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

Abstract

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.

From cryogenic to on‐scalp magnetoencephalography for the evaluation of paediatric epilepsy

“…35 Connectivity analyses may also explain the neural substrates underlying behavioural or neuropsychological disturbances (e.g. they may explain attention disorders and memory impairments in patients with childhood absence epilepsy or the maintenance of awareness despite generalized spike-wave discharges 34 ) or predict the response to antiseizure medication (e.g. they may differentiate responders and non-responders to ethosuximide among patients with childhood absence epilepsy 34 ).…”

“…MEG helps to better understand the physiopathology of paediatric epilepsies and to assess treatment/prognosis markers using source localization and connectivity analyses (e.g. in childhood absence epilepsy as an example of generalized epilepsy, 34 or in epileptic encephalopathies with continuous spike–waves during sleep as an example of focal epilepsy 35 ).…”

“…As illustrative examples, MEG studies have demonstrated that the pre‐ictal state activity of childhood absence epilepsy (i.e. 50 ms before seizure onset) is focal, 34 highlighting the continuum between focal and generalized epilepsies, which start from a local brain area with rapid subsequent generalization. MEG studies have also contributed to a better understanding of the pathophysiology of epileptic encephalopathies with continuous spike–waves during sleep by demonstrating the spatiotemporal dynamics of epileptiform discharges, 26,35 and their relationship with metabolic neural changes 35 …”

Synthetic Epileptic Brain Activities with TripleGAN

“…EEG source localization is the problem of estimating the source of EEG activity from a given scalp EEG distribution, which is usually called the inverse problem of EEG. At present, the methods used to locate EEG activity sources mainly include equivalent current dipole (ECD) [16], sparse and Bayesian framework [17], beamforming and scanning algorithms [18], minimize L2 normal family [19], and nonlinear post hoc normalization [20]. In recent years, more researches have been made on introducing the timing pattern of the signal in the process of determining the position of the source signal [16][17][18].…”

“…At present, the methods used to locate EEG activity sources mainly include equivalent current dipole (ECD) [16], sparse and Bayesian framework [17], beamforming and scanning algorithms [18], minimize L2 normal family [19], and nonlinear post hoc normalization [20]. In recent years, more researches have been made on introducing the timing pattern of the signal in the process of determining the position of the source signal [16][17][18]. After introducing the time information, the adjacent temporal signals can provide more observation data for the underdetermined EEG inverse problem, thus compressing the solution space and making the inverse problem easier to solve.…”