Sit Down Before Reading: A Memoir by Dave Bexfield
No matter how much I wish it, the evening of January 26, 2002, will never fully fade. Laura and I seldom speak of it, it rarely comes up in conversation with friends, and I have not written about it, not once. But the evening randomly invades my thoughts, replaying over and over like a skipping record. And then, just as suddenly, it recedes into a remote corner of memories waiting to reawaken.
The night always unfolds the same way, the script never deviating. The warm exhale of a sunny afternoon in Tucson gives way to the setting sun for a rare reunion of high school best friends: Laura, Fay, and Gretchen.
The women form one team, their spouses the other. Sixty seconds on the clock. “Die hard….” “Bruce Willis!” “Like a virgin….” “Madonna!” When it comes to charades, Randy acts out Madonna. Disturbingly. Pounding on the front door interrupts our Celebrity match and reams of laughter. It’s 11:15.
It's his wife. She’s in the car. No pulse. “Does anyone know CPR!” Fay yells. We unbuckle her seatbelt and gently lay her down on the cooling pavement. Two fingers up from the sternum. Cue the Bee-Gees and follow the beat. Firm pressure, but not too firm. One-and-two-and-three. The muffled snap of ribs is unavoidable. Don’t stop until help arrives. The wails of sirens get closer. Where are they? Stuck at the gate, what’s the code? Ten minutes pass. Laura relieves me. The EMTs relieve her. We all sit on the curb, stunned. The ambulance eventually pulls away, its siren off. The woman’s perfume lingers, stuck on our clothing, in our hair, we can still taste it.
Failure. Sometimes it’s poor technique, or poor planning, or poor execution. Sometimes it’s just bad luck. And sometimes, despite the best of efforts, it’s inevitable. But failure always informs.
In science, to loosely quote Samuel Beckett’s often misinterpreted mantra, there is a “fail better” attitude. If scientists keep trying and fail a little less with each attempt, that’s progress. Eventually, though, those incremental improvements get smaller and smaller. In medicine, barring an outright cure, researchers ultimately will face a wall of failure. And as they peer up that façade, decisions are made as to whether to look for another way over the wall or to accept that the approach taken, while not perfect, is good enough—that an acceptable degree of failure is inevitable.
But what if it’s not inevitable? What if the answer lies not predictably tucked away in the little successes, but buried deeply within the failures? With all my treatment disappointments to tame my nonexistent MS, my case embodies the epic fail, a meme-worthy cavalcade of faceplants, endos, and bellyflops as I skittered down life’s Slip ’N Slide for 17 years with a misdiagnosis. I failed MS medications because I have Lyme disease. And based on that 2019 research of MS prevalence in the US—the one with the map that unmistakably parallels tick country—others misdiagnosed must be failing their MS treatments, too.
My journey into disease modifying drugs for multiple sclerosis began in typical fashion with the most benign, side-effect free medication on the market: daily injections of Copaxone. After an uneventful three years of daily injections—unsurprising, given that there are few anecdotal stories of it conflicting with Lyme disease and even reports that it may lead to some temporary improvement—I switched to Rebif in the fall of 2009 hoping to calm the plodding, but not yet alarming, disease progression. This led to my first obvious treatment misfire. It did the opposite of calming, instead accelerating my disability in breathtaking fashion, like injecting nitrous into the engine of a souped-up Dodge Charger being driven by Vin Diesel. This reaction, it turns out, is not uncommon. “Disease breakthrough” occurs frequently with beta interferons, as an estimated “30-50% of MS patients do not respond to IFN-β” and worse, “in some cases, IFN-β exacerbates MS.” But why? The 2017 study continues:
Recent discoveries on human samples from patients with relapse remitting MS, neuromyelitis optica, psoriasis, rheumatoid arthritis, systemic lupus erythematosus and ulcerative colitis, indicate that IFN-β is ineffective and may worsen the clinical status in diverse diseases when a TH17 immune response is prominent.
