Early epileptiform EEG activity in infants with tuberous sclerosis complex predicts epilepsy and neurodevelopmental outcomes

Objective: To study the association between timing and characteristics of the first electroencephalography (EEG) with epileptiform discharges (ED-EEG) and epilepsy and neurodevelopment at 24 months in infants with tuberous sclerosis complex (TSC). Methods: Patients enrolled in the prospective Epileptogenesis in a genetic model of epilepsy – Tuberous sclerosis complex (EPISTOP) trial, had serial EEG monitoring until the age of 24 months. The timing and characteristics of the first ED-EEG were studied in relation to clinical outcome. Epilepsy-related outcomes were analyzed separately in a conventionally followed group (initiation of vigabatrin after seizure onset) and a preventive group (initiation of vigabatrin before seizures, but after appearance of interictal epileptiform discharges [IEDs]). Results: Eighty-three infants with TSC were enrolled at a median age of 28 days (interquartile range [IQR] 14–54). Seventy-nine of 83 patients (95%) developed epileptiform discharges at a median age of 77 days (IQR 23–111). Patients with a pathogenic TSC2 variant were significantly younger (P-value.009) at first ED-EEG and more frequently had multifocal IED (P-value.042) than patients with a pathogenic TSC1 variant. A younger age at first ED-EEG was significantly associated with lower cognitive (P-value.010), language (P-value.001), and motor (P-value.013) developmental quotients at 24 months. In the conventional group, 48 of 60 developed seizures. In this group, the presence of focal slowing on the first ED-EEG was predictive of earlier seizure onset (P-value.030). Earlier recording of epileptiform discharges (P-value.019), especially when multifocal (P-value.026) was associated with higher risk of drug-resistant epilepsy. In the preventive group, timing, distribution of IED, or focal slowing, was not associated with the epilepsy outcomes. However, when multifocal IEDs were present on the first ED-EEG, preventive treatment delayed the onset of seizures significantly (P-value <.001). Significance: Early EEG findings help to identify TSC infants at risk of severe epilepsy and neurodevelopmental delay and those who may benefit from preventive treatment with vigabatrin.