Understanding & Treating Autoimmune-Associated Epilepsy - Claude Steriade, NYU Langone Health, USA
Claude Steriade, epileptologist from NYU Langone Health, discusses autoimmune-associated epilepsy and the intersection between epilepsy and immunology. She explains the diagnosis, treatments, and impacts of autoimmune epilepsies on patients' quality of life, including seizures, psychiatric and cognitive morbidities, and the need for a multidisciplinary approach to patient care.
Reported by Torie Robinson | Edited and produced by Carrot Cruncher Media.
Podcast
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00:00 Claude Steriade
“In some types of Autoimmune Encephalitis (leading to acute symptomatic seizures), there can be a viral trigger. So, for example, an NMDA receptor encephalitis can follow herpes simplex encephalitis.”
00:13 Torie Robinson
Fellow homo sapiens! Welcome back to, or welcome to: Epilepsy Sparks Insights. There are heaps of autoimmune diseases out there, like, say, Crohn’s Disease, or Rheumatoid Arthritis, Lupus, MS, or Psoriasis. Well, joining the delightful pack is Autoimmune-Associated Epilepsy - which is brought about by antibodies - and differs from Autoimmune Encephalitis - all of which shall be explained to us today by star specialist epileptologist Claude Steriade from NYU Langone Health, US!
Also, please don’t forget to like, comment and subscribe to our channel. Because only about 18% of our regular viewers or listeners are actual subscribers - so it’ll really help us with the algorithm if you could like, comment and subscribe today, and then we can get the messages about the epilepsies out to more people around the world.
00:59 Claude Steriade
Thanks for having me. So, I am a neurologist. I work at New York University in the Epilepsy Center. And my area of interest is the world where immunology and epilepsy interfaces; so, my clinical and research interest is basically people whose seizures may be driven by an autoimmune problem and how we can better identify them and how we can better treat them.
01:24 Torie Robinson
So, when I think of autoimmune stuff, I'm thinking of, gosh, a type of arthritis, or I don't know, I automatically think of HIV as well, an autoimmune thing - very different(!), but... So, what is an autoimmune epilepsy? How does that work?
01:41 Claude Steriade
So, the entity of autoimmunity associated seizures basically came out of the finding that some people can develop a collection of neurologic symptoms because of inflammation in the brain caused by antibodies that can target various proteins in the brain. And that syndrome is called Autoimmune Encephalitis. And that's a syndrome that typically presents with rapidly progressive mental status changes, psychiatric changes, cognitive changes, and often seizures too. And in these cases, the seizures don't get better with traditional anti-seizure medication types of treatments, but they do get better when you treat the autoimmune problem with immunotherapy. And so, out of this came the idea that there may be people out there who have ongoing chronic seizures that may also be due to these same types of antibodies that target various neuronal proteins, and that some of these patients may not have, like, the full syndrome of Autoimmune Encephalitis, they may not be presenting rapidly progressive cognitive changes, et cetera, but they may be primarily presenting with chronic seizures - that's driven by an autoimmune cause. And so, that's what I'm more interested in; is the idea that there are some people out there who have epilepsy, who have ongoing chronic seizures that's driven by an autoimmune problem. And in these patients, there's really 2 things happening: at the very beginning of their disease, there is primarily an autoimmune problem that's driving the seizures. And as the disease goes on and on, then this autoimmune problem leads to injury to the brain, and then that turns into scar tissue, which then becomes the primary cause of the seizures that are going on. And that entity is called Autoimmune-Associated Epilepsy. And the term “associated” was very carefully chosen to show that it's really not purely an autoimmune problem; it's associated with an autoimmune problem because like I said, in many of these patients over time, and pretty much in everybody over enough period of time(!), then it's really a structural problem that sort of sets in that becomes a primary cause of the ongoing seizures.
03:54 Torie Robinson
Basically, if a person has refractory epilepsy (uncontrolled seizures), it can lead to brain damage (structural damage to parts of the brain)?
