Q: What happens when your autoimmune encephalitis treatments aren’t working?
A: You relinquish all unnecessary obligations, neglect your blog, and trade your human friends for Squishmallows who think no less of you for spending hours on end in bed.
Joking aside, it’s an exhausting and demoralizing road. While being diagnosed with autoimmune encephalitis (AE) in the first place is scary, failing treatments that normally give people their lives back is despairing. Recognition of the failure is slow. You’re told to hang tight and be patient for the immune system to adjust; but as months pass by without sustained improvements, the feeling that something is wrong begins to take hold.
The following runs through your head: Am I overreacting? Do I have permanent damage? Can this situation be salvaged? Will it be like this forever? Can I just give up and resign from this reality?
Embracing trial and error, and being fed up with the status quo
If you’re lucky, you have a doctor that realizes just how pernicious AE—brain inflammation—can be. More importantly, they realize they have multiple tools at their disposal to treat it and take responsibility for actually wielding them.
This can mean going beyond steroids, beyond IVIG, and sometimes even beyond rituximab (Rituxan). As far as I can tell, the doctors who create the best outcomes for their patients recognize that the amount of medications required is highly individual and that treatment responses are not always trackable via standard tests, especially for complex diseases like AE. And treating AE is ultimately a game of trial and error—part science, part art. The research can only run so deep for a rare disease that just started receiving attention in 2005.
Since I was diagnosed with AE in the summer of 2019, I’ve been put on methylprednisolone (Solu-Medrol), IVIG, Rituxan, plasmapheresis, and tocilizumab (Actemra) at varying doses, intervals, and timeframes. And just recently, I started mycophenolate mofetil (Cellcept) and received an infusion of cyclophosphamide (Cytoxan).
None of these are a surprising choice of therapies; they are all described in the medical literature as appropriate treatment options for autoimmune encephalitis. But what IS surprising to most people is that my doctors are actually:
- exercising all these options;
- overlapping some of them; and/or
- bothering to still treat me at all, given the protracted course of my illness (which began in 2014) and the fact I can still walk and talk.
It should not be surprising, but it is given the current paradigm of (arguably) conservative treatment that the average patient is offered. And sadly, a nontrivial subset of these surprised people are patients/caregivers that are still struggling, face seemingly impossible medical barriers, and rightfully suspect that there could be benefit from further treatment due to signs that their or their loved one’s inflammation is poorly controlled.
It’s heartbreaking to hear these stories and realize how easily I could be circling that drain.
That’s actually why I’m forcing myself to grind through the cognitive fog and write again. Some recent conversations have reminded me of how many people are needlessly struggling with obstacles on their AE journey, ones that can bypass others completely, all because of some stroke of dumb luck such as:
- The first doctor that saw the patient in the emergency room performed a spinal tap and believed the issue was neurologic rather than psychiatric.
- The patient lives in province/state “X” where a critical medication is on the formulary covered by the government/insurance plan—not province/state “Y” where a critical medication requires special authorization and is typically denied.
- The previously seronegative patient turned seropositive during a relapse, suddenly lending credibility to the diagnosis and making treatments more accessible.
While the field of autoimmune neurology is relatively new, it is not so new that one different roll of the dice should be able to dictate the outcome of a patient so profoundly. It is unsettling how many more junctures my own AE journey could have been derailed at, the above bullet points being just a sampling.
There is clearly a need for greater physician awareness, better standards of care, and shifts to the present paradigm of treatment. And the more that patients/caregivers challenge the status quo, the sooner that change will come.
My goal in speaking out is to help level the playing field for those being caught in the AE quicksand. I’m far from the only person out there who deserves the opportunity to take another shot at permanent recovery. To those that have humbled me by sharing your stories or provided encouragement for me to keep plodding forward, thanks for galvanizing me into ending a four month writing hiatus.
