Everolimus Reduces Seizure Frequency in Tuberous Sclerosis Complex

Background/Purpose: Tuberous sclerosis complex (TSC) is a multisystem disease caused by a mutation of the TSC 1 or TSC 2 gene which results in hyperactivation of the mTOR signaling pathway. Despite a broad clinical spectrum, TSC is mainly characterized by epilepsy which affects 75 to 90% of patients. Vigabatrin has successfully been used as a first-line antiepileptic drug (AED) in the treatment of TS-associated seizures. However, long-term seizure control remains challenging as more than 60% of patients develop refractory epilepsy. The mTOR inhibitor everolimus provides a novel therapeutic option based on the pathophysiology of TSC. First clinical results show that everolimus is highly effective in the treatment of TSC-associated epilepsy.

Methods: Three patients (age range: 3–14 years) were treated with everolimus (dosage: 2.5–10 mg/day) due to subependymal giant cell astrocytomas (SEGA). Despite various combinations of AED, seizure control could not be achieved in these patients who experienced up to 40 seizures per day prior to treatment with everolimus.

Results: With an everolimus blood level of 3 to 10 µg/L, all patients showed a reduction of seizure frequency of up to 90%. One patient remained seizure free. Additionally, we observed significant progress in motor and socioemotional development.

Conclusions: Our results corroborate published data of the EXIST-3 trial. Everolimus results in significant reduction of seizure frequency and therefore is a potent AED for TSC-associated epilepsy. Additional studies are necessary to elucidate if the observed developmental progress is due to better seizure control or is a direct effect of mTOR inhibition.

No conflict of interest has been declared by the author(s).