Central mechanisms of cranial nerve stimulation for epilepsy

Abstract

Stimulation of peripheral cranial nerves has been shown to exert anticonvulsant effects in animal models as well as in human patients. Specifically, stimulation of both the trigeminal and vagus nerves has been shown in multiple clinical trials to be anticonvulsant, and stimulation of these nerves at therapeutic levels does not cause pain or negatively affect brain function. However, the neuronal mechanisms by which such stimulation exerts therapeutic effects are not well understood. In this review, the possible locations of action for trigeminal nerve stimulation (TNS) and vagus nerve stimulation (VNS) are explored. Additionally, the multiple time scales on which TNS and VNS function are discussed.

Neurostimulation for Drug-Resistant Epilepsy

“…31 This provides further support for the antiepileptic effect of TNS and may explain why bilateral stimulation is more effective than unilateral stimulation. 30,31 In a pilot feasibility trial, 14 subjects with severe epilepsy were enrolled in an open-label feasibility study of eTNS. 10 Subjects entered a 1-month pretreatment baseline and were thereafter treated with eTNS for a minimum of 12 hours daily; they were allowed to control the amplitude of current delivered and were instructed to use the maximum comfortable level.…”

“…30,31 More recently, Fanselow and colleagues measured cortical local field potentials with unilateral stimulation of the trigeminal nerve in a rat model and confirmed that TNS results in direct inhibition of pyramidal cortical neurons contralateral to the side of stimulation. 31 This provides further support for the antiepileptic effect of TNS and may explain why bilateral stimulation is more effective than unilateral stimulation. 30,31 In a pilot feasibility trial, 14 subjects with severe epilepsy were enrolled in an open-label feasibility study of eTNS.…”

“…30 In a series of studies, a rat pentylenetetrazole seizure model was used to demonstrate that infraorbital TNS results in reductions in seizure activity. 30,31 These studies concluded that the magnitude of the seizure-reduction effect increases as the amplitude and frequency of stimulation increase, and that bilateral stimulation is more effective than unilateral stimulation. 30,31 More recently, Fanselow and colleagues measured cortical local field potentials with unilateral stimulation of the trigeminal nerve in a rat model and confirmed that TNS results in direct inhibition of pyramidal cortical neurons contralateral to the side of stimulation.…”

“…30,31 These studies concluded that the magnitude of the seizure-reduction effect increases as the amplitude and frequency of stimulation increase, and that bilateral stimulation is more effective than unilateral stimulation. 30,31 More recently, Fanselow and colleagues measured cortical local field potentials with unilateral stimulation of the trigeminal nerve in a rat model and confirmed that TNS results in direct inhibition of pyramidal cortical neurons contralateral to the side of stimulation. 31 This provides further support for the antiepileptic effect of TNS and may explain why bilateral stimulation is more effective than unilateral stimulation.…”

The Potential Use of Trigeminal Nerve Stimulation in the Treatment of Epilepsy

“…The potential use of trigeminal nerve stimulation in the treatment of epilepsy AEDs, the antiepileptic mechanism of action of eTNS appears to be related to reductions in cortical excitability [5][6][7][8], but critically, with physiologic effects focused only on targeted regions of the brain. The efficacy of adjunctive eTNS in reducing seizure frequency has been studied in open-label [9] and double-blind controlled studies [10] and outcomes are in line with other successful adjunctive treatments, albeit with smaller trials to date.…”