Epilepsy in newborns with tuberous sclerosis complex.

Background: Epilepsy affects up to 90% of TSC patients and majority of them have seizure at the age of 3-5 months, after a period of latent epileptogenesis, but some develop epilepsy earlier.

Aims: The aim of this work was to identify incidence, clinical characteristics, and risk factors for neonatal onset of epilepsy in a large cohort of TSC patients.

Methods: A retrospective review of medical data of 421 TSC patients was performed. Patients who developed epilepsy within first 4 weeks of life were included in the study. Clinical and treatment data, EEG, MRI, and genetic analyses were assessed.

Results: Epilepsy was present in 366 (86.9%) patients. Twenty-one (5.7%) developed epilepsy as newborns. Mean follow-up was 44.86 (6-170) months. Six patients were seizure free and 15 had drug-resistant seizures at the end of follow-up. Mental retardation was found in 81% of patients. In 11 (52.4%) patients brain MRI revealed large malformations of cerebral cortex, meeting the criteria for focal cortical dysplasia (FCD). FCD was revealed in both TSC1 and TSC2 mutation cases. Other risk factors for neonatal epilepsy included: perinatal complications and congenital SEGAs. Presence of FCD was associated with more severe epilepsy and worse neuropsychological outcome. Epilepsy surgery resulted in improvement in seizure control.

Conclusions: Neonatal onset of epilepsy in TSC is frequently associated with large malformations of cerebral cortex. Patients with FCD are at high risk of severe drug-resistant epilepsy and poor neuropsychological outcome. Early epilepsy surgery may be beneficial and should be considered in such cases.