Epilepsy surgery in children with genetic etiologies: A prospective evaluation of current practices and outcomes

Jason Coryell; Rani Singh; Adam P Ostendorf; Mariah Eisner; Allyson Alexander; Krista Eschbach; Daniel W Shrey; Joffre Olaya; Michael A Ciliberto; Cemal Karakas; Samir Karia; Nancy McNamara; Erin Fedak Romanowski; Ammar Kheder; Javarayee Pradeep; Shilpa B Reddy; Michael J McCormack; Jeffrey Bolton; Steven Wolf; Patricia McGoldrick; Jason S Hauptman; Debopam Samanta; Priya Tatachar; Joseph Sullivan; Kurtis Auguste; Ernesto Gonzalez-Giraldo; Ahmad Marashly; Dewi F Depositario-Cabacar; Lily C Wong-Kisiel; Scott Perry

doi:10.1016/j.seizure.2023.10.011

Epilepsy surgery in children with genetic etiologies: A prospective evaluation of current practices and outcomes

Seizure. 2023 Dec:113:6-12. doi: 10.1016/j.seizure.2023.10.011. Epub 2023 Oct 25.

Authors

Jason Coryell¹, Rani Singh², Adam P Ostendorf³, Mariah Eisner⁴, Allyson Alexander⁵, Krista Eschbach⁶, Daniel W Shrey⁷, Joffre Olaya⁷, Michael A Ciliberto⁸, Cemal Karakas⁹, Samir Karia⁹, Nancy McNamara¹⁰, Erin Fedak Romanowski¹⁰, Ammar Kheder¹¹, Javarayee Pradeep¹², Shilpa B Reddy¹³, Michael J McCormack¹³, Jeffrey Bolton¹⁴, Steven Wolf¹⁵, Patricia McGoldrick¹⁵, Jason S Hauptman¹⁶, Debopam Samanta¹⁷, Priya Tatachar¹⁸, Joseph Sullivan¹⁹, Kurtis Auguste¹⁹, Ernesto Gonzalez-Giraldo¹⁹, Ahmad Marashly²⁰, Dewi F Depositario-Cabacar²¹, Lily C Wong-Kisiel²², Scott Perry²³

Affiliations

¹ Department of Pediatrics, Oregon Health & Sciences University, CDRC-P, 707 SW Gaines Rd, Portland, OR 97239, USA. Electronic address: coryellj@ohsu.edu.
² Division of Neurology, Department of Pediatrics, Atrium Health/Levine Children's Hospital, Charlotte, NC, USA.
³ Department of Pediatrics, Nationwide Children's Hospital, Ohio State University, Columbus, OH, USA.
⁴ Biostatistics Resource at Nationwide Children's Hospital, Columbus, Ohio, USA.
⁵ Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Division of Pediatric Neurosurgery, Children's Hospital Colorado, Aurora, CO, USA.
⁶ Department of Neurology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁷ Children's Hospital of Orange County, Orange, CA, USA.
⁸ Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
⁹ Department of Neurology, Division of Child Neurology, Norton Children's Hospital, University of Louisville School of Medicine, Louisville, KY, USA.
¹⁰ Department of Pediatrics, Section of Pediatric Neurology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.
¹¹ Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA, USA.
¹² Department of Pediatric Neurology, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA.
¹³ Department of Pediatrics, Vanderbilt University Medical Center, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN, USA.
¹⁴ Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
¹⁵ Boston Children's Health Physicians of New York and Connecticut, Maria Fareri Children's Hospital, New York Medical College, Valhalla, NY, USA.
¹⁶ Division of Pediatric Neurosurgery, University of Washington/Seattle Children's Hospital, Seattle, WA, USA.
¹⁷ Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
¹⁸ Department of Pediatrics, Ann and Robert H Lurie Children's Hospital, Chicago, IL, USA.
¹⁹ University of California San Francisco Weill Institute for Neurosciences, Benioff Children's Hospital, San Francisco, CA, USA.
²⁰ Department of Neurology, Johns Hopkins, Baltimore, MD, USA.
²¹ Center for Neuroscience, Children's National Hospital, George Washington University School of Medicine, Washington, DC, USA.
²² Department of Neurology, Divisions of Child Neurology and Epilepsy, Mayo Clinic College of Medicine, Rochester, MN, USA.
²³ Jane and John Justin Institute for Mind Health, Cook Children's Medical Center, Fort Worth, TX, USA.

PMID: 38189708
DOI: 10.1016/j.seizure.2023.10.011

Abstract

Objective: This study assesses current practices and outcomes of epilepsy surgery in children with a genetic etiology. It explores the pre-surgical workup, types of surgeries, and post-surgical outcomes in a broad array of disorders.

Methods: Patients ≤18 years who completed epilepsy surgery and had a known genetic etiology prior to surgical intervention were extrapolated from the Pediatric Epilepsy Research Consortium (PERC) surgery database, across 18 US centers. Data were assessed univariably by neuroimaging and EEG results, genetic group (structural gene, other gene, chromosomal), and curative intent. Outcomes were based on a modified International League Against Epilepsy (ILAE) outcome score.

Results: Of 81 children with genetic epilepsy, 72 % had daily seizures when referred for surgery evaluation, which occurred a median of 2.2 years (IQR 0.3, 5.2) after developing drug resistance. Following surgery, 68 % of subjects had >50 % seizure reduction, with 33 % achieving seizure freedom [median follow-up 11 months (IQR 6, 17). Seizure freedom was most common in the monogenic structural group, but significant palliation was present across all groups. Presence of a single EEG focus was associated with a greater likelihood of seizure freedom (p=0.02).

Significance: There are meaningful seizure reductions following epilepsy surgery in the majority of children with a genetic etiology, even in the absence of a single structural lesion and across a broad spectrum of genetic causes. These findings highlight the need for expedited referral for epilepsy surgery and support of a broadened view of which children may benefit from epilepsy surgery, even when the intent is palliative.

Keywords: Epilepsy; Genetic; Pediatric; Surgery.

MeSH terms

Child
Databases, Factual
Epilepsy* / genetics
Epilepsy* / surgery
Humans
Neuroimaging
Probability
Seizures