Epilepsy Surgery, Neuroplasticity, & Memory - Jon Kleen, UCSF (University of California, San Francisco) Medical Center, USA
People forget to bring up memory issues with their neurologist…because of their memory issues! Discover the potentials and limitations of neurosurgery and neuroplasticity with epileptologist Jon Kleen from UCSF medical Center.
Reported by Torie Robinson | Edited and produced by Carrot Cruncher Media.
Podcast
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00:00 Jon Kleen
“These are things that we're doing to try to help, but they can have their own potential drawbacks too. That's a real concern about if, you know, if someone's a potential candidate for surgery and removing that area, that's great, but what if it overlaps with an area [of the brain] that they need? You know, and, you know, I mentioned before, we're studying normal brain activity in a lot of these patients with these electrodes implanted, but, you know, some of those areas are abnormal. And so, they may have some residual function that we're using to try to understand how the brain works in general…”
00:29 Torie Robinson
Fellow homo sapiens! Welcome to, or welcome to: Epilepsy Sparks Insights.
When people think of epilepsy, they usually just think of seizures along - seriously, this is true of many in the medical field too. What epileptologists, epilepsy nurses, and people with an epilepsy can tell you, is that it’s often WAY more than seizures, and challenges faced by so many of us include issues with memory and cognition. Last week, star epileptologist and neuroscientist Jon Kleen, gave us a brill intro into our fascinating little seahorse - the hippocampus! - and the challenges it commonly faces with temporal lobe epilepsy. Today Jon and I chat about the benefits of intracranial recordings for surgery work-ups, neuroplasticity, and the pros and cons of certain treatments when it comes to cognition, and more!
Please don’t forget to like, comment and subscribe to the channel if you haven’t already, so that we can spread the word and education about the epilepsies to more and more people.
01:21 Jon Kleen
My name’s Jon Kleen, I’m an epileptologist over at UCSF Medical Center in San Francisco, California, and so, 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.
01:47 Torie Robinson
Do you know what I've heard from other people - and I totally relate to this - is that sometimes they'll come to an appointment and if they haven't written down what they were going to say, they'll forget what they were going to say! And so, it can be really hard to actually, ironically, remember that they have… they need to say something about their memory. And…
02:05 Jon Kleen
Yeah…!
02:06 Torie Robinson
Yeah, I guess you come across… but you're very aware of the of this potentially being an issue. So, I imagine you bring this up in appointments - do you do bring up things about memory and cognition and overall life rather than solely looking at seizure control?
02:19 Jon Kleen
And often I'll just notice it in the visits sometimes. They'll just tell me like, I'll ask them like “How was the last couple of weeks for you? Any increase in seizures?”. And they'll say… they'll look over at their parents (if they're there), [or] like their friend in the room, just like “Am I having seizures?”, and they just have such trouble remembering. So, I'll ask about it, you know, I'll probe a little bit more in terms of what domains they're having trouble with. A lot of times, like I said, word finding difficulty is one aspect we hear a lot, but also just, you know, “...a conversation I had last week or last month”. Or “I was in class all last week and I could barely remember any of this stuff. I had to like, just, study so hard, like, later.”, and those are big challenges you know. These are really important times in a lot… in everybody's life, you know, our whole life is important but I have people in college or in grad school or working a really high level job; these are areas where they really need their brain, their noggin, as much as possible. And it's really important to hear that and to work with them on it. And, you know, I mentioned adjusting medications as a possibility for things, but again, we don't really have great evidence that medicine changes are going to be a slam-dunk way to improve someone's cognition. We do know that if they're having seizures, that's definitely going to tire out those brain areas more. So, it's another big reason to get seizures controlled. But there's no medicines, like, that I could just say “Here, take this pill. It's going to improve your cognition at this point.” Hoping that'll be the case down the road, that'd be wonderful for other neurological disorders as well(!) there are some. But I think other things, like neural stimulation, that could potentially help in the future as long as we get better targets. That's one of the focuses in my lab is like, not just saying “Oh, let's stimulate and see what happens to try to improve cognition.”, but let's actually understand the network in a lot more detailed way. To get better targets from the get-go; to get things that are going to be more high yield to improve cognition, but…
04:23 Torie Robinson
I was going to ask you more about your lab and in your focus or foci at the moment, because you can… where we can say “cognition” it’s like, it's quite a broad statement. What are you focusing on right now?
