Abstracts

Rationale: Tuberous Sclerosis Complex (TSC) is a dominant genetic disorder caused by mutations in either TSC1 or TSC2 genes. Brain lesions present as cortical tubers, subependymal nodules and subependymal giant cell astrocytomas (SEGA). Up to 90% of TSC patients have epilepsy, most of whom have onset in infancy or early childhood. (Jacobs J, Epilepsia 2008, 49(5):816). Epilepsy is often refractory to antiepileptic drugs (AED) and an unfavorable course has been described in those children with seizure onset in the first year of life, as their risk for developmental and social regression is compounded by their frequent seizures and epileptic encephalopathy. (Madhavan D, Epilepsia 2007, 48(8):1625). AEDs combined with non-medical treatments such as the ketogenic diet or vagal nerve stimulator (VNS) can provide adequate seizure control for a portion of these children. However, for many of them the most effective option is epilepsy surgery that sufficiently disrupts the epileptogenic network formed by multiple foci. (Weiner HL, Pediatrics 2006, 117:1494; Baumgartner J, Neurosurgery 1997, 27:311). Here we describe a stepwise surgical approach in five children with TSC and multiple epileptogenic foci that combines corpus callosotomy and cortical resection. Methods: Five children ages 4-17 years with TSC and refractory epilepsy underwent surgery at our institution in the last three years. Age at seizure onset was between 8 weeks and 18 months of life. Seizure types were variable and included complex partial, atonic, atypical absence and mixed flexor spasms. All children experienced multiple daily seizures despite multiple AEDs and VNS (3 patients). All received a Phase I evaluation that included cerebral magnetic resonance imaging (3TMRI), video-Electroencephalogram (VEEG), and magnetoencephalography (MEG). Corpus callosotomy was performed in all patients. Phase II evaluation with bilateral subdural grids of electrodes was performed in 4 patients, and unilateral grids in one patient. Bilateral resections were performed in 4 patients, and unilateral in one. Two patients had a resection prior to care by our group. Results: IEEG revealed multifocal but stereotypical patterns of propagation with clearly lateralized and regionalized onset. MEG spike localization was often multifocal, and coincided with IEEG patterns of seizure onset and propagation, as well as with location of tubers or areas of dysplasia seen on 3TMRI. Two patients underwent repeat phase II or III before complete seizure control was achieved, often requiring resection of multiple distinct and independent foci. All patients are currently seizure free, with period of seizure freedom ranging from 3 to 34 months. Language and social interactiveness improved in all. Surgical complications included mild hemiparesis in one patient that improved with therapy, and superficial incision infection in one patient which resolved with antibiotics. Conclusions: A stepwise surgical approach combining corpus callosotomy and multiple resections in TSC children can lead to seizure freedom and improved developmental outcome.