Focal to bilateral tonic-clonic seizures predict pharmacoresistance in focal cortical dysplasia-related epilepsy

Phat Chang, Center for Neuroscience Research, Children's National Hospital, The George Washington University School of Medicine, Washington, District of Columbia, USA.
Hua Xie, Center for Neuroscience Research, Children's National Hospital, The George Washington University School of Medicine, Washington, District of Columbia, USA.
Venkata Sita Illapani, Center for Neuroscience Research, Children's National Hospital, The George Washington University School of Medicine, Washington, District of Columbia, USA.
Xiaozhen You, Center for Neuroscience Research, Children's National Hospital, The George Washington University School of Medicine, Washington, District of Columbia, USA.
Tayyba Anwar, Center for Neuroscience Research, Children's National Hospital, The George Washington University School of Medicine, Washington, District of Columbia, USA.
Archana Pasupuleti, Center for Neuroscience Research, Children's National Hospital, The George Washington University School of Medicine, Washington, District of Columbia, USA.
Thuy-Anh Vu, Center for Neuroscience Research, Children's National Hospital, The George Washington University School of Medicine, Washington, District of Columbia, USA.
L Gilbert Vezina, Center for Neuroscience Research, Children's National Hospital, The George Washington University School of Medicine, Washington, District of Columbia, USA.
Taha Gholipour, Center for Neuroscience Research, Children's National Hospital, The George Washington University School of Medicine, Washington, District of Columbia, USA.
Chima O. Oluigbo, Center for Neuroscience Research, Children's National Hospital, The George Washington University School of Medicine, Washington, District of Columbia, USA.
Anqing Zhang, Division of Biostatistics and Study Methodology, Children's National Research Institute, Washington, District of Columbia, USA.
William Davis Gaillard, Center for Neuroscience Research, Children's National Hospital, The George Washington University School of Medicine, Washington, District of Columbia, USA.
Nathan T. Cohen, Center for Neuroscience Research, Children's National Hospital, The George Washington University School of Medicine, Washington, District of Columbia, USA.

Document Type

Journal Article

Publication Date

6-22-2023

Journal

Epilepsia

DOI

10.1111/epi.17700

Keywords

FCD; default mode network; drug-resistant epilepsy; pharmacoresistant epilepsy

Abstract

OBJECTIVE: Focal cortical dysplasia (FCD) is the most common etiology of surgically-remediable epilepsy in children. Eighty-seven percent of patients with FCD develop epilepsy (75% is pharmacoresistant epilepsy [PRE]). Focal to bilateral tonic-clonic (FTBTC) seizures are associated with worse surgical outcomes. We hypothesized that children with FCD-related epilepsy with FTBTC seizures are more likely to develop PRE due to lesion interaction with restricted cortical neural networks. METHODS: Patients were selected retrospectively from radiology and surgical databases from Children's National Hospital. INCLUSION CRITERIA: 3T magnetic resonance imaging (MRI)-confirmed FCD from January 2011 to January 2020; ages 0 days to 22 years at MRI; and 18 months of documented follow-up. FCD dominant network (Yeo 7-network parcellation) was determined. Association of FTBTC seizures with epilepsy severity, surgical outcome, and dominant network was tested. Binomial regression was used to evaluate predictors (FTBTC seizures, age at seizure onset, pathology, hemisphere, lobe) of pharmacoresistance and Engel outcome. Regression was used to evaluate predictors (age at seizure onset, pathology, lobe, percentage default mode network [DMN] overlap) of FTBTC seizures. RESULTS: One hundred seventeen patients had a median age at seizure onset of 3.00 years (interquartile range [IQR] .42-5.59 years). Eighty-three patients had PRE (71%); 34 had pharmacosensitive epilepsy (PSE) (29%). Twenty patients (17%) had FTBTC seizures. Seventy-three patients underwent epilepsy surgery. Multivariate regression showed that FTBTC seizures are associated with an increased risk of PRE (odds ratio [OR] 6.41, 95% confidence interval [CI] 1.21-33.98, p = .02). FCD hemisphere/lobe was not associated with PRE. Percentage DMN overlap predicts FTBTC seizures. Seventy-two percent (n = 52) overall and 53% (n = 9) of patients with FTBTC seizures achieved Engel class I outcome. SIGNIFICANCE: In a heterogeneous population of surgical and non-operated patients with FCD-related epilepsy, the presence of FTBTC seizures is associated with a tremendous risk of PRE. This finding is a recognizable marker to help neurologists identify those children with FCD-related epilepsy at high risk of PRE and can flag patients for earlier consideration of potentially curative surgery. The FCD-dominant network also contributes to FTBTC seizure clinical expression.

Department

Neurology

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