The potential use of trigeminal nerve stimulation in the treatment of epilepsy.

Abstract

Editorial For reprint orders, please contact reprints@future-science.com Therapeutic Delivery The potential use of trigeminal nerve stimulation in the treatment of epilepsy “ ...after billions of R&D dollars to develop new drugs, this needle has not budged. A new approach is needed. ” Keywords: adjunctive treatment • anti-convulsant • bilateral stimulation • brain stimulation • cranial nerve stimulation • drug resistance • epilepsy • neuromodulation • non-invasive • trigeminal nerve stimulation Among neurological disorders, epilepsy poses an enormous clinical and societal problem, affecting approximately 50,000,000 people worldwide [1] . For individual patients, the presence of a chronic brain disorder marked by episodic convulsions and loss of control of mental and physical actions can limit occupational and social achievement. From a macro perspective, epilepsy is associated with considerable societal economic burden, accounting for a substantial proportion of the ‘disability adjusted life years’ ascribed to neurological illnesses [2] . Critically, approxi- mately a third of patients with epilepsy have ‘drug resistant epilepsy (DRE),’ character- ized as having persistent seizures despite hav- ing tried at least two different antiepileptic drugs (AEDs) [3] . Of the roughly three dozen AEDs used in the USA, approximately half have been introduced over the past four decades, and while strides have been made in improving efficacy and tolerability, the clinical challenge of DRE persists at roughly a third of all patients with epilepsy: stated differently, after billions of R&D dollars to develop new drugs, this needle has not budged. A new approach is needed. Neuromodulation interventions offer an alternative to the administration of phar- maceutical products. These therapies are intended to alter brain function by applying electric or magnetic fields to the CNS, either directly to the CNS as in deep brain stimula- tion, or via peripheral or cranial nerves, as in vagus nerve stimulation. Some key theoretical advantages of neuromodulation over drug 10.4155/TDE.14.120 © 2015 Future Science Ltd therapy are the lack of systemic exposure to key organ systems, the absence of drug–drug interactions and a reduced risk of teratogenic- ity. In epilepsy, these approaches have offered new hope because they utilize very different mechanisms of action than the medications, by directly changing regional brain activity, and commercially successful neuromodula- tion products, such as deep brain stimulation for Parkinson’s Disease, have been implanted in approximately 8000 to 10,000 new patients per year worldwide [4] . Although many of these patients have benefited from their implants, the absolute numbers stand in stark contrast to the tens of millions of patients who are inad- equately treated with medications and clearly need new therapeutic options. Therapeutic delivery for the surgically implantable devices has been limited, with issues around risks and costs of implantation and explantation, the limited availability of requisite surgical exper- tise, an inability to screen preoperatively for who will benefit and patient acceptability of an implanted system. Noninvasive and minimally invasive neurmodulation approaches might offer the advantages of neuromodulation without the challenges of surgical implantation. Trigemi- nal nerve stimulation (TNS) is a new therapy for epilepsy that can offer ‘neuromodulation without implantation.’ Noninvasive external TNS (eTNS) offers the therapeutic benefits of neuromodulation with the convenience of a prescribed pharmaceutical and yet without the side effects of a typical AED. In studies to date, subjects have applied an ‘electric patch’ Ther. Deliv. (2015) 6(3), 273–275 Ian A Cook Author for correspondence University of California, Los Angeles, CA, USA and NeuroSigma, Inc, Los Angeles, CA, USA iancookmd@ gmail.com Colin P Kealey University of California, Los Angeles, CA, USA and NeuroSigma, Inc, Los Angeles, CA, USA Christopher M DeGiorgio University of California, Los Angeles, CA, USA and NeuroSigma, Inc, Los Angeles, CA, USA part of ISSN 2041-5990