1. Carl E. Stafstrom, MD, PhD* 1. 2. *Associate Professor of Pediatrics and Neurology, Tufts University School of Medicine; Director, Epilepsy Center for Children, The Floating Hospital for Children at New England Medical Center, Boston, MA. Seizures are one of the most common neurologic disorders affecting children. As many as 5% of children experience a seizure during childhood. Although many epilepsies, especially refractory ones, are managed by specialists in pediatric neurology or epilepsy, general pediatricians often are called upon to manage children who have both acute and chronic seizures. Therefore, it is important to understand some of the basic pathophysiologic mechanisms underlying epileptic seizures. This understanding will allow the physician to choose the most appropriate medication for the given seizure type and clinical setting. Seizures can be a particular challenge to treat. Fortunately, in addition to the armamentarium of anticonvulsant agents previously available, a profusion of new antiepileptic drugs (AEDs) has appeared in the past 5 years. Some of these drugs are designed to address specific pathophysiologic defects in the sequence of events leading to the generation or spread of seizures. The purpose of this article is to review the principles of cellular neurophysiology as a foundation for understanding how normal neuronal function goes awry in epilepsy. First, normal synaptic transmission and neuronal firing are summarized. Next, the pathophysiology of acute and chronic seizures is discussed. Finally, the mechanisms by which AEDs control the hyperexcitability that underlies epilepsy are considered. ### DEFINITIONS A seizure is a temporary disruption of brain function due to the hypersynchronous, excessive discharge of cortical neurons. Sometimes the term epileptic seizure is used to distinguish from a nonepileptic seizure such as a pseudoseizure, which is not caused by hypersynchronous firing of neurons. The clinical manifestations of a seizure depend on the specific region and extent of brain involvement and may include an alteration in motor function, sensation, alertness, perception, autonomic function, or all of these. Any person can experience a seizure in the appropriate clinical setting (eg, meningitis, hypoglycemia, toxin ingestion), attesting to the …
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