Electrocorticographic evidence of perituberal cortex epileptogenicity in tuberous sclerosis complex

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p></jats:sec>

Neurophysiological evidence of preserved connectivity in tuber tissue

“…The observed physiologic and imaging phenomena, the presence of robust MEPs from nTMS stimulation and preserved CS tracts identified by DTI tractography, within the tuber tissue in our patient provide functional and structural support of the intermixing of tuber and functional tissue. This is in agreement with current pathological [4], [26] diffusion imaging [27], and with physiological evidence of widespread and variable degrees of pathology in TSC [28], [29], [30], [31].…”

Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

“…Cortical tubers are considered to represent the neuropathologic substrate of epilepsy in TSC patients. Despite recent advances in imaging and electrophysiologic techniques, the functional role of tubers as the epileptogenic zone remains a matter of some debate [216][217][218][219]. Increasing evidence supports the importance of the perituberal cortex in TSC (for reviews see [165,218] and [219]).…”

“…Despite recent advances in imaging and electrophysiologic techniques, the functional role of tubers as the epileptogenic zone remains a matter of some debate [216][217][218][219]. Increasing evidence supports the importance of the perituberal cortex in TSC (for reviews see [165,218] and [219]). Accordingly, although epilepsy surgery targeting tubers may result in seizure freedom, [216,220] some patients continue to have seizures after tuber resection and, in fact, cases of TSC patients becoming seizure-free after resection of nontuberal cortex have been reported [221] (for a review see [165]).…”

Epilepsy Surgery in Patients With Tuberous Sclerosis

“…Такая подклассификация различных типов тубе-ров отсутствует в двух последних работах, в которых рассматривается вопрос генерации эпилептических приступов: в пределах туберов или в прилежащих об-ластях коры, согласно одному исследованию [50], большинство эпилептических приступов генерируют-ся внутри туберов, в то время как в другом [47] сооб-щалось о гетерогенных ситуациях -зоны развития эпилептических приступов в пределах туберов и вне их (т. е. в коре, прилегающей к туберам).…”