Cognitive Impairments In Epilepsy - Jon Kleen, UCSF (University of California, San Francisco) Medical Center, USA
Learn all about how people can have memory and other cognitive struggles as part of their epilepsy - in part 1 of 2 with epileptologist Jon Kleen from the UCSF Medical Center, USA! Jon speaks about his career focus, types of cognitive impairments, impacts on quality of life, and more.
Reported by Torie Robinson | Edited and produced by Carrot Cruncher Media.
Podcast
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00:00 Jon Kleen
“So, it really comes down to what the patient tells us, you know. If they have perfect seizure control and they are having terrible cognitive impairments and we look at their EEG and they're having a lot of spikes, like, all the time; that's a case where I would be like, I don't know, should we maybe adjust the medicines, even though they're not having seizures, would it help?”00:19 Torie Robinson
Fellow homo sapiens! Welcome back to Epilepsy Sparks Insights.
Lots of people with an epilepsy can tell you that memory issues are one of their biggest challenges. Cognitive deficits - whether they be permanent or transient - can be disabling for learning, employment, relationships, confidence, and overall quality of life. So, I’m delighted to introduce to you the multi-award winning neurologist, epileptologist, and neuroscientist, PI of the Kleen Lab, Jon Kleen from UCSF, US!
Please don’t forget to like, comment and subscribe to the channel so that we can spread awareness and understanding of the epilepsies around the world.00:54 Jon Kleen
I do a bunch of different things, but kind of 2 main domains. One is the clinician - so, I see patients with epilepsy in both the clinics, so the outpatient side, and then also the inpatient side. We have an epilepsy monitoring unit, and we also read the EEG for anyone who's got an EEG on in the entire hospital (ICUs, et cetera). So, that is my clinical realm. And then I have a lab as well where I study a couple of main things, but mainly cognition, particularly cognition and epilepsy or how epilepsy affects memory, cognition in general. And then also just studying, basically, seizures, intracranial seizure activity, meaning from sensors actually implanted inside the brain to try to understand if we can, basically, make better ways to detect where seizures come from and how they spread and hopefully cure them with surgery or at least reduce them with stimulators. So yeah.01:44 :Torie Robinson (01:14.933)
“Cure”'s a dodgy word, isn't it? It's like, ideally, but we have to be careful, I think, with the term.01:49 Jon Kleen
Yeah, absolutely. There's really… when we say “Cure”, it's at least stopping seizures is kind of like… is that a cure? But at least that's as close as we can get for, like, stopping something like epilepsy. So, we can do it with resection surgery and have to talk about that more. But really all of our other methods are basically reducing seizures, which are, you know, the essence of epilepsy. And if we can just at least get rid of those for patients, that's just… it can be life changing.02:14 Torie Robinson (01:47.285)
Yeah....but it…and it is... and certainly can be, but the going on the cognition side and mental health is another thing that's all part of epilepsy (in my opinion). But what led you to focus on the cognition side? Because I haven't spoken to anybody who's gone “Hmm, that's my thing!” before!02:31 Jon Kleen
Yeah, well, I don't want to, like, go too far back(!). but, basically, like, back in college, I was in like a psychology class, and we were talking about just the psychological domains. I picked up a textbook and I saw this section about the hippocampus (which is a structure deep in the brain, important for memory) and I was reading about the research that they were doing in memory, and I was like, just really amazed that you could understand how like the brain circuits actually worked. I thought, you know, I always thought the brain is just so complicated. But then I just got really pumped about it, and got into research in college, and started studying that more and more. And then I went to grad school and did my PhD, and a lab that was working on memory was also working on epilepsy. And I thought the two combined was, like, pretty interesting, especially as a direct clinical translation to it. But then I didn't understand how intertwined they were at the time. Actually there's, you know, memory, epilepsy and cognitive impairments kind of go hand in hand a lot. And there was just so much work to be done. So, it really got me very pumped, very motivated to continue this work.03:36 Torie Robinson
And it was for this work and what you've achieved so far that you got a couple of awards, I believe, correct?03:41 Jon Kleen
So yeah, there's the Dreyfus Penry AAN Award last year and then the Emerging Scholar Award from the ANA (so, the American Neurological Association). Yeah, definitely got lucky there. Also, Young Investigator Award a few years before that from the AES, but really, it's just, I mean, a lot of support from these organisations for this sort of, you know, they, and a lot of other people know that this is a very important problem; cognition and epilepsy. And it's, you know, getting those is just really also just inspiring to me to get back in the lab and like really push forward on what we're doing here. So.04:12 Torie Robinson
