Epilepsy Currents
Epilepsy Currents Podcasts will bring you all the features you know and love about the journal in an innovative format you can take with you wherever you go. The primary content of Epilepsy Currents consists of commentaries written by our expert editorial board on recent high-impact research papers in Epilepsy. Each podcast episode will highlight one of these recent publications and the accompanying commentary. High-yield topics of interest to our engaged epilepsy community will be presented and discussed by one of our contributing editors and the original authors to give you an in-depth, rigorous, and personal view of current topics in epilepsy and the people behind them. Topics will include both clinical and basic sciences, emphasizing bringing our larger community together around the mission we share: To advance research, education, and practice for all professionals working in epilepsy.
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Epilepsy Currents - Episode 5 - "More Than Meets the Eye: Human Versus Computer in the Neuroimaging of Temporal Lobe Epilepsy"
03/29/2024
Epilepsy Currents - Episode 5 - "More Than Meets the Eye: Human Versus Computer in the Neuroimaging of Temporal Lobe Epilepsy"
Join Dr. Bermeo in a conversation with Dr. Ezequiel Gleichgerrcht, Dr. Erik Kaestner, and Dr. Peter Widdess Walsh, as they discuss the article, "More Than Meets the Eye: Human Versus Computer in the Neuroimaging of Temporal Lobe Epilepsy". Click to read the article. This podcast was sponsored by the . We’d also like to acknowledge contributing editor Dr. Rohit Marawar, and the team at Sage Publishing. Summary This fantastic Epilepsy Currents podcast episode delves into a groundbreaking study on the application of artificial intelligence (AI) in differentiating temporal lobe epilepsy from Alzheimer's disease and healthy controls using MRI-based deep learning. The study, co-authored by Dr. Ezequiel Gleichgerrcht and Dr. Erik Kaestner, demonstrated AI's potential to significantly improve the accuracy of neuroimaging analysis in epilepsy. The commentary by Dr. Peter Widdess-Walsh provided a critical examination of these findings, highlighting the practical implications for clinical practice and the limitations of current methodologies. The discussion framed AI not only as a tool for enhancing diagnostic accuracy but also as a means to uncover subtle neurobiological differences between diseases, potentially leading to more personalized treatment approaches. Key Takeaways High Diagnostic Accuracy with AI: The study highlighted showed that AI, specifically convolutional neural networks (CNNs), could differentiate between temporal lobe epilepsy, Alzheimer's disease, and healthy controls with high accuracy. This demonstrates AI's capability to identify nuanced patterns in neuroimaging that may not be visible to the human eye. AI Identifies Subtle Neurological Differences: The inclusion of Alzheimer's disease as a comparative group in the study was strategic to determine if the AI was recognizing temporal lobe epilepsy based on hippocampal atrophy alone or other disease-specific patterns. The findings suggest that AI can discern epilepsy-related patterns beyond the typical markers, indicating a profound potential for AI in understanding complex neurological conditions. Impact on Clinical Practice: Dr. Widdess-Walsh's commentary underscores the importance of these findings for clinical practice. AI's superior detection rate compared to human analysis (90% versus 47%) suggests that AI could significantly augment clinicians' ability to diagnose temporal lobe epilepsy, potentially leading to earlier and more accurate interventions. Limitations and Ethical Considerations: Despite AI's impressive capabilities, the podcast discussion acknowledges limitations, including the current inability of AI systems to interpret scans holistically, consider clinical context, or replace human decision-making. These factors highlight the need for AI to be used as an adjunct tool in clinical practice, enhancing rather than replacing the expertise of healthcare professionals. Future Directions and Challenges: The episode concludes with reflections on the broader implications of AI in neurology, from predicting surgery outcomes to possibly revolutionizing epilepsy care. However, challenges such as external validation, regulatory approval, and integration into clinical workflows must be addressed to fully realize AI's potential in epilepsy diagnosis and treatment. Transcript Adriana Bermeo, MD (Host): Hello and welcome to episode five of Epilepsy Currents podcast. Today, we will be talking about the use of artificial intelligence and machine learning in the study of temporal lobe epilepsy. I am your host, Adriana Bermeo. I am the senior podcast editor for Epilepsy Currents, the official journal of the American Epilepsy Society. Today, I am joined by a team of experts in this very exciting neurodiagnostic arena. I want to first welcome contributing editor, Dr. Peter Widdess-Walsh, who wrote the commentary "More Than Meets the Eye: Human vs. Computer Neuroimaging of Temporal Lobe Epilepsy." This commentary was published on December 2023 issue of Epilepsy Currents. Dr. Widdess-Walsh is a consultant neurologist and Clinical Associate Professor at Beaumont Hospital in Dublin, Ireland. Peter, welcome to Epilepsy Currents podcast. podcast. Peter Widdess-Walsh, MD: Thank you very much, Adriana. I'm delighted to be here. Host: Thank you for being here. It is also my pleasure to welcome Dr. Ezequiel Zeke Gleichgerrcht, who authored the work that inspired this commentary titled, "MRI Based Deep Learning Can Discriminate Between Temporal Lobe Epilepsy, Alzheimer's Disease, and Healthy Controls. Their paper was published in Nature Communications Medicine in 2023. Dr. Gleichgerrcht is an Assistant Professor of Neurology at Emory University. Zeke, welcome. Ezequiel Gleichgerrcht, MD: Thank you. Thanks for having me. Host: We are also joined by Dr. Erik Kaestner, co-author on the original paper and lead author on other related publications addressing the use of artificial intelligence in epilepsy. Dr. Kaestner is a postdoctoral scholar at University of California, San Diego. Erik, thanks for being with us today. Erik Kaestner, PhD: Thank you. Excited for the conversation. Host: Very good. I can tell you that artificial intelligence is one of the most requested topics when we ask our listeners and the epilepsy community. The challenges and opportunities presented by the use of AI in almost every aspect of our daily life, but particularly in healthcare, are intriguing, exciting, and potentially concerning to some. But before we start discussing AI, Peter, can you share with our listeners what is the added value of expanded neuroradiology in the care of patients with epilepsy? Peter Widdess-Walsh, MD: Thanks, Adriana. And thank you for highlighting this very interesting and topical article for the podcast. And many thanks to Dr. Gleichgerrcht and Dr. Kaestner for being