Evaluation of epileptogenic networks in children with tuberous sclerosis complex using EEG-fMRI

Purpose: Ninety percent of patients with tuberous sclerosis complex (TSC) have epilepsy. Identification of epileptogenic areas can be difficult and studies are needed to characterize the epileptogenic network in more detail. Methods: Five children with TSC and focal epilepsy were studied using simultaneous EEG and functional MRI recordings. Tubers were marked by a neuroradiologist on the anatomical MRI. Spike-associated BOLD (blood oxygenation level-dependent) responses were superimposed with lesions. Results: Thirteen different types of interictal epileptiform discharges (IED) were analyzed with 12 showing a BOLD response, all involving more than one tuber. Five studies had tubers with activations exclusively within the lesion, three studies had lesional activations extending to perilesional areas, and two studies had activations involving exclusively perilesional areas of at least one tuber. Deactivations exclusively within a tuber were found in six studies, lesional deactivations extending to perilesional areas were found in four studies, and tubers with exclusively perilesional deactivations were found in five studies. A BOLD response was found in at least one tuber in the lobe of IED generation and presumed seizure onset (according to telemetry) in all patients. In four patients, the same tubers were involved following different IED localizations. The observed changes were always multifocal, sometimes involving tubers distant from the IED field. Discussion: These findings suggest extended epileptogenic networks in patients with TSC, which exceed networks described in PET and SPECT studies. It was possible to identify specific interictally active tubers. EEG-fMRI provides a noninvasive method to select tubers and areas at their borders for further presurgical investigations.