Project Proposal - michaelrees/Trigeminal_Stimulation GitHub Wiki

Trigeminal Nerve stimulation is an emerging neuromodulation treatment for epilepsy. The trigeminal nerve is composed of sensory afferents, and has three primary facial branches that project bilaterally out of the skull both above and below the eye socket. Like the Vagus nerve, the Trigeminal Nerve projects to the nucleus tractus solitarius (NTS), locus coeruleus, and the reticular formation. These brainstem structures are believed to play an important role in seizure inhibition. NeuroSigma’s Monarch eTNS System is a novel approach to treating epilepsy by stimulating the Trigeminal Nerve through surface electrical stimulation. With the eTNS system, the trigeminal nerve is stimulated for a recommended minimum of 12 hours per day by surface electrodes that deliver current anywhere from 8-25mA at a frequency of 120Hz with a duty cycle of 30 seconds on followed by 30 seconds off[6]. The Monarch eTNS system stimulates the Trigeminal nerve through either surface electrodes contacting the face infraorbitally (below the eye socket) to target the trigeminal maxillary nerve (V2 branch), or supraorbitally to target the trigeminal ophthalmic nerve (V1 branch). From either of these branches, the afferent signals reach the trigeminal ganglion, which can then reach deeper portions of the brain through either the trigeminal brainstem nuclei or the nucleus tractus solitarius (NTS)[5]. In a Phase II randomized control trial of the eTNS, 40% of patients experienced at least a 50% decrease in seizures by the end of 18 weeks in addition to improved depression scores for majority of patients. eTNS is non-invasive, has low risk, and treatment can be easily removed.

Though the mechanism of therapy is not well understood, it is hypothesized that stimulation of the trigeminal nerve acts on the NTS in a similar manner to vagal nerve stimulation (VNS)[5]. We propose using computational modelling to test the hypothesis that surface stimulation with the given parameters is sufficient to stimulate a hypothetical trigeminal nerve with a given nerve fiber diameter and distance from stimulation. If the stimulation is sufficient, then that would add to the feasibility of trigeminal nerve stimulation. We also propose exploring the possibility that other facial nerves may be stimulated and thus contribute to the observed therapeutic results.

Key Sources

[1] DeGiorgio, Christopher M., Erika E. Fanselow, Lara M. Schrader, and Ian A. Cook. “Trigeminal Nerve Stimulation: Seminal Animal and Human Studies for Epilepsy and Depression.” Neurosurgery Clinics of North America, Epilepsy Surgery: The Emerging Field of Neuromodulation, 22, no. 4 (October 2011): 449–56. doi:10.1016/j.nec.2011.07.001.

[2] DeGiorgio, Christopher M., Alan Shewmon, Diane Murray, and Todd Whitehurst. “Pilot Study of Trigeminal Nerve Stimulation (TNS) for Epilepsy: A Proof-of-Concept Trial.” Epilepsia 47, no. 7 (July 1, 2006): 1213–15. doi:10.1111/j.1528-1167.2006.00594.x. [3] DeGiorgio, Christopher M., D. Alan Shewmon, and Todd Whitehurst. “Trigeminal Nerve Stimulation for Epilepsy.” Neurology 61, no. 3 (August 12, 2003): 421–22. doi:10.1212/01.WNL.0000073982.42650.57.

[4]DeGiorgio, Christopher M., Jason Soss, Ian A. Cook, Daniela Markovic, Jeffrey Gornbein, Diana Murray, Sandra Oviedo, et al. “Randomized Controlled Trial of Trigeminal Nerve Stimulation for Drug-Resistant Epilepsy.” Neurology 80, no. 9 (February 26, 2013): 786–91. doi:10.1212/WNL.0b013e318285c11a.

[5] Fanselow, ErikaE. “Central Mechanisms of Cranial Nerve Stimulation for Epilepsy.” Surgical Neurology International 3, no. 5 (2012): 247. doi:10.4103/2152-7806.103014.

[6] Fisher, Robert S. “Benefits of Trigeminal Nerve Stimulation.” Epilepsy & Behavior 22, no. 4 (December 2011): 615–16. doi:10.1016/j.yebeh.2011.09.024.

[7] Slaght, Sean, Muna Said, Elaine Hughes, Sithara Ramdas, Mark Richardson, Robert Elwes, and Lina Nashef. “External Trigeminal Nerve Stimulation (etns) for Epilepsy.” Journal of Neurology, Neurosurgery & Psychiatry 85, no. 10 (October 1, 2014): e4–e4. doi:10.1136/jnnp-2014-309236.77.