here with us. We know that MRI is a key tool in finding the underlying cause of focal epilepsy. However, up to 30% of MRIs are non-lesional. That is, there is no visible lesion responsible for the patient's epilepsy. We can sometimes lower this non-lesional percentage by using additional MRI techniques such as volumetry or various additional sequences or higher strength magnets. But these are not universally available or have limitations, so there's a gap there. We know that there is a focal epileptogenic network, but we cannot see it. And it is partly due to limitations of MRI technology, which are improving all the time, but it's partly due to limitations of what we can see visually with the human eye. There are also human error rates in analyzing MRI, even with skilled radiologists known as perceptual errors. A shrunken, bright hippocampus is easier to see than subtle alterations in grey matter volumes. Particularly in surgically remediable epilepsies, finding a lesion or visualizing the epileptic network can make a huge difference in a better patient outcome after surgery. And even in non-surgical patients, it's very reassuring to have an imaging correlate of the epilepsy that you know is clinically present. I'm not an AI expert and I wrote the commentary from the perspective of an epileptologist in clinical practice like many of our listeners. So, it was fascinating to learn more about AI and how it might fit into our daily practice in this area. The authors used the term computer vision in this article, and I'm excited to learn more about how computer vision can help us in the diagnosis of epilepsy. Host: Thank you very much. We are certainly excited to see how we can advance our field further than what we are practicing at the moment. Zeke, could you paint the picture as for how is AI revolutionizing the field of radiology and particularly when it comes to neuroimaging analysis? Ezequiel Gleichgerrcht, MD: Yeah, absolutely. And I think we start acknowledging that AI is becoming this true transformative force in medicine. Like you said, neuroimaging is by no means the exception. So for instance, if we think about AI and how it gives us frameworks to analyze huge amounts of imaging data, the pace and precision with which it can achieve it is unattainable by humans alone, right? Humans not using this computer vision that Peter was mentioning. So, let's talk about neuroimaging specifically. AI algorithms can sift through MRI, CT scans, and, almost do a first pass at detecting abnormalities from brain tumors, there's applications for aneurysms, areas affected by stroke, you name it. Of course, our interest is in epilepsy, but we know how crucial early and accurate detection of some of these findings can be. So, you know, when trying to answer this question, how is it revolutionizing the field of radiology? I think it's really about how the accurate detection of these findings can be instrumental in patient care. So, AI applied to neuroimaging can help us mostly scale detection of brain diseases and have tremendous impact on outcomes. But it's not just about detection of disease, right? AI now can support decisions about care tailoring or personalization of patient care, because if you can combine neuroimaging and health data, now you can offer insights that lead to more tailored strategies. For example, in other studies, we have shown that using AI, we can predict who becomes seizure free after epilepsy surgery based exclusively on preoperative imaging. And we found accuracies that are 30% points higher than what humans achieve just based on their combination of health data alone. You know, when I think about the revolution of AI, it's also paving the way for prediction or predictive analysis, things like forecasting disease progression or identifying when seizures will happen, for example, for a given patient. So, it's certainly a very exciting time for AI and neuroimaging and epilepsy. Host: Wow, that's a lot of changes expected for the future in the way we practice. Erik, I want to bring it to you for those of us who are not tech wizards. Can you break down what this idea of convolutional neural network or CNN, what it is and how it could transform the way we interpret, particularly neuroimaging and MRI scans? Erik Kaestner, PhD: So at its heart, a convolutional neural network is a way to learn patterns and data. And so for this particular project, we gave it a task. We said, "Can you differentiate patients with temporal lobe epilepsy from patients with Alzheimer's disease from healthy controls?" And we provided T1 images of the brain to do this. And so, In a lot of ways, it's very similar to what a neuroradiologist is doing. You present a neuroradiologist with an image of the brain and you ask for some sort of call on what they're seeing. So to understand what the neuroradiologist is doing, I'm going to have to defer to my colleagues in neuroscience. But it's a little more straightforward for the CNN. So, a CNN is made up of a series of layers, and each layer basically performs a small set of computations. And so, the first layer, which is given access to the image of the brain, takes little pieces of the image, performs its calculations, passes that image on to the next layer, it performs its little calculations, passes that on to the next layer. And the number of layers is dependent on the person building it, so you decide how many layers there are. And eventually, all of this data arrives at the final layer, which makes a decision. It says, "I think this is a patient with TLE," "I think this is a patient with Alzheimer's," or "I think this is a healthy control." and so as for how this can transform how we interpret MRI scans, I've actually discovered over the last year, that this is an extremely robust debate that's kind of ongoing in the field. Because like I mentioned, there's a lot of similarities in the tasks that neuroradiologists are being asked to do and what we can ask a convolutional neural network to do. And so, I was giving a talk recently and someone came up afterwards. A clinician came up afterwards and said, "Well, why would I trust this? You know, I have no idea what these numbers mean or where they're coming from or what the model's doing," which I think is a very fair question. Another person on the panel gave a good answer, which I'll crib from a little bit, which was, "Well, when you go to the doctor, can you really see what the doctor's brain is doing before they give you kind of their advice?" And so, I think this is a great way to think about what these networks, what these convolutional neural networks need to produce in order to gain the trust of the clinicians and of the patients. And so, in kind of a bedrock level, there's the behavior. You know, does the model get it right? Can we kind of trust it to give us the right answer over many patients? Then beyond that, we also need to think about how sure the model is. What information is it using? Is it using the proper information that we as clinicians