04:02 Claude Steriade
Yeah, so, we know that from, you know, epilepsy in other situations; that chronic seizures can lead to injury primarily to the hippocampus.
04:11 Torie Robinson
Hmm.
Claude Steriade
But in addition to that, we know that the autoimmune problem in and of itself is actually dangerous for cells. So, it's called T-cell cytotoxicity, and that's the primary problem that's going on in Autoimmunity-Associated Epilepsy is their T cells are actually causing neuronal injury and over enough time that leads to enough neuronal loss that there's going to be an ongoing epilepsy from that.
04:37 Torie Robinson
So, what causes the autoimmune disorder though? Is it a genetic thing? Is it an infection? I've read somewhere it could be induced by a cancer…
04:47 Claude Steriade
There is different triggers in different people and most of the time we don't really get an answer for that. Because that's the primary question that people ask is “Well, why did it happen to me? Nobody else in my family has this, et cetera.” So, what we know is that people who have Autoimmune-Associated Epilepsy very often have other autoimmune problems in their body. So, for example, they may have type 1 diabetes. They may have Hashimoto's thyroiditis. So, there probably is some sort of genetic predisposition to autoimmunity, and they can have autoimmunity in their brain just like in the rest of their body. In some types of Autoimmune Encephalitis leading to acute symptomatic seizures, there can be a viral trigger. So, for example, an NMDA receptor encephalitis can follow herpes simplex encephalitis.And like you said, in some cases there can be an underlying cancer. Typically, when there's an underlying cancer triggering an autoimmune problem - it's a very small cancer. We're not talking like metastasised cancer, we're talking [about] a cancer that's typically undiagnosed at the onset of the neurologic symptoms and it's the investigation of the neurologic symptoms that leads to the discovery of this underlying cancer that's typically very treatable with cancer treatments. But that cancer can sometimes signal to the immune system there's something there that shouldn't be there; it's foreign, the immune system in trying to fight the cancer sort of starts creating these antibodies that can then recognise the brain and then create a neurologic syndrome.
06:09 Torie Robinson
How are people diagnosed with this then? Do they come in and, like, when they have… they're having ongoing seizures ([e.g.] status epilepticus), or does it take a while? What do you need to do to make the diagnosis?
06:21 Claude Steriade
So, I feel like there's probably 2 main situations where people end up being diagnosed with this. So, the first clinical situation is going to be when people have acute symptomatic seizures from Autoimmune Encephalitis. And that's going to be the type of situation where someone comes into the hospital; typically acutely sick with different neurologic symptoms. They may initially have a seizure, but then shortly after they become confused, they're not acting like themselves, et cetera. And then that's a situation where I think clinicians are pretty good at identifying this. I think we're very attuned to that now and this diagnostic workup essentially lies around the idea of testing patients for these various antibodies that target neuronal proteins, looking for an underlying trigger like a cancer, you know, getting the basic brain MRI, EEG, et cetera, that can sort-of indicate the diagnosis are supported, getting a lumbar puncture to look for any evidence of inflammation. And in that situation, very often a diagnosis comes more quickly and then immunotherapy is initiated - typically early on. The second situation where patients get diagnosed, and that's usually the setting where the diagnosis comes later, is the category of Autoimmune-Associated Epilepsy; where a patient may have chronic ongoing seizures that, where something is just a little bit off. You know, they don't have any risk factors for epilepsy, it started late in life and became rapidly hard to control with anti-seizure medications. They may have, you know, more severe than expected cognitive issues with their seizures. They may have associated psychiatric symptoms that may be out of proportion to what we're used to seeing with epilepsy. They may have seizures coming from both temporal lobes. They may have certain types of seizures which are associated with an autoimmune cause of seizures like seizures triggered by music like we see in GAD65 associated epilepsy or autonomic seizures where people get goosebumps or palpitations or a rushing sensation over their body, seizures that are very frequent (like, happening every day). So, there's a lot of different sort-of characteristics that may sort of bring a light bulb to their clinician to say “Hey, there's something going on here that's not quite right.” and then that's gonna trigger a similar kind of workup with these antibodies targeting neuronal proteins that you're gonna check in blood and spinal fluid. Typically, you do check for an underlying malignancy, you know, get a lumbar puncture for other markers of inflammation in addition to all of the usual tests that we get in epilepsy. But, as you can imagine, what I described is that there's a lot of different, sort-of phenotypic clues, but we're a little bit behind compared to the Autoimmune-Encephalitis-situation in terms of having a really solid understanding of like what's “good enough, or what's enough” to trigger a workup. And so, a lot of these patients will end up getting worked up a little bit later in the game because it's a little bit less clear who deserves a workup, who's high enough risk to carry one of these antibodies and who isn't. The issue that this leads to is that similarly to the first category of patients that I discussed; time is of the essence. You know, the longer someone has been having these seizures, the longer they've had this autoimmune problem, the more likely it is that there's been some structural injury and the less likely it is that they'll respond to immunotherapy. And most of the time when you diagnose someone with Autoimmune-Associated Epilepsy you don't expect to completely take their seizures away if you treat the autoimmune problem. Because, most of the time there is some structural injury that's there, and the question is how much inflammation there still is that you can address with immunotherapy.