04:34 Jon Kleen
Oh, yeah, so we actually studied that phenomenon I mentioned before (transient cognitive impairment) - I studied that a lot in the past and we've studied it more recently as well - but we're also looking more into the mechanisms of it. For example, when you have a spike in one area, the brain is highly interconnected and so it can propagate to other areas of the brain. And those other areas are all of a sudden getting sort-of a pulse of information that is sort of scrambled and that's got to throw things off a little bit.
05:03 Torie Robinson
Right.
04:37 Jon Kleen
So, we're trying to understand whether the effects of spikes are not just, not just local to where they occur, but perhaps in downstream interconnected areas as well…
05:13 Torie Robinson
Ahh!
05:13 Jon Kleen
…and for that we study intracranial recordings a lot. These are recordings that are only done in patients with severe epilepsy in whom we think we could really pinpoint the location of the seizures (where they start).
05:28 Torie Robinson
Done prior to surgery, right?
05:29 Jon Kleen
Exactly, yeah. And it's a surgery in itself in terms of implanting the electrodes. But… it’s really important also just to capture a seizure happening on those electrodes. So, they stay with us in the monitoring unit and we get that captured and then they go… Once we pinpoint where it is, we can take them to the operating room and hopefully remove that area that's just causing trouble and not contributing significantly to their daily function, their cognitive function.
05:53 Torie Robinson
So, you can be more specific in what you remove rather than, you know, just getting a big spoon and scooping out the whole lobe. You can take out just the bits you need to. Is that kind of it?
06:02 Jon Kleen
That's exactly right. And, you know, it’s a really important surgery because like I said before, for some people we quote “cure” and again, “cure” is like a very broad word to use, but stop the seizures in over half the patients, sometimes like even 2 thirds or more of the patients that go for surgery (depending on the type of resection, again, like meaning resection (just removing the bad area that we do)). So, that's, that’s a great thing that can happen for patients. But along the course of it, they're having recordings inside their brain and they're hanging out in the monitoring unit with us. And, you know, with amazing staff, of course, you'd need a really highly trained, you know, 24-7 staff to make sure that the patients are safe, all that, if they have a seizure.
But a lot of times the patients will just be hanging out and kind of bored, to be honest! And they'll say, they'll want to participate and volunteer for the tasks, you know. And if they do, then we're like “Yeah, sure you could! Can you name a couple of these pictures or can you do this task where you, like, listen to these beeps that are gonna happen?”. And, you know, to them it's just maybe passing time, but they know that it also is contributing to super important research for people with epilepsy, for people… just a lot of people, because we're trying to understand memory. Colleagues of mine are trying to understand language deeply, but these are electrodes actually on top of or in the brain tissue, so it's an unprecedented way to get highly detailed information about how the brain works.
07:29 Torie Robinson
So exciting. And you know what, I speak to heaps of patients who will say “Mate, [I’m] totally up for it. If I can help in any way, why not?!”, you know, ‘cause they can be some of the people who understand the impact on [the] lives of so many other people. And they don't just affect the people with the diagnosis - I'm sure you come across… like, they really impact families and partners and, and things like that as well, sometimes even more (dare I say it), than the actual patient themselves.
07:55 Jon Kleen
And sometimes the patients will tell me that they feel terrible that they, you know, their family members have to, like, help them with all these different things: remembering the medicines, you know, if they're sometimes… isn't that wild, like if you miss your medicines, you're more likely to have seizures and then that's going to affect your cognition. But coming back around, remembering your medicines in the first place, you need your cognition for that in your memory.
