Abstracts

Rationale: Ninety percent of patients with TSC have epilepsy and seizures commonly start in early childhood. Seizures are often medically refractory and closely linked with mental retardation and behavioural abnormalities. Identification of epileptogenic areas can be difficult, as multiple tubers and extensive networks are involved ictally and interictally. Simultaneous recording of EEG and functional MRI (fMRI) is a non-invasive tool to evaluate such epileptogenic networks. In this study, EEG-fMRI is used for the first time to delineate the irritative zone in children with TSC.Methods: Five children with focal epilepsy were evaluated; all were diagnosed with TSC based on clinical criteria and genetic testing. Scanning consisted of 20 minutes EEG-fMRI at 3T under sedative induced sleep. EEG was recorded from 30 scalp sites using an MRI compatible cap. EEG was filtered and spikes were identified according to spatial distribution and morphology. Each spike type was analyzed as a seperate event of a single general linear model, constituting a separate EEG-fMRI study. Spike timings were used for an event-related analysis. Tubers, subependymal nodules and subependymal giant-cell astrocytomas were marked by a neuroradiologist on MRI, based on T1, T2 and FLAIR images. Positive and negative BOLD (Blood Oxygenation Level-Dependent)responses were analyzed relative to the lesions and EEG focus.Results: One patient was scanned twice and 4 patients showed more than one spike type, which resulted in 13 studies. A BOLD response was observed 12/13 studies (93.3%) and in all more than one tuber was involved. Ten studies showed activations as well as deactivations and two studies showed only deactivations. Lesional activations were seen in 6/13 studies (46.2%). In 4 studies activation extended to perilesional areas and one study showed exclusively perilesional activation. Eight studies showed lesional deactivations (61.5%), with 4 extending to perilesional areas. Deactivations limited to perilesional areas were seen in 6 studies (64.1%). In all patients at least one tuber in the lobe of interictal spike generation, and presumed seizure onset (according to telemetry), showed a BOLD response. In all studies the observed changes were multifocal and sometimes tubers distant from the spike field were involved.Conclusions: In all children with TSC BOLD responses involving several tubers were observed during interictal spike generation. Although BOLD responses were limited to parts of the lesion in all tubers, extension beyond tuber boundaries and even exclusive involvement of perilesional areas was noted. All together these findings suggest a large epileptogenic network in patients with TSC. This network extends the one described in PET and SPECT studies, which often suggest only one or a few tubers to show intrinsic epileptogenicity. Nevertheless it confirms results from MEG and neurocognitive studies finding widespread brain changes in patients with TSC. This has to be kept in mind when planning surgical intervention in these patients.