Well, it's great to have, you know, the large organisations recognising the importance and significance of a reduced level of cognition for people and the impact on quality of life. So, tell us about how cognition is often negatively impacted by epilepsy. Because I can say personally, memory issues are a huge thing. I mean, part of the reason, yes, I've had a temporal lobe resection, but also, you know, medications, potential seizures, you know, it’s the whole thing. How does it really work? And what, do you have any statistics on that?04:40 Jon Kleen
How is it intertwined? Or how do patients experience it in general? So, memory is one of the most commonly reported problems in epilepsy. But, when you look from study to study, the numbers reported kind of vary. And so, a lot of it's survey-based. But if you do more formal neuropsychological testing, you can pick up on a lot more cognitive deficits; especially specific cognitive deficits more distinctly and more quantified. But, you know, for example, we had a study that we put out last year just on this symptom that patients will very frequently describe, which is just word finding difficulty. And this study was in patients with called drug-resistant seizures, or they tried multiple medicines already. But, we had 79% of those patients reported word-finding difficulty. So, it's a pretty prominent problem. Some of the more recent research can cite (in general) memory as a memory impairment in general. We can see in up to half of patients with epilepsy. People also report problems with attention, problems with just, sort of, what we call executive functions, so switching from one task to another, those can be really difficult. But I will definitely say that memory in some form is, memory impairment in some form is probably the most common thing that I hear from patients. And it's not really surprising given, you know, what epilepsy is and where it is in the brain and how it affects things. One of the most common areas in the brain to generate seizures, or at least to be the seizure onset zone is the hippocampus, my favourite!06:14 Torie Robinson (06:25.237)
“Favourite”! Can't say it's mine, but yeah, sure!06:16 Jon Kleen
But that's a super important structure for epilepsy! It's also very old machinery in our brain: it does this incredible thing where, you know, it takes us back in time to whenever we want to remember something happened before, or helps us pull out facts information. So, you know, if epilepsy is affecting the circuits there… they're exquisitely sensitive/to go awry/ to have issues!06:40 Torie Robinson
I guess, so you're talking generally about people with temporal lobe epilepsy, then (if we're talking about the hippocampus)? And are you talking about, like people who might be having focal seizures or, or generalised seizures or both? Do you have a focus there?
06:55 Jon Kleen
So, if the focus of the seizures is in the temporal lobe, you would expect temporal lobe dysfunction. But you can have an epilepsy focus kind of anywhere in the brain. So, the frontal lobe is very important for that sort of executive function I talked about before; where people would switch from one thing to another or other sort of really high-level cognitive tasks that humans are really good at, right? But if you have epilepsy there and it's disrupting certain sections or certain circuits there, it's going to slow your ability to process information. Some people may even have their epilepsy area overlapping with language areas. So, language areas are important for understanding what people are saying or for producing what they want to say for speech. And so that can weigh into the word finding difficulty reported for patients a lot as well. But there's a lot of different things, as you can imagine, that could cause the symptom of trouble finding a word. Again, memory, trouble producing the word. So, it can be a really mixed picture from person to person.07:52 Torie Robinson
And does your research show that this is largely or partially because of some sclerosis for for example, or brain damage itself? Or is there a genetic factor? Or is it, could it largely be down to the anti-seizure medications or sleep issues or stress all interacting? Do you know?08:13 Jon Kleen
You know, it's still a huge area of ongoing research, right? But I can tell you, I know a lot of different main causes of it. And so, I like to think of it in, sort of, compartmentalised way. You mentioned really important influences, which are medications. They can definitely slow down cognition depending on the medicine, certain ones are worse than others. And then sleep loss, stress, these are things that can affect anybody with memory problems. But particularly people that are prone to memory problems, those factors will amplify their memory impairments. So, that's sort of the epilepsy-adjacent or related factors, right? And then we have the factors directly related to epilepsy. And I like to put these in groups in terms of… because they're so broad, right? They can be broad! I like to group them by… we call it “static” or sort of “permanent” impairments or changes that cause impairments. And that's really related to what I mentioned before, the circuit changes or really the aetiology of the epilepsy or the cause. So, primary generalised epilepsy, like you mentioned: that can sometimes be due to, you know, we call