08:14 Torie Robinson
And also, sometimes, it feels like I need to have the cognition that you're taking away from me to take these drugs again, which often negatively impacts my quality of life anyway.
08:25 Jon Kleen
Mm-hmm..
08:26 Torie Robinson
And then - when you're talking about surgery - okay, great if you know 70% or so (generally) of people might not have seizures anymore, but then they may have even greater loss of cognitive function because of the surgery, maybe.
08:41 Jon Kleen
Yeah..
08:41 Torie Robinson
And that you don't necessarily just come off medications anyway… So. it's not, like, a great big gold star just to have the surgery. It's not… because the epilepsy and cognitive issues really can impact a person's life. It's not just about the seizures.
08:59 Jon Kleen
These are things that we're doing to try to help, but they can have their own potential drawbacks too. That's a real concern about if, you know, if someone's a potential candidate for surgery and removing that area, that's great, but what if it overlaps with an area [of the brain] that they need? You know, and, you know, I mentioned before, we're studying normal brain activity in a lot of these patients with these electrodes implanted, but you know, some of those areas are abnormal. And so, they may have some residual function that we're using to try to understand how the brain works in general… but, that's a potential bad thing if this bad area is overlapping with the good area, or especially areas that the person needs in their everyday life that they will really, really notice if they have problems with it. So, speech, language, if we have seizure zone areas in the language cortex, that's a super-obvious deficit that would happen later.
Luckily, we don't just kind of cross our fingers, right? There's a lot of ways that we are very careful about the potential tissue that we would remove in a surgery. And we do very formal testing on that. We can do stimulation mapping where we stimulate pairs of electrodes and try to pinpoint like where the actual needed cortex/needed area of the brain is compared to the area that the patient may not need. With epilepsy, we'll see a lot of remapping actually over the course of years-decades where the brain kind of learns that this area is not really functioning well. So, let’s shift that over to the complete other side, or let’s use like this sort of strategy that depends more on this area of the brain instead of this area to get around this problem that I'm encountering in my daily life.
10:34 Torie Robinson
Do you see that in adults as well? Because I know that we talk about, you know, “plasticity” all the time, it's quite a cool word, but there are certainly limitations, right? And the older we get, the less that… it's not as easy, necessarily, to use another part of the brain - or, it can take a lot longer. But, do you see, like, this happening in older patients as well as younger ones?
10:55 Jon Kleen
To an extent, yeah, I mean, it really depends on the age a lot of times. So, the older someone is, you know, getting into like the 30s, 40s, 50s, and beyond, it's even tougher for them to just sort of regain that function over time. But it is definitely, you definitely don't want to even bother… or not bother… or you definitely want to try to improve these functions, right?! So, we always would have them work with speech therapists, speech therapists, like professional people after something like a surgery to improve that function.
You know, there's not like a pill we can be like “Oh, you have memory impairments and epilepsy? Sure. This pill will take care of that!”! We don't have a stimulation way to do it right now. There's stimulation for tremor. There's stimulation for a lot of other, you know… for seizures too. But to improve cognition directly, there's nothing that exists quite yet. That's, that’s, you know, certainly not FDA approved. Hopefully we'll get there someday. But what we do have are certain things that we know is going to help.
One is of course, reducing seizures as much as we can. And then two, is like finding better medicines that aren't going to give you side effects, optimising sleep, reducing stress, but to actively manage cognitive impairment: there is one thing that's been up and coming kind of in the last 15 years called HOBSCOTCH. I don't know if you ever heard about it, but it's through the CDC. So it's funded by, like, you know, a government organisation.
