ABSTRACT
INTRODUCTIONEpilepsy is the most common acute neurologic problem in the United States [1] and one of the most prevalent neurological illnesses in the world, affecting an estimated 1% to 3% of the global population [2]. A 2000 study estimated that the economic burden of epilepsy in the United States alone exceeds $12 billion per year [3, 4]. Individuals with epilepsy report significantly lower scores on health-related quality of life measures than the general public, and their scores decrease as a seizure frequency increases [5]. Repeated seizures may lead to impaired cognitive performance, which can affect social interaction and employment. Epilepsy in general is associated with a two-to three-fold increase in mortality, and patients with uncontrolled seizures have up to a 40 times greater risk of mortality than those whose seizures are controlled [6]. In approximately 40% of patients, the cause of death
is thought to be directly related to epilepsy [7] and may include the underlying causative neurologic disorder, accidents during a seizure, status epilepticus (i.e., continuous seizures of longer than 5 min duration), suicide, treatment-related death, and sudden unexpected death in epilepsy (SUDEP).Despite advances in modern antiepileptic drug therapy, approximately 30% of adults with epilepsy remain refractory to medical treatment [8], and there is considerable interest in developing alternative therapies, surgical and otherwise. Dietary modifications [9], immunotherapy [10], and extracranial electrical stimulation of either the vagus or trigeminal nerve have all emerged as interventions with therapeutic potential that is beginning to be realized. Since the preliminary cerebellar stimulation studies by Irving Cooper in the late 1970s, intracranial electrical stimulation, which includes both deep brain stimulation (DBS) and cortical neurostimulation, has also made important advances in the treatment of medically refractive epilepsy [11, 12].While there have been numerous case studies and small, uncontrolled studies reporting on the efficacy of a plethora of stimulation targets for epilepsy, this chapter focuses on the targets and techniques that are supported by controlled, blinded clinical trials. We will also briefly discuss the investigational rationale for target choice, current theories of the therapeutic mechanism, and the most pertinent areas of future research in neurostimulation for epilepsy. BACKGROUND AND PATHOPHYSIOLOGYThe term “epilepsy” refers to a predisposition to experience recurrent unprovoked seizures [13], which are episodes of abnormal, excessive or synchronous neural activity. Epilepsy is classified by its clinical features, which include coexisting conditions, history of onset, the frequency, severity and duration of seizures, and by the cause and locus of seizure onset. Epilepsy and the seizures associated with them can be divided into three broad categories: (1) primary generalized, (2) partial (with a focal onset), and (3) undetermined. Seizures can also be categorized by the type of physical response they elicit, such as atonic (loss of muscle tone), tonic (increased muscle tone and stiffening), and clonic (repeated jerking).
