Journal article
Factors Associated With More Medication Trials Before Surgical Evaluation and Postsurgical Outcomes in Pediatric Drug-Resistant Epilepsy
Neurology, Vol.105(9), e214198
11/11/2025
DOI: 10.1212/WNL.0000000000214198
PMID: 41056528
Abstract
Background and Objectives
Despite strong evidence supporting timely surgical evaluation, many children with drug-resistant epilepsy undergo multiple antiseizure medication (ASM) trials before surgery. Because guidelines recommend evaluation after failure of 2 appropriate ASMs, evaluation after failure of >2 ASMs serves as a clinically relevant benchmark. The aim of this study was to identify factors associated with initiation of surgical evaluation after failure of >2 ASMs and evaluate its association with seizure freedom.
Methods
We performed a retrospective analysis using the Pediatric Epilepsy Research Consortium Surgery Database, including 24 US pediatric epilepsy centers. Children aged 18 years and younger who initiated epilepsy surgery evaluation between January 2018 and February 2023 were included. Timing of evaluation was defined by the number of ASM failures before first phase I evaluation (≤2 vs >2). Unadjusted analyses and multivariable logistic regression were used to identify predictors of later evaluation and assess its association with seizure freedom, adjusting for etiology, seizure type, MRI findings, and surgical procedure.
Results
Among 1,767 patients, 802 (45.4%) initiated surgical evaluation after failing ≤2 ASMs and 965 (54.6%) after failing >2 ASMs, with a median age at seizure onset of 5.96 and 4.00 years, respectively. Factors independently associated with later initiation of surgical evaluation included genetic etiology (odds ratio [OR] 1.83, 95% CI 1.28–2.60), generalized seizures (OR 2.64, 95% CI 1.58–4.40), daily seizures (OR 1.69, 95% CI 1.33–2.14), multiple seizure types (OR 1.59, 95% CI 1.39–1.82), normal MRI (OR 1.82, 95% CI 1.52–2.18), and abnormal neurologic examination (OR 2.44, 95% CI 2.01–2.96). Surgical intervention rates were similar (∼50%) between groups. Patients who initiated surgical evaluation after failure of ≤2 ASMs had significantly higher seizure freedom rates (60.8% vs 39.3%, p < 0.001). On multivariable analysis, failure of >2 ASMs before surgical evaluation was independently associated with lower odds of seizure freedom (OR 0.66, 95% CI 0.45–0.96, p = 0.028).
Discussion
Initiation of surgical evaluation after failure of more than 2 ASMs is associated with more complex epilepsy phenotypes and lower rates of seizure freedom. However, 80% of these patients still experienced a >50% reduction in seizures, highlighting the therapeutic benefits of timely epilepsy surgery—even when seizure freedom is unlikely—regardless of epilepsy subtype.
Details
- Title: Subtitle
- Factors Associated With More Medication Trials Before Surgical Evaluation and Postsurgical Outcomes in Pediatric Drug-Resistant Epilepsy
- Creators
- Debopam Samanta - University of Arkansas for Medical SciencesGrace Newell - Children's Hospital ColoradoAvery Robert Caraway - Cook Children's Medical CenterEmily Brock - Cook Children's Medical CenterGregory W Albert - University of Arkansas for Medical SciencesEdward John Novotny - Seattle Children's HospitalDewi Frances Depositario Cabacar - Children's NationalChima O Oluigbo - Children's NationalWilliam D Gaillard - Children's NationalPriyamvada Tatachar - Northwestern UniversityJeffrey Brian Bolton - Boston Children's HospitalLily Wong-Kisiel - Mayo Clinic in ArizonaErin Fedak Romanowski - University of MichiganNancy A Mcnamara - University of MichiganKrista Eschbach - Children's Hospital ColoradoAllyson L Alexander - Children's Hospital ColoradoKurtis I Auguste - University of California, San FranciscoErnesto Gonzalez-Giraldo - University of California, San FranciscoDanilo Bernardo - University of California, San FranciscoAdam P Ostendorf - Nationwide Children's HospitalJason Coryell - Doernbecher Children's HospitalSamir Karia - University of LouisvilleCemal Karakas - Norton HealthcarePradeep K Javarayee - Medical College of WisconsinPilar D Pichon - Children's Hospital of Orange CountyJoffre Olaya - Children's Hospital of Orange CountyDaniel W Shrey - Children's Hospital of Orange CountyShilpa B Reddy - Monroe Carell Jr. Children's HospitalAbhinaya Ganesh - Monroe Carell Jr. Children's HospitalJason S Hauptman - Barrow Neurological InstituteRani K Singh - Atrium Medical CenteMichael Ciliberto - University of Iowa Stead Family Children’s HospitalAhmad Marashly - Johns Hopkins UniversityZachary M Grinspan - Cornell UniversitySrishti Nangia - Weill Cornell MedicineKristen Arredondo - The University of Texas at AustinDerryl J Miller - Riley Hospital for ChildrenShifteh Sattar - Rady Children's Hospital-San DiegoMaria Montenegro - Rady Children's Hospital-San DiegoNitin Agarwal - Minnesota Epilepsy GroupFernando N Galan - Nemours Children's Health SystemJanelle Wagner - Medical University of South CarolinaTaylor J Abel - University of PittsburghAndrew T Knox - University of Wisconsin–MadisonM Scott Perry - Cook Children's Medical Center
- Resource Type
- Journal article
- Publication Details
- Neurology, Vol.105(9), e214198
- DOI
- 10.1212/WNL.0000000000214198
- PMID
- 41056528
- NLM abbreviation
- Neurology
- ISSN
- 0028-3878
- eISSN
- 1526-632X
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS; PHILADELPHIA
- Language
- English
- Date published
- 11/11/2025
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Neurology (Pediatrics)
- Record Identifier
- 9985014896702771
Metrics
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