Reexamining the mechanisms underlying autoimmunity
As mentioned above: I recently started Cellcept and Cytoxan in an effort to pull me out of my relapse that began in spring 2021. We had added Actemra to my regimen in July, hoping that would turn things around; but after 5 monthly infusions with transient improvements only and no compounding benefits, my primary neurologist agreed to pull me back into the hospital for plasmapheresis. It had worked beautifully for me in January 2021 and we were hopeful another 5 rounds over 10 days would work the same the second time around.
It turned out to be a bust. I’m glad I went through with it though; otherwise, I would always wonder whether plasmapheresis paired with stronger maintenance therapy would be a viable solution, rather than having to progress to chemotherapy. Again, it goes back to that whole “trial and error” concept. You evaluate the options based on your unique clinical scenario, make a strategic decision, compare the results with existing scientific knowledge, and synthesize all available data to inform your next steps. Along the way, you progressively refine your mental models.
But that’s not the approach you’ll find all doctors using. A few years back, my treatments were stalled by the terribly ignorant no detectable antibody = no autoimmune encephalitis explanation. Somewhere in the middle, it was the poorly reasoned it’s impossible to relapse on Rituxan you probably never had encephalitis but rather just have adult ADHD explanation. And now, several doctors later—and after scoring 2 standard deviations higher on an IQ test as a direct result of plasmapheresis, not psychostimulants used to treat an attention disorder—we’ve landed on an explanation that contains a couple more shreds of logic.
The doctor in charge of my current treatment plan is a neuro-oncologist who, in addition to cancer, treats a number of autoimmune conditions beyond just AE including myasthenia gravis and neuromyelitis optica. He explained to me in simplistic terms that when it comes to autoimmune neurological diseases, he looks at the individual and in broad strokes considers how much of the immune dysfunction is antibody-mediated/humoral vs. how much is cell-mediated. Response to treatment can provide clues.
IVIG, Rituxan, and plasmapheresis are known to be most effective for addressing antibody-mediated autoimmunity; since I’ve had diminishing returns from these treatments over the past few years, he suspects a significant proportion of my autoimmunity is now cell-mediated. This would also fit with the theory that I have GAD65 encephalitis, which is thought to involve a T-cell mediated immune response. While the call is debatable, both him and my other neurologist consider me a true GAD65 positive patient now rather than a seronegative one, as the antibody appeared in my serum and rose in titre on the 3 occasions we checked last year. Either way, my primary doc is confident that it’s time to move on to medications that target both B AND T cells—in my specific case, Cellcept and a Cytoxan.
Now, I am not a medical professional who can responsibly assess the validity of this framework; but this neuro-oncologist is well-respected amongst his peers, and the rationale for his decisions make a hell of a lot more sense to me than the ones provided to me by other doctors in the past. While Rituxan initially got me back to baseline in 2019 and is a highly effective, permanent solution for many patients, it upsets me when doctors are adamant that Rituxan is a magic bullet for treating AE and that any ongoing symptoms absolutely cannot be due to uncontrolled brain inflammation. Or said a little differently: if your previous AE symptoms return but your CD19 test results are at 0, your AE is well-managed and we’ve finished our job. This hard-and-fast conclusion seems incredibly irresponsible and lazy to me, when even a cursory glance through the medical literature yields hundreds of articles discussing the utility of alternative treatment strategies across a number of AE scenarios.
The takeaway here is that if you are dealing with ongoing levels of significant dysfunction, experienced a period of relative normalcy followed by a return of disabling symptoms, or your specialist has limited experience with treating AE, there may be further runway to explore.
I say that with a note of caution, being careful to acknowledge not everyone is going to benefit from seeking further treatment and some are already working with wonderful doctors who are truly doing everything they feasibly can. But judging from going through 12 neurologists myself and hearing the experiences of hundreds of patients/caregivers, chances are your doctors may not have painted the full picture of the options out there. There is more to the immune system and the mechanisms underlying autoimmunity than what the average neurologist appreciates.
If you want to explore other options or doctors, take some time to educate yourself first. Otherwise, it’s going to be hard to effectively advocate for yourself or your loved one. Without slogging through research publications, listening to the experts in the field, and/or joining support groups to hear from others living with this illness, you tend to reach a ceiling on how far you can get. Alternatively, you might gain reassuring perspectives that help you realize your team of doctors is already handling everything appropriately.
