Early Seizure Onset in TSC: Probing for Prognostic Markers

Introduction: Tuberous sclerosis complex (TSC) may be considered a genetic developmental and epileptic encephalopathy (Scheffer et al 2017), according to the fundamental contribution of both genetic factors and epileptic activity. The aim of our study is to verify whether strict monitoring of electroencephalography (EEG) activity and clinical observation before seizure onset may give prognostic clues to developmental outcome in TSC children.

Methods: Since the perinatal suspicion of TSC due to ultrasound detection of cardiac rhabdomyomas, six babies (4 M and 2 F) were followed with EEG monitorings and neurological evaluations every 2 to 4 months, up to 2 years. Patients underwent a complete clinical, neuroimaging, genetic, and developmental assessment as recommended for TSC.

Results: Four of the babies developed epilepsy: epileptic spasms were the first seizures in three babies, one started with focal seizures. Cognitive development was normal in the children with no epilepsy, but also in two children in which spasms were controlled by vigabatrin and no other seizure types occurred. The two children with drug-resistant, multiple type seizures developed intellectual disability and autistic features. All children except one (who did not develop epilepsy) carried a TSC2 mutation. At brain magnetic resonance imaging multiple cortical and subcortical tubers and subependymal nodules were evident in all the patients.

Discussion: In TSC, seizure onset in the first year of life is recognized to negatively contribute in worsening the final outcome. In our limited sample of children, the major contribution to neurodevelopment seems not only linked to seizure onset but rather to the opportunity of their prompt control.

No conflict of interest has been declared by the author(s).