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• W2007685536 abstract "The decade of the 1930s gave witness to three major advances in the field of epilepsy: the application of electroencephalography; the development of the antiepileptic drug, diphenylhydantoin (Dilantin); and the beginnings of major neurosurgical treatment, especially of temporal lobe-limbic epilepsy (complex partial seizures, psychomotor epilepsy) and related studies of pathology and pathophysiology. The recording of the electroencephalogram (EEG) of man was developed and published by Hans Berger from 1929–1938 in 14 reports. These have been translated and republished in a special volume by Pierre Gloor (Gloor, 1969). Berger’s work was based upon an extensive background of investigations of the electrical activity of the brain beginning in the 1890s, and described in the thorough book by Brazier (1961). Mainly neurophysiologists from Eastern Europe studied such activity, utilizing brain from experimental animals. Berger recorded potentials from human subjects with epilepsy, even activity associated with seizures, but not actual spike discharges. The validation of such human EEG recording was accomplished by Adrian and Matthews (1934). The first major EEG recording of human seizure activity was carried out by Gibbs et al. (1935). Following this publication, clinical EEG laboratories for diagnosis and follow-up of patients with epilepsy were established in the United States, Great Britain, and continental Europe. Even during World War II, EEG had limited utilization in military neurologic activities related to brain injuries. During the last more than 70 years, EEG applications in the diagnosis and treatment of epilepsy have been extensive, with associated development of special techniques of EEG, especially spike, analysis. In recent years, the techniques of concomitant EEG and video visualization (video-EEG monitoring) have been developed and utilized extensively, especially in evaluating patients for surgical treatment of localized-origin epilepsies (Gotman et al., 1985). In addition, the method of EEG recording of the ambulatory patient, outside of the limited confines of the laboratory, has been a major advance (Stores, 1980; Ebersole, 1988). One can look forward to the combined utilization of EEG and magnetic resonance imaging (MRI), especially functional MRI, in three dimensions, in further studies of epilepsy and its diagnosis and treatment. It is important to note, however, that these techniques reveal only reflections of the epileptic process. The discovery and development of the major anticonvulsant drug, diphenylhydantoin (phenytoin, Dilantin) could be regarded as possibly the first major application of “translational neuroscience,” a prominent consideration in evaluating research in the medical science at the present time. The “basic laboratory” phase was the application of seizure threshold measurements (as seen with electrical stimulation) of the brain of experimental animals (cats) by Putnam and Merritt. This measure was developed to enable the evaluation of an antiepileptic drug based on the structure of phenobarbital, a known anticonvulsant but with marked unwanted sedative properties. These investigators were given a number of drugs by a pharmaceutical company, and the one that most successfully raised seizure threshold—and had the least sedative effect—was diphenylhydantoin. The report of the experimental work was published in Science by Putnam and Merritt (1937). The next step, the “translational” one, was the treatment of patients with epilepsy, especially those with generalized “grand mal” seizures. The successful results were published in the JAMA by Merritt and Putnam (1938). An extensive history of “Putnam, Merritt and the Discovery of Dilantin” was written by Friedlander (1986), and published in Epilepsia. He refers to a pertinent commentary by Rowland (1982) concerning this achievement by Putnam and Merritt: They devised a simple and reliable method to test drugs of anticonvulsant effect. They showed that anticonvulsant effects in cats accurately predicted effects in humans: Phenytoin was the first anticonvulsant drug to be tested in animals before it was given to human subjects. They showed that anticonvulsant and sedative effects of drugs could be separated. They showed that a single drug might be much more effective in treating some seizure types than others. This differentiation implied that pathogenic mechanisms of different types of seizures were also different. They discovered the efficacy of phenytoin and—45 years later (now more than 70 years later!)—this drug is still a mainstay of treatment. Their work opened the way to the development of other anticonvulsant drugs. The development of surgical treatment of the epilepsies really had its origin in 1886 with the publication of the work of Sir Victor Horsley on “Brain Surgery” (Horsley, 1886). This work was reproduced in the book Surgical Treatment of the Epilepsies (edited by Engel, 1987), based on a 1986 conference. However, the actual initial major application of surgery to epileptic patients was not reported until the publication by Foerster and Penfield (1930)on the structural basis of traumatic epilepsy and the results of radical operation. Penfield made this surgical procedure his major activity, with publications of results from 1936 onward (Penfield, 1936). Other neurosurgical reports began to appear in the 1950s (Bailey & Gibbs, 1951; Falconer et al., 1955). Reports on operations on children also began to appear somewhat later (Davidson & Falconer, 1975; Lindsay et al., 1984). The removal of the “epileptogenic brain tissue” has led to the extensive studies of the involved pathology, especially that of mesial temporal sclerosis and its origin, still a matter of much research and mystery (Armstrong & Bruton, 1987; Babb & Brown, 1987). Such considerations have led to studies of cellular sprouting, cortical dysplasias, and “double pathology.” An important, still fascinating, extensive study of neuronal dendritic abnormalities of temporal lobe epileptic hippocampal dentate structures (distorted granules, spine loss) was published in Epilepsia (Scheibel et al., 1974). The Golgi technique used in that study showed many structural changes in dendrites that have yet to be explained, either in origin or effect. For example, this pathology has been related to possible progressive cognitive decline in patients with epilepsy (Poulos, 2008), with the dendritic abnormalities interfering with information processing. There is no doubt that traumatic brain injury leads to an epileptic seizure state, either early on or after an interval of time during which the epileptic process develops. In addition, the interseizure state of brain functioning—including behavior and psychological status—remains often an unknown. These problems represent matters requiring much present-day attention. Other aspects of epilepsy to occupy future direction are those related to genetic studies, of which many are now ongoing, and those involving electrical stimulation of various epileptogenic regions. Much information has been collected, but progress in prevention and therapy is slow in coming, especially in regard to the many patients with “refractory epilepsy.” I confirm that I have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Disclosure: I have no conflicts of interest to disclose." @default.
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• W2007685536 title "Reflections of a previous editor ofEpilepsia" @default.
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