and researchers have wanted to use? And also, we need to improve the outputs to a way that is interpretable by the human. Host: Thank you very much. We will certainly discuss a little bit about how this difference is so remarkable and how can we trust it better. But I am curious to know why did your team decide to choose these particular control groups? What is similar or different between the Alzheimer's patients, and the relationship to healthy subjects? Dr. Gleichgerrcht, I'm curious, how did you decide to use these groups? Ezequiel Gleichgerrcht, MD: Yeah. Thanks for the question because we thought about it a lot. And I'd say the rationale for having an Alzheimer's disease group they are competing against the TLE and the healthy controls for the machine to classify was at least twofold. On the one hand, we have literature, I would say, for the past two decades or so, showing that patients with temporal lobe epilepsy, at least at the group level, have patterns of atrophy that are widespread, right? So, it's not that we just see atrophy in the hippocampus or even in the temporal lobes. At the group level, the patterns of atrophy for TLE are sometimes extratemporal and even contralateral to the side of seizures. So, that was one side of the rationale. On the other hand, you know, in a prior paper, I believe it was in 2021, we had already shown that AI could identify who had temporal lobe epilepsy solely from the clinical MRI. And we had that benchmark to ask ourselves this question, almost as the next natural step: Is the machine detecting TLE simply based on detecting hippocampal atrophy, or is it detecting widespread epilepsy-related patterns that the humans are not typically paying attention to? So, when we included Alzheimer's disease as a third group that offered this competing disorder with prominent hippocampal atrophy, right? That is the core of pathology in Alzheimer's disease, then we were trying to answer the question, is it, again, just the hippocampal atrophy driving the classification? And, again, hippocampal atrophy being pervasive in Alzheimer's disease, but also in so many TLE patients. And, I want to say that when we asked this question, the natural reaction was, "Well, we also have to make sure that the machine is not just detecting older versus younger brains." Because, of course, if it's detecting just age related patterns, of course, it's going to do a great job at distinguishing Alzheimer's disease from temporal lobe epilepsy, because the mean averages of those populations are so radically different. So, a lot of our method, and I invite the audience to go and read about this, was about removing the effect of age on the brain images before we entered those images into the machine to have it classify disease. We put a lot of thought into it. And I think we had a model that can be replicated for other diseases where you're training a machine to try and detect the disease independently of all these other confounding factors like age and patterns of atrophy. Host: So much to discern from all of these conditions that may have multiple targets in the brain. In order to go deeper a little bit into the technicalities of the study and in order to help our listeners read the paper and understand it, Erik, can you please unpack some of the jargon for our listeners? Could you explain terms like accuracy, precision, recall, the F1 score? What do they mean when someone reads the paper? How should they read these variables? Erik Kaestner, PhD: Yeah. So, kind of in the analogy I was using earlier of how does the model gain our trust, these are kind of the bedrock elements where we're just asking, "Can you do the task? Can you get it right?" And so for something like accuracy, you're just saying, "All right, patient by patient, control by control, overall, are you able to get these accurate to some degree?" And then, we can go a little deeper and look at each individual condition, and that's where something like F1 score comes in where we can start to say, "How are you performing on patients with TLE?" How are you performing on patients with Alzheimer's?" And so, F1 score basically combines two of the other measures you mentioned, precision and recall. And precision says when the model claims that someone is a patient with TLE, is it right often? You know, is it kind of just saying this is a patient with TLE to everyone, and so we can't really trust it? Or is it being more conservative and kind of giving you a high level of accuracy within that specific patient group? And then, you have something like recall. Recall says of the patients with TLE in the cohort, Were you able to identify a large proportion of them or not? And so often these two measures, you can maximize one, but it hurts you in the other. So if you just guess patient with TLE for every single image you come across, then your recall will be quite high, because you will identify every single patient with TLE, but your precision will be quite low because, basically, every time you say it's a patient with TLE, you're going one for three. And so, F1 score is very useful because it combines these two. And so if a model is cheating in some way, it'll kind of reveal it by showing, "Okay, I don't think it's actually being quite truthful with us essentially. I don't think it's being fair." And so, like I said, once you've kind of interrogated the model's behavior in this way and said, "Okay, it seems to be doing the task quite well, then you can go on to the next step and start to interrogate it in other ways." Host: I want to go to Peter. You know, in your commentary, you highlighted how the AI showed a success rate in detecting temporal lobe epilepsy of 90% compared to the human eyes, 47%, which is humbling. And I wonder what is your take on these AI outperforming the human eye. And how do you think AI assisted temporal lobe epilepsy detection will mean for our clinical practice? Peter Widdess-Walsh, MB: Adriana, that's a great question. I would emphasize that we have to be careful with AI tools as to what exactly this particular AI tool used in the study, it was the carefully selected unilateral temporal lobe epilepsy and their T1 weighted MRI images. Patients with distorting structural lesions such as tumors or malformations were excluded. Most of the scans visible to the human eye had mesial temporal sclerosis. So we see that the AI tool that the authors developed was quite a bit better at picking up these other cases that were not visible to the human eye. As I mentioned, there are limits to the human vision processing system, and we can only spontaneously analyze so many areas at once. I gave the example in the commentary of the invisible gorilla study, an experiment where an image of an angry gorilla was placed over the lung area of a chest CT, and then radiologists looking for lung nodules missed the gorilla image 83 percent of the time due to attentive and perceptual error. So, I think AI imaging tools can help us see what we cannot see and also reduce this...
