Contributions of Magnetoencephalography to Understanding Mechanisms of Generalized Epilepsies: Blurring the Boundary Between Focal and Generalized Epilepsies?

According to the latest operational 2017 ILAE classification of epileptic seizures, the generalized epileptic seizure is still conceptualized as "originating at some point within and rapidly engaging, bilaterally distributed networks." In contrast, the focal epileptic seizure is defined as "originating within networks limited to one hemisphere." Hence, one of the main concepts of "generalized" and "focal" epilepsy comes from EEG descriptions before the era of source localization, and a presumed simultaneous bilateral onset and bi-synchrony of epileptiform discharges remains a hallmark for generalized seizures. Current literature on the pathophysiology of generalized epilepsy supports the concept of a cortical epileptogenic focus triggering rapidly generalized epileptic discharges involving intact corticothalamic and corticocortical networks, known as the cortical focus theory. Likewise, focal epilepsy with rich connectivity can give rise to generalized spike and wave discharges resulting from widespread bilateral synchronization. Therefore, making this key distinction between generalized and focal epilepsy may be challenging in some cases, and for the first time, a combined generalized and focal epilepsy is categorized in the 2017 ILAE classification. Nevertheless, treatment options, such as the choice of antiseizure medications or surgical treatment, are the reason behind the importance of accurate epilepsy classification. Over the past several decades, plentiful scientific research on the pathophysiology of generalized epilepsy has been conducted using non-invasive neuroimaging and postprocessing of the electromagnetic neural signal by measuring the spatiotemporal and interhemispheric latency of bi-synchronous or generalized epileptiform discharges as well as network analysis to identify diagnostic and prognostic biomarkers for accurate diagnosis of the two major types of epilepsy. Among all the advanced techniques, magnetoencephalography (MEG) and multiple other methods provide excellent temporal and spatial resolution, inherently suited to analyzing and visualizing the propagation of generalized EEG activities. This article aims to provide a comprehensive literature review of recent innovations in MEG methodology using source localization and network analysis techniques that contributed to the literature of idiopathic generalized epilepsy in terms of pathophysiology and clinical prognosis, thus further blurring the boundary between focal and generalized epilepsy.