50: Seizures and Epilepsy

Introduction

• Classification of Seizures and the Epilepsies Is Important for Pathogenesis and Treatment

  • Seizures Are Temporary Disruptions of Brain Function

  • Epilepsy Is the Chronic Condition of Recurrent Seizures

• The Electroencephalogram Represents the Collective Behavior of Cortical Neurons

• Focal Seizures Originate Within a Small Group of Neurons Known as a Seizure Focus

  • Neurons in a Seizure Focus Have Characteristic Activity

  • The Breakdown of Surround Inhibition Leads to Synchronization

  • The Spread of Focal Seizures Involves Normal Cortical Circuitry

• Primary Generalized Seizures Are Driven by Thalamocortical Circuits

• Locating the Seizure Focus Is Critical to the Surgical Treatment of Epilepsy

• Prolonged Seizures Can Cause Brain Damage

  • Repeated Convulsive Seizures Are a Medical Emergency

  • Excitotoxicity Underlies Seizure-Related Brain Damage

• The Factors Leading to Development of Epilepsy Are an Unfolding Mystery

  • Among the Genetic Causes of Epilepsy Are Ion Channel Mutations

  • Epilepsies Involving Focal Seizures May Be a Maladaptive Response to Injury

• An Overall View

Until quite recently the function and organization of the human cerebral cortex—the structure of the brain concerned with perceptual, motor, and cognitive functions—has eluded both clinicians and neuroscientists. In the past the analysis of brain function relied in large part on observations of the behavioral consequences of brain damage caused by strokes or trauma. These natural experiments provided much of the early evidence that distinct brain regions serve specific functions (see Chapter 1).

Observation of patients with seizures and epilepsy has been equally important in the study of brain function because the behavioral consequences of these disorders vary with the brain regions from which they originate. Seizures are temporary disruptions of brain function resulting from abnormal, excessive neuronal activity; epilepsy is a chronic condition of repeated seizures. For centuries understanding the neurological origins of seizures was confounded by the dramatic, sometimes bizarre behaviors associated with seizures. Epilepsy was widely associated with possession by evil spirits, while seizures were thought to reflect oracular, prescient, or special creative powers.

The Greeks in the time of Hippocrates (circa 400 bc) were aware that head injuries to one side of the brain could cause seizure activity on the opposite side of the body. In those earlier times the diagnosis of epilepsy was probably much broader than the contemporary definition. Other causes of episodic unconsciousness, such as syncope as well as mass hysteria and psychogenic seizures, were almost certainly classified with epilepsy. Moreover, historical writings typically describe generalized convulsive seizures involving both cerebral hemispheres. Thus it is likely that focal seizures involving a limited area of the brain were misdiagnosed or never diagnosed at all. Even today it can be difficult for physicians to distinguish between episodic loss of consciousness and the various types of seizures. Nevertheless, as our ability to treat and even cure epilepsy continues to improve, these diagnostic distinctions take on increasing significance.

The modern neurobiological analysis of epilepsy began with John Hughlings Jackson's work in London in the 1860s. ...