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Chapter 52 - Epilepsy

Nancy Foldvary Elaine Wyllie

History and Definitions

Basic Mechanisms of Epileptogenesis

Epileptic Seizures

Generalized Seizures Partial (Focal) Seizures General Approach to the Initial Seizure Epilepsies and Epilepsy Syndromes

Localization-related (Focal) Epilepsies and Syndromes Generalized Epilepsies and Epileptic Syndromes Neuropharmacology of the Antiepileptic Drugs

Pharmacological Principles

Principles of Antiepileptic Drug Treatment

Drug Interactions

Clinical Use and Adverse Effects of Specific Antiepileptic Drugs Surgical Treatment General Principles

Surface and Intracranial Electroencephalography


Specific Surgeries

Reviews and Selected Updates



Epilepsy, from the Greek epilepsia (a taking hold of or seizing) is a chronic disorder characterized by a spontaneous tendency for recurrent seizures. Seizures are the clinical manifestation of abnormally hyperexcitable cortical neurons. Whereas all patients with epilepsy have seizures, many more patients have a single seizure during life and are not considered to have epilepsy.

The earliest descriptions of epilepsy appear in Mesopotamian writings from the fifth millennium bc. Persons with epileptic seizures were believed to be possessed by demons or evil spirits, and as a result, the disorder became known as the sacred disease. In the book On the Sacred Disease, a collection of Hippocratic writings from around 400 bc, the notion that epilepsy was caused by the gods and should be treated by the invocation of supernatural powers was challenged. In these writings, epilepsy was described as a hereditary disease caused by an overflow of phlegm in the brain. Treatment interventions, including proper diet and hygiene, were suggested in lieu of superstitious remedies. Nevertheless, during the middle ages, the drinking of human blood, trephination, skull cauterization, and sterilization were routinely practiced to cleanse the body of evil spirits and reduce the likelihood of transmission. 'i]

By the eighteenth century, epilepsy became recognized as a chronic disorder of cerebral function. In the latter half of the nineteenth century, the British neurologist John Hughlings Jackson hypothesized that epilepsy was due to hyperexcitable cerebral gray matter. By correlating focal motor seizure semiology with postmortem pathological examinations, Jackson was the first to localize epileptogenic lesions. In 1886, the first surgery for epilepsy was performed by Sir Victor Horsley, who resected a traumatic cortical scar in a patient with focal motor seizures, rendering him seizure-free.

The invention of the electroencephalogram in 1929 had a profound impact on the diagnosis and classification of the epilepsies. During the 1930s and 1940s, Wilbur Penfield and colleagues mapped the primary sensory and motor cortices in human subjects, advancing the concept of functional localization. In the last several decades, a universally accepted classification of epileptic seizures and syndromes emerged through advancements in electrophysiology, neuroimaging, and molecular biology.

Epilepsy affects six to seven per 1000 population in the United States, and 40 to 50 new cases per 100,000 develop annually. '2 The risk of epilepsy increases from approximately 1 percent at birth through early adulthood to 3 percent by age 75 years. In two thirds of cases, the etiology is not identified.


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