Abstracts

Rationale: Epilepsy affects 80-90% of patients with Tuberous Sclerosis Complex (TSC) leading to psychiatric and behavioral comorbidities, including developmental delay and autism spectrum disorder. Recently, two large randomized, double blinded studies on preventive treatment of epilepsy have been published, demonstrating beneficial effect of early intervention. However, little is known about long term effect of preventive treatment. In the current study we assessed long-term outcome of preventively treated patients in comparison to the outcomes of patients treated after first seizures.

Methods: Two groups of TSC children treated in the Children’s Memorial Health Institute (CMHI) in Warsaw have been analyzed in the study: 1/ those treated within the open label trail published in 2011 and EPIMARKER project with the history of preventive treatment with vigabatrin started before 2 years of age, and 2/ children who received vigabatrin after the first clinical seizures.
All patients have been examined during a follow-up visit when the following data have been collected: age at onset of epilepsy, age at onset of treatment, number of antiseizure medications, presence of seizures at follow-up visit, psychological assessment including PEDS-QL for children and parents and TAND questionnaire.
The study has been approved by the institutional Ethical Board (decision Nr 20/KBE/2023).

Results: Twenty-nine patients aged 5-16 years (mean: 9.3 years; median: 9 years) received vigabatrin preventively and 34 children aged from 4 to 17 years (mean: 11 years; median: 11) were treated after first seizure. Genetic background was established in 43 children. The proportion of TSC2/TSC1 genotypes was similar in both groups (81% in standard treatment group vs 81.8 in preventive group).
At the follow-up visit preventive treatment was associated with statistically significant lower risk of epilepsy (21% in the preventive group vs. 53% in the standard one; p=0.009). Less children with preventive treatment demonstrated frequent seizures (14% vs 50%, respectively) (p=0.026). A non-significant trend was observed towards fewer antiseizure medications in the preventive treatment group (48% vs 71%, p=0.071). Intellectual disability was more profound and reported significantly more frequently in patients treated after seizures than those who received preventive vigabatrin. In standard treatment group 85% of patients demonstrated different forms of intellectual disability, versus 55.2 % in preventive group (p=0.008). There were no differences in the quality-of-life reports.

Conclusions: Preventive treatment with vigabatrin in infancy improves long-term neuropsychiatric and epilepsy outcomes in children with TSC.

Funding: A grant of the CMHI financed by the Ministry of Education and Science (S196/2022), grant EPIMARKER of the Polish National Center for Research and Development (STRATEGMED3/306306/4/2016), and Medical Research Agency grant ViRAP No 2019/ABM/01/00034/P/06.