Rationale:
Managing intractable epilepsy in patient with epilepsy of childbearing potential (PWECP) poses risks due to seizures in pregnancy and antiseizure medication (ASM) teratogenicity, leading to major congenital malformations (MCMs). Current American Academy of Neurology (AAN) guidelines (based on pre-August 2022 studies) recommend lamotrigine, levetiracetam, or oxcarbazepine with daily folic acid. These guidelines exclude newer ASMs like cenobamate and brivaracetam. This report presents a case on combination cenobamate and brivaracetam use in pregnancy and lactation.
Methods:
Our patient is a right-handed female with a history of intractable symptomatic localization-related epilepsy, presenting with focal impaired awareness seizures. Her first seizure occurred at 14 months (febrile), followed by afebrile seizures beginning at age 3 years. She previously failed multiple ASMs, including clonazepam, gabapentin, oxcarbazepine, levetiracetam, lamotrigine, zonisamide, and phenytoin, due to inadequate seizure control or intolerable side effects. EMU admissions documented multiple typical events, concluding a poorly localized left hemispheric seizure onset zone. Brain MRI revealed bilateral mesial temporal sclerosis (left > right). She previously declined further presurgical evaluation with SEEG. Her current and most recent ASM regimen consists of cenobamate and brivaracetam.
At 27 years and 5 months of age, the patient reported a 5-6 week pregnancy. At that time, trough levels were cenobamate 12 mcg/mL and brivaracetam 1.60 µg/mL. Following a discussion regarding the limited data on newer ASMs in pregnancy and the risks of seizures on fetal development, a shared decision was made to continue both cenobamate 200 mg once daily and brivaracetam 100 mg twice daily, with clonazepam 0.5 mg as needed for rescue. She also continued folic acid 1 mg daily. The patient adhered to her ASM regimen without missing any doses throughout her pregnancy. She experienced total 3 seizures in 1st trimester; 2 seizures during the 3rd trimester (at 36 weeks gestation), for which she took a single 0.5 mg dose of clonazepam. Follow-up ASM blood levels were not obtained.
Results:
Patient delivered a live female infant at 39w 1d via spontaneous vaginal delivery with epidural anesthesia. Birth weight was 3935g, length was 54cm. Apgar scores were 7 (1min) and 9 (5min). Complication: 3rd-degree perineal laceration. Intact placenta with 3-vessel cord was noted. Pediatric evaluation did not report MCMs. Infant is achieving developmental milestones. Patient breastfed for 1 month, then bottle-fed. Infant is 9 weeks old and healthy at the time of this case report.
Conclusions: This case describes a normal pregnancy outcome in a young female with intractable localization-related epilepsy on combination cenobamate and brivaracetam. To our knowledge, this is the first reported pregnancy outcome with this specific ASM combination. This offers reassuring, preliminary evidence that cenobamate and brivaracetam may be safely continued in pregnancy when benefits outweigh risks, especially in intractable epilepsy. Generalizability is limited; larger prospective studies are needed to confirm these findings.
Funding: Does not apply.