Join Dr.Marawar in a conversation with Dr. Chalongchai Phitsanuwong and Dr. Priyamvada Tatachar as they discuss the article, "Add-on ketogenic diet versus antiseizure medications alone in children with developmental and epileptic encephalopathies: a prospective comparative cohort study" and its accompanying Epilepsy Currents commentary "Drugs, Diets, and DEEs: A Comparative Review of Medical and Dietary Treatments in Developmental and Epileptic Encephalopathies". Click here to read the article. This podcast was sponsored by UCB. We'd like to acknowledge Epilepsy Currents podcast editor Dr. Adriana Bermeo-Ovalle, contributing editor Dr. Rohit Marawar, and the team at Sage. This episode covers a 2025 Frontiers in Neurology study by Hu et al. and its accompanying Epilepsy Currents commentary on ketogenic diet therapy for developmental and epileptic encephalopathies (DEEs). Host Dr. Rohit Marawar speaks with Dr. Chalongchai Phitsanuwong and Dr. Priyamvada Tatachar about the study's findings that add-on ketogenic diet nearly doubled seizure-freedom rates versus medication adjustment alone, and produced meaningfully better developmental/cognitive outcomes. They discuss the rationale for earlier diet initiation, practical implementation (patient evaluation, dietician-led clinics, monitoring), manageable side effects, the search for response biomarkers, referral pathways for general neurologists, and the future of DEE treatment moving toward genetically targeted therapies alongside continued diet use. Key takeaways: 1. Ketogenic diet outperformed medication adjustment alone: ~50% seizure response rate vs. ~29%, and ~20% seizure-free vs. ~10% (RR 1.73 for response, RR 1.9 for seizure freedom), consistent with prior literature (40-60% response, 10-30% freedom in DEEs). 2. Developmental gains, not just seizure control, may be the more striking finding: 36% vs. 5% showed developmental improvement on formal assessment, occurring even without medication changes, suggesting the diet has an intrinsic neuroprotective effect independent of seizure reduction. 3. Both experts argue for earlier initiation of ketogenic diet, especially in syndromes like epilepsy with myoclonic-atonic seizures (Doose syndrome, 79% response rate) and infantile epileptic spasms, rather than reserving it as a last resort after drug resistance and developmental regression are already established. 4. Side effects (mostly GI, constipation, "keto flu") are generally mild and manageable with proper monitoring (renal, bone health, lipids, micronutrients), and only ~3% discontinued therapy in the study; dedicated multidisciplinary keto clinics significantly improve feasibility and adherence. 5. No validated biomarker yet predicts individual response to the diet (early signals around acetylcarnitine levels), but resources exist for clinicians to start a program, including the Charlie Foundation, Matthew's Friends Foundation, the International Neurological Ketogenic Diet Society, and ILAE regional clinic listings. Dr. Rohit Marawar (Host): Imagine a child whose first year of life is measured not in milestones, but in seizures, dozens a day, while medication after medication is tried and falls short, and development quietly regresses. For children with developmental and epileptic encephalopathies, this is an all too common story. But what if one of our oldest therapies, a carefully formulated diet, could change not just the seizures, but the trajectory of a child's development? Welcome to the Epilepsy Currents podcast, the podcast for Epilepsy Currents Journal, exploring the latest research and expert commentaries from the world of epilepsy. UCB is the proud sponsor of this episode, Episode Number 12 of Epilepsy Currents podcast. I'm your host and associate editor for the podcast, Rohit Marawar. Today, we are discussing a prospective comparative cohort study by Hu and colleagues, published in Frontiers in Neurology in 2025, and the accompanying Epilepsy Currents commentary, Drugs, Diets, and DEEs to help us unpack what this means for clinical practice. We are joined by two expert voices in pediatric epilepsy. First is Dr. Chalongchai Phitsanuwong, author of the commentary. Dr. Phitsanuwong is a pediatric epileptologist with a focus on ketogenic diet therapy, practicing at Bumrungrad International Hospital in Bangkok, Thailand. Welcome, Dr. Phitsanuwong. Chalongchai Phitsanuwong, MD: Hello and good evening. Thank you very much for having me today. Host: And then, we are also joined by Dr. Priyamvada Tatachar, a pediatric epileptologist based in Chicago with a special interest in tuberous sclerosis and who also contributed to the commentary. Welcome, Dr. Tatachar. Priyamvada Tatachar, MBBS, MD: Good morning from Chicago, and thank you for having me on this podcast. Host: Great to have you both with us. Let's dive in. Dr. Phitsanuwong, I'm going to start with you. To set the stage for