn’t mince words.
“I hope you (and Laura) have a clear idea of just how much hostility and venom you are in for,” he wrote. “Personally, I have been shocked at the arrogance and lack of openness that the mere mention of Lyme elicits from those in the medical community. The lack of humility combined with such vehemence from otherwise rational, caring people is shocking to me.
“I don't care how ironclad your evidence and logic are, there will be plenty of dispute,” Randall warned. “Anything touched by the word ‘Lyme’ will be radioactive and will require a lot of careful language.” He then provided his own list of health issues ranked by physician respectability for comparison. 1. MS, 2. Syphilis, 3. Russian Nerve Agent, 4. Demonic Oppression, 5. Lyme Disease. At least it made me laugh as I digested the new findings.
According to these latest estimates, if you live in the western US (where Lyme-carrying ticks are relatively uncommon), have undiagnosed Lyme disease, and visit a doctor to investigate, the odds that you ultimately will be misdiagnosed instead with multiple sclerosis appear to be nothing short of terrifying: 73%.
>>Math check: Given the nationwide MS prevalence of 309.2 cases per 100K from the 2019 study and an assumption of a 30% misdiagnosis rate that does not vary by region, we calculate a “true” nationwide MS prevalence of 309.2 x 0.70 = 216.4 cases per 100K. And given the 2019 published number of MS cases in the West per 100K of 272.7, this means that the number of cases of Lyme misdiagnosed as MS in the West per 100K is 272.7 – 216.4 = 56.3. Add this to an estimated 20.8 Lyme cases per 100K in the West (the CDC-documented 2.08 Lyme cases per 100K in the West, multiplied by the CDC estimated multiplier of 10 to account for missed cases), and you get 56.3 + 20.8 = 77.1 as the “true” Lyme prevalence in the West. Then, the chance of being diagnosed with MS when you actually have Lyme is 56.3 / 77.1 * 100 = 73.0%. Note that if we had adjusted the “true” Lyme prevalence in the West downward to account for some of those cases being in the MS misdiagnosed group, this percentage would actually be higher!
Where the tickborne disease is more prevalent, the rates seemingly dip precipitously with physician experience: given the misdiagnosis assumptions laid out in this analysis, there is a 21% chance your Lyme will be missed in the Midwest and a 17.7% risk in the South (that is, the total number of Lyme cases is much higher than in the West, so the number of cases mistakenly diagnosed as MS is a much smaller portion of the whole). In the Northeast, where Lyme disease is as ubiquitous as Yankee and Red Sox ballcaps? A much more believable 4.6% of Lyme cases escape the watchful eyes of practitioners, as opposed to Southern doctors being the best at detecting the tick infection when assuming a more conservative 12.6% nationwide misdiagnosis rate.
But inside the numbers there is a revealing horror. Extrapolating the statistics to calculate the specific rate of MS misdiagnosis by region is stomach churning. If you live in the West or in the South, there looks to be a 20.6% chance—better than 1 in 5—that you have been misdiagnosed and are afflicted with Lyme disease.
>>Math check: as shown above, the number of cases of Lyme misdiagnosed as MS in the West per 100K is 56.3, so the percent chance of being misdiagnosed there = 56.3 / 272.7 * 100 = 20.6%.
This rate lines up with other general MS misdiagnosis estimates, as researchers have long believed that nearly 15% of MS diagnoses are wrong… they just hardly ever have pointed the finger at Lyme. I would imagine in areas where ticks carrying Lyme disease are rarely found, say the Southwest and Southern California as opposed to the Pacific Northwest where the Lyme-carrying ixodes pacificus tick resides, the odds that your MS diagnosis is erroneous drops to the low teens or even into the single digits—that is, folks in those areas would probably be less likely to pick up Lyme because they would need to travel elsewhere to do so (like Lyme, CT in 2004!).
The opposite is true if you live in a Shangri-La for blacklegged ticks.
Residents of the upper Midwest and far Northeast, who have watched the tick population explode in recent decades, unwittingly were sitting mallards to this invasion. Despite better awareness and no doubt more vigilance to avoid getting latched onto by an infected tick, the sheer numbers overwhelmed the best of defenses. According to these new estimates, the percent of MS cases that are actually Lyme disease in the Midwest is a staggering 38.7%, in the Northeast an ungodly 42.6%. Worse, in blazing tick endemic hotspots—i.e., looking at you rural Pennsylvania and the Minnesota lake region—the odds that you are living with a misdiagnosis of MS likely crest 50%, a coin flip.