channelopathies, problems with certain ion channels. And that's affected like all over the brain. So, you could affect… you could anticipate that they have multiple domains of cognition affected. But hippocampal sclerosis is a great example of… it's one of the most common things that we see where the circuits inside the hippocampus and other areas in the inner part of the temporal lobe; they are rearranged and sometimes it's not just the rearrangement, it can be just hyper connections. So, cells and neurons connected to each other a bit too much, causing more excitability. You can also have the loss of certain types of cells, including these things called like inhibitory interneurons, things that are supposed to “tone down” the excessive activity. So, if you have less restraint because you're losing more of those neurons, you make the network more excitable and that can lead to seizures, but it can also lead to dysfunction in those same areas.10:07 Torie Robinson
And some of that dysfunction can't necessarily - excuse me if this is wrong - but can't necessarily be sorted with seizure control depends upon the level of damage maybe that that already is?10:18 Jon Kleen
Yeah, exactly. And that's why we refer to it… sometimes it's like, we say “permanent”. It's a very deep word to use and I hate to use it, but at the same time, those are circuit changes that are, you know, we can't just go in and rewire every single circuit, you know. So, those are changes that are probably lasting. It may be due to injury in that same area - so, traumatic brain injury or other strokes, things like this can cause long-term damage in these areas that can lead to seizures over time. But, again, this is referring to static or aetiology-based or cause-based changes that are relatively permanent. It's different, though, than the effect of seizures and what we call interictal discharges. So, I put these in a different domain called, like temporary or “transient impairments”. And I think of them on a scale of time, right, so, if you have a seizure - like, especially a long seizure, things like status epilepticus, for example, for a very long seizure - then you're going to obviously have cognitive problems that entire time. That's of course!11:22 Torie Robinson
Yeah.11:22 Jon Kleen
Or even - depending on the type of seizure, of course - but some… if it's just a focal seizure, that's still a big deal depending on which networks it's affecting. It can knock out someone's memory, their ability to lay down new memories for a longer, for a long period. But it may be on the order of like an hour or like 5 minutes. And then they're kind of back around and up functioning again. And then all the way to the other end of the spectrum are these transient cognitive impairments due to just discharges in the brain. So, a seizure is, you know, repetitive discharges that go, continue and continue for minutes, seconds or minutes. But these are just discharges that usually happen maybe for a couple hundred milliseconds before they're gone. Or really, like, the short part of it is less than 100 milliseconds. Sometimes they can be repetitive bursts, but they may just last 1 or 2 seconds.12:08 Torie Robinson
What are they doing faffing about just having, like, a millisecond activity - rather than a whole, you know, rather than a more significant seizure? And also do these just happen in people with.. who have regular epileptic seizures?12:23 Jon Kleen
So, we don't really hear about spikes much/too much. Yeah, so when you put an EEG on, in, let's say, 100 people with epilepsy, with known epilepsy, put an EEG on. Even if they don't have a seizure during the EEG, you can often tell that they have epilepsy because they will have these little discharges; these little waveforms that are quick in blips of activity. Those are usually coming from the area that wants to generate a seizure if it can, an excitable area, the seizure onset zone.12:50 Torie Robinson
It's like it's trying, sort of, in between.12:54 Jon Kleen
Yeah, it's just like a little spark of activity, but it's not… it doesn't continue and go on to a seizure. If someone was to be on less medicines, then you might see a lot more of those and you might see them eventually kind of transition to a seizure because it just sort of sparking, sparking, and then it goes. But often they're just, like, occasional; maybe somebody will have once a minute or something or so. Sometimes people have them like every couple of seconds though - I have patients where, you know, under RNS, so intracranial monitoring, they're out walking around, you can actually see they're having spikes every couple of seconds in certain areas. So, it really ranges, right? But in those moments when this little, sort of, spike or spark is occurring, it's an abnormal burst of electrical activity, right? It's really short, but it's going to just pull a bunch of neurons really locally into that activity. And even if they're not that close by, they might still be affected by this electrical wave that happens in that local area. But then it's gone, you know, so, you've kind of briefly scrambled the activity in that local area. And because it's very local, it doesn't, like, spread, right? We...you're only going to see it really if you test for a function that's important for that area.14:06 Torie Robinson
Right.14:07 Jon Kleen
