Abstracts

Rationale: Tuberous sclerosis complex (TSC) is a rare genetic multisystem disorder. Central nervous system is one of the most commonly and severely affected organ systems. Epilepsy is reported in 70% to 90% of patients, and usually appears in the first year of life. Although considerable information on TSC has been obtained from recent research, there are still many gaps in understanding the course of disease manifestations, interventions and their outcomes, presence of comorbidities, and quality of life. In addition, most data on epilepsy were obtained from small series or single-center studies. To address these knowledge gaps, an international prospective registry, TOSCA was developed collaboratively by medical experts, patient representatives, and a pharmaceutical company (Novartis). Methods: Patients of any age with a diagnosis of TSC and a documented visit within 12 months preceding enrollment or newly diagnosed individuals are eligible for the study. TOSCA includes a core data set with general mandatory information on patients' disease manifestations and subsections to collect additional data on selected topics. Estimated enrollment is approximately 2000 patients in 31 countries. After the current enrollment period of about 24 months (the baseline), a follow-up observation period of up to 5 years is planned. Interim analyses are performed annually with data available starting from 2014. Here, we focus on the first interim analysis of epilepsy-related data. Results: As of July 12, 2013, baseline core data from 508 patients had been entered in the database (45% male). Median age was 16 years (range: 0-71 years), median age at TSC diagnosis was 1 year (range: 0-67 years). Genetic testing was reported for 301/508 (59%) with mutations in TSC1 identified in 61 (20%) and TSC2 in 194 (65%). Four hundred twenty-five (84%; 46% males) had epilepsy: infantile spasms (IS) in 166/425 (39%) and focal seizures (FS) in 279/425 (66%). IS were reported in 44% of patients with mutations in TSC2 compared to 16% of patients with mutations in TSC1. One hundred twenty-two out of 166 (74%) patients with IS were treated with GABAergics and 28/166 (17%) with ACTH. GABAergics were used as single agent in 67/166 (40%) and in association with hormonal therapy in 19/166 (11%). IS were controlled in 69%. FS were reported in 49% and 64% of patients with mutations in TSC1 and TSC2, respectively. FS were diagnosed at age ≤ 2yrs in 74% of patients. FS were treated with GABAergics in 191 (69%, as single agent in 26%). FS were controlled in 51%. Conclusions: First interim analysis underlines the feasibility of this registry and shows preliminary data on IS and FS in a large multicenter European cohort of TSC. IS and FS are highly prevalent with epilepsy onset occurring mainly during the first 2 years of life. IS was more prevalent in patients with TSC2 mutations. One-third of IS patients and a half of FS patients did not respond to the major therapies available. These data confirm the literature from small series and single-center studies. A further detailed data collection on epilepsy is in progress.