Webinar: Epilepsy and Neurodegenerative Disorders: The Relationship Between Stroke and Seizures

Epilepsy is commonly associated with many neurodegenerative disorders – which are characterized by motor neuron loss. While stroke is not considered a neurodegenerative disorder, it is commonly associated with many of these disorders (dementia, Parkinson’s, etc.) that primarily occur in older adults. There has been a great deal of focus among the research community on the relationship between stroke and seizures, as a 2013 study found that 7% of patients who suffered a stroke went on to develop epilepsy.1 Post-stroke seizures are often associated with significantly increased mortality and severe disability in patients with a history of stroke. Unraveling these associations is a high clinical and research priority. Trials of interventions to prevent seizures may be warranted.2

In this webinar, attendees will learn:

  1. the epidemiology of post-stroke epilepsy.
  2. the complications of post-stroke epilepsy.
  3. the international efforts to promote research on this topic, as well as the challenges associated with them.

1Conrad J, Pawlowski M, Dogan M, et al. Seizures after cerebrovascular events: Risk factors and clinical features. Seizure. 2013;22(4):275-82. doi:1016/j.seizure.2013.01.014

2https://pubmed.ncbi.nlm.nih.gov/37721736/

This will be the first in a series of CURE Epilepsy webinars that will discuss the relationship between epilepsy and neurodegenerative disorders, released intermittently over the next year. Please see www.CUREepilepsy.org/webinars for more information on all of our webinars.

 


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About the Speaker:

Dr. Nishant K. Mishra is the convener of the International Post Stroke Epilepsy Research Consortium (IPSERC), which he founded with Dr. Patrick Kwan, a Professor of Epileptology at Monash University, in 2021.  He has been an active stroke researcher for the last two decades and currently focuses on understanding the mechanisms of post-stroke epilepsy. Advances in acute stroke management have led to improved survival after stroke, and therefore, more people are expected to have post-stroke epilepsy. It has become critical to speak to stroke patients to create awareness about the complications of stroke and understand their needs, e.g., how this condition affects their care and their quality of life.  For example, these patients struggle to get back to driving because of physical deficits, including challenges from neglect and apraxia and the risk of unexpected future complications like seizures. Some stroke patients suffer from early seizures, e.g., acute symptomatic seizures and status epilepticus, and are, therefore, on antiseizure medications. Despite antiseizure medicines, many patients suffer from seizure recurrence. Dr Mishra will share his independent viewpoints about this medical problem in this webinar.

He is currently employed as the Stroke Director at the West Haven VA Medical Center and a stroke neurologist at the Yale New Haven Hospital. As a full-time faculty at Yale University, he conducts clinical research to improve the care of stroke patients.

 

Q&A with Dr. Nishant K. Mishra

For people who have had a stroke and they’re concerned about what the consequences of that could be, how would you recommend having a discussion with the doctor? Because often you’re seen by a stroke doctor and then you move on to somebody else. So who’s the right person to bring these concerns to, and how does somebody who’s had a stroke have this conversation? What are your recommendations?

I think this is a very important question and I think so commonly when patients develop stroke and they come to our clinics, we typically deal with the medications. We talk about aspirin, Plavix, or the need for anti-coagulation test to look for a presence of atrial fibrillation, more of these kind of questions. We don’t typically discuss mood, cognition, fatigue, post-stroke epilepsy, which I think are also important topics that we as stroke physicians should be tackling, discussing to offer a comprehensive care to our stroke population.

Same goes to, in terms of questions around driving, for instance. We want to know which patient population is at a higher risk of having a post-stroke epilepsy and are they able to or should we let them drive or not? So there are many questions that linger in the mind of patients and through the effort like this, thanks to your organization, we need to really promote this topic so that our clinic follow-ups from the stroke standpoint are really more comprehensive wherein we are tackling not only the medicine aspect but also cognitive poststroke epilepsy.

I think stroke doctors are the right doctors who should be tackling it early on. Obviously, we send patients for rehab and our MDs with physical medicine and rehabilitation training experience, another set of colleagues who should be able to guide this patient population. Epileptologist as well. I’m really delighted to see a lot of discussion on cardiovascular disease management in the epilepsy conferences these days. So I think even though our specialties are different, our mission is same, which is to promote outcomes in our patient population. So we should feel comfortable tackling these questions.

Would you consider the genesis of epilepsy as a type of TBI?

From the stroke standpoint, after a stroke, there are some animal data, some research from various colleagues that suggest that there is activation of the inflammatory pathways. There is a damage to blood brain barrier. There are certain molecules like TGF beta which seep into this blood-brain barrier, disrupted regions, accumulation of albumin.

There are some biological mechanisms which have been talked about and linked to the occurrence of post-stroke epileptogenesis. One would imagine that because inflammation is the cause and if we use anti-inflammatory agents, we should be able to prevent post-stroke epilepsy. It’s very simplistic, however, because as we know the inflammation is on the one hand it’s useful because it helps repair the bodies once it’s undergoing the effect of the injury.

