Comparison of outcomes after stereoelectroencephalography and subdural grid monitoring in pediatric tuberous sclerosis complex.

OBJECTIVE: Patients with tuberous sclerosis complex (TSC) epilepsy present with unique clinical challenges such as early seizure onset and high rates of intractability and multifocality. Although there are numerous studies about the safety and efficacy of stereoelectroencephalography (SEEG), this topic has not been studied in TSC patients who have distinct epilepsy profiles. The authors investigated subdural grid (SDG) and SEEG monitoring to determine whether these procedures lead to similar seizure and safety outcomes and to identify features unique to this pediatric population. METHODS: TSC patients who underwent SDG or SEEG placement and a second epilepsy surgery during the period from 2007 to 2021 were included in this single-center retrospective cohort analysis. Various patient, hospitalization, and epilepsy characteristics were collected. RESULTS: A total of 50 TSC patients were included in this study: 30 were included in the SDG cohort and 20 in the SEEG cohort. Baseline weekly seizure count did not significantly differ between the 2 groups (p = 0.412). The SEEG group had a greater mean baseline number of antiepileptic drugs (AEDs) (3.0 vs 2.0, p = 0.003), higher rate of previous surgical interventions (25% vs 0%, p = 0.007), and larger proportion of patients who underwent bilateral monitoring (50% vs 13.3%, p = 0.005). Despite this, there was no significant difference in seizure freedom between the SDG and SEEG cohorts. The mean reduction in seizure count was 84.9% and 47.8% of patients were seizure free at last follow-up (mean 79.4 months). SEEG trended toward being a safer procedure than SDG monitoring, with a shorter mean ICU stay (0.7 days vs 3.9 days, p < 0.001), lower blood transfusion rate (0% vs 13.3%, p = 0.140), and lower surgical complication rate (0% vs 10%, p = 0.265). CONCLUSIONS: In the comparison of the SDG and SEEG cohorts, the SEEG group included patients who appeared to receive more aggressive management and have a higher rate of multifocality, more prior surgical interventions, more AEDs at baseline, and a higher rate of bilateral invasive monitoring. Despite this, the SEEG cohort had similar seizure outcomes and a trend toward increased safety. Based on these findings, SEEG appears to allow for monitoring of a wider breadth of TSC patients given its minimally invasive nature and its relative simplicity for monitoring numerous regions of the brain.

Association of earlier surgery with improved postoperative language development in children with tuberous sclerosis complex.

OBJECTIVE: The authors evaluated the impact of the timing of epilepsy surgery on postoperative neurocognitive outcomes in a cohort of children followed in the multiinstitutional Tuberous Sclerosis Complex (TSC) Autism Center of Excellence Research Network (TACERN) study. METHODS: Twenty-seven of 159 patients in the TACERN cohort had drug-refractory epilepsy and underwent surgery. Ages at surgery ranged from 15.86 to 154.14 weeks (median 91.93 weeks). Changes in patients' first preoperative (10-58 weeks) to last postoperative (155-188 weeks) scores on three neuropsychological tests-the Mullen Scales of Early Learning (MSEL), the Vineland Adaptive Behavior Scales, 2nd edition (VABS-2), and the Preschool Language Scales, 5th edition (PLS-5)-were calculated. Pearson correlation and multivariate linear regression models were used to correlate test outcomes separately with age at surgery and duration of epilepsy prior to surgery. Analyses were separately conducted for patients whose seizure burdens decreased postoperatively (n = 21) and those whose seizure burdens did not (n = 6). Regression analysis was specifically focused on the 21 patients who achieved successful seizure control. RESULTS: Age at surgery was significantly negatively correlated with the change in the combined verbal subtests of the MSEL (R = -0.45, p = 0.039) and predicted this score in a multivariate linear regression model (ß = -0.09, p = 0.035). Similar trends were seen in the total language score of the PLS-5 (R = -0.4, p = 0.089; ß = -0.12, p = 0.014) and in analyses examining the duration of epilepsy prior to surgery as the independent variable of interest. Associations between age at surgery and duration of epilepsy prior to surgery with changes in the verbal subscores of VABS-2 were more variable (R = -0.15, p = 0.52; ß = -0.05, p = 0.482). CONCLUSIONS: Earlier surgery and shorter epilepsy duration prior to surgery were associated with greater improvement in postoperative language in patients with TSC. Prospective or comparative effectiveness clinical trials are needed to further elucidate surgical timing impacts on neurocognitive outcomes.

Epilepsy Is Heterogeneous in Early-Life Tuberous Sclerosis Complex.

BACKGROUND: Epilepsy in tuberous sclerosis complex (TSC) typically presents with early onset, multiple seizure types, and intractability. However, variability is observed among individuals. Here, detailed individual data on seizure characteristics collected prospectively during early life were used to define epilepsy profiles in this population. METHODS: Children aged zero to 36 months were followed longitudinally. Caregivers kept daily seizure diaries, including onset and daily counts for each seizure type. Patients with >70% seizure diary completion and >365 diary days were included. Developmental outcomes at 36 months were compared between subgroups. RESULTS: Epilepsy was seen in 124 of 156 (79%) participants. Seizure onset occurred from zero to 29.5 months; 93% had onset before age 12 months. Focal seizures and epileptic spasms were most common. Number of seizures (for median 897 days) ranged from 1 to 9128. Hierarchical clustering based on six metrics of seizure burden (age of onset, total seizures, ratio of seizure days to nonseizure days, seizures per seizure day, and worst seven- and 30-day stretches) revealed two distinct groups with broadly favorable and unfavorable epilepsy profiles. Subpopulations within each group showed clinically meaningful differences in seizure burden. Groups with higher seizure burden had worse developmental outcomes at 36 months. CONCLUSIONS: Although epilepsy is highly prevalent in TSC, not all young children with TSC have the same epilepsy profile. At least two phenotypic subpopulations are discernible based on seizure burden. Early and aggressive treatments for epilepsy in TSC may be best leveraged by targeting specific subgroups based on phenotype severity.