As you reread that last paragraph with incredulity and skepticism, convinced these numbers have been pulled out of delusional hindquarters, how many potential ticks did you spot among those 4 sentences and 108 words? Even though you would never feel their bite—they conveniently (and thoughtfully) numb their victims so that their bites are totally painless—you’d notice them for sure, right? Did you count 52? Nymphs, those young, blacklegged suckers seeking out their first blood meal, are teensy tiny, about the size of a period or the dot over the letter “i.” They might grow to the size of a degree sign (˚) before they transmit the bacteria that causes Lyme disease and/or potentially other tickborne infections like Babesia, Bartonella, or Anaplasma. And then, when they are through snacking on your red deliciousness—maybe in your scalp, behind a knee, or in an armpit—they drop off, happily sated. And blissfully still undetected.
Life stages of Ixodes scapularis; credit: CDC
You also probably breezed by arguably the most consequential address ever delivered in the history of modern medicine. It was right there, in Chapter 28: Hidden in Plain Sight, unironically hidden in plain sight alongside the maps detailing Lyme’s encroachment into the world of multiple sclerosis. The should-have-been groundbreaking speech, republished as a paper two years later, had every potential to change the trajectory of Lyme disease, MS, and autoimmune disease in general, dramatically reshaping healthcare and rewriting medical knowledge worldwide… if only a single researcher in the decades following had managed to put the puzzle pieces together. But fate, as it so often has in this story, interceded, irrevocably changing the course of history.
Welcome to Miami
When Elvis returned from West Germany after serving two years in the military, he received a very special welcome from a Mr. Frank Sinatra at the luxurious Fontainebleau Hotel, Miami Beach’s largest and poshest resort. More than 50 million Americans viewed the televised special, the most watched show of 1960, and the event cemented the hotel as the trendiest of the trendy, becoming a destination not only for celebrities but also for well-heeled conventiongoers. The doctors, scientists, and researchers attending the forthcoming 90th annual meeting of the American Public Health Association were urged not to delay their lodging plans. Rooms in the area started at $5 a night, but swankier digs like those at the Fontainebleau exceeded (gasp!) $10 and were sure to sell out. “The New Jersey group has reserved a block of rooms in one of the first-class hotels, and to date 50 persons—mostly members of the Health Officers Association and their wives—have signed up for the tour.” The promotional blurb for the gathering was breathless in its promises.
So rapid are the advances in medicine and its allied fields that today's health worker must continually exchange “new truths for old” with an Aladdin-like facility. To sort out the increasingly available new knowledge and apply it promptly and diligently to one’s own professional discipline is without doubt the greatest current challenge faced by all of us in public health. We submit, however, that there are not too many meetings of the caliber of the one to be held in Miami Beach, October 15 to 19. The 1962 meeting is one from which every public health worker may expect to gain “new truths” that can be applied to the daily task of achieving better health for all America’s citizens.
Room rates for Miami Beach hotels; Fontainebleau Hotel in 1962
Dr. Leonard T. Kurland spoke on the penultimate day of the meeting, presenting his talk Geographic and climactic aspects of multiple sclerosis, a review of current hypotheses to the Epidemiology Section on October 18, 1962. Seven years earlier, Dr. Kurland had started working at the National Institutes of Health to found the Neuroepidemiology Branch, and he wanted to highlight MS’s latest epidemiological theories as the disease “has an unusual geographic distribution which has defied an explanation that might elucidate its cause or lead to effective treatment or prevention.” His opening sentences that day were prescient.
Unfortunately, in multiple sclerosis there is no specific laboratory or clinical procedure to confirm the diagnosis of multiple sclerosis cases, nor do we have assurance that what we count as cases are the same disease entity. Because there are many neurological diseases of genetic and unknown etiology which resemble multiple sclerosis, the diagnosis is often reached only after the patient has had more than one episode and other possibilities have been excluded. The error of diagnosis is greatest early in the disease; yet the early cases are the very ones which might facilitate identification of some predisposing or disease precipitating experience.
He warned of myriad challenges when trying to tease out potential geographic red flags, as the research “may be biased if severity of the illness or longevity of the patients differ geographically or if there is appreciable migration of patients into or out of the community under study.” Race didn’t appear to influence the diagnosis of MS, nor did ancestry or a host of other suspected connections. But the north-to-south gradient was definitely there, he noted. “In the northern hemisphere it is more prevalent among the people of northern Europe, Great Britain, Canada, and the northern United States. … In these areas the rates are in the high to moderately high range, and it is difficult to see any pattern which would suggest a difference in risk for the northern Europeans as compared to those in Canada and the northern United States.” Likewise, “among the people of the tropics and subtropics, the rates are considerably lower.” Curiously, though, in hotspots for MS, rates were higher in smaller—i.e., more rural—communities.
