Neuromodulation in the Treatment of Epilepsy

Abstract

Neuromodulation devices are used in the treatment of medically refractory epilepsy. This has been defined as epilepsy with persistent seizures despite adequate trials of at least two anti-epileptic drugs (AEDs). In most cases of medically refractory partial epilepsy, the first choice of treatment is resective surgery if the seizure focus can be definitively localized and if surgery can be safely performed without causing intolerable neurologic deficits. Patients with medically refractory epilepsy who are not candidates for potentially curative surgery may benefit from the implantation of a neuromodulation device. While most of these devices require surgical implantation, they provide a significant added seizure reduction without typical medication side effects. Furthermore, the efficacy of these devices continues to improve over years. There are currently no head-to-head trials comparing the different neuromodulation devices but efficacy appears to be roughly similar. The choice of device therefore depends on the type of epilepsy, whether the seizure focus can be identified, and other clinical factors. Vagal Nerve Stimulation (VNS) does not require identification of the seizure focus and also carries an FDA indication for depression. While in the United States VNS is only approved for use in partial epilepsy, it is commonly used off-label to treat generalized seizures as well. VNS delivers stimulation on a scheduled basis, in response to patient activation, or in response to heart rate increases serving as a proxy for seizures. Responsive Neurostimulation (RNS) requires the identification of up to two seizure foci and delivers stimulation only in response to the detection of epileptiform activity. While it requires intracranial placement of electrodes, it allows for long-term monitoring of electrographic seizures and may be effective where VNS has not produced an optimal response. Deep brain stimulation of the anterior nucleus of the thalamus is not FDA approved at this time but is available in Europe and many other parts of the world. While it also carries an indication only for partial epilepsy, it does not require identification of the seizure focus and may be particularly helpful for temporal lobe epilepsy. It also appears effective in cases where VNS has not been sufficiently helpful. The Trigeminal Nerve Stimulation (TNS) system is another treatment modality which is not yet FDA approved but is available in Europe and other countries. Its mechanism of action is similar to the VNS system and it also appears to have anti-depression effects in addition to anti-epileptic benefits. However, the most compelling feature of TNS is that it is not implanted but rather applied to the skin with transdermal electrodes, typically at night.