And what can kick a TH17 immune response into high gear? But of course. “Patients with Lyme disease often develop pronounced TH17 immune responses that may help control early infection. However, late in the disease, excessive TH17 responses may be disadvantageous.”
I had started taking Rebif nearly five years after my tick bite, late in the disease, and the results were disastrous, as I went from walking to walker in just a few months. A quick search of the papers studying this disturbing disability trajectory with interferons revealed that researchers had also noticed. They had definitely noticed.
In one large 15-year observational study comparing an intra muscular interferon beta to a placebo, early disease activity was predictably more common in the placebo group, 41-45.5% as opposed to 23.5-29% in the treatment arm. The treatment clearly works to help contain MS in the majority of patients. But then things get far more interesting.
Among those who noticeably went downhill while taking beta interferon, their “persistent disease activity predicted severe EDSS worsening” far beyond the placebo group. “Particular attention should be paid to gadolinium-enhancing lesions on IFNβ therapy, as their presence strongly correlates with severe disability 15 years later.” It was originally thought that neutralizing antibodies triggered these precipitous declines, but researchers in another study could find no evidence of that, instead concluding that “most likely, the spontaneously occurring variation in underlying disease activity between patients causes the varying level of breakthrough disease observed in IFNβ-treated patients with multiple sclerosis.” Translation: they have no clue why some people get so much worse on this type of treatment.
Study after study support this curious trend of a subgroup of MS patients getting noticeably worse while taking beta interferons. For instance, researchers in Canada “found 39% of patients receiving therapy experienced either a medium or high level of concern of breakthrough after a year of treatment, and 89% of these patients went on to develop further breakthrough over years 2–4.” The percentage of patients negatively affected differs somewhat by location, but generally appears to hover around the 30% mark—nearly one third of all people on treatment with interferons.
After my Rebif failure, I moved on to the highly effective disease modifying drug natalizumab, commercially known as Tysabri. I received only a single infusion of the monthly drug before I relapsed. Looking back, this was not because the DMT failed, but because I had recently initiated doxycycline, which triggered a relapse-like Herxheimer reaction. Even so, while my experience with Tysabri shed little light on how Lyme disease may or may not interact with the medication, drilling into the research is revealing.
Most patients do well on Tysabri, especially those who initiated treatment with stable disease. And by all accounts, it appears Tysabri does not adversely affect Lyme disease, which like MS, can remain relatively benign in a subset of patients. That complicates matters. Because Tysabri might not harm someone suffering from Lyme, there is no clear way to differentiate someone with stable MS vs stable Lyme. But for Lyme patients who are not stable, they would be expected to continue to deteriorate with or without Tysabri. Fortunately, researchers in the oft-cited AFFIRM clinical trial were able to isolate just this group.
“In patients with highly active disease at baseline, the proportion who were free of disease activity over 2 years was significantly greater in the natalizumab group than in the placebo group.” According to clinical measures, barely 11% of those receiving the placebo remained disease free. But in the natalizumab group? That soars to 67%. Tysabri demonstrably suppresses MS and is effective in treating aggressive forms of the disease. Only 33% continued to progress despite previously highly active disease. Again, though, another failure rate of one third.
My next treatment was the ultimate hammer: autologous hematopoietic stem cell transplantation (aHSCT). As I’ve discussed in detail in previous chapters, the transplant worked wonders for the first couple of years, dramatically reversing myriad disabilities. This, I discovered recently, must have been the result of receiving an extended dose of IV cefepime, an antibiotic that also treats Lyme. But because my course of antibiotics was limited—10 days instead of the recommended 2-4 weeks for Lyme disease—the gains didn’t hold.
Once again, when it comes to transplant outcomes, differentiating between patients with MS and Lyme appears to be daunting, and is made more challenging by the accompanying use of antibiotics. Cefepime, critically, is often given as standard protocol in HSCT, meaning that most patients, regardless of disease type, should do well for the first couple of years. And countless studies reflect that expectation, with success rates exceeding 90 percent. (Conversely, those with Lyme who get transplanted without getting these IV antibiotics, say at facilities that don’t follow standard protocols, are destined to fail swiftly, likely within months.) But there are tells even during this stage that may be able to unmask the Lyme disease interlopers.