As Dr. Kurland dove more into the details of the latitude gradient, he pointed out anomalies, particularly Japan, where survey “results failed to show a variation in multiple sclerosis prevalence rates” in the country with relatively few cases of the disease—perhaps, he suggested, because study of MS in the Land of the Rising Sun was in its nascence. But it was his discussion of Dr. Geoffrey Dean’s research in South Africa in the late 1940s which revealed MS is “far more common among European immigrants to South Africa than among persons of European stock born and raised in South Africa,” that made this amateur researcher freeze.
Dr. Kurland (left) conducting field research in Guam.
Dean’s more recent studies show that multiple sclerosis does occur in South African born persons who have not been overseas, but the rate is very low—about 2 per 100,000. … Among the immigrants from European countries the prevalence of multiple sclerosis is nearly as high as in the country of their origin. Dean’s most interesting finding is that the prevalence of multiple sclerosis in South African born persons who visit Europe is about seven and a half times greater than in South African born persons who do not leave Africa.
Dr. Dean apparently relayed these findings directly to Dr. Kurland outside traditional published studies. In his paper, Dr. Kurland referenced the data in a footnote as simply “personal communication.” But that communication must have set off alarm bells in the Bethesda, Maryland-based researcher as he examined other similar studies, including research in Israel by Dr. Milton Alter. There was only one possible explanation, one reminiscent of “the calls are coming from inside the house” trope popular in horror movies: somehow, most cases of multiple sclerosis in these areas were contracted after patients lived in or visited Europe. But that’s not all these researchers discovered.
Both Alter and Dean have computed a minimum latent period (from presumed exposure in the "high risk" temperate areas to the onset of symptoms after migration) of about 9 to 12 years among immigrants to Israel and South Africa. Although this procedure introduces several gross assumptions, it is the first reasonable effort to approach the question of an "incubation period" in such a chronic disease. The present mechanism does not enable one to determine the upper limit of such a latent interval.
What is triggering MS? Diet deficiencies appeared unlikely, Dr. Kurland said, as “there is no convincing evidence that any of these play a direct role,” dismissing Dr. Roy Swank’s low-fat regimen and others. Viruses and allergens were investigated, but again, “clear, reproducible evidence” was absent. Sunlight exposure and solar radiation, even a study on fluorescent lighting, offered clues but nothing conclusive. Examining straight latitude left researchers intrigued but unsatisfied, so they focused on geomagnetic latitude. When that didn’t pan out, what about altitude? Meh. Genetics, then! Indeed, “familial incidence is higher than would be expected by chance,” but the neuroepidemiologist points out that “the difficulty is that these findings do not differentiate between the effects of an environmental exposure common to members of the same family and a genetic disease.” Finally, he postulated that “multiple sclerosis may be a syndrome in which a specific agent prevalent in the temperate zones is rare or absent in the subtropics and tropics, accounting for the differential incidence geographically.”
In his conclusion, the neuroepidemiologist speculated “that some climatologic condition influences the frequency of the disease. It is unknown whether this effect is a direct one on the patient or an indirect effect on the animal or plant life in his environment.” He even acknowledged that there was one other intriguing possibility….
A Pennsylvania Rose
Rose Ichelson wasn’t a medical researcher’s wife, nor was she invited to present at the 1962 public health meeting in Miami Beach. Dr. Ichelson had been the Director of Research for St. Luke’s and Children’s Medical Center in Philadelphia, Pennsylvania, and in 1955 the bacteriologist presented evidence of a potentially earth-shaking discovery: the “successful” culture of spirochetes from the spinal fluid of multiple sclerosis patients. Successful is in quotes in Dr. Kurland’s speech transcript.
At the time of her discovery, newspapers picked up the story and even Time magazine ran a piece, albeit it chockfull of doubt and dismissiveness.
Philadelphia Bacteriologist Rose Ichelson, 59, reported success in cultivating an obscure microbe, Spirochaeta myelophthora, which she has found in the spinal fluid of MS victims. Inference: multiple sclerosis is caused by the spirochete, and early attack on it should lead to cure or alleviation. Trouble is that nothing conclusive connects the germ with the disease. (A dozen better-understood diseases have been attributed to microbes that were later proved not guilty.) If MS is laid to infection, it becomes almost impossible to explain why it so rarely attacks both husband and wife, or both of identical twins.