Speaking of experts, there are a few opportunities through February to hear from some major names in the field:
- The International Autoimmune Encephalitis Society has organized a free Speaker Series in honour of Autoimmune Encephalitis Awareness Month, details for which can be found here: https://autoimmune-encephalitis.org/ae-awareness-month-events-february-2022/
- Northwell Health, led by Dr. Souhhel Najjar and organized in collaboration with PANDAS Network, is presenting a $25 conference on World Encephalitis Day (February 22) titled Understanding the Spectrum of Childhood Encephalitis including PANDAS and PANS. Sign up here: https://www.ccevent.site/2022-02-22-enc/
- Texas Children’s Hospital is hosting a virtual AE morning on February 12 with the opportunity to hear from adult and pediatric neurologists, rehab specialists, a neuropsychologist, and Dr. Eyal Muscal. Register here free or by donation: https://www.eventbrite.com/e/a-morning-with-your-ae-team-tickets-260340023017
As for me, I’ll be doing my best to keep advocating for AE awareness and better outcomes while I recover in the months ahead. You can expect to see a return to more regular posting here, Facebook, Instagram, Twitter, and maybe even beyond. To stay up to date with the latest, sign up below:
You may be interested in taking a look at the following next:
The AE Awareness Month Podcast Series
Relapsing… again. Autoimmune encephalitis round #3: Let’s go
This is what it took to lift me out of an autoimmune encephalitis relapse
The Real-World Challenges of Surviving an Autoimmune Encephalitis Diagnosis
Autoimmune Encephalitis Recovery, Part 1: A Look Behind the Scenes of Emotional Breakdown
Autoimmune Encephalitis Recovery, Part 2: The Day-to-Day Emotional Challenges
The 7 Ways To Piss Off Your Neurologist, As Told By An Encephalitis Survivor
Recovery and the amount of treatment needed is so individualized. One issue also can be if there is brain injury that the individual needs to recover from as well as if they have ongoing seizures which may not be evident except on eeg but can have a large effect on memory and executive function. Relapse is so frustrating, I have not experienced it myself, but I would imagine once you think that you can be on your way to recovery, back it comes to cause more issues. It sounds as if you are in good hands. I think that patients should ask questions until they understand the plan of care. Consider getting a second opinion, they may not have anything else to offer and may tell you that your doctor is providing good care but it helps to eliminate the questions you may have. Research continues to move the bar on treatment and understanding of the disease. I am glad that you are writing again.
Thanks Mari! Yes, there are so many facets to the AE journey and solutions certainly aren’t one-size-fits-all. I’m very glad for the doctors who customize their approach to the needs of the individual patient!
Thanks for this read. Comforting to know i’m not the only one in this position of not responding to standard treatment and feeling devastated about it. Your advice is encouraging to do more research on doctors that can assist further
Don’t give up. I hope you find good doctors and receive excellent care so you can heal up!
Squishmallows are the best, my kiddos have them on their beds and i often fall asleep on one. Although i toss them to the end of the bed once they are asleep, as i feel the foam is probably toxic. Stupid off gassing! I am sorry to hear that the treatment plan didn’t keep you in recovery. I hope the next phase has a better result. Sounds like your doctor is actually thinking hard about things! I am glad you got a seropositive finding on file! I have different issues relating to encephalitis recovery, and i’ve found a lot of help using the curable app. Especially in helping my nervous system to stay in healing mode when a flare starts to show up. Check it out! Now i don’t get anxious when symptoms start to creep back. Best wishes!
Hehe it always makes me smile when other adults out there share their Squishmallows enjoyment with me! I have accumulated quite a number of them since I discovered them about a year ago lol.
While last year’s treatment plan was definitely a disappointment, it seems that things are gradually starting to go in the right direction now . Thanks for sharing about the app, I’ll check it out! Wishing you fewer flares and symptoms in the days ahead ❤️