Pediatric refractory epilepsy related to tuberous sclerosis complex: A retrospective-cohort study of diagnosis and treatment

Background

Tuberous sclerosis complex (TSC) patients often develop refractory epilepsy (RE). The present study evaluated numerous risk factors associated with TSC to determine risk factors of RE.

Methods

After enrollment, 315 pediatric patients with TSC-associated epilepsy were divided into control and RE groups. Multimodal data were used to characterize risk factors for RE, including clinical data, anti-seizure medication (ASM) or sirolimus use, family history, genotype, seizure types, neuroimaging and EEG findings, and developmental assessments.

Results

Infantile spasms, number of ASMs being taken, clustered seizures, family history, TSC2 mutation, and presence of type II and Ⅲ lesions were positively correlated with RE. Age of onset, age of first hospital visit, and use of vigabatrin were negatively correlated with RE. MRI findings suggest lesion type is more important than lesion size and location in predicting RE. There were significant differences in spasms and delayed motor development or cognitive delay between the control and RE groups. Valproate was the most common ASM used, followed by vigabatrin and oxcarbazepine. Risk of RE was increased as much as 1.63-fold by the presence of type II lesions.

Conclusions

Age of onset, infantile spasms, type II lesions, TSC2 mutation status, family history, and clustered seizures were identified as potential risk factors for the development of RE. ASM should be recommended for TSC patients even in cases with subclinical epileptiform EEG discharge. Using vigabatrin and sirolimus earlier in childhood may reduce the occurrence of RE.