Living with Epilepsy-Addressing the Cognitive Difficulties of Epilepsy

Video Transcription

So, these are my disclosures. I want to thank especially the CDC that has funded the Mew Network for many years. All the others are not necessarily of relevance.  So, what do I want you to learn today? First, how can we address the impact of cognitive difficulties in epilepsy? And I want to be very practical about this, like what can we do?  Not only study it, then know about studies that really do this, and be informed really also about not only these cognitive behavioral approaches, but also where we ventured out,  tried to do brain stimulation for cognition, know a little bit about the symposium this  morning where we talked about spikes and indirect discharges and how they interfere with cognition.  And then finally, I want you to learn about self-management programs that are effective for cognitive difficulties.  So, what I'm going to tell you is a little bit of a story or a journey where we went over many years in terms of cognition in epilepsy.  And it has been well described that patients, especially with temporal lobe epilepsy, have cognitive problems. We know all of this.  Not all cognition is memory, but a lot are impaired that way. If we do epilepsy surgery, also an interesting thing, we may add additional cognitive deficits,  but basically the patient would develop those anyway if they continue with their seizures and their epilepsy. Also the memory loss is quite variable.  You see exactly the two exact patients, and one has good memory and the other one does not, and it's unclear what underlies that.  And also just the overall number of seizures does not really affect the memory. And there is a big difference between subjective and objective memory loss that what the patients  perceive as their memory function may be very different from what we measure. And taking all those things together, what we already talked about with comorbidities  of epilepsies, we know that seizures and depression have a bidirectional relationship. If you have epilepsy and seizures, you're more likely to have depression and vice versa.  And both of those things have a significant impact on quality of life. If you have more seizure, your quality of life goes down a little bit.  However, if you have depression, it really goes down quite significantly, and depression may actually have a greater impact on quality of life than seizures.  If we reduce the seizures a little bit, as good doctors, the quality of life may go up  a little bit, but if we really want to assure good quality of life of our patients, we basically need to make the patient seizure-free, and that's not always realistic.  If we now add in that the patient has cognitive problems, and the quality of life goes even  down further, and we know that depression also affects your cognition, and if your cognition  is even more affected by the depression, and you have not controlled seizures, your quality of life is really poor, and we better start thinking about doing an intervention.  How important is cognition? And there is a study, which is actually now 12 years old, but it's still very relevant,  and I hope in those meetings we have made a lot of difference since then, but if you ask the patients, memory is number three of their worry if they have epilepsy.  If you talk to the doctors, it's number 12, and I hope if you walk out of this room you have changed your mind regarding this.  Also patients find memory and mood problems often more disabling than the actual seizures themselves, and also this recent interesting study is that the gain of employment after  epilepsy surgery is actually dependent on executive function and working memory. So cognitive difficulties are a big thing that need to be addressed, and I'm sure you  all sit in your room with your patients, and they complain about their memory. So I come from a world of epilepsy surgery, and doing resections, and then going into  brain stimulation, and it's all cool and fine. So the idea was initially, you know, could we maybe, if we do brain stimulation for seizures,  maybe we could also do brain stimulation for cognition. And there was this paper in six patients, the New England Journal, that kind of studied  50 hertz stimulation in intracranial patients and showed that you may have an improvement of memory. Great. We thought, great thing. We'll do the same thing.  We did it in 49 patients, and guess what? It didn't work. So that was kind of a big, big bummer.  However, here you see the task, one of the tasks we used, that we show the patient while they're in the epilepsy unit.  We show them a word list, then they get distracted, that they don't remember the last word, and then they have to recall.  And however, in that study of these 49 patients, there was one patient who could recall, like, two words out of the 12.  And then we did lateral temporal stimulation, and out of a sudden, he could recall 12 out  of 12 words, which was quite remarkable, but on a group level, we didn't see the same effect. And a lot of smart people in collaboration, so this was a multi-center collaboration,  and was actually led by Mike Kahana at Penn. They came up with this, what we call now classifier-driven deep brain stimulation, and what this is,  if your brain is in a good state where you will remember well, the only thing stimulation can do is kind of mess it up.  But if your brain is in a state where you don't remember well, then you may do something with the stimulation, and that's exactly what we did.  We took patients with intracranial recordings, we established a spectral pattern, with machine  learning, we actually established this classifier, so what is a good and a bad memory pattern, and we only triggered stimulation if the brain was in a poor memory state.  This is where we stimulated, and actually, lo and behold, if you stimulate the lateral temporal cortex, you can improve memory, and as we had the classifier, we could actually  measure this now electrically, and we also saw a change in classifier stimulation. What we showed with this is that lateral temporal stimulation can improve memory.  However, you have to think about this, it's a great result, but instead, so we could improve  memory by like 20%, but instead of remembering two words, you may remember like 2.8 words, and is this really relevant, clinically relevant to be implemented?  We looked a little bit, and this relates to what was discussed this morning, and interictal activity and how it affects memory, and that was discussed also this morning, this was  our task, and if you have spikes in those regions, you will interfere with memory. The hippocampal spikes will only affect recall, not encoding.  And these interictal spikes, what affects them, of course, whether they are left or right sided, because our task is a word memory task, where the spikes occur, as well as what  is the overall rate of interictal spikes, and what is the white matter propagation. So the question then comes, maybe what we could do, we could read these interictal discharges  for better cognitive performance to make them go away.  And this is an age-old question, should we treat the EEG or not, and this was also discussed  this morning, and we can endlessly discuss this, there's probably no real answer to that. We looked a little bit, how would we treat it?  Maybe we give patients medications, where we already kind of alluded to, and there are some medications that reduce the amount of interictal spikes, and those are like levitiracetin  and carbamazetin, are kind of the winners on this. However, we all know, giving more medications will not make the patient's cognition better.  The more medication we give, the worse the cognition. So and then I just want to present you very briefly this interesting sideways event, which  is actually music and interictal spikes.  There was this one study where this Mozart sonata actually was shown to decrease interictal spikes. When I heard this the first time, I thought this is all total nonsense.  