A review of the scientific foundations of current clinical practice
The Pathophysiology of Epileptic Seizures: A Primer For Pediatricians
Carl E. Stafstrom, MD, PhD* Introduction
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, aremanaged 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 andclinical 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. Thepurpose of this article is to review the principles of cellular neurophysiology as a
*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. 342
foundation for understanding how normal neuronal function goes awry in epilepsy. First, normal synaptictransmission 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.
Seizures and Epilepsy
A seizure is a temporary disruption of brain function due to the hypersynchronous, excessive discharge of cortical neurons. Sometimesthe 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 canexperience a seizure in the appropriate clinical setting (eg, meningitis, hypoglycemia, toxin ingestion), attesting to the innate capacity of even a “normal” brain to support hypersynchronous discharges, at least temporarily. Epilepsy is the condition of recurrent, unprovoked seizures (two or more), usually in a person who
has a predisposition because of a chronic pathologic state (eg, braintumor, cerebral dysgenesis, posttraumatic scar) or genetics. Approximately 1% to 2% of the population suffers from epilepsy, making it the second most common neurologic disorder (after stroke), affecting more than 2 million persons in the United States. An epilepsy syndrome refers to a group of clinical characteristics that consistently occur together, with seizures as a primary manifestation. Suchfeatures might include similar age of onset, electroencephalographic findings, precipitating factors, inheritance pattern, natural history, prognosis, and response to AEDs. Epilepsy syndromes in childhood include infantile spasms, febrile seizures, childhood absence epilepsy, benign rolandic epilepsy (BRE), and juvenile myoclonic epilepsy.
The electroencephalogram (EEG) isthe primary tool for recording electrical activity of the human brain. Small metal disk electrodes are attached to the scalp at specified locations. When sufficiently amplified, voltage changes generated in neocortical neurons are recorded on the EEG as waveforms of various frequencies, amplitudes, and morphology. EEG patterns vary according to the child’s age, state of alertness, and genetic...