NEWS
CURE Epilepsy Webinar: The Relationship Between Stroke and Seizures
Speaker: Nishant K. Mishra, MD, PhD, FRCP
Convener, International Post-Stroke Epilepsy Research Consortium
Webinar
https://www.youtube.com/watch?v=UwY4qsvnWAE
Transcript
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:
the epidemiology of post-stroke epilepsy.
the complications of post-stroke epilepsy.
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/
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 to look for the presence of atrial fibrillation, more of this kind of questions. We don’t typically discuss mood, cognition, fatigue, or post-stroke epilepsy, which I think are also important topics that we, as stroke physicians, should be tackling, discussing to offer comprehensive care to our stroke population.
The same goes in terms of questions about driving, for instance. We want to know which patient population is at a higher risk of having post-stroke epilepsy and whether they are able to or should we let them drive or not? So there are many questions that linger in the minds of patients, and through 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 the 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 and some research from various colleagues that suggest that there is activation of the inflammatory pathways. There is damage to the blood-brain barrier. There are certain molecules like TGF beta that seep into this blood-brain barrier, disrupted regions, and accumulation of albumin.
There are some biological mechanisms that 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, inflammation is, on the one hand it’s useful because it helps repair the body 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 anticoagulant dabigatran inhibiting some of these pathways and is associated with reducing the risk of epileptogenesis in 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 research of that kind needs to first go through the animals and 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 that is suffering from other cardiovascular risk factors. We really need to do 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 anyway, but it again hasn’t been tested in clinical trials. The same would go with the statins, the medications like atorvastatin 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 statins have a pleiotropic effect, which means that in addition to reducing the levels of cholesterol in the blood, they also keep the blood vessels healthy and reduce the inflammation there. So, in short, it seems like there is a need for more investigation to understand the inflammatory pathways, which again requires a 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 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 a 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 a few other countries in Europe. So our goal with this consortium is to bring in colleagues with a range of different expertise in stroke epilepsy, animal models, 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 seizure management. They’re doing a pilot study. 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 research on a topic that is not meaningful to the patient population, does no service to the field. So we are interested. We are creating writing surveys, which soon we will be spreading across different countries, trying to understand what it is that’s meaningful in terms of patient-reported outcomes to the patient, their caregivers, and family members. So, these are the kinds of questions that we need to tackle and create a framework so that we can have larger future studies that are more meaningful and really advance the field.
Source: CURE Epilepsy; https://cureepilepsy.org/event_type/webinar-epilepsy-and-neurodegenerative-disorders-the-relationship-between-stroke-and-seizures/
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