Research Priorities and Clinical Insights in Lennox-Gastaut Syndrome

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EP: 1.Identifying Gaps in Lennox-Gastaut Syndrome Care Across the Lifespan

EP: 2.Collaborative Strategies to Enhance Care and Data Sharing in LGS

EP: 3.Enhancing Clinical Management of LGS Through Collaboration With Stakeholders

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EP: 4.Research Priorities and Clinical Insights in Lennox-Gastaut Syndrome

EP: 5.Enhancing Design of LGS Clinical Trials and Patient Care in Rare Epilepsies

EP: 6.2025 LGS Meeting Reflections and Engagement Opportunities in Research

Lennox-Gastaut syndrome (LGS) is a rare epilepsy syndrome that typically begins in childhood and is associated with frequent seizures, cognitive impairment, and long-term disability. Earlier this summer, the LGS Foundation hosted its 3rd biennial LGS Research Meeting of the Minds, held July 21–22, 2025, bringing together caregivers, researchers, health care providers, scientists, advocacy representatives, and industry partners to discuss clinically relevant strategies to advance evidence-based LGS care across the lifespan.

In collaboration with LGS Foundation, NeurologyLive^® held a roundtable discussion with 2 pediatric experts who attended and participated in the meeting. Throughout the panel discussion, the duo covered topics like major gaps in LGS care, fostering connections among diverse stakeholders, and shaping strategies to guide future research. The guests featured in this panel included Scott Perry, MD, head of neurosciences at the Jane and John Justin Neurosciences Center of Cook Children’s Medical Center, and Gita Gupta, MD, MS, assistant professor of pediatrics at the Johns Hopkins University.

In this fourth episode, clinicians highlighted key areas of focus in LGS, emphasizing the importance of interdisciplinary collaboration. Perry noted that the 2025 LGS Research Meeting of the Mind facilitated new perspectives on research priorities, particularly around developing robust biomarkers and understanding the underlying pathways leading to slow spike-wave activity. Gupta then stressed the limited systematic research on sleep in children with LGS, underscoring its potential role as both a biomarker and a modifiable factor influencing neurodevelopmental outcomes. In the discussion, the duo of experts also addressed gaps in patient registries and the need to identify optimal treatment strategies.

Transcript edited for clarity. Click here to view more content of the LGS Foundation.

Isabella Ciccone, MPH: Going off some of the collaboration that was happening and a lot of conversations, what clinical insights emerged from interdisciplinary conversations that you believe can impact care as well, for LGS?

Scott Perry, MD: There are a lot of things. That's a tough one, because what came out of it was a lot of ideas of what we're going to do collaboratively to answer the questions. I guess you just get a new perspective, basically, of your topic area when you have other people there to collaborate. Like I said, we focus, as epileptologists, on seizures, but when we start to talk about sleep and how sleep impacts that, or vice versa, how seizures impact sleep, and start to work off each other and get new ideas. The purpose of the meeting was to leave with a clear understanding of where we needed to direct our energy in the next several years, and where the foundation needs to direct their energy and their funding in the next several years. And that we definitely came away with. We had a session that we called our “Evidence SmackDown,” which was basically a bracket of lots of areas that we had identified as gaps that needed to be addressed, and we debated those areas down until we got down to 3 to focus on.

In the coming years, we really want to focus on developing robust biomarkers of LGS. The reasons for that are numerous, but one of the more important ones is that LGS is somewhat difficult to diagnose because it requires 3 categories of findings, and they're not always present at the same time. For that reason, the diagnosis doesn't always get made, because people don't put the pieces together over the lifespan. Some biomarkers might help enhance that. We also talked about patient registries and making those more robust. And then finally, what I mentioned in the beginning—the gap of trying to identify what’s the best treatment for the condition.

Isabella Ciccone, MPH: I was going to ask, in terms of research priorities, where is the field looking right now? With that, is there anything else that you think needs to be studied further—maybe in certain populations, maybe patients with other comorbidities, or, as we talked about, even sleep?

Gita Gupta, MS, MS: Well, I was going to say, being somewhat of an outsider to this group, I don't think I can fairly comment on the research priorities as a whole. But I personally have been trying to help understand the sleep of children with LGS, and to be honest, there's very little-known right now. We know clinically, parents tell us so much about their children's sleep and what a concern it is, and this just hasn't been systematically studied. So personally, we have to start from the very beginning: what's the most feasible way to assess sleep in kids with LGS? Not every child is the same—we can't apply the same techniques to all children. We must do what's feasible and reasonable for kids with LGS. Then we have to figure out what exactly is going on with the sleep of children with LGS.

We suspect that there's a wide range of sleep disorders—sleep-disordered breathing, circadian rhythm disorders, meaning problems with sleep schedules, insomnia. And then also, what does that mean? Is that part of the biomarker piece of the puzzle? I again, this hasn't been systematically studied, but I've anecdotally heard people say that one of the earlier signs that parents noticed that something was potentially evolving with their child was sleep disruption. Sleep changed, and then seizures started evolving. I'm not saying that's the case for every child, but this is something we have to more systematically understand and clearly define the relationships between sleep and LGS. Are the sleep disorders an outcome, or are they a biomarker—or both?

And then lastly, does treating sleep disorders alter the neurodevelopmental outcomes of younger children with LGS, and can we help repair some of the neuronal pathways involved in learning by trying to optimize sleep? There are so many questions, and so much work to be done in this small piece of the pie. I think there are also many questions in general when it comes to treatment and even classification.

Scott Perry, MD: I think one of the big things for me, that a lot of people really want to focus on and get to, is understanding how we get to the slow spike wave of LGS. One of the criticisms people have with LGS as a syndrome is that there are so many things—so many etiologies that end in LGS. And for that reason, is it really one thing? And it is. Even though we have all these etiologies, they all end up with an epileptic encephalopathy with slow spike wave and paroxysmal fast frequency. So, what is it that gets people to that point? If we can understand that pathway, then that's really our opportunity to intervene early in life, because we want to intervene before we get to the slow spike wave, before we develop that last piece of the puzzle to get the LGS diagnosis. That’s going to be an important piece to get to. There was a lot of interest around understanding that, talking about animal models and other ways we could get to understanding it so that we can interrupt that process.