Ictal MEG-EEG Study to Localize the Onset of Generalized Seizures: To See Beyond What Meets the Eye

<b>Introduction:</b> Patients with generalized epilepsy are rarely referred for advanced diagnostics like magnetoencephalography (MEG). This is due to the assumption that generalized seizures cannot be localized noninvasively. <b>Methods:</b> We present simultaneous MEG (306 channels) and EEG (64 channels) data from seven patients with drug-resistant generalized epilepsy. Three patients experienced typical generalized seizures during their MEG clinical evaluation. In total, 38 epileptiform events (three seizures, 35 interictal discharges) were analyzed using two software platforms and three localization methods: equivalent current dipole (ECD), sLORETA (via SWARM), and dynamic statistical parametric mapping (dSPM). Individual head models were created from each patient's MRI. <b>Results:</b> MEG successfully localized seizure onset zones, showing distinct hypersynchronous discharges on all sensors as well as alternately during interictal discharges. Localization was consistent across methods and generalized events within subjects, revealing cortical sources in all cases, with rapid propagation (27-60 ms) across networks. <b>Conclusions:</b> This study demonstrates that MEG can meaningfully localize both seizures and interictal discharges in generalized epilepsy. This supports a broader use for MEG beyond focal epilepsy. Incorporating MEG in drug-resistant cases including generalized epilepsies may improve diagnosis and guide treatments including non-surgical options.