Focal to Bilateral Tonic-clonic Seizures Are a Marker of Pharmacoresistance in Focal Cortical Dysplasia-related Epilepsy
Abstract number :
1.231
Submission category :
4. Clinical Epilepsy / 4D. Prognosis
Year :
2022
Submission ID :
2204156
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:23 AM
Authors :
Nathan Cohen, MD – Children's National Hospital; Phat Chang, MPH – Children's National Hospital; Xiaozhen You, PhD – Children's National Hospital; Tayyba Anwar, MD – Children's National Hospital; Archana Pasupuleti, MD – Children's National Hospital; Susanne Yoon, MD – Children's National Hospital; Thuy-Anh Vu, MD – Children's National Hospital; L. Gilbert Vezina, MD – Children's National Hospital; Taha Gholipour, MD – George Washington University Epilepsy Center; Chima Oluigbo, MD – Children's National Hospital; William Gaillard, MD – Children's National Hospital
Rationale: Focal cortical dysplasia (FCD) is the most common etiology of surgically-remediable epilepsy in children. Eighty-seven percent of patients with FCD develop epilepsy, three-fourths of which is pharmacoresistant (PRE), but one-fourth remains pharmacosensitive (PSE). Focal to bilateral tonic-clonic (FTBTC) seizures are associated with a larger epileptogenic network. We hypothesized that children with FCD-related epilepsy with FTBTC seizures are more likely to develop PRE.
Methods: Patients were selected retrospectively from centralized radiology and epilepsy surgery databases at Children’s National Hospital. Inclusion criteria were: 3T MRI-confirmed FCD from January, 2011 to January, 2020; ages 0 days to 22 years at MRI; at least 18 months of documented follow-up after MRI. Records were excluded if there was dual pathology (except for mesial temporal sclerosis), hemimegalencephaly, or tuberous sclerosis complex present in imaging or history. We tracked age at seizure onset, demographic data, date of MRI, dates 1st/2nd/3rd antiseizure medication (ASM) prescribed, reason for ASM discontinuation, and epilepsy characteristics. PRE was defined as starting 3rd ASM (due to failing two prior adequately-dosed ASMs) or having undergone surgery. Jamovi (jamovi.org) was used for statistical analysis. The association of FTBTC seizures with epilepsy severity (PRE or PSE) and surgical outcome (Engel I vs. Not Engel I) was tested using Chi-Square. Multivariate binomial regression was used to evaluate clinical and radiologic predictors of pharmacoresistance (age of seizure onset, FCD hemisphere, FCD lobe, and presence or absence of FTBTC seizures) to a binarized outcome of PRE vs. PSE.
Results: A total of 124 patients were included with median age of seizure onset 2.71y (IQR 0.75-6y). Ninety-two patients had PRE (74%); 32 had PSE (26%). Twenty-four (19%) patients had FTBTC seizures. Eighty-two patients had epilepsy surgery with 72% Engel I outcome. The presence of FTBTC seizures is associated with PRE (χ2, p=0.029); the absence of FTBTC seizures showed a trend with Engel I outcome (p=0.052). Multivariate regression showed presence of FTBTC seizures is associated with increased risk of PRE (OR 6.47 95%CI 1.3-32.4, p=0.02). Age at seizure onset is negatively correlated with PRE (OR 0.97 95%CI 0.78-0.97, p=0.01). FCD hemisphere and lobar distribution are not associated with PRE.
Conclusions: In a heterogeneous population of children with FCD-related epilepsy, including surgical and unoperated patients, we find that the presence of FTBTC seizures is associated with an increased risk of PRE. This finding is a novel recognizable clinical marker to help neurologists identify those children with FCD-related epilepsy at risk of PRE, and who therefore may benefit from earlier surgical evaluation. The absence of FTBTC seizures in FCD-related epilepsy has a trend association with Engel I outcome, which may indicate these FCDs engage a more limited network, thus allowing for improved surgical outcome.
Funding: NTC is supported by the PERF Shields Research Grant and the CNRI Chief Research Officer Award. This work was supported by DC-IDDRC NICHD NIH P50 HD105328.
Clinical Epilepsy