Abstracts

Rationale: Up to 90% of children with Tuberous Sclerosis Complex (TSC) develop epilepsy, and in up to 2/3 of these, seizures are refractory to medical management. Refractory seizures are strongly associated with adverse neurodevelopmental outcomes. While refractory epilepsy prompts the consideration of early epilepsy surgery, there is scant understanding of neurodevelopmental and surgical outcomes in this population. We investigated these outcomes following epilepsy surgery in a population of children with refractory epilepsy and TSC who underwent epilepsy surgery before the age of two years. Methods: From 160 children enrolled in the TSC Autism Center of Excellence Network (TACERN), a prospective multicenter observational study of early predictors of epilepsy and autism spectrum disorder, 19 children had epilepsy surgery before age two. Demographic and clinical data was retrieved from TACERN case report forms, with electronic medical records providing information on procedural details, complications and surgical outcomes. Developmental outcomes were assessed with the Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behavior Scales- Second Edition (Vineland-II) and the Preschool Language Scales - 5th Edition (PLS-5). Mean developmental scores were compared between four groups: 1) epilepsy surgery (N=19), 2) never developed seizures (N=32), 3) medically controlled seizures (N=42), 4) developed refractory epilepsy but no surgery (N=33). Results: In the surgical group, 74% were female. 89% had a TSC2 mutation, and 11% had no identifiable mutation. Median age at seizure onset was 2.2 months (0.3-10.9), and for the surgically targeted seizure type 4.7 months (0.3 -12.8). The targeted seizure type was focal dyscognitive in all cases; however, 13 (68%) also had infantile spasms, with onset before the targeted seizure type in 8 (42%). Median age at surgery was 16.9 months (3.7-21.3). Surgical approaches included tuberectomy in 7/19, multiple tuberectomy or tuberectomy with adjacent white matter resection in 8 and partial lobectomy in 4. Surgical complications occurred in 11 (58%) – although some deficits were anticipated and many were minor. The mean duration of follow-up after surgery was 22.8 months (range 12-48). 12 (63%) had a favorable surgical outcome (Engel I-II), and 10 (53%) had an excellent outcome (Engel I) for the targeted seizure type. 9 (47%) had ongoing seizures distinct from the targeted type or developed a new seizure type. 5 (26%) underwent at least one additional epilepsy surgery.Developmental scores for those that never developed seizures remained stable over time. Those with seizures showed a decline in scores (MSEL and Vineland-II) or attenuated gains (PLS-5) over time, with the lowest mean scores in the surgical group (before surgery), followed by the refractory group and then the medically controlled group. Post-operatively, the epilepsy surgery group showed a positive but non-significant increase in mean Vineland-II Standard Scores (SS), MSEL SS and PLS-5 Total Language Scores, surpassing the refractory group in the latter two tests (Figure 1). Gains in language development were also evident in language subtests of the MSEL and Vineland-II and were more distinct in those with favorable surgical outcome (Figure 2). Motor scales showed a less consistent improvement between tests. Conclusions: In TSC, surgical outcome metrics extend beyond Engel classification and goals should include neurodevelopmental gains. A prospective multicenter early epilepsy surgical study including tailored neurodevelopmental outcomes is needed to more accurately assess the potential benefit of surgical intervention in this population. Funding: NIH P20 NS080199 and U01 NS082320