On the other hand, if it persists long enough can be detrimental. And where exactly is the right balance? We don’t know. Unfortunately, we don’t have targeted therapies for this. There are some studies which… For instance, there is a study in which people have… There’s this one person investigator who has looked at the newer and anticoagulant dabigatran inhibiting some of these pathways and is associated with reducing the risk of epileptogenesis in the animal models.

Dabigatran is an anticoagulant. There is a possible way to remove the anticoagulant effect of these molecules and retain the potential antiepileptogenic, anti-inflammatory pathways. But the research of that kind needs to first go through the animals, needs to be validated. It has to go through phase one, phase two studies, and then eventually. There is also some talk on the topic that there are already some anti-inflammatory agents, which we are used to using and may potentially be repurposed.

But those medications are for really other inflammatory diseases to safely offer them to a patient population which is suffering from other cardiovascular risk factors. We really need to do a thorough thinking and test them in a safe way in clinical trials before anything like that would be available for patients. There is one colleague who is looking at the fact of Losartan, which is an antihypertensive agent. And based on some animal model studies, it may have some effect in saving the blood-brain barrier from getting worse or securing the blood-brain barrier.

We use Losartan for blood pressure management anyways, but it again hasn’t been tested in the clinical trials. Same would go with the statins, the medications like atorvastatin about which I showed you in one of the slides, that there is a systematic review and meta-analysis which suggested that it’s associated with reduced risk of post-stroke epilepsy that again needs to be tested in clinical trials.

We know that the statins have a pleiotropic effect, which means that in addition to reducing the levels of the cholesterol in the blood, it also keeps the blood vessels healthy and reduces the inflammation there. So in short, it seems like there is a need for more investigation from understanding the inflammatory pathways, which again requires more collaborative global effort.

Can you talk about the group that you have convened and what you hope to achieve in the next few years?

So the need for the consortium came from the realization that on the one hand I showed you in one slide that the risk of having post-stroke epilepsy is very high in the older population, age above 60. We also know that stroke is a global problem. A large number of patient population have stroke, but the estimates for post-stroke epilepsy is around 10%, eight to 10% depending on which study we look at. So no single center would be able to accumulate significantly large number of patient population to allow meaningful analysis of their data to reach conclusions.

So for instance, the select score, the study that I showed those colleagues, they accumulated collected data from multiple centers in Switzerland and few other countries in Europe. So our goal with this consortium is to bring in colleagues with range of different expertise in stroke epilepsy, animal model, data mining and first highlight the important questions, show that this question is important and also write collaborative grants so that we are able to, number one, detect the meaningful biomarkers, which can be used for clinical trial design and also discuss the design issues potentially also start running some clinical trials using some drugs which appear to have some signal of anti-epileptogenesis for instance, my colleague and co-convener, Patrick Kwan, who’s an epileptologist in Monash, Australia leading figure in the field.

He and his colleagues are doing an investigation looking at Perampanel. Perampanel is a medication for a seizure management. They’re doing a pilot study. And there is another colleague, senior colleague, Dr. Matthias Koepp. He’s testing one anti-seizure medication. But we need to really come together so that we are able to design trials, which really serve the purpose because we would not want our effort to go waste doing running trials, which are poorly designed. One more mission that I have, and I would like the support of everyone here is what is it about this condition that makes most sense to our patient population? Why is it so important? Right?

Dr. Mishra doing a research on a topic that is not meaningful to patient population, does no service to the field. So we are interested. We are creating writing surveys, which soon we will be spreading across in different countries, trying to understand what is it that’s meaningful in terms of patient-reported outcomes to the patient, their caregivers, family members. So, these are the kind of question which we need to tackle and create a framework so that we can have larger future studies which are more meaningful and really advance the field.

 


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.

Young students in a classroom raising their hands to answer a question.

Epilepsy’s Impact on Learning and School Performance

This webinar highlights the latest research on how epilepsy impacts cognition, learning, and school performance.

The webinar is presented by Dr. Madison Berl, a neuropsychologist at Children’s National Hospital in Washington, DC. Dr. Berl’s presentation is followed by an interactive Q&A session. Some of the questions you might hear addressed include:

  • How do schools build an IEP for a child with epilepsy?
  • Are there services available to help my child transition into adulthood?
  • What laws are in place to support my child?

Resources Listed in this Presentation and compiled by Dr. Berl


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Attention/Processing Speed Resources:

Executive Functioning Challenges Resources:

Memory:

Audience Q&A with Dr. Madison Berl

Do you have any sense on how successful the percentage of cases are aided by programs like CogMed and how great the impact is?