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Epilepsy Currents - Episode 4 - "Dobbs vs Jackson - Epilepsy Reproductive Health and Abortion"
10/23/2023
Epilepsy Currents - Episode 4 - "Dobbs vs Jackson - Epilepsy Reproductive Health and Abortion"
Join Dr. Bermeo in a conversation with Dr. Page Pennell and Dr. Alison Pack as they discuss the article, "Dobbs Versus Jackson: Epilepsy, Reproductive Health, and Abortion". Click to read the article. This podcast was sponsored by the . We’d also like to acknowledge contributing editor Dr. Rohit Marawar, and the team at Sage Publishing. Summary: In this episode of the Epilepsy Currents podcast, Dr. Adriana Bermeo discusses the Supreme Court's decision on Dobbs v Jackson and its implications for people living with epilepsy. She is joined by Dr. Allison Pack, a professor of neurology at Columbia University, and Dr. Page Pennell, the chair of the Department of Neurology at the University of Pittsburgh School of Medicine. They discuss the key points and historical significance of the Roe v. Wade and Dobbs v Jackson rulings, the current state-by-state variation of abortion access in the United States, and the impact on women and people of childbearing age living with epilepsy. They also address the importance of contraception, the risks of anti-seizure medications during pregnancy, and the need for evidence-based care and advocacy for patients. Resources such as the Guttmacher Institute and the National Abortion Federation Hotline are mentioned for further information and support. 5 Key Takeaways: 1. The Supreme Court's decision on Dobbs v Jackson has significant consequences for persons living with epilepsy and their access to abortion. 2. The current state-by-state variation of abortion access in the United States is complex and can range from very restrictive to most protective. 3. Planned pregnancies are crucial for individuals with epilepsy to optimize outcomes for both the individual and the developing fetus. 4. Effective contraception is important for individuals with epilepsy, and options such as long-acting reversible contraception (IUDs) and birth control pills should be considered. 5. Neurologists and epilepsy specialists should advocate for their patients' rights and women's rights, ensuring that medical decisions are made by qualified practitioners based on evidence and with respect for the individual patient. Resources such as the Guttmacher Institute and the National Abortion Federation Hotline can provide information and support. Transcript Dr. Adriana Bermeo (00:05): Hello and welcome to episode four of Epilepsy Currents podcast. I am your host, Adriana Bermeo. I am the senior podcast editor for Epilepsy Currents, the official journal of the American Epilepsy Society. It is my pleasure to welcome today's guest to talk about the Supreme Court's decision on Dobbs v Jackson and its consequences for persons living with epilepsy. We have two very special guests to help us understand the implications of this ruling on reproductive health and access to abortion for people living with epilepsy of childbearing potential. First, I want to welcome Dr. Pack, senior author of a commentary titled Dobbs versus Jackson Epilepsy Reproductive Health and Abortion, published online first in the May, 2023 issue of Epilepsy Currents. Dr. Pack is a professor of neurology at Columbia University. She's the Chief division of Epilepsy and sleep at New York Presbyterian, Columbia University Medical Center. I also want to especially welcome Dr. Page Pennell, who's the Henry B. Hickman Professor of Neurology and chair of the Department of Neurology at the University of Pittsburgh School of Medicine. Dr. Pennell is a global expert on the management of pregnancy-related issues in epilepsy, and she's also a past president of the American Epilepsy Society. Dr. Pack, let me start with you. Most of our listeners are familiar with Roe versus Wade and Dobbs versus Jackson Supreme Court rulings, but could you give us a quick refresher on the key points and historical significance of these two landmark cases? Dr. Allison Pack (01:43): Thank you very much, Adriana, and it's a pleasure to be here today and I want to thank the American Epilepsy Society for supporting this discussion as we go through our discussion today. Today we will be referring to persons with epilepsy of childbearing potential. Please recognize that we are aware that not all individuals who seek pregnancy or become pregnant identify as a woman. So I'm going to go through right now the court rulings ruling Roe v. Wade was enacted in 1973. In this ruling, the court ruled that the Constitution of the United States generally protected a right to abortion. This ruling was reaffirmed in 1992 in the ruling Planned Parenthood of Southeastern Pennsylvania versus Casey. Dobbs v Jackson was enacted on June 24th, 2022. With this ruling, the Constitution does not confer a right to abortion. Essentially, Roe v. Wade and Planned Parenthood of Southeastern Pennsylvania versus Casey were overturned. The authority to regulate abortion went back to the state and the constitutional right to abortion was eliminated. Dr. Adriana Bermeo (03:08): Thanks, Dr. Pack, you were mentioning how things went back to the state, and as we know, the legal landscape of these rulings then are evolving. Acknowledging this is a moving target, could you please help us understand the current state-by-state variation of abortion access in the United States, and what does this mean for the physicians practicing in the different states? Dr. Allison Pack (03:37): Well, I have to say understanding the state-by-state variations is quite complex. I would draw all of your attention to the Guttmacher Institute, and there's a very good website whereby you can see the map of the United States and the outline of the various regulations or the various degrees of restriction. And these vary from most restrictive occurring in over 15 states whereby abortion is banned at 12 weeks and later. There are very restrictive, which bans abortion at 12 weeks and later. Some restrictions starting at the third trimester. Protective, it's banned at fetal viability between 24 and 26 weeks, and very protective whereby it's banned at fetal viability. And then there's some other regulations that give more protections than those states that are protective and then most protective whereby there is no restriction based on gestational age. As I mentioned earlier, the most restrictive; this includes, for example, Kentucky, Texas, very restrictive, North Carolina, Georgia, some restrictions, Virginia protective, Illinois, very protective New York, and then most protective, there's only one, and that is the state of Oregon. So it is important to understand that there are varying degrees of restrictions across the United States in these different categories. And as I mentioned earlier, I would draw your attention to the website from the Guttmacher Institute, which really is very helpful for you to understand what the restrictions are or not in the state that you live. Dr. Adriana Bermeo (05:29): Thank you very much, Dr. Pennell. Can I turn it to you? Can you please help us understand how these rulings affect particularly women and person of childbearing age or childbearing potential living with epilepsy? Dr. Page Pennel (05:42): Yes. Thank you also for inviting me for this very important podcast and to sit alongside Dr. Pack who is such an expert in this area. So unplanned pregnancies in the general population are known to have a higher complication rate, but especially in persons with epilepsy, it's incredibly important to have a Planned Pregnancy and for the woman to have the best seizure control possible for her with the medication regimen and vitamin regimen that will provide the opportunity for the safety of the developing fetus. Pregnancy also carries a risk to women directly and with persons with epilepsy there are reports of elevated maternal mortality. Studies in the UK have actually shown that the elevated rates of death in persons with epilepsy are due to SUDEP or sudden unexpected death in epilepsy. So if a woman with epilepsy goes into a pregnancy unplanned and also with a high seizure burden, the chances that pregnancy will be unsafe for her and her developing fetus are much higher. And if she doesn't have the opportunity to make a decision with her clinician about what to do after that time, it can be particularly devastating. Dr. Adriana Bermeo (07:05): Dr. Pack, your commentary in Epilepsy Currents really makes the point that neurologists ,epileptologists and the organizations who represent their interests should care and take action in protecting patients' rights and women's rights. Can you please expand on this idea? Why should neurologists and epilepsy specialists care? Dr. Allison Pack (07:29): Well as individuals or practitioners who take care of persons with epilepsy of childbearing potential, we want to provide the optimal environment both for seizure control and pregnancy outcomes for the individual as well as the developing fetus. It is as the American Epilepsy Society has stated, critically important that medical decisions are made by qualified practitioners and that this be done based on evidence with respect for the individual patient. Therefore, the decisions made for the outcome or the health of the individual should be up to the practitioner and patient themselves or the person with epilepsy. Many of our anti-seizure medications may increase the risk of unplanned pregnancy. This is important. It's important that the individual has an unplanned pregnancy and are in a state whereby there are extreme restrictions. Again, as I mentioned, the decision should be left up to the provider and the person with epilepsy. As well, many anti-seizure medications, notably valproic acid, can increase the risk of adverse or negative pregnancy outcomes. As practitioners, we need to be aware of and advocate for the patients that should this occur to these individuals, that