Abstracts

Rationale: Increasingly tuberous sclerosis complex (TSC) is diagnosed prenatally or in the neonatal period before the onset of epilepsy. This provides an opportunity to validate the utility of EEG as a biomarker for epilepsy in the TSC infant and opening an opportunity for early intervention. This is of critical importance because 80% of TSC individuals will develop epilepsy (60% refractory epilepsy). These are the results from a multicenter prospective observational study of TSC infants focusing on epileptogenesis with EEG, clinical seizure onset, and developmental outcome at 24 months of age. Methods: TSC infants were recruited from 5 TSC centers. Enrollment inclusion criteria included: 1) age > 7 months, 2) history of seizures or 3) current or past treatment with AEDs or mTOR inhibitor. All infants underwent serial physical examinations, 1 hour video-EEGs and developmental assessments. Once seizure onset occurred, the TSC infants were treated based on standard of care. Categorical outcomes were summarized by percentages and between-group differences assessed using chi-square tests. Continuous outcomes were summarized by means, medians, standard deviation and ranges; between-group differences were evaluated with ANOVA models. Linear mixed models were used to evaluate longitudinal outcomes. All analyses were performed in SAS version 9.4. Results: The primary analysis included 32 subjects and 6 subjects were pretreated with AEDs because of electrographic seizures on EEG before clinical seizure onset (separate sub-analysis). Gender was distributed -22 Males (58%) and 16 females (42%), and average age at enrollment was 82.4 days +/- 59.8. Subjects had genetic testing: TSC1-7(20%), TSC2- 26(74%), No Mutation Identified (NMI)- 2(6%), pending-3 subjects. For the analyses, subjects were divided into 4 groups. Seventeen of the 32 subjects had evidence of EEG interictal epileptiform activity prior to clinical seizure onset (True Positives) and 3 subjects had no evidence of epileptiform activity prior to their clinical seizure onset (False Negatives). Seven subjects had a normal EEG and never developed seizures (True Negatives) and 5 subjects had EEG interictal epileptiform activity but did not develop seizures (False Positives).  Summary of the statistical analysis is in Table 1. Focal seizures (FS) occurred in (35%), epileptic spasms (ES) in 30% and a combination of ES and FS occurred in 30% and 1had a generalized tonic clonic seizure (5%). Twelve of the 32 subjects remained seizure free. The Mullen Scales of Early Learning and Vineland Adaptive Behavioral Composite Scores were analyzed between 6 subgroups (Fig.1). Conclusions: This study highlights the importance of early and close EEG surveillance in TSC infants before seizure onset. There is a critical window between the emergence of epileptiform discharges and the onset of clinical seizures, providing an opportunity to implement disease-modifying antiepileptogenic strategies. This study also illustrates the developmental outcome differences between TSC infants with refractory epilepsy. Funding: NINDS-P20-NS080199, UO1-NS082320 and the Tuberous Sclerosis Alliance