Treatment for Lyme is most effective when delivered early in the disease and before the marauding spirochetes take up deep residence in the body. Looking at my case, my transplant was done more than five years after my tick bite and after I had accrued significant disability. If I had received HCST a few years earlier, that short course of IV antibiotics very well may have held for five or more years. My gains, already dramatic, may have been even more breathtaking.
Based on my experience, one would expect those with Lyme disease to exhibit big gains in the first six to twelve months. For those early in their journey with a disability—likely labeled with relapse remitting MS—they may then experience a lengthy remission. But for those who get transplanted later in the evolution of their disease, a gradual decline likely will occur, generally beginning in year two or three. Among those transplant patients with a diagnosis of secondary progressive multiple sclerosis, a later and more advanced form of the disease, the success rate for those who actually have Lyme will drop further.
A 2021 study examined long-term outcomes for stem cell transplantation, and their numbers bear out the above predictions. “Among patients with RRMS, disability worsening–free survival was 85.5% at 5 years and 71.3% at 10 years. In patients with progressive MS, disability worsening–free survival was 71.0% and 57.2% at 5 and 10 years, respectively.” Ominously, the same 30-percent failure rate observed for other MS treatments resurfaces: for RRMS at 10 years and for SPMS at 5 years.
Again and Again
After HSCT, to ease back into the idea that I had to reenter the world of disease modifying treatments, I briefly tried Aubagio, a daily oral pill that is a rather conservative treatment. Maybe it would help? Nope. I continued my slow, lumbering decline, and my neuro suggested we turn to a more aggressive therapy, starting with Rituxan, often used to treat other autoimmune diseases like rheumatoid arthritis. After that first infusion went smoothly and I stopped noticeably backsliding, we upgraded six months later to its sister drug Ocrevus, tweaked specifically for MS.
Despite compelling evidence of Lyme disease meddlers in a number of MS drug studies, documenting the treatment “failures” of these two popular MS drugs is far harder to evaluate, as both B-cell depleters do not appear to conflict with the tickborne disease and may even stabilize it in cases, slowing its advance. One study examined case reports of people taking Rituximab for their autoimmune diseases who also were infected with Lyme disease. There were no major issues, and the authors concluded that “the outcome 1 year after antibiotic treatment, as used for immunocompetent patients, is excellent.”
If you recall, I transitioned off Ocrevus not because of a dramatic treatment failure but because it blunted the effectiveness of the vaccine for Covid. That left only two “big guns” I had yet to try. Insurance had repeatedly denied Lemtrada (alemtuzumab), leaving Mavenclad (cladribine) as my final option. A 5-year study looked at the effectiveness of cladribine and reported that “70% of participants did not experience persistent disease worsening that lasted more than 6 months.” Lucky me, I was in the bottom 30%—there’s that number again—as the drug triggered a cavalcade of debilitating UTIs. My unfortunate experience wasn’t an odd outlier. Another study found that as many 21.9% of patients like myself experienced significant disease breakthrough in year 1.
There are more than 20 disease modifying treatments approved for MS in the United States, too many to break down and analyze each for Lyme disease impostors in a rollicking medical memoir. The 30% number, though, crops up a lot. A lot, a lot. For instance, patients discontinuing the popular oral therapy Tecfidera (dimethyl fumarate) due to disease breakthrough? 30% says a pivotal study in The New England Journal of Medicine.
And Lemtrada, John Connor’s salvage MS drug that did nothing of the sort for him? Like Mavenclad, it is hugely effective, but there is a caveat. “The pooled prevalence of infective complications in patients with multiple sclerosis (MS) treated with alemtuzumab is 24%,” found a 2021 study. The authors concluded that “clinicians should be aware that the prevalence of serious infections during alemtuzumab treatment can be higher than expected from [randomized controlled trials] … Peculiar opportunistic infections should be considered when evaluating a patient treated with alemtuzumab who develops signs of infection.”