09:48 Torie Robinson
So, [at] what stage of a person's epilepsy…or seizure…when their seizures start, do you, on average, see them? Because I guess ideally you would see them almost straight away…
10:01 Claude Steriade
Yeah.
10:01 Torie Robinson
…and then maybe you could treat the inflammation and then maybe fingers crossed, they could be seizure free. What's the, I mean, is it like 2, 5, 10 years or…?
Claude Steriade
I mean, it's so variable, like, I've seen patients like within months of their seizures, and those are patients that do a lot better. And I've also seen patients who have had seizures, you know, for 5, 10 years and that's when they get diagnosed. And typically, they, you know, have a worse outcome -although I… you always, you know, give everybody benefit of the doubt and give it a full try to treat an underlying autoimmune problem if you think there's evidence for one. But, I would say that it's really variable and probably the patients that get diagnosed earlier are the ones that have more of those, like, clinical features that, you know, raise a red flag. We also get patients who will, like, walk into the office where nobody is suspected of an autoimmune problem - that was like my first LGI1 I had in my clinical practices and attending was a woman who was referred to, like, typical Friday afternoon, last patient of the day, and she walked in, she said, well, I just had, you know, 1 seizure (and she had a convulsion) and that's the story that she came with. She was sent from the ED. There was no one had suspected an autoimmune problem. But when I asked her questions, she actually had these repeated episodes (which she didn't think anything of), where she felt like something bad was going to happen, she would get this, like, foreboding kind of sensation with palpitations, her whole face would get flushed, and she was like “Actually, this is happening many times a day.” and it started a little bit before the convulsion and she didn't have any cognitive complaints, but I tested her, and she had terrible memory even though she was this practicing nurse and, you know, that, she turned out to be my first LGI1! And she just walked into clinic one day as a new onset seizure, you know, and I think it could have been very possible: if she had not had somebody who had asked the specific questions about these types of autonomic seizures and then the cognitive testing, that she could have just been treated as a 1-time seizure and she could have gone on for months and months…
11:57 Torie Robinson
Yeah!
11:57 Claude Steriade
…before being diagnosed! So, it really gets to asking the specific questions to get to those other features that are gonna then raise then, you know, the red flag that there might be something with the autoimmune going on!
12:07 Torie Robinson
So, would you say Autoimmune Epilepsies are quite common?
12:10 Claude Steriade
I don't… it depends what you mean by “common”! So, there's been a lot of studies looking at this and the literature is a little bit all over the place!