they do have options available to them to optimize their health as well as the outcome of the developing fetus. Dr. Adriana Bermeo (09:10): Thank you so much for that. That definitely brings the point that we're all part of the caregiving team of our patient and their family. Dr. Pennell, these rulings also bring up attention to contraception. Could you please tell us about the most contraceptive options available for persons with epilepsy of childbearing potential and how widespread the use of these methods are and how effective they are and how are they different in people with epilepsy than in other individuals? Dr. Page Pennel (09:44): Yeah, certainly, as Dr. Pack pointed out it is very important that we discuss actually as the person caring for our patients with epilepsy, that we have these discussions with them about how important planned pregnancies are, which begins with effective contraception. Some studies found that up to 65% of women with epilepsy had reported at least one unplanned pregnancy. So this is certainly a very important and prevalent consideration. The most effective contraception we like to encourage is under the band of long-acting reversible contraception, which are the various IUDs. This could be a copper IUD or it could be an IUD that has progestin as part of its mechanism of action. But the progestin just works in the endometrial cavity and does not depend upon blood levels for its effectiveness. So therefore, even if a woman is on an enzyme-inducing anti-seizure medication, the IUD still has a very high effectiveness rate of over 99%. (10:50): However, thanks to the collaborations we've had over the years with our wonderful colleagues and contraceptive gynecology made me very much aware that there are so many factors that go into decision-making. And many women in the US in particular are not open to the idea of an IUD. So our message should not be that you need to use an IUD or else nothing that's definitely should not be our message. Combined oral contraceptive pills, birth control pills are still the most commonly used form of contraception and will be very commonly used in our patients as well. So we do need to know about the interactions, but if they're on an enzyme-inducing, anti-seizure medication, we need to make them aware of that, encourage backup barrier methods, et cetera. And when we think about the enzyme-inducing medications, we also need to be aware it's not just an old-generation versus new-generation story. (11:48): A lot of our newer medications also can lower the hormone levels from these hormonal contraceptives. Some of those medications, some people may be surprised to know include for instance, cenobamate, rufinamide, clobazam. So we need to have the discussion if they are going to use a hormonal form of contraception such as birth control pills or the vaginal ring to just let them know that they should also consider a backup barrier method, but also give them information about the more effective types of contraception. We also like to encourage, there's a progestin implant, the brand named Nexplanon, which has a very high effectiveness rate for contraception, but again, that can be affected if they're on a strong enzyme inducer. So again, we need to consider the medications they're on in their contraceptive choices. Dr. Adriana Bermeo (12:46): Great. Dr. Pennell, I'm going to stay with you because following the conversation on contraceptions, we also know a lot from collaborative groups and teams that you've been part of that anti-seizure medications can pose some risks for pregnancy of children of adults living with epilepsy. Can you briefly remind us of the potential risk of congenital malformations and neurodevelopmental issues related to exposure to medications and how these risks are related to our conversation of access to abortion? Dr. Page Pennel (13:20): Yeah, certainly. Thank you. I do like to remind us, we can get discouraged about all the things we don't know in this field, but how far we have come because the conversation used to be that all anti-seizure medications are very teratogenic and have a high risk to the developing fetus. But now we do have a lot of information to provide evidence-based counseling and care that we do have some medications that have very low rates of major congenital malformation, also known as birth defects. And these rates are really similar to the general population. The medications that really stand out with the most abundant information supporting this are lamotrigine, levetiracetam and oxcarbazepine. But we also know other medications have very, very high rates of these major congenital malformations. And the one that has the greatest risk is valproic acid. We also now have information on some medications about the neurodevelopmental outcomes, and so that some medications have very low neurodevelopmental risk. (14:26): And with that we have lamotrigine and levetiracetam in that safe category. But then again, we have higher risk medications such as valproate. We now have increasing information about the concern on fetal neurodevelopment for topiramate. We also know that topiramate can lower the fetal growth and result in small-for-gestational age and also has a sort of medium rate of the malformations. So topiramate is becoming another medication that is starting to have greater restriction on it just placed in Europe and maybe coming out in the United States as well for use and persons of even reproductive potential. So it's so important to be able to get on the best medication regimen for that person and also at the right dose that will help to control their seizures the best possible. It's also important that they're taking folic acid well prior to conception. If all of those things aren't lined up, we know that the risk for the developing fetus as well as the mother is higher. And that's where if they're not in an ideal situation and not having access to making decisions about continuing the pregnancy is more devastating. Out of all the malformations, the one that certainly has such a high morbidity is neural tube defects. And so that is one in particular of the malformations that often will garner a conversation about the possibility of termination if the person is in a state, that is an option. Dr. Adriana Bermeo (16:12): Thank you for that answer as well. Dr. Pack, can you help us understand other specific issues or risks for people with epilepsy that neurologists and epileptologists should be mindful of when giving perinatal counseling, particularly when we consider genetic causes of epilepsy? Is there anything that you discuss with your patients, especially considering these new abortion rulings? Dr. Allison Pack (16:39): I think there's several issues here, and one of the things that's very important is something that Dr. Pennell touched upon earlier is that planned pregnancies are associated with better outcomes, and for individuals with epilepsy, planned pregnancies are important to optimize outcomes not only for the individual but for the developing fetus. As such, just to highlight a point that Dr. Pennell made earlier, it's important in that setting for the individual to be using effective contraception and recognize a nationwide healthcare claims database, finding that 63% of individuals with epilepsy either use no contraception or used ineffective contraception. So part of your perinatal counseling should be on the importance of planned pregnancies. There are certainly some genetic epilepsies and individuals who may have children at risk for this. That would be important within genetic counseling to have that genetic counseling done prior to pregnancy. So important points here: planned pregnancy, genetic counseling, keep in mind that that does pertain to a few individuals, not the vast majority of individuals with epilepsy. (18:02): And then the other piece that's important is that some of the malformations that Dr. Pennell spoke about earlier may not become evident until much later in the pregnancy. So for example, we routinely counsel that individuals get an anatomic ultrasound, which typically occurs between 16 and 20 weeks. If the individual who were pregnant with epilepsy were pregnant, were to find out that there was a malformation, the very restricted states ban abortion at 12 weeks or later. So for many of these individuals, this would be, if there a malformation was found at that anatomic ultrasound screening, this would be too late in those states. So just to summarize and go over again, it's important to emphasize that planned pregnancies will optimize the outcome both for the individual with epilepsy as well as for the developing fetus. Effective contraception is an important component of this. There are some genetic conditions whereby it would be important to have that information or have that genetic counseling prior to getting pregnant and recognize some malformations may not become evident until later in the pregnancy where in many states, abortion is not an option. Importantly, though, please understand as we go through this topic, that with planned pregnancies, with focusing on choosing optimal anti-seizure medications, as discussed by Dr. Pennell, most individuals do have normal healthy pregnancies. Dr. Adriana Bermeo (19:47): Dr. Pennell, are there any specific concerns related to minorities or people of color in regards to access to care, pregnancy planning, and access to abortion? Dr. Page Pennel (20:03): Thank you for that very important question. We know that a lot of things we're talking about when it comes to any medical care, we have to consider also how it affects our underrepresented minorities because there are differences as access to care and higher complication rates, and many of these situations just such as this one. So when you look at just access to abortion services alone, that a much higher percentage of minorities do receive abortions than are in the general population. There's a lot of reasons that come into this, whether it's...
