Authors :
Presenting Author: Sergiusz Jozwiak, MD, PhD – The Children's Memorial Health Institute
Julita Borkowska, MD – Neurology and Epileptology – The Children's Memorial Health Institute; Dariusz Chmielewski, MD – Neurology and Epileptology – The Children's Memorial Health Institute; Katarzyna Kotulska, MD, PhD – Neurology and Epileptology – The Children's Memorial Health Institute; Anna Makulec, MD – Medical University of Warsaw; Krzysztof Sadowski, MD, PhD – Neurology and Epileptology – The Children's Memorial Health Institute; Kamil Sijko, MSc, PhD – Transition Technologies, Warsaw, Poland; Dominika Smialek, MD – Medical University of Warsaw; Elzbieta Solowiej, MD, PhD – Medical University of Warsaw; Monika Szkop, Msc – Neurology and Epileptology – The Children's Memorial Health Institute
Rationale:
Epilepsy in Tuberous Sclerosis Complex (TSC) patients is characterized by early onset and drug-resistance in the majority of cases. In recent years, preventive strategies based on the introduction of antiseizure medication before the onset of clinical seizures and after the onset of epileptic discharges on EEG were showed to reduce the risk and severity of epilepsy in TSC children. Our small open label study showed that antiseizure medication might be successfully withdrawn in patients treated preventively. In the EPIMARKER study, we aimed to assess the success and risk factors for antiseizure medications withdrawal in TSC patients.
:
The EPIMARKER study was two-center, observational trial carried out between 2017 and 2022. All patients with definite diagnosis of TSC, aged from three to eighteen years, who were treated with antiseizure medications and were seizure free for at least two years were eligible for the study. Since enrolment the patients were followed for 12 months with clinical workouts and EEG recordings every three months. During the first six months, the antiseizure medications were tapered off, and starting from month seven, patients were free of antiseizure treatment. The primary endpoint of the study was the recurrence of seizures during the follow-up period.
:
Forty patients (16 girls and 24 boys, aged 3-18 years) were included in the study. Five patients dropped out. Among 35 patients who completed the study, 12 had received preventive treatment with vigabatrin, and 23 were treated after the onset of clinical seizures. Seizures recurred in 12 (34%) patients who completed the study: three (25%) in the preventive group and eight (35%) in the group treated after seizures. Patients in the preventive group were significantly younger at the timepoint of medication withdrawal than patients treated after the onset of seizures (median age: five years versus 9.5 years). The factors associated with the increased risk of relapse were: treatment initiation before the age of six months (seven relapses in 14 patients; 50% versus five relapses in 21 older patients; 24%) and history of treatment with more than one antiseizure medication (seven relapses in 17 patients; 41% versus three relapses in 16 patients who received only vigabatrin; 19%).
:
Antiseizure medication withdrawal may be successful in TSC patients who are free of seizures for at least two years, especially if they developed epilepsy later than in six months of age and were treated with only one medication. In preventively treated patients, the antiseizure medication withdrawal might be decided at younger age, reducing the risk of treatment associated adverse events.
Funding:
The study has been partly funded by the EJP RD project (grant agreement No. 825575) financed by the HORYZONT2020 Program co-financed by the program of the Ministry of Education and Science "PMW" in the years 2019-2023 grant EPIMARKER of the Polish National Center for Research and Development no. STRATEGMED3/306306/4/2016, grant VIRAP (Project number 2019/ABM/01/00034) and a statutory grant of the Children’s Memorial Health Institute financed by the Ministry of Science and Higher Education no. S196/2022
.