Genetic, Molecular, Neuroanatomic, and Electrophysiologic Mechanisms of Chemically Induced Seizures
Pp. 3-16 (14)
Ernest C. Lee and Stefanos N. Kales
Traditionally, chemically-induced seizures have received little detailed emphasis in general neurology literature. The few articles that describe correlations between seizures and chemical exposure(s) usually focus on clinical effects rather than underlying pathophysiological mechanisms. Conclusions of studies from various biological disciplines are discussed in order to convey a global understanding of chemically-induced seizure mechanisms. Theoretical mechanisms underlying the progression from a seizure occurring only with external induction to a seizure occurring spontaneously (epilepsy) are also discussed. A generally accepted model of epileptogensis is that of kindling, in which the clinical manifestations of seizures increase as seizures are repeatedly induced. Recent studies are beginning to reveal just how this kindling phenomenon might occur through permanent genetic and microneuroanatomic alterations induced by aberrant excessive electrical impulse activity, via direct physiologic injury, or through unintended adverse consequences of repair mechanisms. Largescale genomic studies are beginning to reveal that many genes likely contribute to seizure induction and the loss of synaptic plasticity observed in epilepsy. Examples of mechanisms underlying specific chemically-induced seizures are discussed including those caused by cyanide, carbon monoxide, and chemical nerve agents. Further research and understanding of fundamental seizure mechanisms will likely lead to the discovery of novel and more effective methods by which to treat and ultimately prevent seizure or epilepsy development. To this end, a review of the basic principles of relevant microscopic neuroanatomy, neuroelectrophysiology, neurotoxicology, and molecular genetics, is presented along with specific examples of chemicals known to elicit seizures.
Harvard Medical School&Harvard School of Public Health, Medical Director, Employee&Industrial Medicine, Cambridge Health Alliance, 1493 Cambridge Street, Macht Bldg, The Cambridge Hospital Room 427, Cambridge, MA 02139, United States.