But if you don't know, you study it. And that's what we did, and we played that sonata to our patients. It should play. Beautiful sonata.  But what, and lo and behold, that sonata, if I go back to this, does reduce your interictal spikes. We don't know whether it makes your cognition better.  If you play other music, such as Wagner, Haydn, music the patient likes, the same effect is not there. It's just this one Mozart sonata. I have no explanation.  I'm happy to discuss this with you. I'm working now with music professors trying to find out what is so special about it. It's just an observation we made.  So coming to all of this, what do we really do to make our patients' cognitions better? So we could do this brain stimulation thing.  It's going to take us another 20 years until we have a brain stimulator that will also affect cognition. The medications are not a really good idea, probably.  We can't play Mozart 24 hours a day because the patients just get crazy. But maybe we could engineer some music that would do it.  And that finally brings us to these cognitive behavioral approaches for memory, self-management approaches and cognitive rehabilitation.  I'm going to talk today about the Hopscotch program. There are other programs out there for cognitive rehabilitation that are also very effective. And how did we come about this?  This was through the Managing Epilepsy Val Network.  Dr. Sadajewicz is going to talk a little bit more about this, which is funded by the CDC.  And it's really a community of practice that also includes advocacy groups to really advance  self-management research in epilepsy, to approach this scientifically, and also to disseminate and implement the programs that were developed within this network.  And here you see also a few other programs that were developed. One is Uplift. This is mindfulness for depression. One is SMART, which is a community-based program similar to PASES.  And then Hopscotch, to which I'm coming right now. So what is Hopscotch? Hopscotch is the Home-Based Self-Management and Cognitive Training Changes Life program.  This is a program that lasts about or takes about 8 to 12 weeks. And we utilize problem-solving therapy and memory strategies to basically cope with memory problems.  And I'm going to show you a little bit how this works. It is a self-management program where patients learn skills to better deal with their disease.  And it's delivered over the phone and now virtually to forego transportation problems. And we wanted it to be easy to implement in any epilepsy clinic or in any community setting.  So how does this work? You see it took us some time until we developed it. I look much younger on this manual. However, this is how it works.  The patient gets a patient manual, gets a memory coach assigned who is trained in the program.  And then the patient has to monitor his or herself for about a week or two what are their specific memory problems, what they have a problem with.  One example is, for example, I'm forgetting my medication every other day.  And then with the coach, the patient has to learn or find possible solutions for the problem. Let it be. I set my iPhone. I ask my mother to remind me. I write it on my mirror.  Whatever they come up with, not what the doctor tells them to do. What they can come up with to solve this problem.  And then they go out into the world for a week or two to basically exercise what they said they would do, and then check in again with the memory coach whether this was a successful  approach or not. And along the way, they learn what's called memory strategies, which is good for everybody's  memory, like setting reminders and having memory routines, et cetera, et cetera, which are really good. How do you remember somebody's names?  There are some tricks to it that are good for everybody. And of course, we go with the times. There's now also an app that is used with the program to just collect data.  So we ran two randomized controlled trials for the program. There was phase one that you see here, where we enrolled 66 adults with weight-listed controls.  And you clearly see that we saw a clear improvement in quality of life. And what was somewhat surprising was also that we saw an improvement in objective cognition,  which was mainly driven by attention. So basically, our patients learned to pay attention, which is not a ‑‑ it's a very important part.  Then we ran the hopscotch phase two, where we enrolled 88 patients. And there we thought, this was actually before the pandemic, we are really smart, and we  just create a purely virtual version of this, and the actual hopscotch version was delivered over the phone, but you would meet with your coach once at the beginning, see them face  to face in person, and then go on and talk with them over the phone. And here you see the really interesting result, the blue line are the in‑person hopscotch,  that is far more effective as the one where we changed nothing else besides having the first version over Webex, the first interaction with the coach was over Webex.  And you see it still is more effective, but the in‑person encounter is much more effective,  and I think we have all learned in the pandemic that there is something to a personal interaction.  We saw a quite significant improvement of quality of life on the QALY 31 of actually  more than 12 points, and also we saw an improvement in their subjective cognition measures, which was actually one of the promise measures that was previously talked about.  Here is a quality analysis of now a hopscotch in the community where we performed interviews and what are the topics, what patients find most helpful in this analysis.  Currently we are running another trial in a different population, more a diverse population in the south, so if you're somewhere in Georgia, please refer to that.  We are also running a study currently to adapt it for post‑traumatic epilepsy where we actually include the patient caregivers and also see does it have an effect on the caregivers.  So now you may ask yourself, how can my patient get hopscotch? There is now, actually we now have the Hopscotch Institute, it's actually led by Dr. Lane Kiriapopoulos,  who does an excellent job with this, and you can, and the Hopscotch Institute has various kind of missions, one is of course to do the research, all the trials I just showed you,  but then also train centers, people, communities in the actual program, deliver education,  and then partner and disseminate with community agents, so what you can do to get your patients  a program, so you can go and you can get trained in the program, actually the American Epilepsy  Society here is partnered with the Hopscotch Institute for training in the program, we had a training this year, actually yesterday for hopscotch coaches, so if you're interested  next year, please sign up for this. You can also refer for virtual hopscotch at the Hopscotch Institute, or refer to delivery  sites who have already adopted the program, quite a few clinical programs, as well as community groups, like have adopted the program, are delivering it to the community, and also  I know your next question is, is this something that's reimbursable, currently we can, if you're a psychologist, you can actually even code and bill for the program.  So with that, what is the impact of clinical care and practice? You need to treat, so you know, to really treat the cognitive difficulties is not an easy thing to do.  You know, the electrical brain stimulation work, maybe a future treatment, I told you everything about this indirect activity, and maybe possibly engineering some music  that has a treatment potential, and then of course that self-management program and other cognitive behavioral rehabilitation programs have shown to be effective to address these  cognitive difficulties. And it's possible to disseminate and implement those programs, it takes some effort, but our patients are certainly worthwhile doing it. Thank you very much.