Home Based Self-Management and Cognitive Training Changes Lives. That's it! But it's basically like, it's a, like a 10 session program. You meet with a person like every week and, it's instead of… it's not, it's kind of like therapy in a way, like mental health therapy, but instead of… you focus on memory and cognition. And I send patients to this a lot because, they try to actually reduce the cost or get no costs if possible. There's even providers that can (like neuropsychologists and nurse practitioners) other people can provide it. But the idea is to basically give evidence-based techniques to help the person self-manage their cognitive impairments. So, memory strategies, not just like “Oh, right, make a list!”, but other things with evidence behind them…
12:56 Torie Robinson
Love it.
12:56 Jon Kleen
…like new tips and tricks, you get, like, homework between those visits. And again, it's all over Zoom now, basically. So it's really convenient, like, kind of, wherever you are in the world. But that's definitely up and coming more recently. And I've, you know, the majority of my patients say that it at least helped to some degree. Some patients, like, rave about it. But the reason I like it is, again, it's evidence based, right? They've got… it's not just like some program that somebody made, it's like [there is] evidence behind it. And it's also… they try to reduce the cost or get it, like, to no-cost if possible, particularly since it's funded through the CDC.
13:26 Torie Robinson
Is it at all accessible to people outside of the US?
13:29 Jon Kleen
I know that the HOBSCOTCH folks are trying to expand. We've got like… there's, like, a big sort of network they're building and UCSF is like one of the sites that we're implementing this in a more streamlined way just to increase patient access. But it's currently focused on, you know, broadening from like the East Coast or like the North East into like the rest of the United States. But absolutely it should be global in my opinion because, again, it's like remote based…
13:54 Torie Robinson
Why not?!
13:54 Jon Kleen
…or just phone based even. Yeah, and you could… and anybody could benefit that way. So, I have a feeling it will probably become that way eventually because it just seems to have, like, accelerated a lot in recent years.
14:04 Torie Robinson
I mean, it sounds amazing, especially for people who, you know… loads of people don't live close to the hospital, right? Or they struggle to get to the hospital for, you know, lack of public transport. or whatever, or they live in a remote area of a country, you know, where they're… you know, lucky if they've got wifi. So…
14:22 Jon Kleen
They're still gonna have cognitive impairments affecting them and they need and they deserve treatment, you know, with whatever we have.
14:28 Torie Robinson
And it's a great investment, I imagine. Well, you know… gosh, I'm promoting this already(!). But something like this is, is a great investment if it helps people, because you're going to get people, you know, better mental health as well, you know, on fewer drugs, probably, the same for their families. You're going to have more people in work…
14:44 Jon Kleen
Potentially, yeah.
14:19 Torie Robinson
…you know, if they're more confident to actually go out and, or more confident to socialize and just have better communities, I think. People forget how important it is for us to have good… good-enough cognitive function that gives you good quality of life.
15:00 Jon Kleen
There's definitely indirect effects that we see. And, you know, HOBSCOTCH is focused on, like, the memory outcomes in particular and hasn't like… they've got other programs through the CDC for epilepsy that are based on mental health and things. But I totally agree. And I've heard from patients that, you know, improving memory, improving cognition, however you do it is probably just going to increase confidence. It's going to improve just quality of life in general that's going to hopefully, indirectly contribute to maybe improving stress, anxiety, mental health, mood. You know, again, we'd have to, like, look at that in a formal way with studies to understand exactly how much, but I definitely hear it from patients.
15:35 Torie Robinson
And reduce seizure frequency because of all that!
15:37 Jon Kleen
Imagine remembering your medications every day instead of missing… I had a patient a couple of months ago who just said “You know, I miss medicines once in a while. Yeah, maybe about 10% of the time.”. I'm like “10%?! That's a lot! That's a huge amount!”. But imagine…and he was. that that person was having some seizures, like breakthroughs here and there. But if that person could be taking all their medicines and not missing any doses because of their memory issues, we could… I mean… imagine… much more impact, right? So, you know, just work with that person on alarms on the phone, having, like, the sort of pill box for the AM and PM, and then, you know, emphasising again, like self-management programs, like HOBSCOTCH again, like, and I'm not, like, I don't have grant funding on HOBSCOTCH. I'm helping with one of the studies that, that they're doing to try to implement it on broader scope, but I'm not, you know, not like a paid representative of HOBSCOTCH by any means.
