Epileptogenesis: From Basic Mechanisms to Clinical Practice*

An abstract presentation on a 15-year audit of epilepsy surgeries performed at a single centre in South Africa. Highlighting seizure outcomes and patient-reported quality of life after surgery. The study hopes to demonstrate the feasibility of epilepsy surgery in resource-limited settings.

Status epilepticus, induced by chemical or electrical stimulation of the hippocampus, is used to cause epilepsy in experimental animals. A series of epileptogenic mechanisms are unleashed during status epilepticus, and these include activation of NMDA receptors, TRK-B pathway, JAK-STAT pathway, and inflammatory molecules. These hypotheses have yet to be tested in patients. It. The growing use of ketamine for status epilepticus treatment provides an unprecedented opportunity to understand whether blocking NMDA receptors impacts epileptogenesis.

Epileptogenesis is the process by which brain networks are functionally altered in a manner that predispose an individual to spontaneous seizures. This process may occur in individuals with acquired brain injury (e.g., traumatic brain injury, stroke) or a neurogenetic disorder (e.g., tuberous sclerosis complex, Sturge-Weber syndrome). Drivers of epileptogenesis include inflammation, neuron loss, plasticity, and circuit reorganization. Evidence from preclinical models suggests that epilepsy can be prevented by modulation of these targets, but translation to humans remains a challenge. Several large-scale international efforts are underway to uncover mechanisms of epileptogenesis and develop biomarkers to identify and monitor epileptogenesis and eventually carry out clinical trials of antiepileptogenic therapies. In this session we will discuss recent efforts to identify and prevent epileptogenesis in tuberous sclerosis complex as well as preclinical and clinical studies in post-traumatic epilepsy and status epilepticus.

Tuberous Sclerosis Complex is an autosomal dominant condition that affects 1 in 6,000 individuals and is the most common genetic cause of epilepsy. Dr. Bebin will discuss the utility of serial EEG surveillance in TSC infants and young children and the importance of the presence of epileptiform activity in predicting who will subsequently develop epilepsy. Results of the EEG Biomarker analysis will be discussed from the PREVeNT trial.