Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 18:16:1569551.
doi: 10.3389/fneur.2025.1569551. eCollection 2025.

Comparative effectiveness of epilepsy surgery versus additional anti-seizure medications for Lennox-Gastaut syndrome: study protocol for a multicenter, mixed-methods study

Sandi Lam  1   2 , Marc Rosenman  3   4 , Tracy Dixon-Salazar  5 , Kelly G Knupp  6 , Liu Lin Thio  7 , Taylor J Abel  8   9 , William P Welch  10   11 , Laurel Reed  12   13 , Stephanie C Randle  14   15 , Rebecca Garcia-Sosa  16   17 , Jason S Hauptman  18 , Carolyn C Foster  3   4 , Elizabeth R Alpern  4   19 , Lu Zhang  1   2 , Nicole Villalba  1   2 , Maura Carroll  1 , Anup D Patel  20
Affiliations

Comparative effectiveness of epilepsy surgery versus additional anti-seizure medications for Lennox-Gastaut syndrome: study protocol for a multicenter, mixed-methods study

Sandi Lam et al. Front Neurol. .

Abstract

Introduction: Lennox-Gastaut Syndrome (LGS) is a severe developmental epileptic encephalopathy without a known cure. Management of symptoms requires substantial care. Treatment options include anti-seizure medications, dietary therapy, and epilepsy surgery. Two main treatment pathways for patients with LGS with drug resistant epilepsy are additional anti-seizure medications or epilepsy surgery, which have been reported to be effective in reduction of seizure burden and improving quality of life. No studies have directly compared the outcomes of using epilepsy surgery versus using additional anti-seizure medications for the treatment of LGS.

Methods: This study is a multicenter, mixed-methods comparative effectiveness study of LGS patients who have undergone epilepsy surgery or have received an LGS-approved medication for treatment resistant seizures. Aim 1 will analyze the effect of surgical therapies and additional medication on two clinical outcomes: (1a) seizure-related healthcare utilization, and (1b) expressive communication, behavior, and parent-reported quality of life. Based on electronic health record review and coding validation as part of Aim 1a, we will develop computable phenotypes for LGS. The phenotypes will inform the analyses in Aim 1a and Aim 2. Aim 2 will describe the real-world utilization of these treatments across multiple healthcare institutions in the United States. Data will be collected from electronic health records, data marts in the National Patient-Centered Clinical Research Network (PCORnet®) format, caregiver surveys, and focus groups.

Discussion: This study of LGS will provide currently unavailable evidence concerning the real-world comparative effectiveness of epilepsy surgeries and additional anti-seizure medications. The outcomes are those that families identify as important: emergency medical care for seizures and patients' functional outcomes. The results of this study may help guide decisions regarding the treatment of LGS and development of computable phenotypes for this rare disease. This study using PCORnet® data will also lay the groundwork for future large-scale studies on LGS and other rare epilepsies.

Clinical trial registration: ClinicalTrials.gov, identifier NCT05374824.

Keywords: Lennox–Gastaut syndrome; anti-seizure medications; comparative effectiveness study; epilepsy; epilepsy surgery.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor SP declared a past co-authorship with the author TA.

Figures

Figure 1
Figure 1
Map of sites. CRNs, clinical research networks; U, University.
Figure 2
Figure 2
LGS classification workflow in Aim 1a. CRCs, clinical research coordinators; EHR, electronic health record; LGS, Lennox–Gastaut syndrome.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. LGS Foundation . How many people have LGS? Available online at: https://www.lgsfoundation.org/about-lgs-2/how-many-people-have-lgs/ (Accessed June 1, 2024).
    1. Asadi-Pooya AA. Lennox-Gastaut syndrome: a comprehensive review. Neurol Sci. (2018) 39:403–14. doi: 10.1007/s10072-017-3188-y, PMID: - DOI - PubMed
    1. Autry AR, Trevathan E, Van Naarden Braun K, Yeargin-Allsopp M. Increased risk of death among children with Lennox-Gastaut syndrome and infantile spasms. J Child Neurol. (2010) 25:441–7. doi: 10.1177/0883073809348355, PMID: - DOI - PubMed
    1. National Institute for Health and Care Excellence. Berg AT, Gaebler-Spira D, Wilkening G, Zelko F, Knupp K, Dixon-Salazar T, et al. Nonseizure consequences of Dravet syndrome, KCNQ2-DEE, KCNB1-DEE, Lennox-Gastaut syndrome, ESES: a functional framework. Epilepsy Behav. (2020) 111:107287. doi: 10.1016/j.yebeh.2020.107287, PMID: - DOI - PubMed
    1. Bourgeois BFD, Douglass LM, Sankar R. Lennox-Gastaut syndrome: a consensus approach to differential diagnosis. Epilepsia. (2014) 55:4–9. doi: 10.1111/epi.12567, PMID: - DOI - PubMed

Associated data

LinkOut - more resources