Abstracts

Rationale: Tuberous Sclerosis (TSC) is one of the leading causes of genetic epilepsy.  Only a small proportion of TSC patients will achieve seizure freedom with anti-seizure drugs. When medical therapies fail to control seizures, surgical interventions such as resective epilepsy surgery or palliative operations such as Vagal Nerve Stimulation and Corpus Callosotomy may be considered.  There is uncertainty with regards to effectiveness of these procedures including seizure freedom rates and the number of anti-seizure drug treatments following surgery.  The development of the TSC Natural History Database by the Tuberous Sclerosis Alliance represents a unique opportunity to obtain real-world data on a large number of participants with TSC with respect to seizure outcomes and drug therapy following epilepsy surgery. Methods: De-identified individual participant data was extracted from pediatric participants with epilepsy using the TSC Natural History Database. Patient data was available from the inception of the database in 2006 through 2016 and was obtained from 18 institutions in the United States. Multiple variables were extracted including seizure type (focal seizures vs. spasms), type of surgical intervention and the number of concomitant anti-seizure drugs required. Results: Of 1668 pediatric participants with epilepsy, 187 (11.2%) underwent epilepsy surgery. In the subset of patients with infantile spasms and focal seizures, individuals who underwent palliative surgical procedures were noted to have significantly worse focal seizure control as compared to those undergoing resective epilepsy surgery; 9 of 31 (29%) vs. 45 of 71 (63%) participants with seizure control, respectively (OR 0.24; p = 0.009). Further, patients who underwent larger resections such as a Lobectomy or greater were noted to be using fewer anti-seizure drugs as compared to patients who underwent a Tuberectomy alone [46 of 71 (64.8%) participants with larger resections on no drug treatments versus 35 of 80 (43.8%) participants with Tuberectomy on no drug treatments p=0.031]. Infantile spasm outcomes were not significantly affected by surgical intervention as compared to those who were exclusively treated medically. Conclusions: Natural history data in the surgical management of epilepsy in TSC is inherently challenging to obtain given the rarity of disease.  Using the TSC natural history database, we found that the number of anti-seizure drugs following resective surgical approaches is significantly reduced when treating focal seizures.  This study also suggests that larger surgical resections may have a role in reducing the total number of anti-seizure drugs required for focal seizure control in TSC patients.  This analysis represents a step toward the development of evidence-based guidelines for neurosurgical intervention in TSC. Funding: GWM is partly supported by the DAVIES/Crandall Endowed Chair for Epilepsy Research at UCLA