Webinar: Autoimmune Epilepsy Treatment Considerations

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.

Webinar: Identification and Treatment of Autoimmune Epilepsy

 

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 

Autoimmune epilepsy is important to diagnose 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 helped viewers understand the difference between paraneoplastic and autoimmune encephalopathies and the difference between acute symptomatic seizures related to autoimmune encephalitis and autoimmune associated epilepsy. Viewers learned about the characteristics and pathophysiological mechanisms of autoimmune encephalitis, when to suspect autoimmune related seizures and epilepsy, and the algorithmic approach to the diagnosis of autoimmune encephalopathies. 

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/.

 


Download Full Transcript

You can learn more about autoimmune epilepsy by watching our webinar Autoimmune Epilepsy Treatment Considerations 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

Could infections like Lyme, Babesia, or Bartonella be possible causes?

So any infection is possible. So, I actually did my training in Massachusetts, so I’ve definitely seen lots of Lyme, but Lyme, one, it’s very inflammatory. Typically, if it’s invading the spinal fluid, but post-infectious, it’s always possible. But at this point, there is no links to any bacterial-type infections.

Can you tell us about seizures that originate or localize in the brain stem?

That is more of an animal model thing, but there definitely is autoimmune encephalitis that also very much attacks the brain Identification and Treatment of Autoimmune Epilepsy Page 15 of 20 stem. I am almost like, how much time do you? The brain stem is a very content area of the brain. And so, you can have a lot of different symptoms. In one form that attacks the brain stem, they do get myoclonus, but they have a lot of sleep dysregulation as well. A lot of times when things are involving deeper areas of the brain though, seizures are not a prominent manifestation, it tends to affect more like movement disorders and coordination just because that’s what that area of the brain does more than actually seizures themselves. So, I typically actually don’t see a lot of those patients, but people tell me about them, but they tend to see my movement disorder colleagues more.

Could autoimmune epilepsy manifest itself as a focal seizure?

It’s almost always focal seizures, when they generalize it’s secondarily generalized. So as opposed to a genetic generalized epilepsy, which affects both sides of the brain at the same time, even when they have a full generalized convulsion, it’s usually secondarily generalized.

Do you see intracranial hypertension in your patients?

That’s an interesting question. There’s sort of idiopathic intracranial hypertension, which I definitely have in my clinic as well, and maybe there’s some link that they’re alluding to, but I don’t know of any link to autoimmune encephalitis, especially if they had preexisting hypertension. That being said when your brain’s inflamed, you can get rises of intracranial pressure, for sure.

How close are we to getting IVIG infusions, FDA approved?

I’m curious if this question is geared more towards to get insurance to pay for it, which is always that all that I do in my clinic. And so, there was a trial with IVIG at Mayo Clinic for LGI1 encephalitis versus placebo. So IVIG is probably more on its way than many others, but I’m not involved in the FDA process. So, I actually don’t know.

Is there a next step if immunotherapy and antiepileptic drug treatment does not work? Or do we not have anything at the moment?

I never give up, really. So, there’s lots of forms of immunosuppression. So, when we were talking about B cell and T cell mediated therapy, so for instance, it was in the newspaper and she signed a media release, but we had a patient with an NMDA receptor encephalitis who was in a coma for about five
months. And we could not get her to wake up. And we used plasmapheresis, IVIG, steroids, rituximab. She even got a chemo drug called cyclophosphamide and nothing touched her, essentially. And so, we used a newer chemo drug that she had been used in Europe, which is chemo for multiple myeloma, which is a B cell malignancy. And she woke up from that.

So there’s lots of different therapies. I didn’t talk about the ketogenic diet either, which seems to have anti-inflammatory properties to it as well.

And there’s also anti-interleukins to anti IL-6, IL-1, which gets used in those kind of NORSE and fires cases if people know what that is, but that is a whole separate lecture. So, what do I do if initial therapy doesn’t work, is I try more. But that being said, sometimes you do palliative surgeries. If one area is structurally very damaged, you could consider surgery or neurostimulation too with various nerve stimulators or even invasive neural stimulators have been used in patients that are autoimmune as well. So, you don’t give up.

Could you elaborate on musicogenic seizures in this context, any recommendations how to proceed when certain types of music are seizure triggers? And what test panels are most appropriate?

Very good question. So musicogenic seizures, there was a case series on it and some people it’s pop music and things like that, but I treat them mostly just like any other seizure, we’re trying to get their seizures under control. So, I don’t necessarily treat them any differently. It depends if somebody has a photic sensitive epilepsy as well, and there’s certain glasses you can avoid, but you can’t avoid the sunshine or something like going through trees and things. There’s certain things you just can’t avoid. And so really the answer is immunotherapy and seizure meds to try to get your seizures under control long term. It’s just more of an interesting phenomenon of reflex seizures that GAD65 seems to get.

What’s the best timing to taper off of an AED in cases of autoimmune epilepsy? How do you go about that?

So we don’t have a good answer to that. We don’t even know who needs long term therapy. So, I’ll just tell you what I do, which is what people more senior with more gray hair did. And so I just do it that way. So basically, it kind depends. I never wean seizure meds and immunotherapy at the same time. Because if you have a breakthrough seizure, you’re not going to know which one you actually need. So that’s rule number one. And so I essentially, like for instance, that guy just told you, LGI1 can be monophasic and we don’t really know who’s going to relapse and who’s not. So, in that patient I slowly wean off. For instance, I was giving him pulse steroids, so I was giving him a thousand milligrams of Methylprednisolone every week.

And I just slowly increase the time of the pulses. So, if it was every week and then every other week, and then as you’re weaning off the immunotherapy, if they relapse, then you give them something long term. So, it depends on the severity too. If they were very severe like an NMDA, I’ll often just continue immunotherapy and everything for about two years, that’s what most people do. And then try to wean after that. Now, if they get off immunotherapy, things are going well, then I’ll probably wean seizure meds too, and see if they can get off. And then I usually do a follow-up EEG and see if there’s anything epileptic as well.

Can multiple food allergies contribute to these autoimmune issues? What about the body being in a constant state of inflammation?

That’s a tough question. So, there is more, we’re learning about the gut microbiome and how it relates to the brain. I don’t think we have any specific links. There’s a lot of research that needs to be done in that, some of which is being done at Northwestern, actually with gut microbiome and effect on the central nervous system. But there’s also key things for instance, people with gluten and celiac disease, which has a very well documented neural celiac and neuro antibodies. So, I think long story short is we don’t know, I don’t know how to answer it better than that. There’s some links, but to the core autoimmune encephalitic antibodies, I am not aware of any true clear associations besides for celiac disease.

What is IVIG??

IVIG is, intravenous immune globulin, essentially when you donate blood, your blood gets divided into, it’s essentially donor antibodies, long story short. It’s concentrated donor antibodies from multiple donors and then it gets concentrated and put into an IV bag. So, when you donate blood there’s red blood cells, platelets, clotting factors, they separate it all out depending on what the patient needs. So intravenous immune globulin is really donor immunoglobulins.

 

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.