Commercial Leader and South Bergen Review; Tuesday, July 2, 1957
Researchers, including the well-regarded neuroepidemiologist Dr. John Kurtzke—who was knee-deep at the time trying to prove his own theory of MS having a viral component—attempted to replicate her findings of the corkscrew bacteria with a flurry of small studies in the late ‘50s and early ‘60s, but all were inconclusive, some researchers even mockingly referring to her microscopic spirochetal images as merely “scratches on the glass.” Her discovery had to be from specimen contamination, others insisted, maybe derived saprophytic spirochetes that were commonly present in the bedsores of patients.
She knew, though, that she was right, and confidently told others that “she was ‘100 percent sure’ that she had isolated the organism,” as her 1961 obituary reported in The New York Times. Dr. Ichelson passed away at age 63, reportedly diligently working on a vaccine for MS at the time of her death, a year before the Miami Beach gathering.
As the country’s leading health experts returned home from a successful 90th incarnation of the annual meeting first held in 1873 in Cincinnati, Ohio, minds soon drifted elsewhere. That Monday, on October 22 at 7 p.m. Eastern, President John F. Kennedy delivered a televised speech to the nation alerting the country of the gravest of threats. The Cuban Missile Crisis had begun. And any urgency to mull, much less follow up on, research presented the week before in Miami Beach was lost to the threat of nuclear Armageddon.
Dr. Kurland went on to have an illustrious career, regarded as the father of neuroepidemiology for his work in MS and, in 1964, for his efforts behind the pioneering Rochester Epidemiology Project, a sweeping medical record undertaking to track for decades the health of residents of Olmsted County, Minnesota. Retiring from the Rochester Mayo Clinic in 1995, he still “believed that a rigorous examination of the occurrence of diseases like multiple sclerosis—including where and how often they strike, among what populations and seasonal variations—might yield more insights than a close examination of individual patients,” writes his New York Times obituary in 2001.
He was right. Although the neurologist never was able to solve the enigma behind the genesis of multiple sclerosis or erase the enduring question marks perpetually trailing the theories of the latitude gradient in the disease, the teasing clues Dr. Kurland predicted were right there all along: the fact that what researchers thought was MS is in reality the mingling of multiple diseases, its unusual geographic distribution revealing this very element. And Dr. Ichelson was right to feel so confident in her discovery as well—that spirochetes and MS were indelibly linked.
Alas, Lyme disease and the ticks that spread the menace weren’t discovered until the early ‘80s, nearly two decades after Dr. Kurland departed the NIH. But it took 70 years since Rose’s spirochetal epiphany for one lone, somewhat delusional, and mildly demented wannabe amateur researcher/health blogger to start stitching together the mountain of anecdotes with the damning science. Unbelievably, those persistent MS question marks that have flummoxed researchers for decades are getting turned upside down into Spanish exclamation points by an unlikely, obscure medical memoir. Time magazine’s observation that “if MS is laid to infection, it becomes almost impossible to explain why it so rarely attacks both husband and wife, or both of identical twins” is now becoming eminently explainable.
That’s because one third of all diagnosed cases of multiple sclerosis aren’t multiple sclerosis. There is no latitude gradient, or lack of sunlight exposure, or a smoking-gun Vitamin D deficiency. After tens of millions of dollars, countless person hours, and more than a half century of study, researchers in the US and around the world have identified… the habitat of ticks. It’s Lyme disease. It has always been Lyme disease.
It’s also the reason Randall the actuary volunteered to assist me all those months ago. Drawn to the outdoors more out of fatherly duty than unbridled passion, he had his suspicions about his own case of MS, despite living in the Lyme-lite Pacific Northwest. Those suspicions were understandably heightened after working with me, and he soon made the unilateral decision to start treating his own disease with doxycycline. I cautioned him that he might not experience the same gains that I had, that a Herxheimer reaction might cloud his recovery, that he might not even have Lyme disease. But then, days later, something truly remarkable began happening.
Meanwhile, in the present day, I got some equally remarkable news. I received a phone call from University of New Mexico Hospital; the letter I wrote had grabbed the attention of the right people. I was officially scheduled to see the Division Chief of Infectious Diseases for an initial, in-person evaluation at UNMH on January 11, twelve days before my wedding anniversary, the personal deadline I set for myself to begin IV antibiotics. For me to have any chance of making my case and keeping my promise to Laura, it had to be no later than the 11th.
What happened next, in a twist I couldn’t possibly have seen coming, was even more unbelievable.