Video Summary

The presentation focused on addressing cognitive difficulties in epilepsy patients, highlighting a journey through various approaches and research efforts. It emphasized practical intervention strategies, including the potential of brain stimulation, cognitive behavioral therapies, and self-management programs such as the Hopscotch program. The speaker shared insights from various studies, noting the variability in memory impact among epilepsy patients and emphasizing the complex interplay between seizures, depression, and cognitive function. Despite some setbacks, such as unsuccessful brain stimulation trials, innovative solutions like the Hopscotch program have shown promise. This program uses cognitive training and therapy to improve memory and quality of life in epilepsy patients. It involves patient engagement, problem-solving therapy, and is adaptable for virtual delivery, although in-person interactions proved more beneficial. The discussion also explored the relationship between music, specifically a Mozart sonata, and reduced interictal spikes, proposing further unexplored therapeutic avenues.

Asset Subtitle

Presenter:

Barbara C. Jobst, MD, PhD, is the Louis and Ruth Frank Endowed Professor of Neurology at the Geisel School of Medicine at Dartmouth and the Chair of the Department of Neurology at Dartmouth Health. She is the Associate Editor of the Journal Neurology and Chair of the Council of Education of the American Epilepsy Society. She has established the translational Epilepsy and Cognition Lab at Dartmouth, Geisel School of Medicine and the HOBSCOTCH Institute. Her research has focused on the description of focal seizure syndrome, outcomes of epilepsy surgery, intracranial neurophysiology, cognitive problems in epilepsy and brain stimulation for epilepsy and memory. She has led the Managing Epilepsy Well Network a thematic research network of the CDC. She has participated in more than 45 studies funded by NIH, the CDC , the National Science Foundation, the Diamond Foundation and the Department of Defense, multiple pharmaceutical industries and device manufactures.

Keywords

epilepsy

cognitive difficulties

brain stimulation

Hopscotch program

memory improvement

Mozart therapy