Results. Thirteen subjects completed the 4-week prospective baseline. Twelve completed 3 months, 10 completed 6 months, and 7 completed 12 months (table e-1). Short-term results from the first seven subjects reported previously are included in this analysis.2 The figure shows results at 3, 6, and 12 months. At 3 months, mean seizure frequency was reduced from a baseline of 2.1 seizures/day to 0.71 seizures/day (66% reduction, p = 0.034, standard error 0.64). At 6 months, mean seizure frequency was 0.92 seizures/day (56% reduction, p = 0.073, standard error 0.64). At 12 months, mean seizure frequency was 0.86 seizures/day (59% reduction, p = 0.058, standard error 0.64). Five subjects experienced greater than 50% reduction at 6 and 12 months; one subject had >90% reduction at 12 months. TNS was well tolerated. Side effects included skin irritation in five subjects, which improved by reducing stimulation to 12-16 hours/day, or with hydrocortisone 1% cream. Tingling, forehead pressure, and headache were reported, but improved with reduction of current. No effect on pulse, blood pressure, or ECG was detected. Discussion. External stimulation of the trigeminal nerve (V1 and V2) was well tolerated, with a mean reduction in seizure frequency of 59% at 12 months. The results of this study build upon data in an animal model, and our short-term report in humans.1,2 Why stimulate the trigeminal nerve for epilepsy? The trigeminal nerve has three bilateral cutaneous branches. 3 These afferent branches (V1-V3) exit foramen 1.25-1.5 inches lateral of the midline, and project to the trigeminal ganglion and the trigeminal nucleus, which projects to the nucleus tractus solitarius and locus ceruleus, all of which play a role in inhibition of seizures. 4-7 The antiepileptic effect of the trigeminal nerve and related structures has been confirmed in animal models.1,4,5 Stimulation of the locus ceruleus suppresses epileptic discharges induced by cobalt and penicillin, and plays a central role in the mechanism of VNS.6,7 In a pentylenetetrazole model, high-frequency stimulation of the trigeminal nerve significantly reduced seizure severity and frequency.1 Bilateral stimulation was more effective than unilateral stimulation, and high frequency stimulation was more effective than low frequency stimulation.1 The data provide a foundation for future randomized studies of TNS in humans. Based on the longterm feasibility and efficacy of this study, we have embarked on a randomized controlled study of high vs low frequency stimulation of the ophthalmic branch (V1) of the trigeminal nerve for intractable epilepsy. Copyright © by AAN Enterprises, InC.
