Abstracts

Neurobeachin Syndrome (NBEA) is an inherited, usually de novo, autosomal dominant gene defect associated with infant or early childhood onset seizures intellectual disability speech delays behavioral abnormalities and psychiatric abnormalities including autism spectrum disorder conditions.  Functioning as a protein kinase A anchor protein, it is involved with synaptic functioning and vesical trafficking and is located on chromosome 13q.  Seizures can be very difficult to treat and may overlap refractive epilepsy including Lennox-Gastaut syndrome type conditions or other developmental epileptic encephalopathy (DEE) patterns.  EEG often has both focal and generalized epileptic spike patterns and polyspike and wave patterns and can include mixed seizure types including focal seizures with secondary generalization, grand mal seizures, myoclonic and tonic drop attack seizures.  Patients often require polytherapy for both seizures and behavior.  We present 2 cases that had seizure improvement using cenobamate.

Retrospective chart review was done reviewing the history of to patient's who had genetic diagnosis of NBEA defect.

Patient 1: 11 year old male with NBEA and refractory epilepsy since age 7, with myoclonic, tonic head drop, staring episodes, and generalized tonic-clonic seizures with daily morning tonic seizures, staring spells, daily  with 2-3 generalized tonic-clonic convulsions per week. He had previously failed several anti-seizure medications(ASM) and the ketogenic diet on clobazam and valproate when seen. He had fenfluramine added and this decreased tonic-clonic seizures, but had to be lowered due to 6 lb weight loss. . Daily tonic and head nodding seizures continued. Cenobamate was titrated every two weeks at age 13 years, and patient became seizure free at a dose of 100mg daily, and was tapered off clobazami after several months being seizure free, he remains delayed in academics but less autistic like and fewer behavioral issues on daily fenfluramine(24mg) , valproate (1350mg), and cenobamate (100mg) at 50.8 kg.

Patient 2 :  32 year old female diagnosed NBEA with epilepsy and autism at age 2 years with comorbid mood disorder, refractory epilepsy. Having failed numerous ASM and two laser ablations, multiple psychaitric medications for behavior, and was having 12-20 sezures of focal secondarily generalized type per year, often related to hormononal changes from ovulation or mentruation.She had numerous episodes not responding with nystagmus briefly or confusion which may also have been short focal seizures with change in awarness which were hard to count. She  failed numerous ASM. She was started on cenobamate and tapered off oxtellar and continued valproate and lorazepam. She went 10 months seizure-free and now has catamenial mild focal seizures (4/year).

See Table 1 for patient details.

NBEA is a rare DEE with refractory epilpesy and identification can lead to better treatment outcomes. Cenobamate therapy in two cases improved both seizure control and behavioral outcome. More research is warranted.