This is an exciting era for clinicians and investigators interested in the mechanisms of epileptogenesis. Advances in technology during the last three decades have made possible the detailed assessment of intracellular electrophysiologic changes, the determination of membrane responses to neurotransmitters, and even the identification and cloning of specific receptors and channels, some of which are mutated in inherited forms of epilepsy. Through these procedures, knowledge of the fundamental biology underlying cellular excitability and membrane stability has been acquired, sites of action and methods of modifying the function of various neurotransmitters have been determined, and our understanding of the manner in which neural networks enhance or impede seizure occurrence has greatly increased. These exciting developments in the laboratory sometimes result in a tendency to overlook important developments that have occurred within the same time period in the more clinically relevant areas of epidemiology, pathology, and genetics. As one peruses the chapters in this section, it becomes clear that these areas have been equally dynamic in terms of the development of new concepts and ideas. The substantial body of knowledge acquired in epidemiology, pathology, and genetics represents more than an addition to the assumptions that have been considered fact for the last three decades. Indeed, current concepts provided by recent studies in epidemiology and genetics contradict various ideas that were considered well established in the 1970s. The present state of our knowledge suggests various directions for future exploration, not only to students of these observational sciences, but also to those addressing basic neurophysiology.

Through application of the techniques of descriptive and experimental epidemiology, our understanding of seizures and the epilepsies as these conditions affect humans has been expanded substantially, and this expansion parallels the explosion of discoveries in basic neurobiology. The discipline of epidemiology provides the rigor and broad scope of view that is lacking in clinical series and case reports, which are often viewed with relative skepticism by basic scientists. It is true that the study of real people is complex, but the study of mechanisms at the level of the single cell is equally difficult to integrate into broader concepts.

The development of sophisticated study designs and analytic methods for human investigations is not the only reason for recent advances in knowledge. An emerging classification for seizures and the epilepsies not only provides definitions of seizure type¹ and aggregation of symptoms,² but also deals with specifics of etiologic classification and case assignment,³ thereby enabling the application of uniform definitions across studies. Although complex and in general relatively expensive, the studies of incidence performed during the last three decades have provided knowledge of the true frequency with which seizures and epilepsy occur in the general population and have also informed our understanding of the interpretive complexities involved in the much more readily available studies of prevalence. Although important in determining service needs, studies of prevalence provide no insight regarding the important areas of etiology, prognosis, and prevention. These discrepancies are elucidated in Chapter 5. The consistency of recent epidemiologic studies of incidence in terms of age of individuals affected and distribution of etiology and seizure type is impressive, and the now-well-accepted concept of epilepsy as a condition that affects the elderly as well as the very young, at least in Western countries, is clear.

The patterns of epilepsy in developing countries are explored thoroughly in Chapter 11. These studies are often difficult because of the lack of organized medical systems in many areas, and interpretations are blurred because of the lack of information derived from clinical and laboratory evaluations generally available in Western countries. Fortunately, incidence data from these areas allow a more accurate assessment of frequency and individuals at risk. It is clear that data from more economically developed countries cannot be directly applied to developing areas, but from many standpoints, epidemiologic patterns are similar. Additional clues are usually present that may allow hypotheses to account for any differences to be generated. For example, there is evidence for urban–rural differences in incidence. In rural areas of underdeveloped countries, many people with epilepsy have never been treated with antiepileptic drugs. Thus, a natural experiment can be undertaken to evaluate the effect of drugs on prognosis. Chapter 4 explores the sociocultural perceptions of epilepsy in such communities and further clarifies the reasons for the social consequences discussed in Chapter 11.

The exploitation of incidence and inception cohorts from industrialized countries (including but not limited to the United States, the United Kingdom, France, Iceland, Sweden, the Netherlands, and Japan) to identify antecedents has been a natural consequence of the identification of incidence cohorts. The results of the systematic evaluation of classic as well as novel risk factors are addressed in Chapter 6. The study of large birth cohorts^8,9 and cohorts with putative risk factors, such as stroke, head injury, infection, and degenerative disease of the nervous system, enable determination of the absolute risk for epilepsy and seizures, provide information regarding the impact of these putative risk factors that is more readily understandable and relevant to clinicians, and may lead to interventions. The role of factors such as adverse prenatal and perinatal events and febrile convulsions is being clarified, and questions regarding the influence of conditions not invariably associated with structural pathology of the brain, such as hypertension, cardiovascular disease, migraine, and such psychiatric disorders as depression and attention-deficit disorder, not only provide new insights into factors that have traditionally been considered
either consequences of epilepsy or only marginally related to epilepsy, but also supply the basis for possible new treatment strategies.^4,5,7