Electrocorticographic evidence of perituberal cortex epileptogenicity in tuberous sclerosis complex

Abstract

Object Tuberous sclerosis complex (TSC) is a multisystem autosomal dominant disorder resulting in hamartomas of several organs. Cortical tubers are the most prominent brain lesions in TSC. Treatment-resistant epilepsy often develops early in life in patients with TSC and is associated with severe intellectual and behavioral impairments. Seizures may remit following epilepsy surgery in selected cases, yet it remains unclear whether the tuber or the perituberal cortex is the source of seizure onset. In this study, the authors reviewed the onset of seizures in patients in whom depth electrodes had been placed within or adjacent to cortical tubers. Methods After obtaining institutional review board approval, the authors retrospectively reviewed data from 12 pediatric patients with multifocal TSC and treatment-resistant epilepsy who had undergone invasive intracranial electroencephalographic monitoring. Tubers were identified on postimplantation MRI, and all depth electrodes were located. Depth electrode contacts were classified visually as either tuber/perituberal cortex or nontuber/nonperituberal cortex. Board-certified clinical neurophysiologists reviewed the seizures to identify all electrodes involved in the ictal onset. Results Among 309 recorded seizures, 104 unique ictal onset patterns were identified. Of the 11 patients with electrodes recording in a tuber, 9 had seizure onsets involving the tuber. Similarly, of the 9 patients with perituberal recording electrodes, 7 had perituberal ictal onsets. Overall, there was no difference in the percentage of contacts involved in seizure onset between the tuber and perituberal cortex. In a subset of 7 patients in whom at least 1 depth electrode contact was within the tuber and 1 was in the perituberal cortex, there was no difference between the percentage of tuber and perituberal onsets. Conclusions Findings demonstrated heterogeneity in the ictal onset patterns as well as involvement of the tuber and perituberal cortex within and between patients. Although the data are limited by the restricted region(s) sampled with intracranial electrodes, they do suggest that cortical hyperexcitability in TSC may derive from the tuber or surrounding cortex.