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INTRODUCTION

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There is widespread consensus that recurrent epileptic seizures need treatment and the first line of treatment invariably involves use of antiepileptic drugs (AEDs). However, experience from several large studies has shown that only about two-thirds of patients can be controlled satisfactorily with AEDs either as monotherapy or combination therapy.1,2 The remaining patients have medically refractory epilepsy and should be evaluated at an epilepsy center to determine if they may be candidates for excisional epilepsy surgery. Of this group approximately 25% will be offered a resection (personal observation), still leaving a sizeable proportion of patients without effective medical control. Seizures in medically refractory patients have a major impact on quality of life (QOL), and may result in injuries or even death.3 Treatment options consist of additional trials of AEDs, ketogenic diet, or vagus nerve stimulation (VNS therapy). Deep brain stimulation remains investigational. Figure 57–1 outlines a treatment algorithm showing the diagnostic and therapeutic approach to a patient with epilepsy.

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Figure 57–1.

Treatment algorithm showing the diagnostic steps and therapeutic approach to a patient with epilepsy.

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In 1987, the Food and Drug Administration (FDA) approved VNS therapy for the adjunctive treatment of partial onset seizures in patients 12 years and older. It has not undergone testing in clinical trials for patients younger than 12 or patients with other seizure types; however, postmarketing experience indicates that VNS is useful in such situations.

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MECHANISMS OF ACTION

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VNS therapy stimulates the left vagus nerve that carries both myelinated and unmyelinated efferent (80%) and afferent (20%) fibers. The parasympathetic efferents are mostly unmyelinated and not much influenced by vagal nerve stimulation. The rationale for choosing the left vagus nerve is that it has fewer cardiac fibers supplying the SA node (although right side VNS implantation has been performed). However, McGregor et al have shown that right-sided VNS implantation is also safe and efficacious.4 Ascending fibers from the vagus nerve reach the nucleus of the Tractus Solitarius; from there widespread projections reach the limbic, reticular, and autonomic regions of the brain as well as other brain stem nuclei like the locus coeruleus and raphe magnocellularis that CSF influence serotonin and norepinephrine levels.5 Lesioning the LC appears to abolish the antiepileptic effect of VNS.

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VNS in monkeys was shown to abort generalized convulsive seizures induced with pentylenetetrazole; this effect persisted beyond the time of actual stimulation.6,7 Studies in humans have shown reduction of interictal spike discharges and prolongation of the interspike interval.8 In addition, VNS is accompanied by a bilateral increase in blood flow to the thalamus, the hypothalamus, and the insular cortex and a bilateral decrease in blood flow to the amygdala, hippocampus, and posterior cingulate gyri. The reduction in thalamic blood flow was shown to correlate with seizure reduction....

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