Authors :
Presenting Author: Ashwaq Alsulami, MD – sick kids hospital - University of Toronto
Olivia Arski, Clinical research coordinator – The hospital for sick children; Elizabeth Donner, Neurology Consultant – The hospital for sick children; Lauren Sham, Neurology Consultant – the hospital for sick children; Maria Zak, Nurse Practitioner – The hospital for sick children
Rationale:
Multiple studies have investigated the impact of mTOR inhibitors on seizure management in Tuberous Sclerosis Complex (TSC), revealing promising results. The EXIST-3 trial, a pivotal study, showcased Everolimus's ability to decrease seizure frequency by over 50% in 38% of TSC patients with treatment-resistant epilepsy, surpassing the placebo group's results of 13%. The primary aim of this study is to investigate the efficacy and tolerability of mTOR inhibitors as adjunctive therapy in patients with TSC and epilepsy treated at SickKids Hospital over a 10-year period. We aim to evaluate the impact of mTOR inhibitors on seizure management and assess the tolerability of these medications in the TSC population. Additionally, we seek to compare the population of patients with drug-resistant epilepsy and TSC at SickKids Hospital to those previously reported in the literature.
Methods:
A retrospective review was conducted to analyze data from children with TSC and epilepsy who received mTOR inhibitors between 2013 and 2022. A total of 13 patients with TSC received mTOR inhibitors as adjunctive therapy, selected from a larger cohort of 95 TSC patients. 65 patients were excluded who had epilepsy or a history of seizures but were not on mTOR inhibitors, as well as 17 patients without an epilepsy diagnosis who were also not on mTOR inhibitors. Among the 13 patients included, 11 had DRE. The type of mTOR inhibitors administered included Everolimus for one patient and Sirolimus for 10 patients. The initial indications for mTOR inhibitor treatment in the epilepsy group consisted of SEGA for four patients, AML for four patients, and DRE for three patients. Among the 13 patients, two did not have epilepsy but were receiving mTOR inhibitors. One patient received Sirolimus, while another patient received both Everolimus and Sirolimus for different indications. In the non-epilepsy group, one patient received mTOR inhibitors for AML, and one patient received treatment for SEGA.
Results: The results showed that out of the 11 patients with DRE who received mTOR inhibitors, five patients 45.5% achieved complete seizure freedom. Among them, four patients had focal non-motor epilepsy, while one patient had focal motor epilepsy. Additionally, three patients 27.4% experienced a substantial reduction in seizures, ranging from 95% to 50%. Furthermore, two patients 18.2% experienced a moderate reduction in seizures, with a range of 50% to 20%. Only one patient 9.1% had a limited reduction in seizures, less than 20%. Additionally, for SEGA outcome,
After 12-18 months of treatment, there were significant reductions in the SEGA volumes in six patients 46%. Regarding adverse effects, the study observed that among the 13 patients who received mTOR inhibitors, one patient 7.6% experienced mouth sores. Additionally, another patient 7.6% developed peripheral edema, which necessitated the discontinuation of the treatment.Conclusions: Our results are congruent with the findings reported in the literature. The incidence of adverse effects observed in our study was relatively low, indicating a favorable tolerability profile for mTOR inhibitor treatment.
Funding: None