The Brain, Seizures and Epilepsy Throughout Life: Understanding a Moving Target

Abstract

The Scope of the Problem The incidence of seizures and of epilepsy varies throughout life, peaking in neonates and children and increasing again after the age of 50 (1-4). In addition to the quantitative measure of the incidence of seizures, the type of seizures (and of epilepsy syndromes) varies with age: for example, febrile seizures take place in infants and children (1, 5-7), whereas the incidence of post-stroke epilepsy increases in adults compared with children (1,3,8). What is the basis of these age-dependent variations? What are the age-specific properties of the brain that contribute to the probability of seizure generation and to the nature of the resulting seizure?A second, reciprocal aspect of the interaction of the age of the brain and seizures involves the effects of a seizure on the structure and function of neurons and neuronal networks. Here, again, clinical evidence suggests that the consequences of a seizure might vary with age. For example, the consequences of status epilepticus (SE) in young children seem to depend on the inciting etiology (9, 10), and, in general, mortality and cognitive outcomes are more favorable than in the adult and elderly individual (11)(12)(13)(14). In contrast, status epilepticus in adult and aging individuals can have major detrimental effects on cognitive function and even survival (14-16). What is the basis of these age-dependent variations? What are the age-specific properties of the brain that modulate the effects of seizures on neuronal integrity and function?These questions are of paramount clinical importance because they should provide clues for developing age-specific diagnostic tools, prognostic models, and intervention strategies. Thus, while the answers to these questions are not fully elucidated, the questions provide a framework for discussing the salient elements of the evolving interaction between the brain and seizures throughout life.The following paragraphs highlight a few of the many facts that influence age-specific seizures and the age-specific consequences of seizures. Because most of the direct information about seizures throughout the life-span often derives from animal models, these are discussed. The author regrets that this overview is not comprehensive and likely omits a number of important publications. Nonetheless, this review serves to illustrate crucial features of the topic. Age-Specific Brain Properties Influence Seizures That Are Generated During Each AgeWhereas brain development from embryonic life to senescence is a continuum, here it is divided into four stages: the neonatal, childhood, adulthood, and aging epochs. The Neonatal Brain and Age-Specific Neonatal SeizuresThe neonatal brain is in a stage of rapid flux from both structural and functional perspectives. Neurons are still being born, circuits are being formed, and synapses are being established (17,18). Synaptic currents are often slower (19), neurotransmitters play trophic roles (20), and circuits are not fully mature (21). These facts predict that seizures may propag...

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