Abstracts

Rationale: eTNS is a promising therapy for DRE. eTNS delivers stimulation to the supraorbital branches of the trigeminal nerves via electrodes adhered to the forehead and an external pulse generator. This enables bilateral stimulation that is inexpensive and easy to discontinue without surgical intervention. This study aims to evaluate a recently developed eTNS electrode and external pulse generator (The Monarch eTNS System, Neurosigma, USA). Effects of eTNS on seizure frequency and mood were assessed. Methods: Adults with DRE and at least one complex partial and/or secondarily generalized seizure in the last three consecutive months underwent 12 hours of eTNS per night. eTNS was delivered to the bilateral supraorbital nerves using 250-µsecond biphasic square wave pulses at 120 Hz for 30 seconds on and 30 seconds off. Seizure frequency one month prior to eTNS was compared to seizure frequency after three months of eTNS. Mood was assessed at baseline and at 3 months using the Beck Depression Inventory (BDI). Results: Of 18 subjects, one had very frequent brief “cognitive glitches” too numerous to accurately quantify.  Another was lost to follow up after the second visit.  Of the remaining 16 subjects, 5 withdrew prior to the 3-month visit due to no improvement in seizures (N = 2) or concern over possible worsening of seizure frequency or severity (N = 3) with eTNS.  4 of the 11 remaining subjects had a = 50% greater reduction in seizure frequency, resulting in a responder rate of 36.4%.  When including the five subjects who dropped out due to perceived neutral or adverse effects on seizure frequency/severity, the responder rate is 4/16 subjects or 25%.  In assessing the effects of eTNS on mood, the average BDI scores before and after three months of eTNS were 9.3 (SD 9.9) and 7.6 (SD 7.0) (p=0.12 one-tailed paired t test), respectively.  However, for the three subjects with moderate to severe depression BDI scores at baseline, the average score declined from 25 (SD 5.9) to 17 (SD 7.1) in three months showing a substantial clinical effect of eTNS in these patients that neared statistical significance despite the very small sample size (p=0.06 one-tailed paired t test). Conclusions: This is the first study to concurrently explore the effects of eTNS on mood and seizure frequency. While this study is limited by small sample size and lack of control arm, eTNS use in DRE showed a responder rate of 25 to 36.4%, consistent with responder rates of 23–31% seen in two key randomized controlled trials that ultimately led to FDA-approval of VNS for DRE (1, 2).  While our data in epilepsy patients with co-morbid moderate to severe depression is limited by very small sample size (N = 3), this preliminary exploration suggests that eTNS has potential as a therapy for individuals with DRE and may be especially useful in DRE patients with co-morbid depression.References:1. Benmenachem E, Manonespaillat R, Ristanovic R. Wilder BJ, Stefan H, Mirza W, Tarver WB, Wernicke JF, Augustinsson L, Barolat G et al. Vagus nerve-stimulation for treatment of partial seizures: a controlled-study of effect on seizures. Epilepsia. 1994;35:616–626.2. Handforth A, DeGiorgio CM, Schachter SC, Uthman BM, Naritoku DK, Tecoma ES, Henry TR, Collins SD, Vaughn BV, Gilmartin RC, et al. Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology. 1998 Jul;51(1):48-55. Funding: NIH, Neurosigma