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Publications

An Overview of Trigeminal Nerve Stimulation: Basic Science, Clinical Results and Future Directions

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Regional PET Activations with Trigeminal Nerve Stimulation (TNS) and Correlation with Therapeutic Response

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Reduction of PTZ-Induced Seizure Activity in Awake Rats by Seizure-Triggered Trigeminal Nerve Stimulation: A History

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Effects of Trigeminal Nerve Stimulation on Neuron Firing and Local Field Potentials in the Neocortex of Awake Rats

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Peer-Reviewed Publications on eTNS (Arranged by Year)

Trigeminal Nerve Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder. Neuromodulation, 2016.

This paper reports the first open pilot study of eTNS as an adjunctive therapy for adults with PTSD and co-occuring major depression. 12 adults with moderate-to-severe symptoms that had not responded to medication treatment received eTNS nightly for 8 weeks. Significant reductions in severity were found for both PTSD and depression symptoms, and the treatment was generally well tolerated. Quality of life measures also improved significantly.


An eight-week, open-trial, pilot feasibility study of trigeminal nerve stimulation in youth with attention-deficit/hyperactivity disorder. Brain Stimulation, 2015.

The first pediatric trial of eTNS examined its use in children with ADHD as a single primary treatment (monotherapy) rather than adjunctive therapy. 24 children, ages 7-14, used eTNS nightly for 8 weeks. Significant improvements were found in the symptoms of ADHD and also in computerized measures of cognitive function. The investigators reported that TNS was well accepted by patients and families, treatment compliance was high, and there were no clinically meaningful side effects.


The potential use of trigeminal nerve stimulation in the treatment of epilepsy. Therapeutic delivery, 2015.

This summary paper describes some of the unmet medical need that has driven innovation with eTNS for epilepsy.


Neuromodulation for Depression Invasive and Noninvasive (Deep Brain Stimulation, Transcranial Magnetic Stimulation, Trigeminal Nerve Stimulation). Neurosurgery Clinics of North America, 2014.

This review paper describes several neuromodulation therapies for use in depression, including eTNS, and provides key references to the scientific literature.


External Trigeminal Nerve Stimulation (eTNS) for Epilepsy: Early Clinical Experience. ILAE Conference, UK 2013.

A poster presented by a Slaght et al. from the Department of Neurology at King’s College, London. Their early clinical experience with eTNS for epilepsy shows a 33% responder rate after 12 weeks of treatment. Improvements in mood and quality of life were also observed. These findings are in-line with results from earlier studies of eTNS for epilepsy.


Trigeminal nerve stimulation in major depressive disorder: Acute outcomes in an open pilot study. Epilepsy and Behavior, 2013

A comprehensive description of the first open pilot investigation of eTNS as adjunctive therapy for major depression. 11 adults with treatment resistant depression received eTNS nightly for 8 weeks. At the end of the trial there were significant reductions in symptom severity on both clinician and patient rating scales. The average decrease in symptom severity was 52%, and 4 of 11 patients achieved remission. There were no serious adverse events during the trial.


Randomised controlled trial of trigeminal nerve stimulation for drug-resistant epilepsy. Neurology, 2013

This paper details results from the first ever double-blind, randomised controlled trial of eTNS for treatment of drug resistant epilepsy. The study found that after 18 weeks of eTNS 40.5% of patients in the treatment group reduced their seizure frequency by 50% or more, versus only 15.6% of patients in the control group. Patients in the treatment group also demonstrated significant improvements in mood that were independent of their change in seizure frequency.


Central mechanisms of cranial nerve stimulation for epilepsy. Surgical Neurology International, 2012

An in-depth review of cranial nerve stimulation techniques for the treatment of epilepsy that discusses mechanisms of action for how these treatments produce their anti-seizure effects and identifies areas for future investigation.


Benefits of trigeminal nerve stimulation. Epilepsy & Behavior, 2012

An editorial written by Dr. Robert Fisher of Stanford University. Dr. Fisher is a pioneer in the field of neuromodulation approaches for treating epilepsy. In this editorial, Dr. Fisher discusses the benefits of trigeminal nerve stimulation and the exciting data that has been produced to date.


Acute and long-term safety of external trigeminal nerve stimulation for drug-resistant epilepsy. Epilepsy & Behavior, 2011

A publication examining the short- and long-term safety data associated with use of eTNS. Notably, there have been no significant adverse events associated with the use of eTNS therapy to date.


Trigeminal nerve stimulation: seminal animal and human studies for epilepsy and depression. Neurosurgery Clinics of North America, 2011

An overview of the pre-clinical animal work. The work first demonstrated the anti-seizure effects of TNS as well as the first clinical studies of non-invasive eTNS therapy for drug resistant epilepsy.


Trigeminal nerve stimulation in major depressive disorder: first proof of concept in an open pilot trial. Epilepsy & Behavior, 2011

This manuscript details interim results from the first-ever trial of eTNS as adjunctive therapy for major depressive disorder. Patients were resistant to medication and used eTNS nightly for 8 weeks. At the end of the trial, patients demonstrated a mean decrease in symptom severity of 52%, indicating a robust anti-depressant effect of eTNS in this preliminary study.


Trigeminal nerve stimulation for epilepsy: long-term feasibility and efficacy. Neurology, 2009

Results from the Phase I study of eTNS for drug resistant epilepsy. Thirteen subjects with severe drug resistant epilepsy (an average of 2.1 seizures/day) were enrolled to receive eTNS for 12 weeks. Twelve of 13 subjects completed the study. Average seizure frequency decreased from 2.1 seizures/day to 0.71 seizures/day. Importantly, these results were sustained in long-term follow-up at 6 and 12 months.


Pilot study of trigeminal nerve stimulation (TNS) for epilepsy: a proof-of-concept trial. Epilepsia, 2006

Results from seven subjects treated with eTNS for their drug resistant epilepsy. Four of seven subjects (57%) had a greater than 50% reduction in seizure frequency.


Trigeminal nerve stimulation for epilepsy. Neurology, 2003

The first publication to provide clinical results on the use of eTNS for treatment of drug resistant epilepsy. This case/series details the experience of the first two patients treated with eTNS.


Reduction of pentylenetetrazole-induced seizure activity in awake rats by seizure-triggered trigeminal nerve stimulation. Journal of Neuroscience, 2000

Details of the pre-clinical animal work demonstrating that TNS has an anti-seizure effect. A series of studies using a rat seizure model showed that high-frequency, bilateral stimulation of the trigeminal nerve results in dramatic reductions in seizure activity. The Monarch eTNS system employs a similar strategy of bilateral, high-frequency stimulation, which may improve efficacy as compared to other cranial nerve stimulation therapies.

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