Abstracts

Rationale: Magnetoencephalography (MEG) is a noninvasive clinical neurophysiological tool used to localize epileptiform activity in focal and multifocal epilepsies. More recently we have expanded its clinical utility for noninvasive functional mapping of the eloquent cortex in patients being evaluated for epilepsy surgery. Patients with presumed generalized epilepsies are seldom referred for a MEG study due to assumptions that these seizures cannot be reliably lateralized or localized in the brain. The International League Against Epilepsy (ILAE) defines generalized epilepsies as a broad group of disorders associated with generalized seizures and interictal discharges, but also recognizes that the onset could be focal within rapidly engaging, bilaterally distributed, networks. In this study we aim to demonstrate a potential application of MEG in localizing the onset of generalized seizures due its superior temporal and spatial resolution. This will impact the way we approach patients with refractory generalized epilepsies in the future, and might lead to precision targeted therapies.


Methods: We analyzed the electromagnetic data of three patients with refractory generalized epilepsy utilizing MEG (306 channels) and electroencephalography (EEG) (64 channels) simultaneously, and captured stereotypical seizures during the recording. Localization analysis of 10 interictal discharges and one seizure was performed using two methods: equivalent current dipole method (ECD) and sLORETA-weighted accurate minimum norm (SWARM) current source distribution method (CURRY, Neuroscan). The individual real head model for each patient was reconstructed from their corresponding T1 MRI images

Results: All three patients had their stereotypical interictal and ictal signatures captured during the MEG/EEG recording with the “classically” associated generalized spike and wave discharges. Specifically, two patients had absence seizures and one had a generalized tonic-clonic seizure. Simultaneous MEG and EEG recordings showed a clear characteristic hypersynchronous discharge across all sensors corresponding to the beginning of the seizure as well as for interictal discharges. Localization analyses were concordant for both ictal and interictal activity on MEG/EEG data in all three patients. Figures 1-3 (A) show the MEG/EEG data at sensor level for seizure onset well as corresponding brain source localization of the ictal onset and rapid propagation of generalized seizure. Figures 1-3 (B) illustrate the localization of the spike-wave pattern corresponding to interictal discharges. All three patients had right frontal (superior and middle frontal gyri) localizations of their ictal and interictal generalized activity.


Conclusions: Noninvasive MEG analysis of ictal and interictal generalized epileptogenic activity can provide valuable information regarding the localization of signal generators even in epileptic disorders recruiting the broad networks rapidly. The clinical utility of MEG should not be limited to the evaluation of focal epilepsies, and should be expanded to analyze generalized epilepsies to guide precision treatment in refractory cases.


Funding: NIH P20GM130447 CoNDA Award