Identification of Focal Epileptogenic Networks in Generalized Epilepsy Using Brain Functional Connectivity Analysis of Bilateral Intracranial EEG Signals

Abstract

Simultaneous bilateral onset and bi-synchrony epileptiform discharges in electroencephalogram (EEG) remain hallmarks for generalized seizures. However, the possibility of an epileptogenic focus triggering rapidly generalized epileptiform discharges has been documented in several studies. Previously, a new multi-stage surgical procedure using bilateral intracranial EEG (iEEG) prior to and post complete corpus callosotomy (CC) was developed to uncover seizure focus in non-lateralizing focal epilepsy. Five patients with drug-resistant generalized epilepsy who underwent this procedure were included in the study. Their bilateral iEEG findings prior to complete CC showed generalized epileptiform discharges with no clear lateralization. Nonetheless, the bilateral ictal iEEG findings post complete CC indicated lateralized or localized seizure onset. This study hypothesized that brain functional connectivity analysis, applied to the pre CC bilateral iEEG recordings, could help identify focal epileptogenic networks in generalized epilepsy. The results indicated that despite diffuse epileptiform discharges, focal features can still be observed in apparent generalized seizures through brain connectivity analysis. The seizure onset localization/lateralization from connectivity analysis demonstrated a good agreement with the bilateral iEEG findings post complete CC and final surgical outcomes. Our study supports the role of focal epileptic networks in generalized seizures.

Altered integrity of corpus callosum in generalized epilepsy in relation to seizure lateralization after corpus callosotomy

“…2 Under this circumstance, the corpus callosum is considered to be a major pathway of seizure propagation in the bilateral epileptic network, which might have different configurations from nonfocal bilateral synchronization. 3 The results of DTI analysis in this study demonstrated that the corpus callosum suffered more structural damage related to demyelination in the lateralized group than in the nonlateralized group, causing reduced FA and increased RD. 4 This finding further indicates that different configurations of bilateral epileptic networks exist in generalized epilepsy with greater or less reliance on the corpus callosum, which inflicts varied structural alterations along their respective pathways.…”

“…eralization. 3,14 In some patients with generalized seizures, focal seizure onset might be discovered following disruption of the rapid propagation between two hemispheres after corpus callosotomy. 2 Therefore, the bilateral epileptic networks in generalized epilepsy with focal onset could have greater reliance on the corpus callosum for seizure propagation than the bilateral epileptic networks in generalized epilepsy with nonfocal bilateral synchronization.…”

Reiterating the role of corpus callosum in generalization of interictal and ictal epileptiform discharges: a case report with post-callosotomy intracranial electroencephalography in Lennox–Gastaut syndrome

“…Drop attacks are the most disabling feature of LGS and are known to be caused by secondary bilateral synchrony. This rapid spread via the CC explains the efficacy of callosotomy in reducing drop attacks in LGS patients [1,[4][5][6][7][8][9][10].…”

Neuronal network models of epileptogenesis

“… 1 Recent network analyses have, however, revealed that these so-called generalized epilepsies are in fact associated with a number of focal abnormalities. 40 …”