So, I was referring to the hippocampus before: if you have someone do a memory test and, you know, ask them to recall things…14:15 Torie Robinson
Or could they get confused as well, maybe, or say the wrong thing? Could that happen?14:17 Jon Kleen
Absolutely. Absolutely. So, it really, again, depends on where the spike is occurring. But if it happens in the language cortex (like the language area is important for production), they might have trouble producing it. If it happens in the areas important for understanding language, they might literally not be able to understand what the person is saying to them at that moment…14:34 Torie Robinson
Gosh.14:36 Jon Kleen
… whereas, like, a second later; they can. And, again, this isn't usually a big deal to the point where we clinicians are trying to, you know, adjust medicines to chase every single spike that happens. But for some patients with a lot of spikes, it can accumulate, and it can add a lot, potentially, to this… the more permanent or static deficits that we see.14:57 Torie Robinson
And I imagine, especially, like, say it happens to someone when you're at school or college or university; it would make things extra difficult, right? Like… and you have to work twice as hard to actually try and remember things for your exam or whatever… however you're, you know, you're going to be assessed. Do you hear that from people?15:17 Jon Kleen
Yeah, you know, we may hear about absence seizures, right? And many of us know about those. Those are longer, though, those are seizures, right.15:25 Torie Robinson
Mmm.15:25 Jon Kleen
Usually, we think of them in the order of, you know, 10 seconds (at least), to be considered a seizure. But sometimes, even if they're, like, 5 seconds, you'll still see the person sort of pause…15:34 Torie Robinson
Mmm.15:34 Jon Kleen
…right? And so, we put these labels on things and call those, like, absence seizures and then spikes, we just refer to as spikes, but, you know, we could have anywhere in between where they're lasting a couple of seconds and disrupting that function locally. So, it really comes down to what the patient tells us, you know. If they have perfect seizure control and they are having terrible cognitive impairments and we look at their EEG and they're having a lot of spikes, like, all the time, that's a case where I would be like “I don't know, should we maybe adjust the medicines, even though they're not having seizures, would it help?”. And it's basically just, you know…there's no guidelines on that sort of approach right now. It's really just using, you know, hearing the patients and hearing what they say, what they describe. And if we do end up adjusting that - since it's very careful adjustments to be sure that we're treating what we hope to treat instead of just, again, chasing, chasing spikes!16:27 Torie Robinson
Thank you so much to Jon, who in part 1 of 2, has provided us with a fab insight into the significance of the cognitive challenges so commonly faced by people with an epilepsy. Please make sure that you do join us next week in episode 2 of 2 with Jon where we talk further, about Epilepsy Surgeries, Neuroplasticity (or lack thereof), & Memory!
Check out more about Jon and his work on the website torierobinson.com (where you can also access the podcast, the video, the 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, and, see you next week! -
Jon Kleen is an epileptologist and assistant professor who specialises in epilepsy care. He is dedicated to improving the lives of people with an epilepsy by stopping their seizures and finding new ways to overcome epilepsy-related cognitive issues, such as memory problems.
Jon is also a neuroscientist with expertise in signal processing (the use of computers to study patterns in large amounts of data), which he applies to cutting-edge diagnostic approaches and emerging therapies for epilepsy, including brain stimulation. As part of his research, he investigates how memory circuits work in the human brain and why they are disrupted in many people with epilepsy. He also develops technology that integrates brainwave recordings with brain images to help pinpoint where seizures start, with the goal of increasing the chance for future curative surgery in patients whose prior treatments failed.
Jon earned a doctorate in neuroscience from Dartmouth College and his medical degree from the Dartmouth Geisel School of Medicine. At UCSF, he completed a residency in neurology, serving as chief resident, and a fellowship in epilepsy. He also completed postdoctoral training in human neurophysiology at UCSF. In 2017, he was elected by UCSF medical students for membership in UCSF's chapter of Alpha Omega Alpha for excellence in teaching.
Jon enjoys spending his free time with family, as well as practicing Spanish and basic Mandarin, bicycling in Golden Gate Park, watching the ocean from San Francisco's landmark Sutro Baths, and getting lost in Wikipedia!
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Kleen Lab: kleen.ucsf.edu
LinkedIn: jon-kleen
UCSF Health profiles: Jonathan Kleen
UCSF Health providers: dr-jon-kleen
UCSF: CSF Neurologist Celebrated for Innovative Epilepsy Research
American Academy of Neurology: scientific-research-award-recipients
American Neurological Association: emerging-scholars-award
Orcid: 0000-0003-2622-3205
ResearchGate: Jonathan-K-Kleen
AES: HOBSCOTCH
BroadcastMed: ucsf-neurologist-recognized-for-innovative-epilepsy-research