Suppression and control of epileptiform activity by electrical stimulation: a review

Epilepsy is a devastating disease affecting /spl sim/1% of the world's population. Although drug therapy is effective in many patients, 25% are not responsive to anticonvulsants. In addition, up to 50% of those receiving regular mediation suffer major side effects. Surgical resection is another treatment also associated with serious complications. An alternative method to control seizure activity is electrical stimulation. Several electrical stimulation protocols have been developed in animal models of epilepsy that can reduce or completely suppress seizures. Moreover, in over 5000 patients worldwide, electrical stimulation has been used to control seizures. The mechanisms underlying some of the techniques of seizure control are not understood. Some stimulation protocols, such as DC stimulation, rely on the effects of fields and currents on the membrane polarization. Other methods using single pulses, such as phase-resetting, desynchronization, and chaos control rely on the modulation of the dynamic properties of the neuronal networks. Both low- and high-frequency periodic stimulation can suppress seizures not only during stimulation, but also by inducing long-term changes in brain function. The purpose of this review is to present these approaches and to discuss their underlying mechanisms and potential for clinical implementation.

I. Introduction

Epilepsy, a chronic disorder of the nervous system affecting 1% of the population, is characterized by the abnormal synchronized firing of a large number of neurons. The large synchronized event is known as a seizure, paroxysmal discharge, or ictal event. Abnormal activity is almost always observed between seizures and is known as interictal activity. These interictal events are short in duration but occur more frequently than ictal events.