But certainly, you know, younger adults, they're going to have, sort of, more plasticity ability, really, to kind of remap functions or to learn new strategies more dynamically that will help address these things and have that kind of laid down permanently for the rest of their life in terms of how to go and get around these problems. But the best scenarios are often with young kids, especially like quite young kids who have tons of plasticity happening and a lot higher rates of neurogenesis. I mean, like, birth of new neurons compared to adults that drops off quite precipitously even through childhood.
17:4 Torie Robinson
Well, like, it’s easy for me to say but, like, if I was younger, and I had been given the opportunity to have a resection when I was in my late teens [I’d say] “Dude, do it!”! I'd have totally done it. I was having so many accidents, injuries. I fell on a railway line during rush hour…
17:21 Jon Kleen
Oh wow…Oh my gosh.
17:21 Torie Robinson
Yeah, I fell off my bike into the middle of the road…
17:25 Jon Kleen
There's so many, you know, injury potentials. Yeah, gosh. Driving is the hottest topic, I'd say, in the clinic with… well, not for everybody, but certain patients…
17:35 Torie Robinson
Yeah.
17:35 Jon Kleen
…just feel so passionate about driving. It's such a big part of independence. But, you know, there's been rare cases, and, you know, still to this day, and throughout the United States and beyond, you know, if a seizure happens and it impairs awareness behind the wheel, it can be terrible. I've heard some very lucky stories too, and not to, like, digress too much, but again, it does get back…
17:55 Torie Robinson
No, you're alright!
17:55 Jon Kleen
…it does get back to the cognitive issue, right. So, it doesn't have to be just a spike, it doesn't have to be status epilepticus because they're permanent impairments, it can be just a focal seizure that's brief, that could be life-threatening for multiple people on the road. I have a patient that described, like, dropping someone off and then all of a sudden being in their parking garage with a big scrape on the side of their car and it's like “Wow, that was the first event that they, that they noticed.”.
18:23 Torie Robinson
I mean, you must hear stories like this all the time, right? It's just wild.
18:27 Jon Kleen
Some patients will get really passionate about it. And it's really just we have to have those like deep, long conversations. But I always tell them “Look, look, I'm actually your biggest fan to try to get you back on the road. We just got to get your seizures out of here. So let's… you know… we need this time frame (that's the state law), and that's a really good… it's, it’s there for a reason. That gives us a really solid amount of time to change these medicines around, get these things stamped out.”. So, you know, I just try to make sure… they get so worried that, you know, I'm… I’m just going to go and report them and I'm like the bad guy, but I'm, like “Look, I'm with you. Let's, like, join hands here and get you there!”!
19:01 Torie Robinson
It means so much to us, and yeah, I can see that you properly empathise as well, which is so important. You don't just sympathise, but you empathise = and that's not something that all clinicians have, you know.
19:12 Jon Kleen
I don't know how you can’t empathise because that's like, you know, if I couldn't drive… the same thing! I don't drive that much because San Francisco is pretty good for, you know, public transportation, but it's not great! And like, you know, I've just Googled, like, bus routes with patients too. Like, you know, I'll be like “Okay, let's just, okay, let's see what an Uber costs, like, from there to the supermarket.” just to try to figure out, like, what we're going to do, right? Cause for the next like, you know, 6 months while we get like the seizures, back under control…
19:38 Torie Robinson
Thank you so much to Jon for such a great chat regarding epilepsy and cognition, especially, the rather integral part that is memory! Do check out more about Jon and his cool work on the website torierobinson.com (where you can also access his 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, and, see you next week!
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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
Orcid: 0000-0003-2622-3205
ResearchGate: Jonathan-K-Kleen
BroadcastMed: ucsf-neurologist-recognized-for-innovative-epilepsy-research