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Epilepsy Currents – Episode 3 "Keto Is Not Just for Kids: A Randomized Trial of a Modified Atkins Diet for Adolescents and Adults With Anti-Seizure Medication Resistant Epilepsy"
06/20/2023
Epilepsy Currents – Episode 3 "Keto Is Not Just for Kids: A Randomized Trial of a Modified Atkins Diet for Adolescents and Adults With Anti-Seizure Medication Resistant Epilepsy"
Join Dr. Bermeo in a conversation with Dr. Mackenzie Cervenka and Dr. Manjari Tripathi as they discuss the article, " Keto is Not Just for Kids: A Randomized Trial of a Modified Atkins Diet for Adolescents and Adults With Anti-Seizure Medication Resistant Epilepsy ". Click to read the article. This podcast was sponsored by the . We’d also like to acknowledge contributing editor Dr. Rohit Marawar, and the team at Sage Publishing. Five Key Takeaways: Effectiveness of Modified Atkins Diet (MAD): The research conducted by Dr. Manjari Tripathi found that 26% of the people who supplemented their drug therapy with the MAD experienced a more than 50% reduction in seizure frequency compared to only 2.5% of people who used only drug therapy. Importantly, some patients even became seizure-free. Improved Quality of Life: Along with a significant decrease in seizures, patients following the MAD also reported improved quality of life and behavior. Difference in Adherence Between Adolescents and Adults: The study found that adults were more likely to adhere to the diet than adolescents, possibly due to a combination of food preferences and possible differences in gut microbiota. Potential Long-Term Effects of Ketogenic Diets: While ketogenic diets can be effective in managing epilepsy, there are potential long-term side effects to consider, such as vitamin and mineral deficiencies, bone loss, risk of nephrolithiasis (kidney stones), and hyperlipidemia (high levels of lipids in the blood), which may lead to cardiovascular and cerebrovascular diseases. Approach to Weaning off the Diet: Dr. Mackenzie Cervenka suggests that weaning off the diet should be considered in a similar manner to removing anti-seizure medication. The decision should be made considering the side effects and the overall burden of the therapy on the patient. Abrupt discontinuation of the diet can result in an increase in seizures, hence the diet should be gradually reduced. Dr. Adriana Bermeo (): Hello, and welcome to episode three of Epilepsy Currents podcast. I am your host, Adriana Bermeo. I am the senior podcast editor for Epilepsy Currents, the official journal of the American Epilepsy Society. It is my pleasure to welcome today's guest to talk about the use of ketogenic diets in the treatment of refractory epilepsy in adolescents and adults. First, I want to welcome our contributing editor for epilepsy current, Dr. Mackenzie Cervenka, who wrote a commentary titled "Keto Is Not Just For Kids: a randomized trial of a modified Atkins diets for adolescents and adults with anti-seizure medication resistant epilepsy". This was published online first in the March, 2023 issue of Epilepsy Currents. Dr. Cervenka is Professor of Neurology at John Hopkins School of Medicine. She's the medical director of the Adult Epilepsy Diet Center and the Adult Epilepsy Monitoring Unit. She developed the John Hopkins Adult Epilepsy Dietary Center in 2010 and has treated nearly 450 adults with epilepsy using ketogenic diet. Dr.Cervenka, welcome to Epilepsy Currents podcast. Dr. Mackenzie Cervenka (): Thank you so much Dr. Bermeo for inviting me as a guest today at the Epilepsy Currents Podcast. Dr. Adriana Bermeo (): It's a pleasure to have you. I also want to specially welcome Dr. Manjari Tripathi, who is the senior author of the publication that inspired this commentary titled "Safety, efficacy, and Tolerability of Modified Atkins Diet in Persons with Drug-Resistant Epilepsy." This was published in Neurology in March of 2023. Dr. Tripathi is a professor of neurology and epilepsy at the All India Institute of Medical Sciences, where she serves as director of the Epilepsy, Behavioral Neurology, and Sleep Medicine Programs. Dr. Tripathi, it's a pleasure to have you. Dr. Manjari Tripathi (): Hi. Thank you. Great being here. Dr. Adriana Bermeo (): Dr. Cervenka, I want to start with you. Our listeners may or may not be familiar with the concept of ketogenic diets for the treatment of epilepsy in adults particularly, but they may not know that there are different options for treatment. Can you please give us an overview of the principles of these dietary treatments and tell us what options can we can offer to our patients Dr. Mackenzie Cervenka (): In our field? We refer to ketogenic diets for epilepsy actually as ketogenic diet therapies. And we do this to distinguish them from ketogenic diets that we typically hear about being used for weight loss or for other purposes, and that are not necessarily recommended or monitored by clinicians or treating teams. Technically, a ketogenic diet therapy is any dietary manipulation that can produce a state of nutritional ketosis, and that is a state where the body metabolizes fatty acids into ketone bodies. Those are beta hydroxybutyrate, acetoacetate, and acetone. There are a whole variety of ketogenic diet therapies, and these include what are called the classic or classical ketogenic diet. This was first described over one century ago. There are also modified versions of this classic ketogenic diet, specifically the Modified Atkins diet and a modified ketogenic diet. In addition to that, there is a low glycemic index diet or treatment, and that can also produce a state of ketosis, although it is not the primary goal of that particular diet, and any of these diets can be supplemented with medium chain triglyceride oil, and that is readily metabolized into ketone bodies. So that can be added to any of these other diets that I mentioned. Finally, these diets can also be combined with fasting, which also, encourages ketosis as well. Dr. Adriana Bermeo (): Thank you so much, Dr. Tripathi. Do different options fit different demographics? Particularly I’m curious of why did your team choose to try specifically the modified Atkins diet in adults and adolescents with refractory epilepsy as opposed to other options as Dr. Cervenka was describing? Dr. Manjari Tripathi (): So this is a very pertinent question. We need to give something which is acceptable, accessible, and affordable. Now, if you look at the traditional classic ketogenic diet, as Dr. Cervenka described it, it's a very restrictive diet, and it's rigid. It's rigid in terms that it restricts the calories and the fluids. It often requires weighing of food, at least in our center, the ketogenic diet requires the patient to be admitted for a washout and monitoring before the diet is started, whereas a modified Atkins diet does not restrict calories. However, it produces the same effect that is ketosis. So, it's more flexible, it's easier on the gut and the palate, and we know that adults and adolescence can be picky eaters and choosy. As you get older, you also get conditioned on the kind of foods that you eat. So in factoring all this, we decided that it'll