Book Review

Idiopathic Generalized Epilepsies: Clinical, experimental, and genetic aspects

N Engl J Med 1995; 333:1088-1089October 19, 1995

Article

Idiopathic Generalized Epilepsies: Clinical, experimental, and genetic aspects
Edited by Alain Malafosse, Pierre Genton, Edouard Hirsch, Christian Marescaux, Dominique Broglin, and Raymond Bernasconi. 538 pp. London, John Libbey, 1995. £45. ISBN: 0-86196-436-5

Idiopathic. Denoting a disease of unknown cause.

— Stedman's Medical Dictionary

Idiopathic. . . . of a disease; of the nature of a primary morbid state; not consequent upon another disease.

— Oxford Universal Dictionary

Few aspects of modern epileptology have created more confusion in North America than the concept of idiopathic epilepsies as defined in the current International Classification of Epilepsies and Epileptic Syndromes (Commission on Classification and Terminology of the International League against Epilepsy, Epilepsia 1989;30:389-99). According to this classification, idiopathic epilepsies are diseases unto themselves, epilepsies sui generis, and constitute a specific group of primary or essential disorders that are familial, age-related, and generally benign. This usage adheres to the older definition of the term “idiopathic” prevalent in Europe, rather than the accepted medical terminology in the United States. It is not uncommon, even in our age of high-resolution magnetic resonance imaging, for a detailed diagnostic evaluation of an epileptic disorder to turn up nothing in patients who do not meet the criteria for an idiopathic epileptic syndrome; such a condition is then called “cryptogenic” in the International Classification. Thus, a patient with symptoms of classic temporal-lobe epilepsy but no clear etiologic event on the basis of history or abnormality on neuroimaging, who most likely has hippocampal sclerosis or a small mesial temporal structural lesion that is beyond the limits of detection with current diagnostic technology, would have been considered to have idiopathic temporal-lobe epilepsy several years ago, but is now considered to have cryptogenic temporal-lobe epilepsy. This distinction, although seemingly subtle and perhaps difficult for many nonepileptologists to understand or remember, is of considerable taxonomic importance, because it fosters recognition of a group of (idiopathic) neurologic conditions characterized by inherited defects in neuronal function that are manifested almost entirely as epileptic seizures, constituting an ideal population for molecular geneticists and biologists to use to investigate the fundamental substrates of diverse epileptic phenomena.

A major challenge confronting the search for genes for epilepsy and their proteins is the identification of homogeneous populations of patients who can be easily classified as having a specific inherited disease. Consequently, detailed descriptive clinical semiology, including electroclinical characterization of ictal events, becomes an essential step in the molecular approach to basic mechanisms. There are a few well-recognized idiopathic partial epileptic syndromes, but a much larger number of idiopathic generalized epilepsies have been described, with varying degrees of consistent clinical presentation, interrelations, and acceptance. Therefore, the idiopathic generalized epileptic syndromes, if adequately identified and characterized, would provide a rich resource for molecular investigation of the epilepsies.

Idiopathic Generalized Epilepsies presents the proceedings of a meeting held in Alsace, France, in 1993, which brought together clinical epileptologists, basic neuroscientists, and molecular geneticists in order to further a multidisciplinary approach to the pathophysiology of idiopathic generalized epilepsies. Readers interested in obtaining clear descriptions of specific idiopathic generalized epileptic syndromes and their underlying basic mechanisms will be greatly disappointed. This dense book is packed with relatively recent experimental data and hypotheses that raise as many questions as are answered. For the serious student of epilepsy, however, this book includes substantial contributions from almost all the major research teams investigating idiopathic generalized epilepsies in humans, as well as in relevant animal models. Each chapter is authoritative, and many have been written by investigators from different centers in order to present a broader perspective. Although the treatment is somewhat uneven, as is a necessary evil of multiauthored works, the book is well organized and sections flow logically to forge a coherent whole. I must admit that whereas I had intended to leaf through the book, I found myself intrigued by the wealth of related material that had been gathered and could not prevent myself from reading almost every chapter.

The book is divided into seven sections. Part 1 presents an overview of the clinical, epidemiologic, and molecular approaches. Part 2 deals with familial neonatal convulsions — the conditions for which gene mapping is most advanced — and infantile convulsions. Part 3 considers the diffuse area of absence seizures and epilepsies, which originate for the most part in childhood and adolescence, although late-onset forms have been described. Part 4 reviews the more circumscribed syndrome of juvenile myoclonic epilepsy and related syndromes — areas in which the clinical controversies that plague the molecular genetic approach are most apparent. This section is noteworthy for its inclusion of the first English translation of the original description of “impulsive petit mal” by Janz and Christian, which was published in Germany in 1957. Part 5 discusses photosensitivity, an epileptic phenomenon, rather than a syndrome, which permeates many epileptic disorders and also exists in isolation. Part 6 is devoted to investigations into the pathophysiology of convulsive seizures in animals. Research with various models of inherited epilepsy, from chickens and rats to the epileptic Papio papio baboon, has elucidated brain-stem as well as cortical mechanisms that may be ubiquitous in epilepsies in humans. Part 7 addresses current therapy, including effects on long-term outcome, stressing that pharmacologic interventions can provide insights into basic mechanisms and that the ultimate objective of research into basic mechanisms is the development of more rational treatments.

I highly recommend this book as a thorough introduction to one of the most promising areas of research in epileptology. Although the field is advancing rapidly, the book contains sufficient important background information to make it a valuable reference source for some time. With its modest price, it deserves a place on the shelves of every epileptologist and medical library.

Jerome Engel, Jr., M.D., Ph.D.
UCLA School of Medicine, Los Angeles, CA 90095