Glutamate is an essential excitatory neurotransmitter in the central nervous system, playing an indispensable role in neuronal development and memory formation. The dysregulation of glutamate receptors and the glutamatergic system is involved in numerous neurological and psychiatric disorders, especially epilepsy. There are two main classes of glutamate receptor, namely ionotropic and metabotropic (mGluRs) receptors. The former stimulate fast excitatory neurotransmission, are N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and kainate; while the latter are G-protein-coupled receptors that mediate glutamatergic activity via intracellular messenger systems. Glutamate, glutamate receptors, and regulation of astrocytes are significantly involved in the pathogenesis of acute seizure and chronic epilepsy. Some glutamate receptor antagonists have been shown to be effective for the treatment of epilepsy, and research and clinical trials are ongoing.

Status epilepticus (SE) is a neurological emergency with a high mortality rate. When compared to chronic epilepsy, it is distinguished by the durability of seizures and frequent resistance to benzodiazepine (BZD). The Receptor Trafficking Hypothesis, which suggests that the downregulation of γ-Aminobutyric acid type A (GABAA) receptors, and upregulation of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors play major roles in the establishment of SE is the most widely accepted hypothesis underlying BZD resistance. NMDA and AMPA are ionotropic glutamate receptor families that have important excitatory roles in the central nervous system (CNS). They are both essential in maintaining the normal function of the brain and are involved in a variety of neuropsychiatric diseases, including epilepsy. Based on animal and human studies, antagonists of NMDA and AMPA receptors have a significant impact in ending SE; albeit most of them are not yet approved to be in clinically therapeutic guidelines, due to their psychomimetic adverse effects. Although there is still a dearth of randomized, prospective research, NMDA antagonists such as ketamine, magnesium sulfate, and the AMPA antagonist, perampanel, are regarded to be reasonable optional adjuvant therapies in controlling SE, refractory SE (RSE) or super-refractory SE (SRSE), though there are still a lack of randomized, prospective studies. This review seeks to summarize and update knowledge on the SE development hypothesis, as well as clinical trials using NMDA and AMPA antagonists in animal and human studies of SE investigations.

Background: Status epilepticus (SE) is a neurological emergency and is usually associated with significant morbidity and mortality rates. Several clinical scales have been proposed to predict the clinical outcome of such incidents, including the Status Epilepticus Severity Score (STESS), the modified STESS (mSTESS), and the Encephalitis-Nonconvulsive Status Epilepticus-Diazepam Resistance-Image Abnormalities-Tracheal intubation (END-IT). Nevertheless, there is still a need for a more practical and precise predictive scale. Methods: This is a retrospective cohort study which examines data from patients with SE in our Department of Neurology between 2009 and 2020. Based on the outcome of each case, the patients were divided into survivor and non-survivor groups. We analyzed the independent factors and adjusted the STESS to achieve a better prediction of prognosis. The predictive accuracy of our new STESS scale was then compared with that of the mSTESS and the END-IT. Results: Data on a total of 59 patients were collected, with 6 of them classified as non-survivors. The effects of the variables of age, sex, underlying disease(s), and type(s) of antiepileptic drug (AED) use showed no significant differences between the survivor and non-survivor groups. Importantly, the number of AEDs used in the first week and the use of thiobarbiturates predicted non-survival. We adjusted the STESS to create the newly modified STESS (nSTESS), which showed a better predictive capacity than the STESS, the mSTESS, and the END-IT. Conclusions: Our adjustment of the STESS with the addition of the factors “number of AEDs within the first week” and “use of thiobarbiturates”, could have a positive impact on the prediction of mortality rates compared with currently used scales. This nSTESS could potentially be useful in clinical practices, for the early prediction of outcomes for patients with SE.

Epilepsy is a common neurological disorder; 1% of people worldwide have epilepsy. Differentiating epileptic seizures from other acute neurological disorders in a clinical setting can be challenging. Approximately one-third of patients have drug-resistant epilepsy that is not well controlled by current antiepileptic drug therapy. Surgical treatment is potentially curative if the epileptogenic focus is accurately localized. Diffusion-weighted imaging (DWI) is an advanced magnetic resonance imaging technique that is sensitive to the diffusion of water molecules and provides additional information on the microstructure of tissue. Qualitative and quantitative analysis of peri-ictal, postictal, and interictal diffusion images can aid the differential diagnosis of seizures and seizure foci localization. This review focused on the fundamentals of DWI and its associated techniques, such as apparent diffusion coefficient, diffusion tensor imaging, and tractography, as well as their impact on epilepsy in terms of differential diagnosis, epileptic foci determination, and prognosis prediction.