Abstracts

Rationale: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder causing hamartomatous lesions in several organ systems including brain, heart, lungs, skin, liver, and kidneys. Epilepsy is the most common presenting symptom of TSC occurring in 65-74% of the patients. Onset of epilepsy is typically in the first year of life, associated with an increased risk of neurodevelopmental and cognitive problems. TuberOus SClerosis registry to increase disease Awareness (TOSCA) is designed to address the knowledge gaps in understanding of TSC and its manifestations. Preliminary epilepsy-related data available from the baseline data of the entire cohort are presented here.Methods: TOSCA has been designed to collect patient data both prospectively and retrospectively. Eligible patients had a documented visit for TSC within 12 months before participation or were newly diagnosed with TSC. TOSCA includes a core section to record patients’ background information and research projects that focus on specific disease manifestations. Patients enrolled in the registry will be followed for up to 5 years. Annual interim analyses are being conducted.Results: As of September 30, 2014 (cutoff date for 2nd interim analysis), the baseline core data from 2093 patients had been analyzed. The median age of patients at consent was 13 years (range, 0-71); the median age at diagnosis of TSC was 1 year (range, 0-69). Epilepsy was reported in 83.5% of the patients with TSC. The majority of patients reported focal seizures (FS, 66.9%), while 38.8% reported infantile spasms (IS). Among patients ≤ 2 years of age, IS were reported in 95.5% and FS in 73.0% of the patients. Patients with TSC2 mutations had a higher frequency of IS than those with TSC1 mutations (46.5% vs 20.8%). FS were reported in 72.2% of the patients with TSC2 mutations and 75.0% of the patients with TSC1 mutations. GABAergic drugs either individually or in combination with other agents were the most commonly used treatment modality for both IS (78.3%) and FS (65.1%). Mammalian target of rapamycin (mTOR) inhibitors were used in 5.2% of the patients with IS and 7.0% of the patients with FS. IS and FS were controlled with the treatment in 71.5% and 58.7% of the patients, respectively. Epilepsy surgery was performed in 3.8% of the patients with IS and 7.0% of the patients with FS.Conclusions: TOSCA database confirms that epilepsy is a very common manifestation occurring early in the course of TSC. IS was observed more often in patients with TSC2 mutations. These findings from TOSCA may represent the best practice in the management of epilepsy associated with TSC including widespread use of GABAergic inhibitors and increasing use of mTOR inhibitors. Patient recruitment could be an inherent bias of the study as the majority of recruitment centers were pediatric neurology clinics. The research project on epilepsy will explore the electroclinical characteristics of epilepsy, evaluate the timing of the interventions to control seizures, and assess the impact of treatment interventions on neurocognitive development.