And I think the reason for that is that a lot of the literature was lumping in acute symptomatic seizures from motor immune encephalitis. So, like the patients who are presenting to the inpatient unit with fulminant seizures, but also very confused, et cetera, like not patients with epilepsy showing up to clinic. A lot of the literature is lumping in that with Autoimmune-Associated Epilepsy. So, some of the literature had figures like up to a fifth of patients with seizures have an autoimmune cause, which is not true! If that was the case, I would be seeing Autoimmune-Associated Epilepsy in a regular epilepsy clinic all the time, and that's not the truth. So, the more rigorous studies have shown that about 1 in 20 people with focal epilepsy of “unknown cause” - which is a subset of epilepsy as a whole - carry these antibodies. So, I wouldn't say that it's common, but I think it's common enough that we need to identify these patients. Because they're really unique in a sense that, you know, when you identify an autoimmune cause of seizures and when you do that early enough, you have such a unique opportunity (that we really don't get a lot of…
13:28 Torie Robinson
Right!
13:28 Claude Steriade
…in epilepsy in general) to treat the underlying cause. And like I said: the success is really variable and in Autoimmune-Associated Epilepsy, because of the nature of the autoimmune problem (which is T-cell mediated cytotoxicity). There is gonna be some structural injury, and generally, I don't tell patients with Autoimmune-Associated Epilepsy “I'm completely gonna fix your problem, your seizures are gonna go away, you're not gonna need to be on any anti-seizure medications.” because that wouldn't be true.
13:54 Torie Robinson
Right.
13:54 Claude Steriade
But, you have an opportunity to impact the underlying problem of their disorder. And if you do it early enough you can do a pretty good job of it, you know. So, I think even though it's probably not very, very common (not as common as some of these earlier studies that were lumping in Autoimmune Encephalitis and acute symptomatic seizures); it happens often enough in clinical practice that it's worth us trying to be mindful of this and trying to become smarter about identifying these patients hopefully earlier on so that we can be more effective when we're treating them.
14:49 Torie Robinson
And I'm just thinking of the impact on people's quality of life later on in life, how that would rather than get some structural damage (because it's taken so long to diagnose or to treat), it will be… and you're saving taxpayers or healthcare providers a lot of money by getting them in early and to, yeah, just treat them more effectively.
14:51 Claude Steriade
Right. I mean, that's the other side to this, right, is thinking about this from a cost-effectiveness point of view. And obviously, I don't think you want to be testing everybody with epilepsy for these antineuronal antibodies - not just for cost reasons, but also because you don't want to get results back of low titer antibodies that have uncertain clinical significance that are going to cause clinical confusion, cause stress to patients (because they have this finding and nobody knows what it means), et cetera. But, you're right that there is a trade-off: if you're limiting a test that does cost some money, you may end up missing a diagnosis, which then, down the line is gonna cost a lot in terms of quality of life to the patient, but also financially, you know, to the system. So, I think there is something to be said for cost-effectiveness of rational screening of populations that are at risk of actually having this problem early in their disease to improve outcomes and, you know, also probably save money to the system - which, I think you're more mindful of! And I'm more mindful of [it] because I trained in a universal health care, and that's still in me. But now I practice in the US. So…!
16:01 Torie Robinson
Thank you very much to Claude who in part 1 of 2, has provided us with such a brilliant insight into what Autoimmune Associated Epilepsy is, how it differs from autoimmune encephalitis, how crucial an early, accurate(!) diagnosis is - for seizure prevention and improving quality of life, and, indeed, for actually preventing sclerosis/scar tissue from developing!
Make sure that you do join us next week in episode 2 of 2 with Claude where we talk about the common symptoms of Autoimmune-Associated Epilepsy beyond seizures!
Check out more about Claude and her work on the website torierobinson.com (where you can also access the podcast, video, and transcription of this episode), and if you haven’t already, don’t forget to like, comment, and subscribe to the channel, share this episode with your friends/colleagues/family members, whoever(!), and see you next week!
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Claude Steriade an epileptologist at NYU Langone Health Epilepsy Center and assistant professor of neurology at the NYU Grossman School of Medicine, USA.
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LinkedIn: claude-steriade
NYU Langone: claude-steriade
ResearchGate: Claude-Steriade
Neurology Live: neurologylive.com/view/2024-clinical-preview-epilepsy-seizure-disorders-claude-steriade
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