Neurometabolism in human epilepsy

The inherent instability of the epileptic brain in many ways can be likened to unstable physical phenomena, such as volcanoes and earthquakes. While on a moment-to-moment basis, the land that gives rise to these events can be described as a static homeostasis, small and unpredictable changes can (repeatedly) set off uncontrolled yet characteristic storms. The epileptic brain resides in a similar “critical state.” What drives the development of a seizure remains heavily debated, but the notion of a homeostatic critical state has led our group to examine the issues of neurometabolic sensitivity and volatility. Brain tissue is well known to be very dependent on available fuel substrate. This, combined with extensive evidence arguing for substantial metabolic dysfunction in epilepsy—significant enough to allow individualized metabolic localization of the seizure focus—has led to investigations regarding how the interdependent metabolism of the elements within the “glialneuronal unit” (GNU) may contribute to the epileptogenic state. In this review, we consider the basis for the metabolic hypothesis, including perspectives from human and animal work, as well as the brain's metabolic physiology. In doing so, we integrate data from our own group and others to indicate how the various pieces of data may be interrelated. Our tools are geared towards studying the human patient, and bring together several areas, including microdialysis, MR-based metabolic imaging and in vitro studies on resected tissue.