Yeah. So for our study and I think there’s one other published study in Epilepsia, it’s about 20% of the kids that were in the study showed a significant improvement. So it’s not nobody, but it’s not a majority either. And so that’s a concern. And I think we don’t have enough information of why those kids responded and the other kids didn’t. So that may be something else about it to learn about too.

And then the second factor is, okay, they improved. Usually they’re improving on the measures that are very specific to that task. So they can repeat more numbers backwards or something like that. But how that actually translates to real life school skills or other skills is really lacking. The other thing that we’ve seen with longitudinal studies, because these programs have been tested a lot more thoroughly in ADHD populations, is that even if they show significant gains on something like math fluency, which we actually found too, it goes away after six months.

So it’s very short lived. And so does that mean that you have to keep doing this training? Does it really change things long term or not? And so those are some questions that are still concerning that it really doesn’t generalize or last in the way that we hope it does.

Advocating for 504 and IEP combinations seems to be a daily challenge. How can we get better resources for the teachers in schools?

Yeah. So that can go in a lot of different levels, right? So, yes, we need more funding for our education system, hands down. I am an advocate of that. In terms of getting the resources for your child, I think you also come to a point where you just have to fight for your own. And use of advocates is wonderful. They can be expensive. It’s like hiring a lawyer. But there are often, at least around here, organizations that have access to advocates that are free or at least at a reduced costs because their nonprofit mission is to help children access the curriculum. And so if you can get an advocate, if your school is not being responsive, really the parents that are the loudest, the squeaky wheel gets the oil, be like a pit bull and just be after them. And nobody likes that when it gets contentious, but sometimes that’s what you need to do for your child.

Are there any thoughts on what it indicates if a child makes huge cognitive gains on seizure meds and with every increase in their seizure medication?

I think that’s a great reminder to know that if there’s great gain, that probably means that was interfering with your child’s ability to learn. And so the medicine’s quieted down that brain activity. I would be very cautious about saying that then more medicines mean better cognitive skills because that can go the other way too. Like making them blotto by giving them too much drugs. And you really have to work with your neurologists about that.

They usually are working with you by doing routine EEGs to see what the EEG looks like. And if some of the problems are like attention, that’s where, again, maybe going to the stimulant medication and it’s not necessarily more anti-epileptic medication but it may be a different medication that could be helpful.

Are there any other options when stimulants don’t seem to work for ADHD?

There are non-stimulants ADHD drugs. So those could be helpful. Again, depending on what is going on, sometimes I’ve seen really the inattention is around sleep. And so I’ve had some parents feel like melatonin at night actually does wonders for the attention during the day because now they’re sleeping better. So I really think you need to dig in to know maybe why that stimulant wasn’t effective and that might open up some other options for other drugs or maybe other interventions. And really then just the behavioral interventions in school are definitely something that needs to be carried out. Whether that’s smaller class size, working in small groups, those kinds of things.

Does failure to medicate for the purpose of mitigating inattention have any impact on longterm development IQs?

I think what if your child is not available to learn, whether they’re sitting in the classroom and not listening or never attended school, it would be the other extreme, then, yes, that can impact their development. So, yes, if you are afraid of medication and decided not to, you may be hampering them because they are just not available to learn. But again, I’m not saying that it’s the only way. It’s just that it is a tool. And I feel most of the parents I work with are more hesitant to add a medication. And so that’s why it sounds like… I’m just telling you not to be hesitant and to consider it. It doesn’t mean that has to be the only way. But for sure, I would just think it should be considered more and I think many parents that I work with are a little bit more afraid than the typical parent because they already are on medications.

At what point do you think that homeschooling is a viable option for a particular child or student?

working with an advocate can be helpful. Fighting that process can be long and hard. And even what’s an acceptable amount of time that your child is not accessing the curriculum? Is one year too long? Is two years too long? And so I can sympathize and empathize with parents that say, “You know what? I can do this better and I can do this at home and we don’t have to waste all this time.” And I have had lots of families that have done a great job at that. I think you have to think about you and what you’re able to do and your willingness. I think there’s lots of tools and resources. We have lots of co-ops around here, so you don’t have to do it on your own. And then again, I would just make sure you at least worked with an advocate or a professional to make that decision just to have the discussion with somebody else so that an issue you hadn’t considered or options you hadn’t considered, that everything was turned over before you made that decision.

Again, some kids it’s just they need to because you know the school that you have access to. Or you know your child. We have some children that really, they’re so variable that they need to sleep till 10 o’clock in the morning and they can work and then they need to take a nap or they are going to be seizing every two hours. And so just because of them, they may do some of their best learning at seven o’clock at night and school’s not open. And a child that really needs that much more flexibility might be another reason to decide to do homeschooling. So there’s lots of factors that go into it. But I would mostly just recommend that having that discussion maybe with several people so that you’re considering all the options. But again, I’ve seen wonderful teachers, parents that are way better teachers than what’s in the school system. So it can definitely be a good decision.