A recent large Finnish study supports these findings. “Serious adverse events were observed in 32.2% of patients … and autoimmune adverse events were observed in 30.6% of patients.” It’s not surprising that “in 2019, the European Medicines Agency (EMA) restricted the use of alemtuzumab for RRMS and initiated a review due to serious autoimmune and cardiovascular adverse events.”
Pulmonary issues are indeed peculiar for people with MS. Same with stroke, same with rheumatological problems, same with respiratory complications. While urinary tract infections are not uncommon in MS, Lemtrada was associated with an increase in that arena as well. All of these “adverse events” are squarely in the domain of untreated Lyme disease.
As evidence revealed by treatment failures mounts, does that mean that 30% of people diagnosed with MS in reality are suffering from Lyme disease? A compelling connection, but in no way is it conclusive. I needed more evidence, better evidence, overwhelming evidence. Good thing there were more than a hundred thousand other MS research studies that I could refer to gather just such evidence.
So, over the coming months I gathered it.
Nothing yet. Refresh, check the spam folder, then repeat—daily, or hourly, or more frequently—until you turn out the lights and tuck the sheets under your chin. Waiting for eagerly anticipated news is always a struggle, particularly when your health may hinge on such news. Even though we first connected in October and had our initial office visit in November, Dr. Alternative—our best hope to get the type of IV antibiotics recommended to treat neurological forms of Lyme disease—had yet to get back to Laura and me as the calendar flipped to December. Knowing he had a full schedule, we were hesitant to push too hard as we had no other viable options, so the two of us did everything else that we could think of behind the scenes to accelerate, or at least get a tiny jump on, the endeavor.
We connected first with a company recommended by Dr. Alternative that specializes in placing PICC lines, the semi-permanent infusion ports often placed in arms. When getting regular infusions, a central line to a vein is far preferable and less stressful than daily pokes. Yes, they were ready to assist when called upon, but they needed detailed doctor orders and would only install the PICC—they did not provide infusion services or supplies. Then we reached out to a home-health group who would be happy to help with that area, but they had their own restrictions. Just ring when we were ready, they said. Will do.
“I’ve called in the prescription to my pharmacy, and you can go pick up the 28-day prescription of ceftriaxone anytime,” said Dr. Alternative on a chilly December afternoon after I caved and bugged him for updates. But Laura and I both knew it would be far more complicated than that. Maybe we could sort out the details once we had drug in hand, which Laura promptly picked up for a relative song the next day. When she arrived home with bags full of a 28-day supply of the necessary antibiotic—56 one-gram vials in powder form—it was worse than we realized.
“We can’t do anything with that,” said the homecare organization flatly. “It needs to be reconstituted in saline in a sterile environment before being infused. Besides, all prescriptions we handle need to be fulfilled by our partner pharmacy. We need specific orders, the number of milliliters of saline required, everything.”
The PICC line company reaffirmed just how wayward we were in trying to get treatment. We needed to start over with our doctor, they recommended. Dr. Alternative was clearly unfamiliar with the process, which was to be expected as he does not specialize in Lyme or infectious disease. This was not his fault. He was just trying his best to help, unlike the majority of doctors who shudder at the mere thought of entertaining a diagnosis related to a tickborne disease. But now… all that effort and all that stress and all that waiting. For what? Where should we turn next? I guess restart and try again, delaying treatment once again for another month or more. It felt so hopeless, pointless.
As our once-optimistic spirits splintered, Laura’s eyes started to glisten, her gaze almost apologizing to me. But this felt uncomfortably different. She wasn’t saying sorry for this latest failure. No, it felt more worrying. Her voice cracked as she choked out words that I never expected to hear her speak, not ever.
“We have to talk. About us.”