Are cortical tubers epileptogenic? Evidence from electrocorticography

Abstract

SUMMARYThe purpose of this study was to characterize the epileptogenicity of tubers and surrounding cortex in patients with tuberous sclerosis complex (TSC). Three pediatric patients with TSC and intractable epilepsy underwent surgical resection of tubers associated with epileptogenic foci. In all patients, presurgical imaging revealed a prominent tuber that correlated on electroencephalography (EEG) with frequent interictal epileptiform discharges and electrographic seizures. Intracranial electrocorticography (ECoG) was performed using subdural grids placed over the tuber and surrounding cortex and depth electrodes positioned directly within the tuber. In all three patients, the depth electrode within the tuber was electrographically silent, whereas the surrounding cortical tissue showed significant epileptiform activity. The tuber and the electrically active adjacent cortex were resected. The patients experienced a drastic reduction in seizure frequency postsurgery. Epileptogenicity of cortical tubers may derive not from the lesion itself, but rather from the perturbation or abnormal development of the surrounding cortex.

LIS1 Deficiency Promotes Dysfunctional Synaptic Integration of Granule Cells Generated in the Developing and Adult Dentate Gyrus

“…These studies have identified important mechanisms leading to specific neuroanatomical pathologies that interrupt normal stages of cortical development. However, seizures can also arise in human brain regions not classified as disorganized Major et al, 2009), and clear evidence for a population of "epileptic" dysplastic neurons has failed to emerge (Cepeda et al, 2003;George and Jacobs, 2011). Using an animal model of human lissencephaly, we show that functional integration of granule cells within the malformed DG is disrupted by LIS1 haploinsufficiency.…”

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

“…Эпилеп-тогенная ткань в основе этого типа туберов отсутству-ет, что было документально подтверждено с помощью инвазивной фиксации ЭЭГ [49], и эти туберы не яв-ляются эпилептогенными, когда находятся строго ин-тракортикально, даже если их размер велик. Эпилеп-тогенными считаются туберы, которые окружены зоной ФКД -эти изменения видны в режиме Т2 и на изображениях, полученных при инверсии-вос-становлении с подавлением сигнала от свободной во-ды (FLAIR), они расцениваются экспертами как ФКД (изменения белого вещества с признаками ФКД) [14,28].…”