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/.
Q&A Transcript
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 healthcare professionals who are familiar with individual medical conditions and needs. CURE Epilepsy 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 healthcare professionals who are familiar with the individual’s specific health situation.