Mechanisms of Disease Epilepsy.pdf

n engl j med 349;13 september 25, 2003 The new england journal of medicine 1257 review article mechanisms of disease Epilepsy Bernard S. Chang, M.D., and Daniel H. Lowenstein, M.D. From the Comprehensive Epilepsy Center, Department of Neurology, Beth Israel Dea- coness Medical Center, and Harvard Med- ical School — both in Boston (B.S.C.); and the University of California San Francisco Epilepsy Center, Department of Neurology, University of California San Francisco, San Francisco (D.H.L.). N Engl J Med 2003;349:1257-66. Copyright ? 2003 Massachusetts Medical Society. pilepsy is one of the most common neurologic problems worldwide. Approximately 2 million persons in the United States have epi- lepsy, and 3 percent of persons in the general population will have epilepsy at some point in their lives. 1 In recent years, important advances have been made in the di- agnosis and treatment of seizure disorders. 2 However, our understanding of the cellu- lar and molecular mechanisms by which epilepsy develops, or epileptogenesis, is still incomplete. In this overview, we highlight some of the prevailing ideas about epileptogenesis by presenting examples of epilepsy syndromes and theories of their mechanisms of origin. Several recent reviews offer more specialized and comprehensive discussions of this topic. 3-5 The term “epilepsy” encompasses a number of different syndromes whose cardinal feature is a predisposition to recurrent unprovoked seizures. Although specific seizures can be classified according to their clinical features (e.g., complex partial seizures and generalized tonic–clonic seizures), 6 epilepsy syndromes can also be classified accord- ing to the type of seizure, the presence or absence of neurologic or developmental ab- normalities, and electroencephalographic (EEG) findings. 7 For example, the syndrome of juvenile myoclonic epilepsy is characterized by the onset of myoclonic seizures, gen- eral