be easier on our patients to have the modified Atkins diet, which is less rigid than the ketogenic diet. And hence we undertook the study with drug resistant epilepsy patients as compared to the classic ketogenic diet. Dr. Adriana Bermeo (): Dr. Cervenka, how well accepted do you find these dietary treatments for among patients when you start them on, but also among neurologists and epileptologists? What, what do you think are the greatest barriers right now for them to be used more broadly in the clinic? Dr. Mackenzie Cervenka (): I think it's interesting to look back at kind of the historical perspective of how the ketogenic diet evolved over time, because when it was initially introduced back in the 1920s, it was the only real treatment for epilepsy that was being looked at the time, and it was very popular then. It was being used for children, it was being used for adolescents and adults, and then anti-seizure medications became more readily available around the 1930s, and it really stopped being used for, for many decades, and it sort of reemerged in the late 1900s. However, when it reemerged, it was primarily in children. And so when you ask the question, how accepted is it as a treatment for epilepsy, I think it varies tremendously because I think now if you look in curricula for pediatric neurology residents, you'll see that ketogenic diet therapy is listed in that curriculum for pediatric neurology residents for a treatment of pediatric epilepsy. Dr. Mackenzie Cervenka (): However, that may not necessarily be the case for adult epilepsy. And when I was in training and when I was learning about this I learned about ketogenic diet therapies from my pediatric epilepsy colleagues and wondered why it was not necessarily being used in adults and asked that question of my pediatric and adult colleagues and really did not have a good understanding of why that was the case. So I kind of delved into that a little bit deeper and discovered that there were plenty of epilepsy syndromes and seizure disorders that, that we knew the ketogenic diet was very effective for in children that adults also had. However, they were not necessarily being offered this therapy. And so really it has not been as well accepted in the adult population as it has been in children up until really the last couple of decades, to be honest. Dr. Mackenzie Cervenka (): Now, something else happened that was very interesting, really around2017, and I refer to it as the keto craze, where the ketogenic diet suddenly became very popular for weight loss or different variations on the theme of the ketogenic diet. And I think this brought the concept of a ketogenic diet into the awareness of the general population such that there have even been individuals with epilepsy who started a diet for weight loss and then discovered that it helped with their seizures and began to investigate this and realized, oh, yes, it's been used to treat epilepsy for over a hundred years. So it's, it's a really interesting evolution. This has actually helped patients because those who have been treated with ketogenic diets have a lot more options with regards to foods that are available now because of the commercial availability of some of these foods being used for the purpose of weight loss. So I, do think that that has, has certainly helped with regards to barriers for the use more broadly in clinic the greatest barriers particularly for adults are the lack of familiarity of adults, neurologists, clinicians with diet therapies. So they have this discomfort just because they don't understand the diets or how to go about counseling patients for following these ketogenic diet therapies. Lack of nutritionist or dietician supports who work specifically with adults and also lack of reimbursement for these services. That is a very, very big barrier, particularly in the United States. Dr. Adriana Bermeo (): Well, hopefully studies like the one we're discussing today will change some of those, you know, people getting more familiar and hopefully permeating all the way to finding more support and, different arenas. Dr. Tripathi, can you please give us an overview of the design and the results of this study you conducted among adolescents and adults with refractory epilepsy? Dr. Manjari Tripathi (): Absolutely. So, when we are actually offering services of a drug-resistant epilepsy clinic, we are left with a large number of people with epilepsy who have been on many medications, typically two or more, and they still continue to have seizure and they cannot be offered epilepsy surgery because they have not been candidates for the same due to lack of a lesion or discordance of data. So we, in this study, prospectively enrolled patients who had been having seizures and they were having as many as 27 seizures per month. So when we enrolled these patients, when we analyzed the data, we found that they had at least 27 seizures per month. So that's a very high seizure frequency, and we followed up these patients for six months after initiating the diet. The patients were randomized into two groups, one group receiving the modified Atkins diet along with the conventional anti-seizure medication, which was not changed during the therapy. Dr. Manjari Tripathi (): That means the patients were stabilized on anti-seizure medicines and they had a baseline seizure frequency before they were enrolled, and the other group continued to have their usual antiseizure medicines without the modified Atkins diet. Now, this diet is a medical diet, it needs monitoring, and our nutritionist and dietician was involved in monitoring these patients. But the assessment was done by a person other than us, and she was looking at the outcomes. We decided to take clinically meaningful outcomes, and in this case, of course, it'll be the reduction of seizures, which would be the primary outcome measure and secondary outcome measures would be change in behavior and quality of life. We also looked at their weight and their lipid profiles just to make sure that they weren't deranged by the end of the study. So basically it was a very well thought out and planned study and was undertaken after a lot of thinking to it as to what more can we offer our patients who are left without the option of surgery. Dr. Manjari Tripathi (): So we had, as I told you, 160 people with epilepsy, which were drug resistant, having at least 27 seizures a month when we saw the results. And they had been having this resistant epilepsy for 10 years or more. So they were really, those, prolonged resistant epilepsy patients, and one doesn't know what to do with them when they're coming. And we've been taught ketogenic diet is for children. So we thought, you know, if we can't offer them something, they get enrolled into the study. What we found when we looked at the results at the end of the study was that 26% of the people who had taken both the drug therapy with modified Atkins diet had more than 50% reduction of seizures compared to only a minuscule 2.5% of people who had received drug therapy alone without the diet. And actually four people in the diet group became free of seizures. Dr. Manjari Tripathi (): So you can imagine