our audience, what exactly are developmental and epileptic encephalopathies, sometimes abbreviated as DEEs, and how often are they likely to be drug resistant? Chalongchai Phitsanuwong, MD: Thank you very much, Dr. Marawar. So, developmental and epileptic encephalopathies, or DEEs, represent some of the most severe forms of epilepsy. It's characterized by frequent seizures and abundant epileptiform activity on the EEG. It is commonly associated with developmental slowing and/or regression, like you said. The current consensus is that both the underlying etiology and the seizures or epileptiform discharges contribute directly to this developmental stagnation or regression. DEEs carry an exceptionally high prevalence of becoming drug-resistant epilepsy, reaching up to 70% in some cohorts, by comparison to the typical 1/3 we see in general epilepsy population. So, more than double the numbers. Host: Dr. Tatachar, from a frontline clinical standpoint, what does the day-to-day burden of a drug-resistant DEE looks like for a child and their family, and where do current medication strategies most often fall short? Priyamvada Tatachar, MBBS, MD: I think the word overwhelming comes to mind when families face the diagnosis of developmental and epileptic encephalopathies. For most patients and parents, the initial diagnosis is basically an uncharted territory that comes with a lot of fear, uncertainty, financial and social burdens, and the day-to-day challenges of caring for a child with significant medical, social, and developmental needs. It's a very daunting situation for them. Now, the current medical management focuses on the perspective of seizure control with several drugs added either alone or in combination for this reason. And as Dr. Phitsanuwong said, DEEs are particularly drug resistant. And based on the child's underlying diagnosis, additional challenges also need to be addressed for these families. Host: Dr. Phitsanuwong, the Hu, et al study, which you wrote the commentary for, found around a 50% seizure response rate with add-on ketogenic diet versus around 29% with anti-seizure medication adjustment alone, and a seizure-free rate of around 20% with diet versus around 10% with ASMs alone, both of which were deemed statistically significant. Now, how meaningful is a difference of that size to you, and how does it compare with what prior studies have shown? Chalongchai Phitsanuwong, MD: I think the result of this study is a highly meaningful context. Seizures in DEEs, like Dr. Tatachar said, are generally very difficult to control and have a high probability, of becoming drug resistant. In this prospective controlled trial, Hu and colleagues evaluated the patient with DEE who was still having seizure despite trying on an average of three anti-seizure medications already. And they found that adding ketogenic diet led to a significant higher seizure response rate. In the study, they defined as more than 50% seizure reduction, and they got the relative risk of 1.73. But what really stands out is the six-month seizure freedom rate from that. The dietary therapy group was nearly twice as likely to achieve the complete seizure freedom compared to continued medication alone, with relative risk of 1.9, so almost double. And this finding also aligned beautifully with the historical retrospective and prospective data that we have, where we typically see the seizure response rate around 40-60% in patients with DEE alongside around 10-30% complete seizure freedom rate. So, I think that it carries quite a meaningful result. Host: Great. Continuing with you, Dr. Phitsanuwong. So beyond seizure counts, the study also reported better EEG improvement and developmental gains in the diet group, 36% versus around 5% on formal assessment. Now, why is that developmental signal so important in this population, and how much weight should we give it? Chalongchai Phitsanuwong, MD: This is very important question because this highlights a critical paradigm shift in how we approach the treatment of DEEs currently. Because DEEs are commonly associated with developmental stagnation and regression that can also worsen over time, our therapeutic success cannot be measured solely just by the seizure control or seizure count. We should also focus equally on the neurodevelopmental and cognitive outcomes. While many anti-seizure medication, they are good, they can effectively reduce seizures. They frequently carry a heavy cognitive burden causing sedation, psychomotor slowing, impaired concentration, particularly in the setting of polypharmacy, which quite common in the patient with DEEs. Ketogenic diet therapy, on the other hand, offers a distinct advantage on this point. Multiple studies has shown that it can actively promote cognitive and developmental improvement, particularly in alertness, attention, and global cognitive abilities. Interestingly, there's one