Abstracts

Rationale: Tuberous sclerosis complex (TSC) is a multi-system genetic condition affecting 1 in 6000 people, which arises due to changes in the mammalian target of Rapamycin (mTOR) pathway. Refractory focal epilepsy is a hallmark of the condition in at least a third of patients¹.

Cenobamate was licenced in the UK as an adjunctive treatment for adults with focal epilepsy from December 2021. Data is limited regarding its effect on seizure frequency in adults with TSC. We reviewed the change in seizure frequency of patients with TSC who were commenced on Cenobamate from January 2022.


Methods: This was a retrospective analysis of electronic patient records. Patients were identified from the hospital database as having a diagnosis of TSC and associated refractory epilepsy. Records were analysed to determine monthly seizure frequency at the point of Cenobamate initiation and again at the time of data collection. Statistical analysis was undertaken by the Wilcoxon signed-rank test. Changes to concurrent anti-seizure medications (ASM) and reported side effects were noted.


Results: 15 patients were identified for analysis. Patients ranged from 23-57 years, 8 (53%) were male. Patients were taking a range of 2-6 concurrent ASMs, 4 patients (26.7%) had vagal nerve stimulators. 1 patient had trialled Everolimus, prescribed for renal angiomyolipoma. Duration of Cenobamate treatment varied from 4-26 months. The minimum maintenance dose of Cenobamate was 75mg once daily.

13 patients (86.7%) reported a reduction in their monthly seizure frequency – see Graph 1. All patients experienced a subjective reduction in seizure severity. The mean monthly number of seizures experienced prior to Cenobamate was 19.9 (maximum=50, minimum=1), at last follow up this decreased to 10.1 (maximum=30, minimum=0). This reduction in seizure frequency was statistically significant p=0.0016.

Cenobamate at a dose of between 75mg and 350mg was well tolerated. Three patients reported side effects - two reported fatigue, 1 reported vertigo and 1 reported diarrhoea, prompting a mild reduction of Cenobamate for this patient. All patients remained on Cenobamate at the end of the study. Concomitant ASMs were either reduced or discontinued in 13 (86.7%) patients – see Graph 2.


Conclusions: Cenobamate is associated with improvement in seizure frequency in patients with TSC, including in those who have tried surgical strategies and Everolimus. Addition of Cenobamate enables reduction of concomitant ASMs with potentially positive effects on quality of life. Use of Cenobamate within this cohort of patients warrants further study.

Funding: None