Prevalence and Risk Factors for Pharmacoresistance in Children With Focal Cortical Dysplasia-Related Epilepsy

Abstract

Background and objectives: Focal cortical dysplasia (FCD) is the most common cause of surgically remediable epilepsy in children. Little is known about the risk factors for the timing and development of pharmacoresistance in this population. This study sought to evaluate the prevalence and risk factors for pharmacoresistance in pediatric FCD-related epilepsy.

Methods: In this retrospective single-center cohort design, patients were identified from search of centralized radiology report database and a central epilepsy surgical database. Inclusion criteria consisted of 3T MRI-confirmed FCD from January, 2011, to January, 2020; ages 0 days to 22 years at MRI; and at least 18 months of documented follow-up after MRI, unless had single seizure or incidentally discovered FCD. Records were excluded if there was dual pathology (except for mesial temporal sclerosis), hemimegalencephaly, or tuberous sclerosis complex present in imaging or history.

Results: One hundred forty-three patients with confirmed FCD met the inclusion criteria. One hundred twenty-four children had epilepsy (87% of patients with FCD) with median age at seizure onset 2.7 years (IQR 0.75-6 years, range 0-17 years). Twelve children (8.5%) had a single lifetime seizure (provoked or unprovoked) or recurrent provoked seizures. Seven children (4.9%) had incidental FCD. Ninety-two patients (74%) of those with epilepsy met criteria for pharmacoresistance. Of children with epilepsy of all types, 93 children (75%) were seizure-free at the last visit; 82 patients underwent epilepsy surgery, of whom 59 (72%) achieved seizure freedom. Seven percent (9/124) achieved seizure freedom with a second ASM and 5.6% (7/124) with a third or more ASMs. Failure of only 1 antiseizure medication is associated with enormous increased incidence and earlier development of pharmacoresistance (OR 346; 95% CI 19.6-6,100); Cox regression showed FCD lobar location, pathologic subtype, and age at seizure onset are not.

Discussion: Failure of 1 antiseizure medication is associated with substantial risk of pharmacoresistance. These data support an operational redefinition of pharmacoresistance, for surgical planning, in FCD-related epilepsy to the failure of 1 antiseizure medication and support early, potentially curative surgery to improve outcomes in this patient population.

Figure 1. Patient Flowchart

Flowchart demonstrating breakdown of patients into groups. SF (seizure-free) indicates the number of patients achieving seizure freedom in that group. Of note, for the PSE group, 9 patients were seizure-free at the last follow-up (5 were on second ASM as monotherapy; 4 were on second ASM as combination therapy). ASM = antiseizure medication; PSE = pharmacosensitive epilepsy.

Figure 2. Kaplan-Meier Curve of Development of Pharmacoresistance by Failure of 1 Antiseizure Medication

Orange line shows those patients with epilepsy and failure of 1 antiseizure medication. Green line shows those patients with pharmacosensitive epilepsy on 1 antiseizure medication.

Figure 3. Boxplot of Age of Seizure Onset (Years) by Pharmacoresistant (PRE) vs Pharmacosensitive Epilepsy (PSE)