Grant: Project Grant

Epilepsy is one of the most common neurologic diseases, with over 380,000 Canadians having seizures that significantly impact their cognitive ability. To address this important clinical issue, we need to better understand the long-term consequences of seizures on brain function. We recently made a remarkable discovery in rodents: after a seizure, a stroke-like event occurs that lasts 60-90 minutes after the seizure ends. This is caused by constricted blood vessels which reduce blood flow and ultimately reduce oxygen delivery to the area of the brain generating the seizure (called the seizure onset zone). Importantly, these oxygen level changes coincide with behavioural and cognitive deficits that are seen immediately following seizures and which persist in between them. We plan to study a group of 55 patients with epilepsy who are undergoing presurgical testing where electrodes are implanted into the brain to precisely record their seizures. Oxygen-sensing probes will be implanted into the presumed seizure onset zone to measure tissue oxygen levels before, during, and immediately after seizures. We will also use magnetic resonance imaging to measure baseline levels of glutathione, which is an antioxidant molecule that is a marker of seizure-induced brain dysfunction. Memory testing will be completed in between seizures and within one hour of a seizure event. We will determine the relationship between memory function and post-seizure oxygen levels as well as glutathione levels measured at baseline. Finally, we will examine clinical factors that may contribute to the risk of developing any of the changes we observe in our study. Our research will provide critical knowledge regarding the impact of repeated seizures and the accompanying oxygen-related stress on memory function in epilepsy patients. Our findings will serve as a benchmark for future clinical trials aimed at reducing the disabling and accumulating cognitive deficits associated with epilepsy.