This webinar provided information to help the audience understand more about autoimmune epilepsy and the different treatment options and considerations, including immunotherapy, for autoimmune related seizures and epilepsies.  

Our body’s immune system is what protects our body against harmful substances. Autoimmune encephalitis is a term that refers to conditions that occur when the body’s immune system mistakenly attacks healthy brain cells, leading to inflammation of the brain. Antibodies may target different brain receptors which impact the type of autoimmune encephalitis. Symptoms may include memory loss, cognition problems, impaired speech, and seizures.¹  

It is important to diagnose autoimmune epilepsy because one of the hallmarks of this condition is that it does not generally respond to typical anti-seizure medications. Immunotherapy is often used to treat people with this condition, by reducing inflammation in the brain.     

This webinar is intended for people living with epilepsy, their family members, and caregivers, and anyone seeking to learn more about autoimmune epilepsy and its treatments.

¹ Lancaster E. The Diagnosis and Treatment of Autoimmune Encephalitis. J Clin Neurol. January, 2016; 12(1):1-13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712273/.

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You can learn more about autoimmune epilepsy by watching our webinar Identification and Treatment of Autoimmune Epilepsy featuring Dr. Stephen VanHaerents.

About the Speaker:
Dr. Stephen VanHaerents is an Assistant Professor in Neurology and Medical Education at Northwestern University Feinberg School of Medicine. His practice focuses on the medical and surgical treatment of epilepsy with particular emphasis on the treatment of medically intractable seizures. His clinical research interests include neurostimulation, identification and treatment of autoimmune-associated epilepsy, and new-onset refractory status epilepticus (NORSE). Additionally, Dr. VanHaerents is deeply invested in medical education and currently serves as the Director of Medical Student Education in Neurology. He also serves as the Co-Chair for the Neurology and Neurosurgery Health Equity, Diversity and Inclusion Committee at Northwestern University Feinberg School of Medicine and Northwestern Medicine.

Q&A with Dr. Stephen VanHaerents

There been success in diagnosing and/or treating somebody Autoimmune Epilepsy Treatment Considerations webinar Page 14 of 19 with a longer history of epilepsy and autonomic dysfunction?

Early is good. This happens where the diagnosis of an autoimmune cause is made much later than desired. And at that point, I usually do do a trial, but sometimes they don’t respond, there’s damage done, and they have persistent epilepsy for instance. And then I still look, is there any component of it that’s still immuno responsive or do they just have a structural epilepsy at this point due to damage from the brain? And so, I do try to still tease that apart to see if there’s any immuno responsive component left, but often, not often. I mean, it depends case by case, but there are many that there’s no further immune component but they do are left with a structural long term epilepsy. And then they kind of go down more of what you think of for standard epilepsy and maybe you think about epilepsy surgery or neurostimulators, things like that.

You’re clearing the blood of the bad antibodies but aren’t they going to come back. Won’t they regenerate and if so, what do you do?

This is an acute treatment that you’re doing, it’s not a long-term maintenance theory. When you’re dealing with someone like NMDA receptor encephalitis that antibody is toxic. If you take it from one mouse without NMDA receptor and encephalitis and put those antibodies in the other mouse, they will become symptomatic. And those intercellular antibodies, not so much. You want to clear the blood to get them out. And so, you clear it, but long term, often we use something called rituximab, which then is an antibody then directed at the bone marrow to stop making. So, you don’t differentiate into those plasma cells, those progenitor plasma cells so you stop making the antibody. But that’s a great question. And you also want to be sure not to give the rituximab before the plasmapheresis then you just wash out your very expensive therapy either. You wash the blood first.

Is it better to treat with carbamazepine or could we use other sodium channel blockers like lacosamide if they don’t want to use.

That is a great question. And I would not use carbamazepine in someone with hyponatremia and for the audience who doesn’t understand why that question was asked is carbamazepine or
oxcarbazepine, that family really is associated with low sodium. And so, you’re right. I would probably use something like Vimpat now keep in mind Vimpat’s not benign. Oh, sorry. I probably should use generic names, lacosamide, sorry. Lacosamide. But some of these patients have autonomic dysfunction too. And so, you do want to really monitor these patients’ parts too. Some of these sodium channel blockers a lot of them can either prolong QTC intervals, which you have four chambers of the heart, and the PR interval is how long it takes from the smaller atrium to get to the ventricles. And so essentially you want to monitor their heart too. When you’re looking at that study, you have to take it with a grain of salt. Yes, and LGI1 carbamazepine did it better, but you have to think about the patient too. And so, what’s best for them at that moment.

You’ve given us the example of this woman who’s experienced real changes in behavior, some inconsistencies, but what other things might tip off family members that might be a cause for concern for autoimmune epilepsy. How do you trigger epilepsy investigation?

