The epilepsies are a complex group of disorders whose common feature is a tendency for hyperexcitability to develop in one or another region of the central nervous system (CNS). Epileptic syndromes and seizure types can be quite variable and may have many causes. Similarly, multiple underlying cellular and molecular mechanisms are likely to be responsible for various epileptiform phenomena. Much research has been, and continues to be, directed at unraveling the mechanisms underlying epileptic events, based on the premise that increased understanding will make it possible to devise either better treatment strategies or better methods to prevent epilepsy.

The hyperexcitable states that underlie the various forms of epilepsy represent complex functional changes in normal brain anatomy, physiology, and pharmacology. To begin to understand such changes, it is necessary to understand the normal brain substrate on which these alterations are occurring and the developmental patterns that result in the normal functioning. The next 15 chapters in this book are devoted to a systematic discussion of the physiology of normal brain function, organized according to the component parts that may be altered when epilepsy develops. Each chapter focuses on one broad area of neuronal activity, starting with an analysis of normal function at the system, cellular, and molecular levels, and then proceeding to a consideration of where this aspect of physiology might be perturbed to produce epilepsy and how naturally occurring forms of epilepsy might involve this system. Initial focus is on the excitability of individual neurons; detailed considerations of synaptic transmission, both excitatory and inhibitory, and synaptic modulation are then presented, followed by discussions of neuronal circuitry in the neocortex and limbic cortex, and the role of various subcortical structures on CNS excitability. Consideration is also given to the regulation of gene expression by both normal and pathologic activity in CNS pathways and the developmental aspects of CNS function. All this material serves as a basic scientific underpinning for the discussions of experimental seizure models and the human epilepsy syndromes, and also provides potential targets for the actions of antiepileptic drugs.

To study epileptic phenomena at a network, cellular, or molecular level, model systems are needed. The second half of this section provides detailed analyses of various experimental models used for studying seizures and epilepsy. Such models can be designed to mimic some forms of human epilepsy closely (see Chapters 36,37,38,39) but, as discussed in Chapter 41, no animal model can mimic all the features of any human epilepsy at this time. Alternatively, much simpler models can be developed that allow the isolation of specific individual epileptiform activity in ways that can be analyzed using a reductionist system. In fact, most of what is known about the cellular mechanisms of specific epileptiform events has been derived from studies of simplified systems and acutely provoked seizure activity. These studies were initially performed using in vivo animal models and, as techniques evolved for analyzing CNS tissue in vitro, they were extended to CNS models in acute slice preparations and cell culture. One of the challenges of modern epilepsy research is to extrapolate such findings to the more complex CNS of humans and the more complex problem of chronic epilepsy. The last chapter in this section discusses attempts at conducting such studies in humans, or at least in human tissue.

Most, if not all, forms of epilepsy develop over a defined time period. That is, at some point in time, the brain functions normally (and may be normal), but either after a specific developmental sequence or in response to some form of injury, a new state develops in which the neuronal circuits become hyperexcitable, leading to spontaneous recurrent seizures. This process, referred to as epileptogenesis, has been too little studied. Much less is currently understood about the process of epileptogenesis than about the phenomenology of seizures. At a clinical level, not much can yet be done to protect individuals who are known to be at high risk for the development of epilepsy, in comparison with what can be done to suppress seizures once they develop.