someone who's on four drugs or more having refractory epilepsy for 10 years or more, getting free of seizures. So four became seizure free. We found significant improvements in quality of life behavior. We did not find any per side effects. The diet was very well tolerated, and overall the patients felt a sense of improvement. However, a word of caution here, we were operating the trial during covid times, so we noted about a third of patients, 33% did not complete the study. However, we did an intention to treat analysis, which kind of overcomes the deficit of the dropouts, and most of them dropped out due to inability to follow up as a part of the COVID 19 pandemic. Some of them could not tolerate the diet, and some of them just dropped out because they felt it wasn't doing anything to them. So this was a limitation of the study, but I guess when we are doing studies which deal with something as a diet, this is bound to happen. So overall, it was a prospective randomized assessor blinded study, and it did pretty well for people who were refractory despite taking four or more medications. Dr. Adriana Bermeo (): It's an, amazing design and study and really, really encouraging results. We noticed that the adult group in your study did better than the adolescents in regards to outcomes. Do you have any ideas of what, what would that have happened? Dr. Manjari Tripathi (): Yeah, so at the end of six months in adolescence, about 36% of the patients who were on the diet had greater than 50% reduction, whereas in the adults it was 57%. Now, there could be several reasons for this, and I think the most important is that if anyone has dealt with this particular age bracket of adolescence, it's a difficult age. Generally, they're very picky about their food. They tend to like their carbs, they tend to binge on fast food, at least in India. The adolescents are typically into an American diet where they would want to have burgers and, you know, cola and, and chips. So, it's very difficult for us to consent them into the diet and any study cannot be done without consenting. So, one is of course that, and the second is, I guess though they were monitored for their compliance and their ketosis. There could be certain gut microbiome differences. We know that the diet works while acting at the neurotransmitters, whether it's promoting the inhibitory neurotransmitters, antioxidant mechanisms, anti-inflammatory mechanisms. It also works through there is a gut microbiome hypothesis for the mechanism of action of the diet. So there could be several other reasons, r this effect that we saw. Dr. Adriana Bermeo (): I am convinced just to hear about the adherence in adolescence. I have a pre-teen at home. Dr. Cervenka. Can you talk to us a little bit about what considerations do we have for adults particularly following ketogenic diet therapies in regards to maybe long-term side effects or anything that they should be particularly wary of? Is there a specific time to them or liberalize the diet or discontinue them? And any practical points for, for our audience in regards adults in this therapy? Dr. Mackenzie Cervenka (): I think it's really important to consider the differences between children and adults when you're considering how to manage the diet long-term. For instance, pediatric epilepsy syndromes may resolve in childhood, and many children are taken off of ketogenic diet therapies within a year or two of after starting them. Often they're taken off of their medicines, they're taken off of therapies, and we really don't have to think about these, what I call long, long side effects. I think particularly about individuals with glucose transporter type one deficiency syndrome, when I get concerned about long, long-term side effects because those are individuals that we believe are going to need to be on diet therapy long-term or perhaps lifelong. And some of those considerations include vitamin and mineral deficiencies. So, in particular zinc selenium, vitamin D carnitine deficiencies, we know that in children, even over the two years that they would typically be on a ketogenic diet therapy, you can see bone loss in those children. Dr. Mackenzie Cervenka (): Typically, once the diet is stopped that reverses itself. However, if you're thinking about an adult who over time is at risk for progressive bone loss, you may be concerned that over time that can accelerate with the ketogenic diet therapy and there's mounting evidence that that could indeed be the case. We also know that nephrolithiasis is a risk with ketogenic diet therapies both in children and adults. And so of course for the longer that you're on a diet, the longer that you're at risk for having that occur. And then there's a body of literature looking at hyperlipidemia and potential risks for cardiovascular and cerebrovascular disease. One of the physicians here at Johns Hopkins investigator Dr. Tanya McDonald is looking into this at Johns Hopkins. And then there are researchers worldwide who are act actively investigating this topic as well, because certainly we're treating epilepsy, but we also don't want to be causing other long-term side effects over the course of a patient's lifetime that they're going to have to be dealing with later. Dr. Mackenzie Cervenka (): So those are really the major ones that we are concerned about. Now with regards to weaning the diet in an adult, my particular approach is to think of it similarly to thinking of anti-seizure medications. So if there is an adult at an appropriate time for removing the anti-seizure medication, I would speak to them about removing the anti-seizure medicine, removing the diet, which of those things they would like to do first, we would look at the side effects and we would look at the overall burden of that therapy in deciding which of them we...
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Epilepsy Currents – Episode 2 “SUDEP Risk Counseling: What We Don’t Do in the Shadows”
03/24/2023
Epilepsy Currents – Episode 2 “SUDEP Risk Counseling: What We Don’t Do in the Shadows”
Join Dr. Bermeo in a conversation with Dr. Erik St Louis and Dr. Eugen Trinka as they discuss the article, "SUDEP Risk Counseling: What We Don’t Do in the Shadows ". Click to read the article. This podcast was sponsored by the .
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Epilepsy Currents - Episode 1 “RNS—It Never Gets Old”
08/26/2022
Epilepsy Currents - Episode 1 “RNS—It Never Gets Old”
Join Dr. Bermeo in a conversation with Dr. Christopher Todd Anderson and Dr. Dileep Nair as they discuss the article, "RNS—It Never Gets Old". Click to read the article. This podcast was sponsored by the .
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Epilepsy Currents Podcast Introduction with Dr. Bermeo
04/26/2022
Epilepsy Currents Podcast Introduction with Dr. Bermeo
Join Dr. Bermeo in a conversation with our contributing editors and the original authors of the literature shaping the field of epilepsy. Epilepsy Currents Podcast will bring you all the features you know and love about the Journal in an innovative format you can take with you wherever you go.
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