That was in my first talk of kind of what are autoimmune seizures like as opposed to other seizures and keep in mind that patients with epilepsy, depending on the location of the epilepsy might have a lot of psychiatric comorbidities related to their epilepsy much higher risk of anxiety, depression, other things. Not everyone with any sort of psychiatric comorbidities autoimmune. I just want to give that kind of caveat off the bat, but the seizures of themselves are typically location-wise. And this is where talking to your doctor is important too, this kind of perisylvian, these kind of autonomic type seizures of the insula and areas and they tend to often be very brief seizures where you can have lots per day. No, when you look at this patient I just presented, she went from never having a seizure, you to having tons of seizures, tons, and they’re very short and brief, and they tend to be very medically refractory off the bat.

That’s not typical of most epilepsies, unless it’s a genetic epilepsy from a young age where they can be very refractory very early. This 27-year-old to develop that refractory of epilepsy in the course of a couple months would be very atypical. And then bilaterality too like having seizures like the guy last time I showed you, he had got left temporal seizure, right temporal seizure, left temporal, like having refractor. And he was 60 something. I forgot his exact age, but refractory epilepsy in a 60 something-year-old bilateral, that’s really hard, and older people with structural epilepsy, usually, it’s from a stroke or maybe they had a brain tumor and it’s from one spot. Maybe it propagates different so they can have different seizure types. Let’s say it’s in their parietal lobe and sometimes it will go backwards and they’ll get a visual aura or sometimes it will go forward, but they have from two different sides that refractory that should really raise your index of suspicion. Something is up here.

If somebody presents what seems like a seizure and they get put on a standard anti-epileptic drug, but then in the workup, it’s determined that, well, perhaps they actually have an autoimmune epilepsy and they go through that process. You’ve described it in your patient that you just presented to us where they titrated off of the immunotherapy and also for her off of the AEDs but that’s a very scary proposition for many to think about coming off of the anti-epileptic drug completely. How do you make those decisions and how do you work through that process??

This is how I usually do it, which is not always a hundred percent standard. And I’m glad actually now I didn’t even think about it, but those two cases, the case in the first one, he was unable to actually come off seizure meds. And I think that part of that reason I believe is that in the first case, he really presented it in September, but I didn’t meet him until March or April. So, there’s a large delay. And one rule of thumb so you do him second, we’ll talk about the patient I just presented first where she was able to come off both. Her cognitive seizure had all stopped really by about eight weeks at that point. She responded very quickly, which is awesome for her and we also got to her very quickly too.

So she really wasn’t that symptomatic without treatment very long. So essentially what I do is I never wean seizure meds and immunosuppression at the same time, because then if they have a breakthrough seizure, you don’t know is it because they have structural damage that now they have epilepsy or is it that they’re having a relapse of their autoimmune encephalitis and need immunotherapy. So, I never wean them at the same time. So, in her, I slowly wean immunotherapy while I kept her seizure medications stable. At which point when she’s off immunotherapy doing great, I usually get a follow-up EEG. Does she have any sharp waves or any epileptic potential whatsoever? At this point in her, she really can’t be driving anyways because it’s still within six months.

She wasn’t driving. And I discussed with her seizure, precautions risk. I usually give them at home rescue too, in case they do Autoimmune Epilepsy Treatment Considerations webinar Page 18 of 19 have a breakthrough seizure. And I educate the family, seizure precautions, things like that. And then we slowly wean off and then once weaned off, I usually do a follow EEG to make sure that there’s no epileptic potential in her there wasn’t, but really we don’t have a perfect marker to mark someone’s epileptogenicity and that’s an area of research that, for another webinar. But anyways, right now we have a limited approach.

I think essentially that time is really the best marker. The longer you can go without seizures. And so, in her now it’s been sixplus years without a seizure. So, she’s doing really well. The other guy, when I weaned him, actually he got off immunotherapy. He was doing great. But when we did the follow-up EEG, he still had epilepsy from discharges, from his temporal lobe. With him, we discussed any potential wean, but in him, he didn’t feel that it was worth the risk. He also took longer to recover. So, it was also over six months. And so, he
was driving again, which is also a big consideration as well. So, it’s really a case by case and discussing with them the different options. I hope that answered that question.

Can you speak to how patients have experienced any changes or flareups in autoimmune epilepsy following COVID infection and any protocols you recommend for these patients? For both presenting for the first time after COVID or they already had autoimmune disease and then got COVID).  

The reality is both. I’ve seen it flare up from both. I mean, the reality is if you kick up the immune system, even with just and by no way am I anti-vax, but with the vaccine, I’ve seen upticks too. You’re activating the immune system if they make autoimmune antibodies, it makes sense. The vast majority of my patients have been totally fine, to be honest. I didn’t know how that would happen, but there are a couple notable ones that it did kick up. And in which case I’ve treated them just like I would. Anyways, I gave them steroids in those cases to bring down inflammation. I just treat it essentially. But luckily it hasn’t Autoimmune Epilepsy Treatment Considerations webinar Page 19 of 19 as bad as I initially was concerned and a lot of us were concerned about when the pandemic first started.

What’s the risk of recurrence and how do you treat it?

I took an NMDA receptor encephalitis patient off rituximab which had worked for her for years when she relapsed, I did give her steroids actually, but then I gave her rituximab to go back on it too. It depends. If there’s something that was working for them before it’s got taken them off, then you restart it.

The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.