Introduction: Epilepsy occurs in 70–90% of patients with tuberous sclerosis complex (TSC). Here we report the baseline and follow-up data of epilepsy from the final analysis of TOSCA study.

Methods: TOSCA, an international TSC registry, collected patient’s data at least once per year for 5 years. Data included seizure type, age at onset and treatment in association with genotype and intellectual ability.

Results: 1845/2211 (83.4%) patients had epilepsy (infantile spasms [IS:39.1%], focal seizures [FS:68.3%]) at baseline. The mean age at diagnosis of IS and FS was 0.4year and 2.7year, respectively. IS was higher in patients with TSC2 vs TSC1mutation (48.2% vs 22.4%). GABAergic drugs were the most common treatment, for both IS (79.3%) and FS (66.2%). Uncontrolled seizures were reported in 16.2%(IS) and 40.3%(FS) of patients. In the follow-ups (F1-F4), 17.1%, 15.0%, 12.9%, 13.3% of patients presented IS and 69.5%, 68.1%, 72.0%, 69.6% had FS, respectively. During the follow-up lack of seizure control increased from 57.2% to 68.2% (IS) and 75.1% to 80.5% (FS). Control of seizures was associated with lower rates of intellectual disability in both IS and FS groups.

Conclusions: FS were the most common form of epilepsy in the TOSCA study. IS was observed more in patients with TSC2 mutations. Follow-up data showed more patients with uncontrolled seizures, both IS and FS, despite greater use of GABAergic inhibitors and ACTH suggesting a high-level of pharmacoresistance. The number of patients decreased during the follow-ups, highlighting the difficulty of collection of data in international natural history registries.